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Go to evolve.elsevier.com/shop to search and browse for products. --- PAGE 3 --- Ruppel’s Manual of Pulmonary Function Testing --- PAGE 5 --- Ruppel’s Manual of Pulmonary Function Testing T WELFTH EDITION Carl D. Mottram, RRT, RPFT, FAARC Associate Professor of Medicine President – PFWConsulting LLC --- PAGE 6 --- Elsevier 3251 Riverport Lane St. Louis, Missouri 63043 RUPPEL'S MANUAL OF PULMONARY FUNCTION TESTING, TWELFTH EDITION ISBN: 978-0-323-76261-8 Copyright © 2023 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notice Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2017, 2013, 2009, 2003, 1998, 1994, 1991, 1986, 1982, 1979, 1975. Senior Content Strategist: Yvonne Alexopoulos Content Development Specialist: Andrae Akeh Publishing Services Manager: Shereen Jameel Senior Project Manager: Manikandan Chandrasekaran Design Direction: Julia Dummitt Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1 --- PAGE 7 --- List of Contributors The editor(s) would like to acknowledge and Katrina M. Hynes, MHA, RRT, RPFT offer grateful thanks for the input of all previous Sr. Manager, Customer Education editions’ contributors, without whom this new People and Culture edition would not have been possible. Vyaire Medical Inc. Mettawa, IL Susan Blonshine, BS, RRT, RPFT, FAARC, AE-C CEO and President David A. Kaminsky, MD Management Professor of Medicine TechEd Consultants, INC. Pulmonary and Critical Care Medicine Mason, MI University of Vermont; Attending Physician Jeffrey M. Haynes, RRT, RPFT, FAARC Pulmonary and Critical Care Medicine Clinical Coordinator University of Vermont Medical Center Pulmonary Function Laboratory Burlington, VT Elliot Health System Manchester, NH v --- PAGE 8 --- Preface The primary functions of the lung are oxygenation • Each test section includes criteria for accept- of mixed venous blood and removal of carbon diox- ability and repeatability, as well as interpretive ide. Gas exchange depends on the integrity of the strategies with criteria that are organized to help entire cardiopulmonary system, including airways, those who perform pulmonary function tests pulmonary blood vessels, alveoli, respiratory mus- adhere to recognized standards. cles, and respiratory control mechanisms. A few • Most of the testing criteria are based on the pulmonary function tests assess individual parts of American Thoracic Society and European the cardiopulmonary system. However, most lung Respiratory Society (ATS-ERS) statements, function tests measure the status of the lungs’ com- with a few based on the clinical practice ponents in an overlapping way. guidelines of the American Association for This twelfth edition describes the most common Respiratory Care. pulmonary function tests, their techniques, and • The interpretive strategies are presented as a se- the pathophysiology that may be evaluated by each ries of questions that can be used as a starting test. Topics covered include the following: point for test interpretation. In this edition, we • Basic tests of lung function, including spirometry, include a flowchart process for systematically in- lung volume measurements (i.e., body plethys- terpreting the basic lung function tests. mography, nitrogen washout, and helium dilu- • Case Studies with real-life patient scenarios, tion), diffusing capacity, and blood gas analysis questions, and discussion topics are included at • Ventilation and ventilatory control, cardiopul- the end of the chapters. monary exercise tests, and pediatric and infant • How To boxes populate specific testing chapters. pulmonary function testing These are step-by-step guides for performing • Specialized test regimens that focus on exhaled function tests. When possible, we provide illus- nitric oxide measurements, forced oscillation trations. These procedures take the guesswork techniques, metabolic studies, disability deter- out of performing an accurate test. mination, and preoperative evaluation • The Evolve Learning Resources feature updated • Bronchial challenge tests that assist the clinician Case Studies in PowerPoint format so that in- in characterizing the hyperreactivity of the airways structors can utilize them during class discus- • Pulmonary function testing equipment, sions. Clinical Scenario slides, organized by quality assurance, and reference values and disease process, provide an in-depth case anal- interpretation ysis, with figures and charts noting lab values and treatment options. Instructors and student study groups can use these to supplement their DISTINCTIVE FEATURES own clinical experiences. The twelfth edition includes many of the features from the previous editions: TEXT UPDATES • Learning objectives for entry-level and advanced practitioners are again included at the beginning • Chapter 1 includes updates related to the 2019 of each chapter. ATS-ERS technical standard. vi --- PAGE 9 --- Preface vii • Chapter 2 is updated per the 2019 ATS-ERS reference for technologists and physicians. Because Technical Standard published in 2019. of the wide variety of methods and equipment used • Chapter 3 is now aligned with the 2017 ATS-ERS in pulmonary function evaluation, some tests are technical standard for the Global Lung Initiative discussed in general terms. For this reason, read- (GLI). ers are encouraged to use the selected bibliogra- • The ERS published their methacholine technical phies provided. The presentation of indications, standard in late 2017 and their indirect testing pathophysiology, and the clinical significance of (e.g., mannitol, exercise, hyperventilation, cold various tests presumes a basic understanding of air) technical standard in 2018. Both have been cardiopulmonary anatomy and physiology. Again, incorporated into Chapter 9. readers are urged to refer to the General References • Updates to several sections are included in included in the selected bibliographies to refresh Chapter 10: their background knowledge of lung function. The ○ Respiratory muscle strength testing— terminology used is that of the American College of Respiratory Muscle Strength testing section Chest Physicians (ACCP)-ATS Joint Committee on has been updated to include the 2019 ERS Pulmonary Nomenclature. In some instances, test Testing Standard and the 2017 reference set names reflect common usage that does not follow for children the ACCP-ATS recommendations. ○ Exhaled nitric oxide—Exhaled nitirc oxide test- ing has been updated to include the 2017 ERS EVOLVE ANCILLARIES Technical Standard on Exhaled Biomarkers and the 2021 ATS Clinical Practice Guideline • Evolve is an interactive learning environment on the Use of FENO to Guide Treatment designed to work in coordination with Ruppel’s ○ Spirometry sections modified based on new Manual of Pulmonary Function Testing, twelfth 2019 ATS-ERS technical standard edition. • Chapter 11 has been updated to reflect new For the student, our Evolve Learning Resources equipment and vendors. include: • Chapter 12 covers the new version of QMS01, • Practice tests to help students apply the knowl- the quality management system document. The edge learned within the text components of the ATS Pulmonary Function • Conversion and correction factors Laboratory (PFL) Accreditation Program are • Helpful equations included. • Reference tables • Chapter 13 includes the new GLI diffusion of • Sample calculations lung capacity for carbon monoxide reference, • Electronic image collection consisting of images published in 2019 and the 2020 GLI Lung from the textbook Volume reference set. For the instructor, our Evolve Learning Resources As in previous editions, each chapter includes include: self-assessment questions. The questions in this edi- • PowerPoint presentations of Case Studies and tion are divided into entry-level and advanced cat- Clinical Scenarios egories. The answers may be found in Appendix A. • Test Bank containing approximately 600 A selected bibliography at the end of each chapter questions is arranged according to topics within the chapter, • Electronic image collection consisting of images including standards and guidelines. from the textbook Instructors may use Evolve to provide an Internet-based course component that reinforces USING THIS BOOK and expands the concepts presented in class. Evolve This manual is intended to serve as a text for stu- may be used to publish the class syllabus, out- dents of pulmonary function testing and as a lines, and lecture notes; set up virtual office hours --- PAGE 10 --- viii Preface and e-mail communication; share important dates instructors to post examinations and manage their and information through the online class calen- grade books online. For more information, visit dar; and encourage student participation through http://evolve.elsevier.com or contact an Elsevier chat rooms and discussion boards. Evolve allows sales representative. --- PAGE 11 --- Author’s Commentary I would like to ac- stages of his career, and I learned so much about knowledge a few his passion for pulmonary physiology testing. Drs. key colleagues and Paul Scanlon, David Driscoll, Bruce Staats, and friends who have Ken Beck treated me as they would a pulmonary contributed to my fellow in training and later as a colleague. These professional suc- individuals were tremendously instrumental in my cess. First, I had understanding of pulmonary physiology and my the honor of be- professional development. Jeff Ward, MEd, RRT, ing educated and FAARC, Mayo Clinic’s former respiratory therapy mentored by Drs. program director, started me on my professional Fred Helmholtz journey with the mindset of inquiry and yearning and Robert (Bob) for knowledge. I would not be the professional I am Hyatt, both giants today without all of their guidance and tutelage. in their field. Dr. I would personally like to thank the contributors Helmholtz, along with colleagues, assisted in the to this edition, Susan Blonshine, Dr. David Kaminsky, development of the G-suit during World War II and Jeffrey Haynes, and Katrina Hynes, for their excel- the nitrogen washout test. After his retirement, he lent subject review. I would also like to thank the continued to have a significant impact on the field staff members and leadership of the Mayo Clinic through his contributions to the National Board Pulmonary Function Laboratories, especially Drs. for Respiratory Care’s credentialing system and Alex Niven and Kaiser Lim. They continue to carry specifically the initiation of the pulmonary func- forward the incredible work the laboratory has been tion credentialing exam. Dr. Hyatt was the first to renown for since its inception by championing Mayo’s describe the flow-volume curve and tests for evalu- primary value of “the needs of the patient come first.” ating respiratory muscle strength. I had the privi- lege of sharing an office with Dr. Hyatt in the later Carl D. Mottram, RRT, RPFT, FAARC ix --- PAGE 12 --- Contents CHAPTER 1 Indications for Pulmonary Function Testing, 1 CHAPTER 2 Spirometry, 41 CHAPTER 3 Diffusing Capacity Tests, 84 CHAPTER 4 Lung Volumes, Airway Resistance, and Gas Distribution Tests, 109 Jeffrey M. Haynes, RRT, RPFT, FAARC CHAPTER 5 Ventilation and Ventilatory Control Tests, 145 CHAPTER 6 Blood Gases and Related Tests, 165 CHAPTER 7 Cardiopulmonary Exercise Testing and Field Tests, 197 CHAPTER 8 Pediatric Pulmonary Function Testing, 251 Katrina M. Hynes, MHA, RRT, RPFT CHAPTER 9 Bronchoprovocation Challenge Testing, 307 CHAPTER 10 Specialized Tests and Evaluations, 332 Katrina M. Hynes, MHA, RRT, RPFT CHAPTER 11 Pulmonary Function Testing Equipment, 367 CHAPTER 12 Quality Systems in the Pulmonary Function Laboratory, 421 Susan Blonshine, BS, RRT, RPFT, FAARC, AE-C CHAPTER 13 Reference Values and Interpretation Strategies, 474 David A. Kaminsky, MD APPENDIX A Answers to Self-Assessment Questions, 497 Index, 499 x --- PAGE 13 --- 1 Chapter Indications for Pulmonary Function Testing CHAPTER OUTLINE Pulmonary Function Tests Congestive Heart Failure Airway Function Tests Lung Transplantation Lung Volume and Ventilation Tests Preliminaries to Patient Testing Diffusing Capacity Tests Testing During a Pandemic Blood Gases and Gas Exchange Tests Before Patient Testing Cardiopulmonary Exercise Tests Patient Preparation (Pretest Instructions) Metabolic Measurements Withholding Medications Indications for Pulmonary Function Testing Smoking Cessation Spirometry Other Patient Preparation Issues Lung Volumes Anthropometric Measurements Diffusing Capacity Physical Assessment Blood Gases Pulmonary History Exercise Tests Test Performance and Sequence Patterns of Impaired Pulmonary Function Technologist-Driven Protocols (Operator-Driven Obstructive Airway Diseases Protocols) Restrictive Lung Disease Patient Instruction Diseases of the Chest Wall and Pleura Summary Neuromuscular Disorders Case Study LEARNING OBJECTIVES After studying the chapter and reviewing the figures, tables, and case studies, you should be able to do the following: Entry-level 1. Categorize pulmonary function tests according to specific purposes. 2. List indications for spirometry, lung volumes, and diffusing capacity. 3. Identify at least one obstructive and one restrictive pulmonary disorder. 4. Relate pulmonary history to indications for performing pulmonary function tests. Advanced 1. Identify three indications for exercise testing. 2. Name at least two diseases in which air trapping may occur. 3. Describe which services are available during Level I and Level II of a pandemic. 4. Describe the use of an operator-adapted protocol for pulmonary function studies. 1 --- PAGE 14 --- 2 Ruppel’s Manual of Pulmonary Function Testing KEY TERMS β2 agonist hyperventilation oximetry body plethysmograph hypoventilation pulse oximetry bronchial challenge maximal expiratory flow volume personal protective equipment capnography (MEFV) (PPE) diffusing capacity (Dlco) maximal midexpiratory flow rate resting energy expenditure (REE) edema (MMFR) spirometry forced vital capacity (FVC) maximal voluntary ventilation vital capacity (VC) hypercapnia (MVV) The chapter provides an overview of pulmonary a surgeon named Hutchinson developed a simple function testing. Common pulmonary function water-sealed spirometer that allowed measurement tests are introduced, and the indications for each of what he named vital capacity, or “vital breath,” as test are discussed. Diseases that commonly require he noted its relationship to survival. Hutchinson pulmonary function tests are described, and guide- popularized the concept of using VC to assess lung lines regarding patient preparation and assessment function and named several other lung compart- are presented. Adequate patient preparation, phys- ments with terms that are still used today. He ob- ical assessment, and pulmonary history help the served that VC was related to the standing height tests provide answers to clinical questions. The im- of the patient. He also developed tables to estimate portance of patient instruction in obtaining valid the expected VC for a healthy patient. The VC was data is discussed. These topics are developed more usually graphed on chart paper, which allowed sub- fully in subsequent chapters. divisions of the VC to be identified (see Chapter 2). PULMONARY FUNCTION TESTS PF TIP 1.1 Many different tests are used to evaluate lung func- Pulmonary function data are usually grouped tion. These tests can be divided into categories based into categories (see Fig. 1.1). The patient’s on the aspect of lung function they measure (Box 1.1). demographic data (age, height, gender, Although the tests can be performed individually, they race, weight) are usually at the top of the report. The PFT data are presented in are often performed in combination. Fig. 1.1 shows a several columns. These columns show the sample pulmonary function test (PFT) report that in- predicted (expected) values, the lower limit of cludes spirometry, lung volumes, diffusing capacity, normal (LLN) or upper limit of normal (ULN), and respiratory muscle strength measurements in a measured values obtained during testing, commonly used format. Determining which tests and the percentage of predicted values for each test (actual/predicted × 100). Be sure to to do depends on the clinical question to be answered. identify which column is actual and which is This question may be explicit, such as “Does the pa- predicted. tient have asthma?” or less obvious, such as “Does this patient who needs thoracic surgery have any pulmo- nary diseases that might complicate the procedure?” Forced vital capacity (FVC) is an enhancement In either case, indications for specific tests are useful of the simple VC test. During the 1930s, Barach ob- (see Boxes 1.2–1.6). served that patients with asthma or emphysema ex- haled more slowly than healthy patients. He noted Airway Function Tests that airflow out of the lungs was important in detect- The most basic test of pulmonary function is the ing obstruction of the airways. Barach used a rotating measurement of vital capacity (VC). This test sim- chart drum (kymograph) to display VC changes as a spi- ply measures the largest volume of air that can be rogram. He even evaluated the effects of bronchodila- moved into or out of the lungs. In the mid-1800s, tor medications using the FVC traced as a spirogram. --- PAGE 15 --- Indications for Pulmonary Function Testing • Chapter 1 3 BOX 1.1 CATEGORIES OF PULMONARY FUNCTION TESTS A. Airway function a. Multiple-breath N 2 1. Simple spirometry b. He equilibration a. Vital capacity (VC), expiratory reserve volume c. Single-breath techniques (ERV), inspiratory capacity (IC) C. Diffusing capacity (Dlco) tests 2. Forced vital capacity (FVC) maneuver 1. Single-breath (breath holding) a. FVC, forced expired volume in the first second 2. Steady state (FEV ), forced expiratory flow (FEF), peak 3. Other techniques 1 expiratory flow (PEF) D. Blood gases and gas exchange tests (1) Prebronchodilator and 1. Blood gas analysis and blood oximetry postbronchodilator a. Shunt studies (2) Prebronchochallenge and 2. Pulse oximetry postbronchochallenge 3. Capnography b. Maximal expiratory flow-volume (MEFV) curves E. Cardiopulmonary exercise tests (1) Prebronchodilator and 1. Simple, noninvasive tests postbronchodilator 2. Tests with exhaled gas analyses (2) Prebronchochallenge and 3. Tests with blood gas analyses postbronchochallenge 4. Tests with flow-volume loops 3. Maximal voluntary ventilation (MVV) 5. Tests with direct laryngoscopy 4. Airway resistance (Raw) and compliance (C) F. Specialized tests L B. Lung volumes and ventilation 1. Respiratory muscle strength testing 1. Functional residual capacity (FRC) a. Maximal respiratory pressures (maximal a. Open-circuit (N washout) inspiratory pressure [MIP]/maximal 2 b. Closed-circuit/rebreathing (He dilution) expiratory pressure [MEP]) c. Thoracic gas volume (Vtg) b. Cough peak flow (CPF) 2. Total lung capacity (TLC), residual volume (RV), c. Sniff nasal inspiratory pressures (SNIPs) RV/TLC ratio 2. Exhaled nitric oxide 3. Minute ventilation, alveolar ventilation, and 3. Forced oscillatory technique dead space G. Metabolic measurements 4. Distribution of ventilation 1. Resting energy expenditure (REE) In 1947, Tiffeneau described measuring the dardize terminology, the MMFR is now referred to volume expired in the first second of a maximal as the forced expiratory flow 25% to 75% (FEF ). 25%–75% exhalation in proportion to the maximal volume In addition to displaying FVC as a volume–time that could be inspired (FEV /IVC [inspiratory vi- spirogram, it can be represented by plotting air- 1 tal capacity]) as an index of airflow obstruction flow against volume. In the late 1950s, Hyatt and (i.e., the Tiffeneau index). Around 1950, Gaensler others began using the flow-volume display to began using a microswitch in conjunction with a assess airway function. The tracing was termed water-sealed spirometer to time FVC. He observed the maximal expiratory flow-volume (MEFV) that healthy patients consistently exhaled approxi- curve. By combining the forced expiration with mately 80% of their FVC in 1 second and almost all an inspiratory maneuver, a closed loop can be dis- of the FVC in 3 seconds. He used the forced expired played. This figure is called the flow-volume loop volume in the first second (FEV ) to assess airway (see Chapter 2). 1 obstruction. In 1955, Leuallen and Fowler demon- Peak expiratory flow (PEF) is measured using ei- strated a graphic method used to assess airflow. ther a flow-sensing spirometer or a peak flow meter. They measured airflow between the 25% and 75% In the 1960s, Wright and McKerrow popularized points on a forced expiratory spirogram. This mea- the use of peak flow to monitor patients with sure was described as the maximal midexpiratory asthma. Peak flow can be readily assessed from the flow rate (MMFR). This and similar measure- flow-volume loop as well. Recently, portable peak ments have been used to describe airflow from both flow meters that allow monitoring at home, as well healthy and airflow-obstructed patients. To stan- as in the hospital or clinic, have been developed. --- PAGE 16 --- 4 Ruppel’s Manual of Pulmonary Function Testing Pulmonary Function Report Patient Information Name: Test K. Subject ID:134732 Test date/time: 9/30/2020 10:04:24 AM Height at test: 75 in Weight at test: 216.41 lb Birth Sex: M Gender: Male Birthdate:12/20/1960 Age at test:59 BMI at test: 27.2 kg/m² Smoking history (pk-yrs): N/A Predicted Group: C Ethnicity:Caucasian Physician: Colin Chapman, M.D. Estimated Lung Age: N/A Technician: ICD-10: (J45.20) Mild intermittent asthma, uncomplicated Referring Dr: Grade: FVC A FEV1 A Grade: FVC B FEV1 B Pre LLN % Pred Zsc –3 –2 Z-Score 2 3 Post % Pred % Chg Zsc –3 –2 Z-Score 2 3 Spirometry at BTPS FVC L 7.24 4.19 132 2.18 7.35 134 2 2.32 FEV1 L 4.87 3.17 116 1.14 4.97 119 2 1.32 FEV1 / FVC % 67 65 –1.40 68 1 –1.27 FEF25–75 [ISO] L/s 2.93 1.66 87 --- 3.14 93 7 --- PEFR L/s 12.18 7.71 118 --- 12.27 118 1 --- FET s 12.64 6.00 --- 14.26 13 --- Pre LLN % Pred Zsc –3 –2 Z-Score 2 3 Lung Volumes (Plethysmography) TLC L 10.63 6.95 131 3.61 SVC L 7.34 4.19 134 2.55 RV L 3.29 1.89 128 1.32 IC L 4.84 2.71 116 --- FRC L 5.79 2.90 149 3.17 ERV L 2.50 0.91 189 --- RV/TLC % 31 32 84 –1.47 Raw cmH2O/L/s 1.61 0.60 95 --- sGaw L/s/cmH2O/L 0.10 0.11 38 --- PF [open] breaths/min 85.47 --- Pre LLN % Pred Zsc –3 –2 Z-Score 2 3 Diffusing Capacity DLCO [Unc] mL/min/mmHg 37.64 24.11 117 0.99 Volume (L-BTPS) DLCO [Cor] mL/min/mmHg 37.64 23.86 118 1.06 8 Kco mL/min/mmHg/L 4.06 3.17 97 –0.19 7 VA [BTPS] L 9.27 6.23 120 1.57 6 Diffusion Time s 9.70 --- 5 Vi/VC % 96 --- Hb g/dL 14.2 12.0 --- 4 3 2 1 Pre LLN % Pred Zsc –3 –2 Z-Score 2 3 Respiratory Muscle 1 2 3 4 5 6 7 8 9 10 1112 13 14 MIP cmH2O 131 49 162 --- Time (s) PIP cmH2O 135 --- MEP cmH2O 125 52 99 --- PEP cmH2O 136 --- CPF L/s 10.55 8.63 87 --- ComPAS Version:Major.Minor.Revision Calibration Date: 9/30/2020 Calibration Data: Temp:26ºC PBar:746mmHg BTPS:1.063 Patient: Subject, Test K. TestDate:9/30/2020 Page: 1 of2 )SPTB=L( emuloV )s/L( wolF 12 FEV1 = 4.87 10 8 6 4 2 0 1 2 3 4 5 6 7 8 9 1011 12 –2 –4 –6 –8 –10 FEV6 = 6.82 FEV1 = 4.87 FIG. 1.1 Sample pulmonary function test report. Lung function tests are grouped by category. The post- bronchodilator data also include the percent (%) change. Both the lower limit of normal (LLN) and Z scores are displayed, the latter with an associated graph, along with the flow-volume loop and volume–time graphs. --- PAGE 17 --- Indications for Pulmonary Function Testing • Chapter 1 5 Past Pulmonary Function Results for this Patient Parameter Today Previous Test Results - Most Recent to Past FVC FEV1 FVC FEV1 FVC FEV1 FVC FEV1 FVC FEV1 Spirometry Grading A A B A E E B B A B 9/30/2020 8/25/2020 % Diff Abs 8/17/2020 % Diff Abs 7/6/2020 % Diff Abs 6/2/2020 % Diff Abs FVC 7.24 7.02 4 0.22 7.06 3 0.18 7.22 1 0.02 7.43 -2 -0.19 FEV 1 4.87 4.86 1 0.01 4.89 <1 -0.02 4.80 2 0.07 5.29 -8 -0.42 TLC 10.63 ---- ---- ---- 10.57 1 0.06 ---- ---- ---- 10.76 -1 -0.13 DLCO [Unc] 37.64 ---- ---- ---- ---- ---- ---- ---- ---- ---- 31.69 16 5.95 Six Minute Walk Study Resting 1 min 2 min 3 min 4 min 5 min 6 min Recovery Min 1 Min 2 Min 3 SpO (%) 98.1 98.0 97.8 97.6 97.1 96.8 96.2 96.0 97.2 97.8 2 HR (bpm) 66 67 69 71 73 80 86 97 90 74 BP (mmHg 122 / 80 134 /82 Dyspnea (1 - 10) 3 Total distance walked in 6 minutes: 733 meters Supplemental oxygen during the test: O2 LabelUnits Predicted distance: 656 meters Previous Test: Percent of predicted: 112 % Last Test Date:9/30/2020 Last Test Distance: Technologist Comments: Good test subject effort and cooperation. Albuterol delivered with a 12-min waiting period. Computer Impression: Normal spirometric values indicate the absence of any significant degree of obstructive pulmonary impairment and/or restrictive ventilatory defect. Bronchodilator therapy was administered followed by repeat spirometric testing. Post-bronchodilator testing failed to demonstrate a significant change in FVC, FEV1, or FEF 25-75. This indicates that this patient may not benefit from continued bronchodilator therapy. The total lung capacity is increased indicating hyperinflation. The carbon monoxide diffusing capacity is normal indicating normal alveolar-capillary surface area for gas exchange. Maximal respiratory muscle pressures are normal. Oxygen saturation by pulse oximetry is satisfactory. The MVV is consistent with the level of FEV1. ComPAS Version: Major.Minor.Revision Calibration Date: 9/30/2020 Calibration Data: Temp:26°C PBar:746mmHg BTPS:1.063 Patient: Subject, Test K. Test Date:9/30/2020 Page: 2 of 2 FIG. 1.1, CONT’D --- PAGE 18 --- 6 Ruppel’s Manual of Pulmonary Function Testing The FVC, FEV , and other flows, along with mography is now widely used. The same equipment 1 flow-volume loops, are all used to measure the pa- can also be used to measure thoracic gas volume tient’s response to bronchodilator medications (see (V ) rapidly and accurately. TG Chapter 2). Tests are performed before and after Lung compliance is measured by passing a small inhalation of a bronchodilator, and the percent- balloon into the esophagus to measure pleural age of change is calculated. The same tests may be pressure. Intrapleural pressure can then be related used to assess airway response after a challenge to to volume changes to estimate the distensibility of the airways. These tests are referred to as bronchial the lung (see Chapter 4). Other less invasive tech- challenge or bronchial provocation tests. The chal- niques are available but not widely used. lenge may be in the form of a nonspecific inhaled agent (e.g., methacholine) or a physical agent (e.g., ex- Lung Volume and Ventilation Tests ercise). In either case, airflow is assessed before and Measurement of lung volume dates to the early after the challenge. The percent change (n ormally 1800s, well before Hutchinson’s development of spi- a d ecrease) after the challenge is calculated (see rometry. Various techniques have been used to esti- Chapter 9). mate the volume of gas remaining in the lung after a Maximal voluntary ventilation (MVV) was complete exhalation. Davy used a hydrogen-d ilution described as early as 1941. Cournand and Richards technique to estimate residual air. This technique originally called it the maximal breathing capacity was later improved by Meneely and Kaltreider using (MBC). In the MVV test, the patient breathes rap- helium (He) instead of hydrogen. Around the same idly and deeply for 12 to 15 seconds. The volume time, Darling, Cournand, and Richards began using of air exchanged is expressed in liters per minute. oxygen breathing to wash nitrogen (N ) out of the 2 The MVV gives an estimate of the peak ventilation lungs. The collection and analysis of the volume of available to meet physiologic demands. exhaled N allowed the functional residual capac- 2 Measurement of respiratory muscle strength ity (FRC) to be estimated. Using simple spirometry is accomplished by assessing maximal inspiratory combined with FRC determinations allows total pressure (MIP) and maximal expiratory pressure lung capacity (TLC) and residual volume (RV) to be (MEP). This is done using either a pressure trans- calculated. The other commonly used method for ducer or a simple aneroid manometer. MIP and MEP measuring lung volumes uses the body plethysmo- are important adjuncts to spirometry for moni- graph to measure V or FRC. Estimation of lung TG toring respiratory muscle function in a variety of volumes from chest radiographs is possible but is pulmonary and nonpulmonary diseases. Black and not widely used. Lung volume can also be estimated Hyatt developed the first device to assess these pa- from computed tomography (CT) scans, but such rameters and called the device a “bugle” because the measurements are seldom performed just for the expiratory maneuver and the device used to mea- purpose of measuring lung volume. sure the pressure were like blowing into a bugle. Closed-circuit (He-dilution) and open-circuit Raw measurements date back to the develop- (N -washout) techniques are both widely used to 2 ment of the body plethysmograph in the early measure FRC. Besides determining lung volumes, 1950s. Comroe, DuBois, and others perfected each technique provides some limited informa- a technique that provided estimates of alveolar tion about the distribution of ventilation within pressure. The patient sits in an airtight box called the lungs. The pattern of N washout can be dis- 2 a plethysmograph (see Chapter 11). The plethysmo- played graphically. The time required for He to graphic method allows the calculation of the pres- equilibrate during rebreathing provides a similar sure drop across the airways related to flow at the index of the evenness of ventilation. In the early mouth (see Chapter 4). This technique originally 1950s and 1960s, Fowler developed a single-breath required complicated monitoring and recording N -washout technique. This method plots the N 2 2 devices. Microprocessors have simplified the mea- concentration in expired gas after a single breath surement of the required signals so that plethys- of 100% oxygen. The single-breath N washout also 2 --- PAGE 19 --- Indications for Pulmonary Function Testing • Chapter 1 7 provides limited information about gas distribu- taining a bicarbonate buffer to the glass electrode. tion in the lungs and allows estimates of the lung The electrode buffer was separated from the blood volume at which airway closure occurs when the being analyzed by a membrane permeable to CO . 2 patient exhales completely (see Chapter 4). This allowed the pressure of CO in the blood to 2 Measurement of resting ventilation requires be measured as a pH change in the electrode. In only a simple gas-metering device and a means of 1956, Leland Clark covered a platinum electrode collecting expired air. Portable computerized spi- with a polypropylene membrane. When a voltage rometers allow minute ventilation, tidal volume was applied to the electrode, O was reduced at the 2 (V ), and breathing rate to be readily measured in platinum cathode in proportion to its partial pres- T almost any setting. Determination of alveolar ven- sure. These three electrodes (pH, Pco2 , and partial tilation or dead space (wasted ventilation) requires pressure of oxygen [Po2 ]) were the basic measure- measurement of the arterial partial pressure of car- ment devices in blood gas analyzers for many years. bon dioxide (Paco2 ) in addition to total ventilation. Miniature electrodes gradually replaced the tradi- Alternately, the partial pressure of carbon dioxide tional electrodes. Today, blood gas analyzers use (Pco2 ) can be estimated from expired CO 2 . The a variety of electrochemical techniques (see Blood availability of blood gas analyzers and exhaled CO Gas Analyzers, Chapter 11) to measure not only pH, 2 analyzers makes these measurements routine. Pco2 , and Po2 but also the various fractions of Hb, such as oxyhemoglobin (O Hb) and carboxyhemo- 2 Diffusing Capacity Tests globin (COHb). Similar methods to measure elec- The basis for the modern single-breath diffusing trolytes (K++, Na++, Cl−) are also included in many capacity (Dlco) test was described by August and blood gas analyzer systems. Transcutaneous elec- Marie Krogh in 1911. They showed that small but trodes using techniques like the classical blood gas measurable differences existed between inspired electrodes are available for the measurement of O 2 and expired gas containing carbon monoxide (CO). and CO tensions (tcpO and tcpCO ). 2 2 2 This change could be related to the uptake of gas Blood oximetry was developed during World across the lung. Although they used the method to War II to monitor the effects of exposure to high- test a series of patients, they did not use the single- altitude flight. During the 1960s, spectrophoto- breath technique for clinical purposes. Around metric analyzers that could measure the total Hb, 1950, Forrester and others revisited the method. along with O Hb and COHb levels, were perfected. 2 They developed it as a tool to measure the gas ex- Blood oximetry testing is commonly combined change capacity of the lung. At about the same with blood gas analysis so that both can be accom- time, Filley and others were promoting other tech- plished with a single instrument. Pulse oximetry niques using CO to measure Dlco. Most of these was developed in the 1970s because of efforts to techniques allowed patients to breathe normally monitor cardiac rate by using a light beam to sense rather than hold their breath. These methods are pulsatile blood flow. It was quickly discovered that called steady-state techniques. Each method has cer- the pulse could be sensed, and changes in light tain limitations. However, the single-breath tech- absorption could also be used to estimate arterial nique is the most widely used and standardized in oxygen saturation. Modern microprocessors have the United States and Europe (see Chapter 3). allowed pulse oximeters that are small and porta- ble, with some devices capable of measuring COHb Blood Gases and Gas Exchange in addition to O saturation. 2 Tests Capnography, or monitoring of exhaled carbon Measurement of gases (O and CO ) in the blood dioxide, was developed in conjunction with the in- 2 2 began with volumetric methods used since the early frared gas analyzer (see Chapter 11). This sensitive 1900s. In 1957, Sanz introduced the glass electrode and rapidly responding analyzer allows exhaled CO 2 to measure the pH of fluids potentiometrically. to be monitored continuously. Most critical care In 1958, Severinghaus added an outer jacket con- units, operating rooms, and emergency departments --- PAGE 20 --- 8 Ruppel’s Manual of Pulmonary Function Testing use some combination of blood gas analysis, pulse subjects to rebreathe from a volume spirometer oximetry, and capnography for patient monitoring. containing added oxygen. Plotting the rate at Blood gas analysis is an integral part of routine pul- which oxygen was consumed derived an estimate monary function testing because it is the definitive of energy expenditure. Similar techniques are test of the basic functions of the lung. used today, except that oxygen consumption and Exhaled nitric oxide (eNO), although not carbon dioxide production are monitored using a measure of blood gas or gas exchange, has exhaled gas analysis. Resting energy expendi- emerged as an important parameter for assess- ture (REE) has replaced BMR as the primary ing inflammatory changes in the lungs. Asthma, variable related to metabolic needs. Although chronic obstructive pulmonary disease (COPD), BMR was used to detect disorders that affected and other pathologies characterized by inflam- metabolism, REE is used to manage critically ill mation of the airways or lung tissue can be mon- patients whose caloric requirements may be diffi- itored by analyzing trace amounts of nitric oxide cult to estimate. (NO) in exhaled gas. INDICATIONS FOR PULMONARY Cardiopulmonary Exercise Tests FUNCTION TESTING Exercise tests commonly use a treadmill or cycle ergometer to impose an external workload that Each category of pulmonary function testing stresses the cardiovascular and musculoskeletal sys- includes specific reasons that the test may be tems. The simplest types of exercise tests are those necessary. These reasons for testing are called in which the patient performs work and only non- indications. Some PFTs have well-defined indica- invasive measurements are made. Such measure- tions. The same indications that apply to one type ments include heart rate and rhythm monitoring of test (e.g., spirometry) may also apply to other using an electrocardiogram (ECG). Other simple, categories. noninvasive measurements are blood pressure and respiratory rate monitoring. Analysis of exhaled Spirometry gas is noninvasive, but the patient does have to Spirometry is the PFT performed most often breathe through a mouthpiece or mask. Ventilation because it is indicated in many situations (see and V can be estimated by collecting the exhaled Box 1.2). Spirometry is often performed as a screen- T air. Analysis of expired gases permits oxygen con- ing procedure. It may be the first test to indicate sumption and CO production to be measured. the presence of pulmonary disease. Spirometry is 2 When invasive measures (blood gas analysis, arte- either recommended or required for the diagnosis rial catheters, pulmonary artery catheters) are used, of obstructive lung disease by the Global Initiative the entire range of physiologic variables that affect for Chronic Obstructive Lung Disease (GOLD), the exercise can be monitored. Computerized exhaled Global Initiative for Asthma (GINA), and numer- gas analysis allows sophisticated measurements to ous other organizations concerned with the diag- be made rapidly while the patient continues to exer- nosis of lung diseases. However, spirometry alone cise (breath-by-breath gas analysis). Simple exercise may not be sufficient to completely define the ex- field tests, such as the 6-Minute Walk Test (6MWT), tent of disease, response to therapy, preoperative have become popular because the distance walked risk, or level of impairment. Spirometry must be correlates well with more sophisticated exercise performed correctly because of the serious impact measurements and with clinical outcomes in a va- its results can have on the patient’s life. It is one of riety of diseases. the few tests that yield a false-positive response if performed poorly because low values are the result. Metabolic Measurements These low results may lead to further testing, inap- Measurement of energy expenditure and caloric propriate diagnosis and treatment, and increased requirements dates to the early 1900s. The basal costs for the patient and the health care delivery metabolic rate (BMR) was measured by allowing system. --- PAGE 21 --- Indications for Pulmonary Function Testing • Chapter 1 9 BOX 1.2 INDICATIONS FOR SPIROMETRY Diagnosis 3. To monitor patients for exacerbations of disease and recovery from exacerbations 1. To evaluate symptoms, signs, or abnormal 4. To monitor people for adverse effects of exposure to laboratory results injurious agents a. Dyspnea, cough, chest discomfort, phlegm a. Employees participating in a respiratory production protection program b. Decreased breath sounds, chest wall abnormalities 5. To watch for adverse reactions to drugs with known c. Abnormal chest x-ray or computed tomography, pulmonary toxicity abnormal arterial blood gases or pulse oximetry a. For example, bleomycin, amiodarone 2. To measure the physiologic effect of the disease or disorder Disability/Impairment Evaluations 3. To screen individuals at risk of having pulmonary 1. To assess patients as part of a rehabilitation program disease 2. To assess risks as part of an insurance evaluation a. Smokers > 45 with symptoms 3. To assess individuals for legal reasons b. Working in a hazardous or dusty environment 4. To assess preoperative risk Other a. Lung resection (lobectomy, pneumonectomy) 1. Research or clinical trials b. Upper abdominal procedures 2. Epidemiologic surveys 5. To assess prognosis 3. Derivation of reference equations 4. Preemployment and lung health monitoring for at- Monitoring risk conditions 1. To assess response to therapeutic intervention 5. To assess health status before beginning at-risk 2. To monitor disease progression physical activities Lung Volumes caused by either restriction or obstruction. If TLC The determination of lung volume usually includes is reduced below the 5th percentile of the predicted the VC and its subdivisions, along with the FRC. value, restriction is present. The severity of the re- From these two basic measurements, TLC and other strictive process is determined by the extent of re- lung volumes can be calculated (see Chapter 4). duction of the TLC. TLC and its components can Lung volumes are almost always measured in con- be determined by several methods. For patients junction with spirometry, although the indications with obstructive lung diseases (COPD, asthma), for them are distinct (see Box 1.3). The most com- lung volumes measured by body plethysmog- mon reason for measuring lung volumes is to iden- raphy may be indicated (see Chapter 4) because tify restrictive lung disease. A reduced VC (or FVC) multiple-breath or single-breath dilution tech- measured with spirometry may suggest restriction, niques may underestimate TLC. In obstructive lung particularly if airflow is normal. Measurement disease, lung volumes are necessary to determine of FRC and determination of TLC are necessary whether air trapping or hyperinflation is present. to confirm restriction because a low FVC can be The degree of hyperinflation, measured by indices BOX 1.3 INDICATIONS FOR LUNG VOLUME DETERMINATION A. Lung volume determinations may be indicated to D. Make preoperative assessments of patients with diagnose or assess the severity of restrictive lung compromised lung function disease (reduced total lung capacity [TLC]) E. Determine the extent of hyperinflation B. Differentiate between obstructive and restrictive F. Assess gas trapping by comparison of disease patterns plethysmographic lung volumes with gas-dilution C. Assess response to therapeutic interventions lung volumes 1. Bronchodilators, steroids G. Standardize other lung function measures (e.g., 2. Lung transplantation, resection, reduction specific conductance) 3. Radiation or chemotherapy --- PAGE 22 --- 10 Ruppel’s Manual of Pulmonary Function Testing such as the IC/TLC ratio, correlates with increased by chemotherapy and radiation therapy for lung mortality in patients who have COPD. cancer. Diffusing Capacity Blood Gases Diffusing capacity is measured by having the pa- Blood gas analysis is often done in conjunction tient inhale a low concentration of CO and a tracer with pulmonary function studies. Blood is drawn gas to determine gas exchange within the lungs from a peripheral artery without being exposed to (Dlco). Several methods of evaluating the uptake air (i.e., anaerobically). The radial artery is often of CO from the lungs are available, but the single- used for a single arterial puncture or indwelling breath technique (Dlcosb) is most used. This catheter. Blood gas analysis includes the measure- method is also called the breath-hold technique be- ment of pH, along with Pco2 and Po2 . Other cal- cause CO transfer is measured during 8 to 12 sec- culated parameters (HCO −, base excess, etc.) are 3 onds of breath holding. Dlco is usually measured often included in the standard blood gas report. in conjunction with spirometry and lung volumes. The same specimen may be used for blood oximetry Although many pulmonary and cardiovascular to measure total Hb, O Hb saturation, COHb, and 2 diseases reduce Dlco (see Box 1.4), it may be ab- methemoglobin (MetHb). normally increased in some cases (see Chapter 3). Blood gas analysis is the ideal measure of pul- Dlco testing is commonly used to monitor dis- monary function because it assesses the two pri- eases caused by dust (pneumoconiosis). These are mary functions of the lung (oxygenation and CO 2 conditions in which lung tissue is infiltrated by removal). Evaluation of many pulmonary disorders substances such as silica or asbestos that disrupt may include blood gas analysis. Specific indications the normal structure of the gas exchange units. for blood gas analysis are listed in Box 1.5. Blood Dlco testing is also used to evaluate pulmonary in- gas analysis is most often used to determine the volvement in systemic diseases such as rheumatoid need for supplemental oxygen and to manage pa- arthritis. Dlco measurements are often included tients who require ventilatory support. Some pul- in the evaluation of patients with obstructive lung monary function measurements require blood gas disease, particularly in emphysema. Dlco tests may analysis as an integral part of the test (i.e., shunt or be indicated to monitor changes in lung function dead-space studies). Blood gas analysis is invasive; (i.e., gas exchange) induced by drugs used to treat noninvasive measurements of oxygenation or gas cardiac arrhythmias, as well as changes caused exchange are often preferred because they are safer BOX 1.4 INDICATIONS FOR Dlco A. Diffusing capacity (Dlco) measurements may be 2. Differentiate types of obstructions indicated to evaluate or follow the progress of a. Emphysema parenchymal lung diseases b. Chronic bronchitis 1. Dusts (asbestos, silica, metals) c. Asthma 2. Organic agents (allergic alveolitis) 3. Predict arterial desaturation during exercise in 3. Drugs (amiodarone, bleomycin) chronic obstructive pulmonary disease B. Evaluate pulmonary involvement in systemic diseases D. Evaluate cardiovascular diseases 1. Rheumatoid arthritis 1. Primary pulmonary hypertension 2. Sarcoidosis 2. Acute or recurrent pulmonary thromboembolism 3. Systemic lupus erythematosus 3. Pulmonary edema and congestive heart failure 4. Systemic sclerosis E. Quantify disability associated with interstitial lung 5. Mixed connective tissue disease disease C. Evaluate obstructive lung disease F. Evaluate pulmonary hemorrhage, polycythemia, or 1. Follow the progression of disease left-to-right shunts (increased Dlco) a. Emphysema b. Cystic fibrosis --- PAGE 23 --- Indications for Pulmonary Function Testing • Chapter 1 11 BOX 1.5 INDICATIONS FOR BLOOD GAS ANALYSIS A. Blood gas analysis and/or blood oximetry may be 3. Nocturnal desaturation indicated to evaluate adequacy of lung function 4. Adequacy of oxygen prescription 1. Ventilation (Paco2 ) C. Monitor ventilatory support 2. Acid–base status 1. Assess or follow respiratory failure a. pH 2. Adjust therapy to improve oxygenation (positive b. Paco2 end-expiratory pressure [PEEP], continuous 3. Oxygenation and oxygen-carrying capacity positive airway pressure [CPAP], pressure support) a. Pao2 D. Document the severity or progression of known b. Total Hb, O Hb, COHb, MetHb pulmonary disease 2 4. Intrapulmonary shunt E. Provide data to correct or corroborate other 5. V /V ratio pulmonary function measurements D T B. Determine need for supplemental oxygen (for 1. Correct Dlco measurements (Hb and COHb) clinical or reimbursement purposes) 2. Determine accuracy of pulse oximetry, 1. Presence or severity of resting hypoxemia transcutaneous monitors, or indwelling blood 2. Exercise desaturation gas devices or less costly. Many noninvasive techniques (e.g., vascular disease, and exercise-induced broncho- pulse oximetry, transcutaneous monitoring, and spasm are respiratory disorders that often require capnography) rely on a blood gas analysis to verify exercise evaluation. Understanding the physiologic their validity (see Chapter 6). basis for the patient’s inability to exercise is an important aspect in prescribing effective therapy Exercise Tests (i.e., cardiac or pulmonary rehabilitation). Exercise Physical exercise stresses the heart, the lungs, and testing may also be required for the determination the pulmonary and peripheral circulatory systems. of disability. Box 1.6 lists specific indications for Exercise testing allows simultaneous evaluation exercise tests. of the cellular, cardiovascular, and ventilatory Equipment used to measure oxygen consump- systems. Cardiopulmonary exercise tests can be tion and CO production during exercise can also 2 used to determine the level of fitness or extent of measure resting metabolic rates. This allows esti- dysfunction. Appropriately designed tests can de- mates of caloric needs in patients who are critically termine the role of cardiac or pulmonary involve- ill. Indications for performing studies of REE are ment. COPD, interstitial lung disease, pulmonary detailed in Chapter 10. BOX 1.6 INDICATIONS FOR EXERCISE TESTING A. Exercise testing may be indicated to evaluate 3. Mixed cardiovascular and pulmonary etiologies exercise intolerance or level of fitness 4. Unexplained dyspnea B. Document or diagnose exercise limitation because a. Deconditioning of fatigue, dyspnea, or pain b. Upper airway abnormalities (e.g., vocal cord 1. Cardiovascular diseases dysfunction) a. Myocardial ischemia or dyskinesis C. Exercise evaluation for cardiac or pulmonary b. Cardiomyopathy rehabilitation c. Congestive heart failure 1. Exercise desaturation/hypoxemia d. Peripheral vascular disease 2. Oxygen prescription e. Selection for heart transplantation D. Assess preoperative risk, particularly lung resection 2. Pulmonary diseases or reduction a. Airway obstruction (including cystic fibrosis) E. Assess disability, particularly related to or hyperreactivity occupational lung disease b. Interstitial lung disease F. Evaluate therapeutic interventions such as heart or c. Pulmonary vascular disease lung transplantation --- PAGE 24 --- 12 Ruppel’s Manual of Pulmonary Function Testing Chronic PATTERNS OF IMPAIRED bronchitis PULMONARY FUNCTION Emphysema B A K Patients are usually referred to the pulmonary func- tion laboratory to evaluate signs or symptoms of E lung disease. In some instances, the clinician may C D wish to exclude a specific diagnosis, such as asthma. H All airflow Indications for different categories of PFTs have F G obstruction been described previously. Sometimes, patients display patterns during testing that are consistent J I with a specific diagnosis. This section presents an overview of some commonly encountered forms of impaired pulmonary function. Obstructive Airway Diseases An obstructive airway disease is one in which air- Asthma flow into or out of the lungs is reduced. This simple FIG. 1.2 Nonproportional diagram depicting the relationship definition includes a variety of pathologic condi- between various components of chronic obstructive pulmonary tions. Some of these conditions are closely related disease (COPD). Emphysema, chronic bronchitis, and asthma overlap to varying degrees (shaded areas). Chronic obstruction in how they cause airway obstruction. For example, in small airways and all airway obstructive diseases (large dashed mucus hypersecretion is a component of chronic square) also overlap. (A) Patients with chronic bronchitis but no bronchitis, asthma, and cystic fibrosis (CF), although airflow obstruction. (B) Patients with anatomic changes related their causes are distinct. to emphysema but no obstruction. (C) Patients with chronic cough and airflow obstruction. (D) Patients with emphysema and obstruction, as demonstrated by spirometry. (E) Combined Chronic Obstructive Pulmonary chronic bronchitis and emphysema, commonly occurring in Disease the same patient, because of cigarette smoking. (F) Combined The term COPD is often used to describe chronic bronchitis and asthma. (G) Combined emphysema and asthma. (H) Combined asthma, chronic bronchitis, and em- long-standing airway obstruction caused by em- physema. (I) Patients with asthma manifested by reversible ob- physema, chronic bronchitis, or sometimes asthma, struction (spirometry or peak flow). (J) Other forms of airway which is not fully reversible. These three conditions obstruction, including cystic fibrosis, bronchiolitis obliterans, or upper airway abnormalities (e.g., vocal cord dysfunction), are may be present alone or in combination (Fig. 1.2). not considered part of COPD. (K) Patients with cough and mor- Bronchiectasis is sometimes considered a component phologic evidence of emphysema but no obstruction. (Modified of COPD. COPD is characterized by dyspnea at rest from American Thoracic Society. [1995]. Standards for the di- or with exertion, often accompanied by a produc- agnosis and care of patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, tive cough. Delineation of the type of obstruction 152, S77–S120.) depends on the history, physical examination, and pulmonary function studies. Unfortunately, the term COPD is used to describe the clinical findings size. The walls of the alveoli undergo destructive of dyspnea or cough without attention to the ac- changes. This destruction results in the overinfla- tual cause. This may lead to inappropriate therapy. tion of lung units. If the process mainly involves the Other similar terms include chronic obstructive lung respiratory bronchioles, the emphysema is termed disease (COLD) and chronic airway obstruction (CAO). centrilobular. If the alveoli are also involved, the term panlobular emphysema is used to describe the pat- Emphysema tern. These distinctions require the examination Emphysema means “air trapping” and is defined of lung tissue either by biopsy or at postmortem. morphologically. The air spaces distal to the ter- Because this is often impractical, emphysema is minal bronchioles are abnormally increased in suspected when there is airway obstruction with --- PAGE 25 --- Indications for Pulmonary Function Testing • Chapter 1 13 air trapping. Physical assessment, chest x-ray or CT studies, and pulmonary function studies are the primary diagnostic tools. Spirometry (FVC, FEV , 1 and FEV /FVC) is used to determine the presence 1 and extent of obstruction. Lung volumes (TLC, RV, IC, and RV/TLC) define the pattern of air trapping or hyperinflation caused by emphysema. Dlco and blood gas analyses are useful in tracking the de- gree of gas exchange abnormality in emphysema. Some form of exercise testing may be necessary if the patient with emphysema is suspected of oxygen desaturation with exertion or to plan pulmonary rehabilitation. Emphysema is caused primarily by cigarette smoking. Repeated inflammation of the respira- tory bronchioles results in tissue destruction. As the disease advances, more and more alveolar walls are destroyed. Loss of elastic tissue results in airway col- lapse, air trapping, and hyperinflation. Some emphy- FIG. 1.3 Chronic obstructive pulmonary disease (COPD) ra- sema is caused by the absence of a protective enzyme, diograph with hyperinflation. α1 -antitrypsin. The lack of this enzyme is caused by a genetic defect. The enzyme α1 -antitrypsin inhibits wasting seems to be common in emphysema, and proteases in the blood from attacking healthy tissue. patients are often below their ideal body weight. As Deficiency of α1 -antitrypsin causes the gradual de- noted, symptoms of chronic bronchitis and asthma struction of alveolar walls, resulting in panlobular may be present as well. emphysema. Chronic exposure to environmental The chest x-ray film of a patient with emphy- pollutants can also contribute to the development sema shows flattened diaphragms and increased air of emphysema. The natural aging of the lung also spaces. The lung fields appear hyperlucent (dark), causes some changes that resemble the disease en- with little vascularity. The heart appears to be hang- tity. The natural decline of elastic recoil in the lung ing from the great vessels (Fig. 1.3). CT scans, es- reduces maximal airflow and increases lung volume pecially spiral CT scans, show a three- dimensional as people age. Surgical removal of lung tissue some- picture of enlarged air spaces and loss of support- times causes the remaining lung to overinflate. ing tissue. CT scans also delineate whether the The main symptom of emphysema is breath- emphysematous changes are localized or spread lessness, either at rest or with exertion. Hypoxemia throughout the lungs. may contribute to this dyspnea, particularly in The physical appearance of the chest confirms advanced emphysema. However, the destruction what is shown radiographically. The chest wall is im- of alveolar walls also causes loss of the capillary mobile with the shoulders elevated. The diameter of bed. Ventilation-perfusion matching may be rela- the chest is increased in the anterior-posterior aspect tively well preserved in patients with emphysema. (so-called barrel chest). There is little diaphragmatic As a result, oxygen levels may be only slightly de- excursion during inspiration. Intercostal retrac- creased, particularly at rest. This type of patient is tions may be prominent. Accessory muscles (neck sometimes called the “pink puffer.” As the disease and shoulders) are used to lift the chest wall. Breath advances, the loss of alveolar surface causes a de- sounds are distant or absent. Patients may need creased ability to oxygenate mixed venous blood. to support the arms and shoulders to catch their Dlco is reduced. The patient becomes increas- breath. Breathing is often done through pursed lips ingly breathless, particularly with exertion. Muscle to alleviate the sensation of dyspnea (Fig. 1.4). --- PAGE 26 --- 14 Ruppel’s Manual of Pulmonary Function Testing number of ciliated epithelial cells decreases. This causes impairment of mucus flow in the airways. Similar changes occur in respiratory bronchioles. Excessive mucus and poor clearance make the patient susceptible to repeated infections. Some patients who have chronic bronchitis caused by cigarette smoking experience a decrease in cough and mucus production after smoking cessation. Some airway changes, however, usually persist. Spirometry is useful in evaluating the extent of airway obstruction caused by bronchitic changes. Dlco may be helpful in distinguishing emphysema and chronic bronchitis; patients with bronchitis may have preserved Dlco, whereas patients with emphysema tend to have reduced Dlco. However, Dlco is usually not normal in chronic bronchitis because of the mismatching of ventilation and per- fusion caused by bronchial obstruction. Chronic cough is the defining symptom of chronic bronchitis. Some patients do not consider cough abnormal and refer to it as “smoker’s cough” or “morning cough.” In addition to cough, chronic bronchitis may produce dyspnea, particularly with exertion. Blood gas abnormalities usually accom- FIG. 1.4 Chronic obstructive pulmonary disease (COPD) pany chronic bronchitis. Ventilation-perfusion signs. Note pursed lips, intercostal retractions, and need to use arms and shoulder for support to catch breath.(From Henry, M., mismatching causes hypoxemia. If hypoxemia is & Stapleton, E. [2010]. EMT prehospital care [4th ed.]. St. Louis, significant and persists, the patient may develop MO: Mosby JEMS.) secondary polycythemia. Cyanosis may be present because of the combination of arterial desaturation Chronic Bronchitis and increased Hb levels. Chronic hypoxemia may Chronic bronchitis is diagnosed by clinical find- also lead to right-sided heart failure (cor pulmonale) ings. It is present when there is excessive mucus with peripheral edema, particularly in the feet and production with a productive cough on most days ankles. Advanced chronic bronchitis is also often for at least 3 months for 2 years or more. The di- accompanied by CO retention (hypercapnia). 2 agnosis is made by excluding other diseases that Unlike the patient with emphysema, the patient also result in excess mucus production. These with chronic bronchitis may show few clinical signs include CF, tuberculosis, abscess, tumors, and of underlying disease. Body weight may be normal bronchiectasis. or increased, with minimal changes to the chest Chronic bronchitis, like emphysema, is caused wall. Patients with bronchitis may appear normal primarily by cigarette smoking. It may also result except for cough and dyspnea. The chest x-ray film from chronic exposure to environmental pollut- in chronic bronchitis differs markedly from that in ants and second hand smoke. Chronic bronchitis emphysema. The congested airways are easily visi- causes the mucous glands that line the airways to ble. The heart may appear enlarged, with the pul- hypertrophy and increase in number. There is also monary vessels prominent. The diaphragms may chronic inflammation of the bronchial wall with appear normal or flattened, depending on the de- infiltration of leukocytes and lymphocytes. The gree of air trapping present. If there is right-sided --- PAGE 27 --- Indications for Pulmonary Function Testing • Chapter 1 15 heart failure, swelling (edema) of the lower extrem- required to manage localized areas of infection. ities is often present. Patients with recurrent hemoptysis may require a Pulmonary infections can seriously aggravate resection of the offending lobe. chronic bronchitis, and patients who have chronic bronchitis tend to have an increased number of Management of Chronic Obstructive Pulmonary chest infections. The appearance of the sputum Disease produced can help predict worsening function. If GOLD, a World Health Organization (WHO) it is normally white, a change to discolored spu- program, works with health care professionals to tum indicates the beginning of an infection. This raise awareness and improve the prevention and may be accompanied by worsened hypoxemia and treatment of COPD. COPD is the third-leading shortness of breath. Early treatment can potentially cause of morbidity and mortality throughout reverse an otherwise serious complication. Failure the world. COPD often includes components to manage the chest infection can result in severe of emphysema and chronic bronchitis (see hypoxemia and hypercapnia with exacerbation Fig. 1.2). This association most likely is due to of right-sided heart failure. Acute respiratory fail- the common risk factor of cigarette smoking. ure superimposed on chronic failure is a common Hyperreactive airways disease (asthma) may also cause of death in patients with COPD. be present. Reversibility of obstruction, however, is usually less than in uncomplicated asthma. Bronchiectasis Bronchiectasis and bronchiolitis are also com- Bronchiectasis is pathologic dilatation of the bron- monly found in patients with COPD. chi. It usually results from the destruction of the An essential ingredient in COPD management is bronchial walls by severe repeated infections, but early diagnosis. GOLD requires spirometry as the some individuals are born with it (congenital bron- primary tool in the diagnosis of COPD. It also clas- chiectasis). The terms saccular, cystic, and tubular are sifies airflow limitation into four grades (GOLD used to describe the appearance of the bronchi. 1, mild; GOLD 2, moderate; GOLD 3, severe; and Most bronchiectasis involves prolonged episodes GOLD 4, very severe). Spirometry is recommended of infection. Bronchiectasis is common in CF and for all smokers with ≥ 20 years of smoking and after bronchial obstruction by a tumor or foreign chronic cough, dyspnea on exertion, mucus hyper- body. When the entire bronchial tree is involved, it secretion, or wheezing. is assumed that the disease is inherited or caused by Treatment of COPD begins with smoking ces- developmental abnormalities. sation and avoiding irritants that inflame the air- The main clinical feature of bronchiectasis is a ways. The rate of decline in lung function (FEV ) in 1 very productive cough. The sputum is usually pu- smokers is approximately twice that of nonsmok- rulent and foul-smelling. Hemoptysis is also com- ers. Smoking cessation decreases the accelerated mon. Frequent bronchopulmonary infections lead decline in most, but not all, smokers. Other mea- to gas exchange abnormalities like those of chronic sures aimed at keeping the airways open are also bronchitis. Right-sided heart failure follows the important. Inhaled bronchodilators, especially β2 advancement of the disease. Chest x-ray studies, agonists, are commonly used. Combinations of β2 bronchograms, and CT scans are used to identify agonists and anticholinergic bronchodilators, to- the type and extent of the disease. As in chronic gether with inhaled corticosteroids (ICSs), provide bronchitis, spirometry may be useful for assessing relief for many patients with COPD. This is often the degree of obstruction and response to therapy. the case even when there is little improvement in Treatment of bronchiectasis includes vigor- airflow assessed by spirometry. Some patients re- ous bronchial hygiene. Regular antibiotic ther- quire oral steroids (e.g., prednisone) to manage apy is used to manage the repeated infections. chronic inflammation. Antibiotics are commonly Bronchoscopy and surgical resection are sometimes used at the first sign of respiratory infections, and --- PAGE 28 --- 16 Ruppel’s Manual of Pulmonary Function Testing vaccination against viral and bacterial (pneumococ- including portable systems. Chronic O supple- 2 cus) infection is recommended. Digitalis and diuret- mentation has been shown to improve survival in ics are most often prescribed for the management of patients with COPD. cor pulmonale. Single-lung transplantation has been used for Breathing retraining, bronchial hygiene patients with end-stage COPD who meet the inclu- measures, and physical reconditioning are im- sion criteria. Although lung transplantation causes portant therapeutic modalities in addition to phar- an immediate improvement in pulmonary func- macologic management. Breathing retraining is tion, there are factors that need to be considered. especially important for the patient with advanced The cost of hospitalization and follow-up care is COPD. Grossly altered pulmonary mechanics fa- extensive, and the lack of donor organs means that vor hyperinflation and the use of accessory mus- many patients with COPD die while awaiting trans- cles. Training in the use of the diaphragm for slow, plantation. The prognosis for those receiving lung relaxed breathing can significantly improve gas transplants is generally good. In some transplant exchange. Pulmonary rehabilitation, particularly recipients, a severe form of airway obstruction physical reconditioning, permits many patients (bronchiolitis obliterans) has been found to occur in with otherwise debilitating disease to maintain the transplanted lung. The reason for this obstruc- their quality of life (Fig. 1.5). tive process is unclear, but the progression is rapid. Supplemental O therapy is indicated in COPD Spirometry is used to monitor transplant recipients 2 when the patient’s oxygen tension at rest or during to detect early changes associated with bronchiol- exercise is less than 55 mm Hg. Oxygen may also itis obliterans (Fig. 1.6). be prescribed when signs of cor pulmonale are Lung volume reduction surgery (LVRS) has also present. Many patients desaturate with exertion been used to treat end-stage COPD. In this pro- only. Exercise testing is the only reliable method cedure, poorly perfused lung tissue is surgically of detecting exertional desaturation. Low-flow O removed. This allows the remaining lung units 2 therapy can be implemented by several methods, to expand with improved ventilation-perfusion matching. This technique works particularly well when there are well-defined areas of trapped gas with little perfusion (bullae). The procedure can be performed by sternotomy or by using a flexible tho- racoscope. With both methods, lung volumes (TLC and RV) are reduced, and spirometry and gas ex- change improve. Spirometry, lung volume measure- ment, and blood gas analysis are used to monitor changes in these patients. Lung volume reduction is expensive, carries significant risk, and does not appear to benefit all patients who have air trapping. Hyperreactive Airway Disease: Asthma Asthma is characterized by reversible airway obstruction. Obstruction is caused by inflam- mation of the mucosal lining of the airways, bronchospasm, and increased airway secretions. Bronchospasm is usually reversed by the inhalation of bronchodilators but may be persistent and severe in some patients. Inflammation is the essential el- FIG. 1.5 Respiratory therapist eliciting feedback from a patient during a pulmonary rehabilitation exercise session. ement in the asthmatic response. Increased airway --- PAGE 29 --- Indications for Pulmonary Function Testing • Chapter 1 17 FEV 1 Pred 2.56 L Best value 2.90 L Serious 2.30 L Critical 1.50 L Trend (FEV [L]: 2.90 personal best value) 1 2.90 Green 2.30 Yellow 1.50 Red FIG. 1.6 Home spirometry trend in a patient following lung transplant. responsiveness is related to the inhalation of anti- BOX 1.7 ASTHMA TRIGGERS gens, viral infections, air pollution, occupational exposure, cold air, and exercise. Spirometry is the A. Allergic agents most useful tool for detecting reversible airway ob- 1. Pollens 2. Animal dander (proteins) struction. Improvement in the FEV or FVC (see 1 3. House dust mites Chapter 2) is the hallmark of reversibility. Raw and 4. Molds specific airway conductance (sGaw) are also useful B. Nonallergic agents in the evaluation of reversible obstruction. PEF, 1. Viral infections measured using portable peak flow meters, can pro- 2. Exercise 3. Cold air vide immediate information for a clinician or pa- 4. Air pollutants (sulfur, nitrogen dioxides) tient to modify therapy. Analysis of eNO can detect 5. Cigarette smoke inflammatory changes in the airways even in the 6. Drugs (aspirin, beta-blockers) absence of spirometric or peak flow abnormalities. 7. Food additives Asthma can occur at any age but often begins 8. Emotional upset C. Occupational exposure during childhood. Even infants can have hyperre- 1. Toluene 2,4-diisocyanate (TDI) active airways (see Chapter 8). Some children with 2. Cotton, wood dusts asthma outgrow the disease, but in others, the dis- 3. Grain ease continues into adulthood. In some individu- 4. Metal salts als, asthma begins in adulthood, usually after age 5. Insecticides 40. There appears to be a hereditary component to asthma; many cases occur in patients who have a also trigger asthma, as can food additives (e.g., me- family history of asthma or allergic disorders. tabisulfites) or emotional upset (e.g., crying, laugh- Agents or events that cause an asthmatic episode ing). All these triggers act on the hyperresponsive are called triggers (Box 1.7). Antigens such as animal airway to produce the symptoms of asthma. dander, pollens, and dusts are the most common The most common presentation of asthma in- triggers. Other common triggers include exposure cludes wheezing, cough, and shortness of breath. to air pollutants, exercise in cold or dry air, occupa- The severity of asthmatic episodes varies, even in tional exposure to dusts or fumes, and viral upper the same individual at different times. In many pa- respiratory infections. Aspirin or other drugs can tients, airway function is relatively normal between --- PAGE 30 --- 18 Ruppel’s Manual of Pulmonary Function Testing intermittent episodes or attacks. Some patients individuals identify and avoid triggers, monitoring have only cough or chest tightness that subsides their peak flows daily, and instructing them on the spontaneously. However, severe episodes may be proper use of medications. life-threatening. In its worst presentation, asthma Pharmacologic management of asthma is usu- causes continuous chest tightness and wheezing ally based on a combination of bronchodilator, that may not respond to the usual therapy. Dyspnea steroid, and antiinflammatory therapy. For some and cough can both be extreme, and if unresolved, patients with mild asthma, a β2 agonist broncho- they can progress to respiratory failure. dilator from a metered-dose inhaler (MDI) may be During an attack, there is usually wheezing, the only treatment required. Various β2 agonists noisy breathing, and prolonged expiratory times. If are available, and these drugs are typically used as the attack is severe, there may be significant air trap- rescue medications. In moderate or severe asthma, ping with decreased breath sounds, similar to the long-acting β2 agonist bronchodilators (e.g., sal- pattern seen in patients with emphysema. Accessory meterol) are usually inhaled on a dosing schedule. muscles of ventilation are used, and breathing may Anticholinergic bronchodilators (e.g., ipratropium be labored. Spirometry or peak flows provide a sim- or tiotropium) have become widely prescribed for ple means of tracking response to bronchodilators. use in conjunction with β2 agonists. Anticholinergic Arterial blood gas testing may be necessary during bronchodilators may be preferred in patients who severe asthmatic episodes. Hypoxemia is commonly experience tachycardia or tremor caused by adren- present because of ventilation-perfusion mismatch- ergic drugs. Although most β2 agonists have a rapid ing. This usually results in acute alveolar hyperven- onset of action (5–15 minutes), anticholinergic tilation that presents itself as respiratory alkalosis bronchodilators typically take 30 to 60 minutes for or metabolic alkalosis in chronic patients and de- peak effect to occur but with much longer-lasting teriorates into respiratory acidosis, which suggests effects. impending respiratory failure. ICSs (e.g., beclomethasone, fluticasone, budesonide, Bronchial provocation tests using methacholine, and mometasone) are the most effective treatment histamine, mannitol, exercise, or hyperventilation for mild, moderate, and severe asthma. Steroids act are often used to make the diagnosis of hyperre- primarily as antiinflammatory agents in the airways active airways in patients who appear normal but and may allow bronchodilators to work more effec- have episodic symptoms. Skin testing is also used tively. Several different preparations are available in to demonstrate sensitivity to inhaled antigens. MDIs or dry-powder inhalers. Combinations of in- Elevated eNO levels are also predictive of the airway haled steroids and long-acting β2 agonist broncho- inflammation common in the patient with asthma dilators seem to be highly effective at preventing and usually correlate with hyperresponsiveness asthma symptoms. Children and adolescents may measured by conventional bronchial challenge tests not respond to inhaled steroids. Corticosteroids, (see Chapter 9). in general, have several adverse side effects, includ- ing a reduction in bone density and adrenal sup- Management of Asthma pression. Inhaled steroids have relatively fewer side GINA, a WHO-sponsored program, and the effects; fungal infection of the oral cavity is a com- National Asthma Education Prevention Program mon problem. Inhaled steroids decrease bone den- (NAEPP) are two resources that provide guidance sity, and their effect on growth in children is not on asthma management. completely understood. The first step in asthma management is avoid- Cromolyn sodium or nedocromil is used to prophy- ing known triggers. In some instances, this is easily lactically prevent bronchoconstriction by blocking accomplished. However, in the case of air pollution the release of mediators from mast cells in the air- or occupational exposure, avoiding the offending ways. They cannot be used for acute episodes but substance may be expensive or impossible. Asthma may decrease the amount of corticosteroids or education usually focuses on helping affected bronchodilators necessary. Cromolyn derivatives --- PAGE 31 --- Indications for Pulmonary Function Testing • Chapter 1 19 are available as a nebulized solution, inhaled pow- suppurative pulmonary disease. In infancy and der, or MDI. early childhood, gastrointestinal manifestations Leukotriene receptor antagonists are also used to re- seem to predominate. As the child gets older, re- duce airway inflammation in asthma. They block spiratory complications related to the tenacious the release of leukotrienes, which potentiate inflam- mucus production take over. Other organ systems matory mediators. These drugs may be effective in may be involved as well. Children with CF tend to cases in which inhaled steroids are not and have remain chronically infected with respiratory patho- been successfully used in conjunction with steroids. gens, such as Staphylococcus aureus, Pseudomonas aeru- Some patients may better accept oral preparations ginosa, or Burkholderia cepacia. of leukotriene inhibitors. Clinical manifestations of CF include chronic Some patients who have severe asthma caused cough and sinusitis, bronchiectasis, and atelecta- by allergies may benefit from drugs that block sis. Hemoptysis and pneumothorax are common. immunoglobulin E (IgE)-mediated responses. Pulmonary function studies may be used to follow Omalizumab blocks IgE from binding to mast the progression of the disease. Spirometry (FEV ) is 1 cells and prevents activation that can lead to frequently measured as an index of the need for lung inflammation. transplantation. Chest x-ray studies show changes A significant tool in the management of asthma consistent with bronchiectasis and honeycombing. is the portable peak flow meter (see Chapters 2 and Atelectasis commonly affects entire lobes because 11). This device allows simple monitoring of airway of mucus impaction. Other complications cen- function by the patient at home, as well as by care- ter on gastrointestinal manifestations (e.g., bowel givers in a variety of settings. Measuring peak flow obstruction and vitamin deficiencies). Most indi- provides objective data to guide both the patient viduals with CF are diagnosed in infancy or early and physician in modifying bronchodilator ther- childhood, based on elevated sweat chloride levels. apy or seeking early treatment. Computerized peak Occasionally, some young adults are not diagnosed flow meters that include symptom history (i.e., an until after age 15. In many instances, adolescents or electronic diary) allow asthma management to be even adults are misdiagnosed as having asthma or tailored to the individual patient’s asthmatic needs. related pulmonary diseases. Misdiagnosis usually occurs in individuals who have mild CF with few Cystic Fibrosis complications. CF is a disease that primarily affects the mucus- producing apparatus of the lungs and pancreas. Management of Cystic Fibrosis CF is an inherited disorder, transmitted as an Removal of the excess mucus produced in CF is the autosomal- recessive trait. In whites, it occurs in ap- primary focus of management. This usually requires proximately 1 in 2500 to 3000 live births; in African bronchial hygiene measures and pharmacologic Americans, CF is much less common, occurring intervention. Bronchodilators are used to reverse in only 1 of 17,000 live births. There are approxi- the bronchospasm that commonly accompanies mately 70,000 to 100,000 people living worldwide chronic inflammation. A genetically engineered with CF. A simple test, the sweat test, measures enzyme is now used to reduce mucus viscosity in the chloride level in sweat, which is elevated in CF. patients with CF. This enzyme (rhDNase) is admin- Some states require a screening blood test for CF istered via an aerosol. This reduces the viscosity of in newborns. CF was once considered a pediatric secretions and improves airflow. Corticosteroids disease because affected individuals rarely lived are used to combat both pulmonary inflammation to adulthood. Improved detection and aggressive and bronchial hyperreactivity. Continuous or inter- treatment have increased the median survival age mittent antibiotics are also a mainstay of care in the well into adulthood. patient with CF. Proper nutrition is similarly im- CF is characterized by the malabsorption of food portant in managing CF. Pancreatic insufficiency because of pancreatic insufficiency and progressive increases the patient’s metabolic rate, even though --- PAGE 32 --- 20 Ruppel’s Manual of Pulmonary Function Testing nutrients are poorly absorbed in the intestine. Tumors are a common cause of large airway Pancreatic enzyme supplements and vitamins are obstruction. Lesions that invade the trachea or required, particularly in children with CF. For indi- main-stem bronchi can significantly diminish viduals with severe CF, lung transplantation has be- airflow. The decrease in flow is related to the de- come a life-saving treatment. Pulmonary function crease in the cross-sectional area of the airway. studies are routinely used to assess lung function If the airway lumen (i.e., the part not obstructed) following transplantation. varies in cross-sectional area with inspiration and expiration, the obstruction is described as variable. Upper or Large Airway Obstruction During inspiration, thoracic pressure decreases, Many obstructive diseases involve the medium or and large airways increase their cross-sectional area. small airways. Sometimes, airway obstruction oc- During expiration, the opposite occurs. If the air- curs in the upper airways (nose, mouth, or pharynx) way is partially obstructed by a tumor, airflow will or in the large thoracic airways (trachea, main-stem be decreased during inspiration and expiration but bronchi). Obstruction can also occur where the more so during expiration. If the tumor reduces the upper and lower airways meet at the vocal cords. cross-sectional area of the airway but does not cause When obstruction occurs below the vocal cords, it to change with the phase of breathing, the ob- the degree of obstruction may vary with changes struction is fixed. In this instance, both inspiratory in thoracic pressure. This occurs because the air- and expiratory flows are reduced approximately ways themselves change size as thoracic pressure equally (see Chapter 2). Tumors involving the up- rises or falls. Obstructive processes above the vo- per airway may cause variable or fixed obstruction. cal cords are not influenced by thoracic pressures If an extrathoracic tumor causes the airway cross but may still vary with airflow, depending on the section to vary with breathing, inspiratory flow is type of lesion involved. Regardless of the location usually reduced. An easy way to remember the cause of the problem, large airway obstruction results in and effect is to use the mnemonic, “What’s in is out, increased work of breathing. Extrathoracic or intra- what’s out is in.” In other words, if the obstruction thoracic airway obstruction is frequently diagnosed is within the thoracic cage, it will affect the expira- using the flow-volume loop or measurements of tory flow-volume curve. In contrast, if the obstruc- Raw (see Chapters 2 and 4). tion is outside of the thoracic cage (i.e., VCD), it will Vocal cord dysfunction (VCD) or damage can affect the inspiratory portion of the flow-volume result in significant airway obstruction. The vocal loop. cords are normally held open or abducted during Neuromuscular disorders that affect the mus- inspiration. When damaged, the vocal cords move cles of the upper airway can also affect airway pa- toward the midline, narrowing the airway open- tency. When the muscles of the pharynx or larynx ing. This type of obstruction limits flow primarily are relaxed (reduced muscle tone), airway collapse during inspiration. In some cases, expiratory flow may occur during the inspiratory phase of breath- may be reduced as well, but inspiratory flow is typ- ing. Any disorder that affects the innervation of ically lower. Common causes of VCD include la- the pharyngeal muscles can cause similar ob- ryngeal muscle weakness or mechanical damage, as structive patterns. Abnormal airflow patterns are sometimes occurs during intubation of the trachea. sometimes seen in patients who have obstructive Severe infections involving the larynx can leave scar sleep apnea, although flow measurements can- tissue on the vocal cords or supporting structures. not predict sleep apnea. Myasthenia gravis affects VCD often mimics asthma. It may become no- the muscles of respiration, including the mus- ticeably worse when ventilation is increased, such cles of the upper airway. Generalized weakness of as during exercise. Neuromuscular disorders can these muscles can result in variable extrathoracic cause paralysis of the vocal cords, also resulting obstruction. in variable extrathoracic airway obstruction (see Both extrathoracic and intrathoracic large air- Chapter 2). way obstructions commonly result from trauma --- PAGE 33 --- Indications for Pulmonary Function Testing • Chapter 1 21 to the airways. This can occur as a result of mo- ● Scarring (fibrosis) caused by radiation or tor vehicle accidents or falls. Scarring or stenosis chemotherapy of the trachea may also occur after prolonged en- ● Transient problems such as pleural effusions, dotracheal intubation or tracheostomy. The typ- abdominal ascites, or pregnancy ical pattern is one of fixed obstruction, although some lesions do vary with the phase of breathing. Pulmonary Fibrosis Granulomatous disease, such as sarcoidosis or tu- Pulmonary fibrosis involves scarring of the lung berculosis, can occasionally cause upper airway with involvement at the alveolar level. Multiple obstruction. Extrinsic airway compression can also causes have been identified, including environmen- reduce airflow. Goiters or mediastinal masses are tal pollutants, smoking, radiation, and connective the most common culprits that compress the air- tissue diseases. Patients who have pulmonary fibro- ways in this way. sis present with dyspnea that increases with exer- tion and a dry, nonproductive cough. Management of Upper or Large Airway Obstruction Pulmonary fibrosis can follow the use of med- Treatment of extrathoracic or intrathoracic large ications such as bleomycin, cyclophosphamide, airway obstruction is aimed at reversing the process methotrexate, or amiodarone. It is also associated produced by the offending lesions. For VCD, stop- with several autoimmune diseases. Rheumatoid ping inappropriate therapy (e.g., steroids) is the arthritis, systemic lupus erythematosus (SLE), and first step. Speech therapy and breathing retraining scleroderma all produce alveolar wall inflammation have been demonstrated to reduce inspiratory ob- and fibrotic changes. As each disease progresses, struction. In severe cases, a mixture of helium and lung volumes are reduced. These reductions in VC oxygen (80% He and 20% O ) may be needed to alle- and TLC occur as fibrosis causes the lungs to be- 2 viate dyspnea and interrupt the episode. Treatment come stiff. Measurement of pulmonary compliance of neuromuscular disease, such as myasthenia gra- (see Chapter 4) is sometimes helpful in quantifying vis, often reverses the associated airway obstruction. the effects of the fibrosis. Dlco (see Chapter 3) is Tumors usually require resection. Some neoplasms often reduced because of loss of lung volume and can be managed by radiation or chemotherapy only. ventilation-perfusion mismatching. The same pro- In either case, spirometry with flow-volume curves cesses also cause hypoxemia at rest that worsens (see Chapter 2) is used to assess airway obstruction. with exertion. Surgical repair of trauma to the upper or large air- When other causes of pulmonary fibrosis have ways directly relieves airway obstruction and re- been ruled out, this condition is called idiopathic duces the work of breathing. pulmonary fibrosis (IPF). IPF is a chronic progressive interstitial lung disease of unknown etiology, char- Restrictive Lung Disease acterized by alveolar wall inflammation, resulting Restrictive lung disease is characterized by the re- in fibrosis. Vascular changes are usually associated duction of lung volumes. The VC and TLC are both with pulmonary hypertension. These patients also reduced below the LLN. Any process that interferes have increasing exertional dyspnea, usually with a with the bellows action of the lungs or chest wall nonproductive cough. Clubbing of the fingers and can cause restriction. Restriction is often associated expiratory rales are common physical findings. On with interstitial lung diseases, including idiopathic the chest x-ray film, infiltrates are visible, and ad- fibrosis, pneumoconiosis, and sarcoidosis, as well vanced IPF shows a honeycombing pattern. as the following: Management of pulmonary fibrosis relies pri- ● Disease of the chest wall and pleura marily on corticosteroids (prednisone). Long-term ● Neuromuscular disorders therapy is usually indicated, with large initial ● Congestive heart failure (CHF) doses followed by tapering and then maintenance. ● Obesity Immunosuppressive agents are sometimes used in ● Lung resection conjunction with steroids in difficult cases. In the --- PAGE 34 --- 22 Ruppel’s Manual of Pulmonary Function Testing most severe presentations, lung transplantation nodules around bronchioles and blood vessels. As may be required. Spirometry, lung volume mea- the silicosis advances, fibrosis occurs. The patient surements, and Dlco are routinely used to monitor usually has cough and dyspnea, especially on exer- the patient’s progress and response to therapeutic tion. In addition to restriction shown by pulmonary interventions. Blood gases and exercise tests may be function studies, some airways may also be ob- needed to gauge the degree of oxygen desaturation structed. As nodules increase in size to more than 1 that is known to occur. cm, the condition is labeled progressive massive fibrosis (PMF). PMF is usually accompanied by hypoxemia Pneumoconiosis and pulmonary hypertension. Treatment of silico- Pneumoconiosis is lung impairment caused by inha- sis is directed at relieving hypoxemia and managing lation of particulate material (e.g., dusts). Specific right-sided heart failure. types of dust exposures have been shown to result Asbestosis results from inhalation of asbestos in pneumoconiosis (Table 1.1). Dust particles in the fibers. Asbestos has been commonly used in the size range between 0.5 and 5.0 microns are consid- manufacture of insulating materials, brake linings, ered most dangerous because they are deposited roofing materials, and fire-resistant materials. As throughout the lung. A carefully taken history of with most pneumoconiosis, the risk of developing the patient’s exposure, including work history, is es- asbestosis is related to the intensity and duration of sential. (See Pulmonary History in the Preliminaries exposure. The onset of symptoms is usually delayed to Patient Testing section.) Most cases of pneumo- for 20 years. Cigarette smoking has been shown to coniosis are characterized by pulmonary fibrosis shorten the period between exposure and onset of and chest x-ray abnormalities. Pulmonary function symptoms. Inhaled asbestos fibers are engulfed by studies typically reveal a restrictive pattern with a alveolar macrophages. Fibrosis in alveolar walls and reduction in Dlco. around bronchioles develops. The visceral pleura Silicosis, caused by inhalation of silica dust, is may also show fibrous deposits. Plaques, made up common. Silica is found in sand, slate, granite, and of collagenous connective tissue, are often found other ores; sandblasters, miners, and ceramic work- on the parietal pleura. The patient experiences dys- ers are a few of the occupations commonly exposed pnea on exertion. PFTs show restriction and im- to silica. Silica is deposited in the lung and ingested paired diffusion (Dlco). The chest x-ray film may by macrophages. This results in the formation of show irregular densities in the lower lung fields, TABLE 1.1 Common Pneumoconiosis Dust Pneumoconiosis Occupation Iron Siderosis Welder, miner Tin Stannosis Metal worker Barium Baritosis Miner, metallurgist, ceramics worker Silica Silicosis (aka grinder disease or Sandblaster, granite worker, brick potter rot) maker, coal miner Asbestos Asbestosis Brake/clutch manufacturer, shipbuilder, steam fitter, insulator Talc Talcosis Ceramics worker, cosmetics maker Beryllium Berylliosis Alloy maker, electronic tube maker, metal worker Coal Coal worker pneumoconiosis Coal miner --- PAGE 35 --- Indications for Pulmonary Function Testing • Chapter 1 23 fibrotic changes (honeycombing), and diaphrag- in patients who have sarcoidosis. Dyspnea and a matic calcifications. COPD and lung cancer are dry, nonproductive cough are the most common also common in patients with asbestosis and are presenting symptoms. Chest x-ray films usually related to cigarette smoking. Treatment consists of show enlargement of the hilar and mediastinal assessment with PFTs (especially Dlco) and relief of lymph nodes. Interstitial infiltrates may also be symptoms. present. Other systems commonly involved in sar- Coal worker’s pneumoconiosis (CWP) is caused by coidosis include the skin, eyes, musculoskeletal sys- an accumulation of coal dust (carbon particles) in tem, heart, and central nervous system. the lungs. It should not be confused with black lung, PFTs show a pattern of restriction with relatively which is a legal term used to describe any chronic normal flows. It is not unusual for sarcoidosis in respiratory disease in a coal miner. Some coal con- the early stages to show completely normal lung tains silica, but CWP begins with a reaction to an function. Dlco may not be reduced except when accumulation of dust called a coal macule. These there is advanced fibrosis of lung tissue. Arterial macules are usually found in the upper lobes. The blood gas measurements may be normal, or there black coal pigment is deposited around the respi- may be hypoxemia. Cardiopulmonary exercise test- ratory bronchioles. Diagnosis of CWP is made by ing may show worsened gas exchange. Diagnosis of history and chest x-ray film interpretation. Onset sarcoidosis is sometimes made via clinical findings of symptoms caused by CWP usually occurs in ad- and chest x-ray examination, but biopsy of affected vanced cases. Coal workers often have respiratory tissue is often necessary. This may involve mediasti- symptoms and physiologic findings consistent noscopy or fiberoptic bronchoscopy. with COPD. These symptoms may be related more Management of sarcoidosis includes medica- to cigarette smoking than to coal dust exposure. tions to treat symptoms such as fever, skin lesions, CWP causes fibrosis, restriction on PFTs, hypox- or arthralgia. Serious complications involving emia, and pulmonary hypertension. As in the case worsening pulmonary function are usually treated of other pneumoconiosis, treatment is aimed at re- with corticosteroids. lief of the symptoms. Diseases of the Chest Wall and Sarcoidosis Pleura Sarcoidosis is a granulomatous disease that affects Several disorders involving the chest wall or pleura multiple organ systems. The lungs are often in- of the lungs result in restrictive patterns on pul- volved. The disease appears most often in the second monary function studies. Conditions affecting the through fourth decades of life. In the United States thorax include kyphoscoliosis and obesity. Pleural it occurs more commonly in African Americans, es- diseases include pleurisy, pleural effusions, and pecially in women. The granulomas found in sar- pneumothorax. coidosis are composed of macrophages, epithelioid Kyphoscoliosis is a condition that involves ab- cells, and other inflammatory cells. Sarcoidosis has normal curvature of the spine both anteriorly an active phase and a nonactive phase. In the active (kyphosis) and laterally (scoliosis). The degree of cur- phase, granulomas form and increase in size. These vature is usually determined by x-rays, with cur- granulomatous lesions may resolve with little or no vature greater than 40 degrees requiring surgery. structural change, or they may cause fibrosis in the Patients who have kyphoscoliosis show rib-cage target organ. In the nonactive phase, inflammation distortion that can lead to recurrent infections, as subsides, but scar tissue usually remains. well as blood gas abnormalities. Depending on the Symptoms of sarcoidosis include fatigue, muscle degree of spinal curvature, the patient may have weakness, fever, and weight loss. Other symptoms normal lung function or restriction. Ventilation involve the specific organ system in which the gran- may be normal. Lung compression usually causes ulomatous changes occur. The lungs and lymph ventilation-perfusion mismatching and hypox- nodes of the mediastinum are frequently involved emia. In severe cases, there may be hypercapnia --- PAGE 36 --- 24 Ruppel’s Manual of Pulmonary Function Testing and respiratory acidosis. Treatment of the disorder pulmonale. Not all patients who are obese show involves prevention of infections and relief of hy- the signs of obesity-hypoventilation syndrome. poxemia if present. Surgical correction is necessary However, pulmonary function studies often show in many cases, and pulmonary function studies are restriction in proportion to the excess weight. used to evaluate patients both preoperatively and Weight reduction relieves many of the associated postoperatively. symptoms. Respiratory stimulants, tracheostomy, Pectus excavatum (sunken chest) is a congenital and continuous positive airway pressure (CPAP) abnormality affecting the development of the ster- are used to manage the obstructive sleep apnea num and ribs of the anterior chest. It is found more component. frequently in boys than in girls (approximately 3:1) Pleurisy and pleural effusions can each result and occurs in about 1 in 300 to 400 births, mak- in restrictive ventilatory patterns. Pleurisy is char- ing it the most common congenital abnormality of acterized by the deposition of a fibrous exudate on the chest. The caved-in chest is usually obvious in the pleural surface. It is associated with other pul- infants but often does not cause significant limita- monary diseases such as pneumonia or lung cancer. tions until adolescence. Pectus excavatum varies in Pleurisy is often accompanied by chest discomfort severity but typically results in a restrictive pattern or pain and may precede the development of pleural on PFTs. Exercise testing or other tests of cardiac effusions. Pleural effusion is an abnormal accumu- performance may be indicated to assess functional lation of fluid in the pleural space. This fluid may limitations in severe cases. Pulmonary function and be either a transudate or an exudate. Transudates exercise tests may also be used to assess improve- occur when there is an imbalance in the hydrostatic ments following corrective surgery. or oncotic pressures, as occurs in CHF. Exudates are Obesity restricts ventilation, especially when associated with infections or with inflammation, as the obesity is severe. Obesity is usually categorized in lung carcinoma. Patients with pleural effusions using body mass index (BMI). BMI equals body usually have symptoms that relate to the extent of weight in kilograms divided by height in meters the effusion. Small effusions often go unnoticed. If squared (BMI = kg/m2). A BMI of 18.5 to 24.9 is the effusion is large, there may be atelectasis from normal, 25 to 29.9 is considered overweight, and compression of lung tissue and associated blood 30 or greater is considered obese. A BMI of 40 or gas changes. PFTs show restriction because of vol- greater is sometimes referred to as morbid obesity. ume loss. In some cases, there is restriction caused The increased mass of the thorax and abdomen in- by splinting because of pain. Treatment of pleurisy terferes with the bellows action of the chest wall, as and pleural effusions is directed toward the under- well as excursion of the diaphragm. TLC and VC are lying cause. Large or unresolved pleural effusions usually preserved in obese individuals, but FRC and often require thoracentesis or chest tube drainage. expiratory reserve volume (ERV) are characteristi- Patients with painful pleural involvement may have cally reduced. Obesity is also sometimes associated difficulty performing spirometry or breath holding with asthma-like symptoms. It is not clear whether as required for Dlco. asthma is related to obesity or if the restriction Pneumothorax is a condition in which air en- caused by obesity contributes to airflow limitation ters the pleural space. This air leak may be caused that mimics asthma. The airflow limitation occurs by a perforation of the lung itself or of the chest secondary to the subject breathing at or near RV. wall (e.g., chest trauma). A small pneumotho- Obesity may also be associated with a more gen- rax may not cause any symptoms. A large pneu- eral syndrome that consists of hypercapnia and mothorax can result in severe dyspnea and chest hypoxemia, sleep apnea, and decreased respiratory pain. Physical examination of the patient reveals drive. The combination of these findings is some- decreased chest movement on the affected side. times called the obesity-hypoventilation syndrome. Breath sounds are usually absent. A chest x-ray Chronic hypoxemia in this syndrome results in study shows a shift of the mediastinum away from polycythemia, pulmonary hypertension, and cor the pneumothorax. Small pneumothoraxes usually --- PAGE 37 --- Indications for Pulmonary Function Testing • Chapter 1 25 resolve without treatment as gas is reabsorbed from sitting positions can demonstrate the functional the pleural space. Large air leaks usually require a impairment. Unilateral paralysis often results from chest tube with appropriate drainage to allow lung damage to one of the phrenic nerves (e.g., trauma, reexpansion. surgery, or tumor). As with bilateral paralysis, there PFTs are usually contraindicated in the presence is a marked change in VC from supine to sitting of pneumothorax. However, undiagnosed pneumo- position. Diagnosis of which side is involved may thorax may present a risk if pulmonary function require a chest x-ray or examination under fluoros- studies are performed. Maneuvers that generate copy. Reduced inspiratory pressures may suggest high intrathoracic pressures (i.e., FVC, MVV, MIP/ diaphragmatic involvement. MEP) can aggravate an untreated pneumothorax. Amyotrophic lateral sclerosis (ALS), or Lou Gehrig The potential for the development of a tension disease, affects the anterior horn cells of the spinal pneumothorax exists when these maneuvers are cord (motor neurons). Progressive muscle weakness performed. In a tension pneumothorax, air enters results in a gradual decrease in VC and TLC, which the pleural space but cannot escape. Increasing is invariably fatal. Pulmonary function studies may pressure compresses the opposite lung as well as be done serially to assess the progression of the the heart and great vessels. Compression of the disease. mediastinum interferes with venous return to the Duchenne muscular dystrophy is caused by a defec- heart and can cause a rapid drop in blood pressure. tive gene for dystrophin (a protein in the muscles). A tension pneumothorax can be fatal if not treated It occurs in about 1 out of every 3600 male infants immediately. Patients referred for pulmonary func- and is an inherited disorder. Symptoms usually tion studies who have a known or suspected pneumo- occur before age 6 and can appear in infancy. VC thorax should be tested very carefully or not at all. In monitoring and respiratory muscle strength mea- many instances, the information obtained may not surements (MIP, MEP) are commonly performed justify the risk to the patient. but may be challenging depending on the age of the patient. Neuromuscular Disorders Guillain–Barré syndrome is a progressive disease Diseases that affect the spinal cord, peripheral in which the body’s immune system attacks the pe- nerves, neuromuscular junctions, and respiratory ripheral nerves. Lower extremity weakness ascends muscles can all cause a restrictive pattern of pulmo- to the upper extremities and face. There may be nary function. Most of these disorders result in an marked respiratory muscle weakness, along with inability to generate normal respiratory pressures. weakness of the pharyngeal and laryngeal muscles. The VC and TLC are often reduced, whereas the RV Many patients eventually require mechanical sup- may be preserved. Some chronic neuromuscular port of ventilation. Serial measurements of the VC, disorders are associated with decreased lung com- MIP, and MEP, cough peak flow (CPF), or sniff na- pliance. Blood gas abnormalities, particularly hy- sal inspiratory pressures (SNIPs) are used to follow poxemia, may result if the degree of involvement is the disease progression (see Chapter 10). severe. Stiff lungs and rapid respiratory rates often Myasthenia gravis is a chronic autoimmune dis- result in respiratory alkalosis (hyperventilation). ease affecting neuromuscular transmission. In my- Progressive muscle weakness results in respiratory asthenia gravis, antibodies produced by the body’s acidosis (hypoventilation) and respiratory failure. immune system block or destroy the receptors Paralysis of the diaphragm may be bilateral or for acetylcholine at the neuromuscular junction, unilateral. Bilateral paralysis may be the end stage which prevents the muscle contraction from oc- of various disorders. The most prominent finding curring. It particularly affects muscles innervated is orthopnea or shortness of breath in the supine by the bulbar nuclei (i.e., face, lips, throat, and position. In the upright position, the patient has neck). The patient with myasthenia gravis has pro- a marked increase in VC and improvement in gas nounced fatigability of the muscles. Speech and exchange. Simple spirometry in the supine and swallowing difficulties can occur with prolonged --- PAGE 38 --- 26 Ruppel’s Manual of Pulmonary Function Testing exercise of the associated muscles. Administration also important in managing CHF. Diuretics such of edrophonium chloride (Tensilon) is sometimes as furosemide (Lasix) are commonly used to reduce used to confirm the diagnosis of myasthenia gra- the afterload on the ventricle. Oxygen therapy may vis; the drug blocks acetylcholinesterase and tem- also help reduce myocardial workload, especially porarily increases muscle strength in patients who if there is hypoxemia. If the cause of CHF is an ar- have myasthenia gravis. When the ventilatory mus- rhythmia, antiarrhythmic agents are typically used. cles become involved, a myasthenic crisis occurs. PFTs, particularly lung volumes and Dlco, may be Progression of a myasthenic crisis can be assessed used to monitor the effects of treatment. using VC and respiratory pressures. Analysis of the flow-volume curve (see Chapter 2) may be helpful Lung Transplantation in detecting upper airway obstruction brought on Lung transplantation has evolved as an effective by muscular weakness. treatment for end-stage lung disease. Lung trans- plantation has been used for patients with CF, Congestive Heart Failure primary pulmonary hypertension, and COPD CHF is often used synonymously with left ventricu- (Table 1.2). Double-lung transplants are usually lar failure. Failure of the left ventricle may be caused performed in patients who have CF, generalized by systemic hypertension, coronary artery disease, bronchiectasis, or some types of COPD. Heart– or aortic insufficiency. CHF may also be associated lung transplants have been used for Eisenmenger with cardiomyopathy, congenital heart defects, and syndrome, pulmonary hypertension with cor pul- left-to-right shunts. In each case, fluid backs up in monale, and end-stage lung disease coexisting with the lungs. The pulmonary venous system becomes severe heart disease. Single-lung transplantation engorged. Fluid may spill into the alveolar spaces has been used effectively in patients with COPD (pulmonary edema) or the pleural space (effusion). who are younger than approximately 60 years old. The patient who has CHF usually has shortness Single-lung transplantation offers the benefit that of breath on exertion, cough, and fatigue. If coro- two recipients can share a single donor’s organs. nary artery disease is the cause of CHF, there may be chest pain (angina) as well. Exertional dyspnea TABLE 1.2 is related to pulmonary venous congestion. The Indications for Lung Transplantation fluid overload in the lungs reduces lung volume and makes the lungs stiff (decreased compliance). Transplant Type Disease State Dyspnea is usually worse when the patient is supine Heart–lung Eisenmenger syndrome, severe (i.e., orthopnea). This orthopnea results from in- cardiac defect Pulmonary hypertension, cor creased pulmonary vascular congestion, which hap- pulmonale pens when interstitial fluid becomes intravascular, End-stage lung disease, coexisting causing an increase in volume, which in turn causes severe cardiac disease vascular engorgement, promoting capillary leak. Double lung Cystic fibrosis Dyspnea brought on by CHF may be difficult to Generalized bronchiectasis distinguish from other causes (e.g., chronic pulmo- COPD with severe chronic nary disease); therefore patients are often referred bronchitis or extensive bullae for pulmonary function studies. The chest x-ray Single lung Restrictive fibrotic lung disease film usually shows increased pulmonary conges- Eisenmenger syndrome (less severe cardiac anomalies) tion. The heart (left ventricle) may appear enlarged, COPD particularly if systemic hypertension is the cause. Primary pulmonary hypertension Treatment of CHF is directed at the underlying cause. Relief of systemic hypertension can reduce the COPD, Chronic obstructive pulmonary disease. Modified from American Thoracic Society. (2014). International myocardial workload. This is usually accomplished guidelines for the selection of lung transplant candidates. American by vasodilator therapy. Reducing fluid retention is Journal of Respiratory and Critical Care Medicine, 158, 335–339. --- PAGE 39 --- Indications for Pulmonary Function Testing • Chapter 1 27 Survival rates for lung transplant recipients have pulmonary complications (e.g., pneumonia) in pa- steadily improved. Longer survival is mainly due tients who are immunosuppressed. There is some to more potent antirejection drugs (e.g., cyclospo- evidence that changes in spirometry (FVC, FEV , 1 rine) and better adjunctive therapy. PFTs are used FEF ) or distribution of gas (as measured by 25%–75% to both assess potential transplant candidates and the single-breath technique) may signal episodes follow them postoperatively. of acute rejection. Chronic rejection is thought to Preoperative evaluation consists of documenta- be associated with the development of BO. This tion of the severity of the specific disease process. pattern is characterized by the development of se- Spirometry, lung volumes, Dlco, and blood gas vere airflow limitation in the transplanted lung. analysis are all used to rank the level of dysfunc- Spirometry, particularly indices of small airway tion. The same tests are also used to detect sudden function such as FEF , may provide the ear- 25% to 75% worsening of lung function that might necessitate liest signs of BO. rapid intervention. Cardiopulmonary exercise test- ing may be indicated to determine the extent of the PRELIMINARIES TO PATIENT physiologic abnormality. For example, a patient TESTING with borderline pulmonary hypertension at rest may develop severe hypertension during even mild Testing During a Pandemic exertion. In 2020, the world was dealing with the global Most transplantation programs list patients as COVID-19 pandemic. This led to professional soci- prospective candidates when their pulmonary dis- eties publishing recommendations on when to uti- ease has advanced beyond predefined limits. An lize pulmonary function testing because the virus extended wait for lung transplantation is a direct may be spread during lung function procedures, result of the shortage of donor organs. Patients are which may induce cough. Even after the COVID-19 often referred for transplant evaluation when a ma- pandemic has subsided, future pandemics may be jor decline in their condition is observed. The term the new reality. The European Respiratory Society transplant window has been used to describe the time (ERS) published its recommendations based on during which the patient is sick enough to require three levels of a pandemic outbreak.⁎ transplantation but healthy enough to have a rea- sonable chance of survival. Level I: High Community Prevalence Posttransplant follow-up relies heavily on PFTs. 1. Establish a screening process and do not test Spirometry has been used extensively to monitor patients with active disease. improvements resulting from transplantation. 2. Perform only essential testing, and limit test- Recipients of double-lung transplants often show ing to spirometry and Dlco. lung function values approaching those of normal 3. Reorganize waiting and testing rooms to re- patients within a few months. Blood gas changes duce exposure. usually occur immediately after surgery. Single- 4. Reorganize the testing schedule to allow for lung transplant (SLT) recipients show similar gains. additional cleaning procedures. However, because SLT patients retain a native lung, 5. Testing should be performed with high- improvement in pulmonary function is usually less efficiency bacterial/viral filters and utilize than when both lungs are replaced. Interpretation single-patient-use disposables (nose clips, of spirometry, lung volumes, and blood gases in mouthpieces). SLT patients is often complicated by the presence of the native lung along with the transplanted lung. ⁎ Adapted from the ERS Recommendation from ERS Besides monitoring improved lung function, Group 9.1 (Respiratory Function Technologists/ PFTs are used to detect rejection and the develop- Scientists). (n.d.). Lung function testing during COVID-19 ment of bronchiolitis obliterans (BO). Rejection pandemic and beyond. https://ers.app.box.com/s/ may be difficult to distinguish from other zs1uu88wy51monr0ewd990itoz4tsn2h. --- PAGE 40 --- 28 Ruppel’s Manual of Pulmonary Function Testing 6. Personal protective equipment (PPE), in- TABLE 1.3 cluding facemasks, face shields and/or gog- Stages of Quality gles, gowns, and gloves, is recommended for The quality management system (QMS) is a major all the testing staff. Hand hygiene is critical level in the health care quality hierarchy and forms the and should be strictly followed by staff and basis for this document. Also see Fig. 1.7.a the subject. The use of a hand sanitizer by the Stage Activities Performed patient prior to entering and exiting the test- Total quality Management approach centered on ing room should be required. management sustained high quality by focusing on Level II: Low Community Prevalence long-term success through customer 1. Essential infection control measures (e.g., satisfaction cleaning, PPE) should be maintained even Quality cost Measurement system for the economic though the prevalence is reduced/ management aspects of the “cost of quality” 2. Exercise testing, nebulization, bronchial chal- Quality Systematic, process-oriented approach lenge testing, and other aerosol-g enerating management to meeting quality objectives procedures should be limited to specific system equipment and testing rooms. Quality Planned and systematic activities 3. Use filters on the exhalation ports of nebuliz- assurance to provide confidence that an ers and exercise testing equipment. organization fulfills requirements for Level III: Controlled quality 1. Return to prepandemic standards for the de- Quality Operational process-control techniques livery of lung function tests. control to fulfill quality requirements for regulatory compliance and Which tests the laboratory provides, when to accreditationb expand diagnostic services beyond the basic tests, and the extra infection precaution steps put in a Cianfrani, C. A., Tsiakals, J. J., & West, J. E. (2002). The ASQ ISO place are the decision of the laboratory manage- 9000:2000 handbook. Milwaukee, WI: American Society for Quality. b International Organization for Standardization. (2005). Quality ment team and the local infection control depart- management systems: Fundamentals and vocabulary. ISO 9000. Geneva, ment. However, basic guidelines from the American Switzerland: International Organization for Standardization. Thoracic Society (ATS) and ERS can be used to as- sist in the decision-making process. The model is characterized by quality elements that Before Patient Testing are essential components of an organization or lab- To provide accurate patient data, the laboratory oratory’s quality system and are called the quality sys- needs to have a defined quality assurance program tem essentials, or QSEs. in place. The Clinical and Laboratory Standards Institute (CLSI), an organization that provides The 12 QSEs guidance for medical laboratories, adapted the 1. Documents and records management concepts found in the International Standards 2. Organization and leadership Organization (ISO) 9001 recommendations and 3. Personnel management applied them to the laboratory setting in a guide- 4. Equipment management line titled “A Quality Management System; a Model 5. Supplier and inventory for Laboratory Services (QMS01-A5).” Table 1.3 6. Process management describes the various hierarchical stages of quality, 7. Information management where a quality management system is a systematic, 8. Nonconforming event management “process-oriented” approach to quality. The quality 9. Assessments system model describes, documents, implements, 10. Continual improvement measures, and monitors the implementation and ef- 11. Customer focus fectiveness of the work operations of the laboratory. 12. Facilities and safety management --- PAGE 41 --- Indications for Pulmonary Function Testing • Chapter 1 29 In the CLSI’s quality system model, these 12 should be instructed to take the bronchodila- QSEs are identified across the laboratory’s “Path of tor when breathing problems require it. Patients Workflow.” In the pulmonary function laboratory, scheduled for a bronchial challenge who inad- the path of workflow (POW) would include pretest, vertently take their bronchodilators may need to test, and posttest activities. Chapter 12 will further be rescheduled because bronchodilators can sig- detail the POW activities and how integrating these nificantly alter airway response and lead to false- concepts into a laboratory’s quality plan ensures negative results. quality testing results (Fig. 1.7). Care should be taken when instructing outpa- Several preliminary steps precede any pulmo- tients about withholding medications. Some pa- nary function study. These include patient prepara- tients may be unable to correctly identify all their tion, physical measurements and assessment, brief medications. Therefore it may be difficult for them pulmonary history, and instructions to the patient to correctly withhold bronchodilators only. Some in the performance of specific test maneuvers. In patients incorrectly withhold all medications. This addition, PFTs are usually done in an ordered se- may cause serious problems for patients who rely on quence. The testing sequence may be determined by insulin (patients with diabetes), antiarrhythmics, or laboratory policy, or it may be adapted for specific antihypertensives used for high blood pressure. If needs using a predefined protocol. the patient is uncertain, it may be preferable not to withhold any medications. Patient Preparation (Pretest Instructions) Smoking Cessation Patient preparation for pulmonary function studies Patients referred for PFTs should be asked to refrain consists mainly of instructions given to the patient from smoking for 1 hour before the test. Smoking in advance of the actual test session. These instruc- cessation is especially important if Dlco tests or ar- tions focus on taking or withholding specific med- terial blood gas tests are ordered. Smoking has been ications, refraining from smoking and eating, and shown to directly reduce Dlco. Smoking also raises other guidelines related to specific tests (e.g., exer- the level of CO in the blood, which also interferes cise tests, blood gases). with the measurement of Dlco (CO back pressure in blood). Increased CO in the blood (COHb) also Withholding Medications makes it difficult to interpret O saturation mea- 2 Patients referred for evaluation of airflow limita- sured by pulse oximetry (see Chapter 6). Smoking tion are often already taking bronchodilators or has been shown to reduce the levels of eNO, which related drugs. If the response to bronchodilators may artifactually reduce the level of NO in patients is to be assessed, bronchodilators should be with- who have airway inflammation. held before testing. The exact length of time to withhold a bronchodilator is dictated by the onset Other Patient Preparation Issues of action and how long it takes for the drug to be Patients referred for PFTs should refrain from eat- metabolized and/or excreted. Guidelines for with- ing a large meal immediately before their appoint- holding specific bronchodilators before simple ment. Two hours is usually sufficient to avoid spirometry are presented in detail in Chapter 2. vomiting or gastric distress during routine testing. Recommendations for withholding medications The same is true if the patient will be exercising before a bronchial challenge test (methacho- as part of the evaluation. Patients scheduled for a line, exercise, hyperventilation, etc.) are found bronchial challenge test (see Chapter 9) have fur- in Chapter 9. Some patients may have difficulty ther defined withholding schedules. Outpatients withholding bronchodilators. In the case of sim- scheduled for metabolic studies may need to fast ple spirometry, the test may be performed if nec- for 8 hours before testing to assure a stable baseline. essary, with an operator comment describing the Patients should refrain from alcohol consumption use of bronchodilators before testing. The patient for at least 8 hours before testing (Box 1.8). --- PAGE 42 --- 30 Ruppel’s Manual of Pulmonary Function Testing Laboratory path of workflow Preexamination Examination Postexamination • Examination • Specimen • Specimen • Specimen • Examination• Examination • Results • Laboratory • Communication • Release of • Specimen ordering collection transport receipt, method performance review and results of alert values final reports management accessioning, selection follow-up interpretation and issuance of and processing preliminary reports Assessments Quality system essentials Continual improvement Documents and Information Nonconforming records management management event management Personnel Supplier and inventory Equipment Process management management management management Organization and Facilities and safety Customer focus leadership management International and national regulatory and accreditation requirements FIG. 1.7 The 12 quality system essentials (QSEs) function as building blocks that are necessary to support any laboratory’s path of workflow and laboratory disciplines. This example represents how the 12 QSEs support a clinical laboratory’s disciplines.(From Clinical and Laboratory Standards Institute. [2019]. CLSI document QMS01-A5. In Quality management system: A model for laboratory services, approved guideline [5th ed.]. Wayne, PA: Clinical and Laboratory Standards Institute.) --- PAGE 43 --- Indications for Pulmonary Function Testing • Chapter 1 31 patient’s declared ethnic origin is preferred. Basic BOX 1.8 PRETEST INSTRUCTIONS FOR physical assessment of the patient’s respiratory sta- LUNG FUNCTION TESTING tus may be needed before and during testing. ● No smoking, vaping, or water pipe use 1 hour be- The patient’s age should be recorded as of the fore the test. last birthday. Some computerized pulmonary func- ● Do not consume intoxicants 8 hours prior to testing. tion systems store the patient’s birth date and cal- ● Do not exercise (e.g., jogging, bicycling, fast walk- culate the age. This approach is helpful, especially ing, aerobics, etc.) for 1 hour before the test. when the patient returns periodically for serial test- ● Do not wear restrictive clothing that may interfere ing. Care should be used when entering specially with taking a deep breath. formatted data (e.g., dates) into a computerized system. Data-entry errors can result in gross over- estimation or underestimation of the patient’s ex- Patients should refrain from vigorous exercise pected values. immediately before testing and should be relaxed Standing height, in centimeters (within 1 dec- and comfortable during the test session. Exercise imal place), should be recorded with the patient can result in circulating catecholamines, which af- barefoot or in stocking feet. A wall-mounted ruler fect airway tone. Depending on the time of exercise (stadiometer) allows the patient to stand with the related to the testing time, exercise can also alter back against the wall and the head close to the ruler. the subject’s cardiac output, resulting in a change If the patient is unable to stand upright, the arm to carbon monoxide uptake. Tight-fitting clothing span or other alternative methods (ulnar length) (e.g., neckties) may need to be loosened during test- should be used. Patients who have a history of ky- ing. Dentures should be left in place; many patients phosis, scoliosis, or related problems should also find it easier to hold the mouthpiece using their have the height estimated using their arm span. dentures. However, if the dentures are loose, they Arm span may be measured using a ruler placed may obstruct the mouthpiece, particularly during on a wall or a tailor’s tape measure (Fig. 1.8A–C). forced expiratory maneuvers. The patient should extend the arms horizontally Some patients may require special accommo- on both sides, and the distance between the tips of dations for PFTs to be performed safely and accu- the middle fingers is then measured. Alternately, rately. Patients, or those referring patients, should the distance from the tip of the middle finger to the understand the requirements of the tests requested. center of the vertebra at the level of the scapula is Patients who are unable to sit or stand may re- measured on each side and then summed. Height quire additional time or equipment for testing to may then be estimated as arm span/1.06 or using be completed. Patients who have a permanent tra- regression equations that account for race, sex, and cheostomy may also require special devices to al- age in addition to arm span. Ulnar length is another low connection to standard pulmonary function method of estimating height in subjects. A mea- circuits. Patients who do not speak the primary surement is made between the points of the elbow language used in the laboratory may require an (olecranon process) and the midpoint of the prom- interpreter to be present during testing. Asking inent bone of the wrist (styloid process), on the left appropriate questions before the patient’s appoint- side if possible (Fig. 1.9). ment can identify each of these special needs. A table is used to convert the ulnar length to an estimated height (Table 1.4). The patient’s weight Anthropometric Measurements in pounds or kilograms (within 0.5 kg) should be Various physical measurements are required for measured with an accurate scale. Although body estimating each patient’s expected level of pulmo- weight is typically not used in the calculation of nary function. Age, height, and weight are usually predicted lung volumes, subjects who are mor- recorded in addition to the patient’s sex. Race or bidly obese may demonstrate a restrictive pattern. ethnic origin should also be recorded. Using the Measurement of weight and calculation of BMI --- PAGE 44 --- 32 Ruppel’s Manual of Pulmonary Function Testing FIG. 1.8 (A) Measurement of height with stadiometer. (B) Measurement of arm span while standing. (C) Measurement of arm span with tailor’s tape. may be helpful for the interpretation of reduced lung volumes (e.g., FRC, ERV). Body weight is used to calculate other reference values (see Chapter 13). When weight is used to predict an expected value, the patient’s ideal body weight should be used, unless noted otherwise. Using actual weight in patients who are obese may overestimate expected values if the reference set is based on subjects with normal weights. Weight is also used to express ox- ygen consumption (i.e., milliliter/kilogram) for ex- ercise and metabolic measurements. The patient’s weight may also be required when lung volumes are determined with the body plethysmograph. Weight is used to estimate body volume in the FIG. 1.9 The arm landmarks used to measure ulnar length to plethysmograph (see Chapter 4). estimate standing height. --- PAGE 45 --- Indications for Pulmonary Function Testing • Chapter 1 33 TABLE 1.4 Converting Ulnar Length to an Estimated Height Height (m) Men (< 65 years) 1.94 1.93 1.91 1.89 1.87 1.85 1.84 1.82 1.80 1.78 1.76 1.75 1.73 1.71 Men (> 65 years) 1.87 1.86 1.84 1.82 1.81 1.79 1.78 1.76 1.75 1.73 1.71 1.70 1.68 1.67 Ulna length (cm) 32.0 31.5 31.0 30.5 30.0 29.5 29.0 28.5 28.0 27.5 27.0 26.5 26.0 25.5 Women (< 65 years) 1.84 1.83 1.81 1.80 1.79 1.77 1.76 1.75 1.73 1.72 1.70 1.69 1.68 1.66 Women (> 65 years) 1.84 1.83 1.81 1.79 1.78 1.76 1.75 1.73 1.71 1.70 1.68 1.66 1.65 1.63 Men (< 65 years) 1.69 1.67 1.66 1.64 1.62 1.60 1.58 1.57 1.55 1.53 1.51 1.49 1.48 1.46 Men (> 65 years) 1.65 1.63 1.62 1.60 1.59 1.57 1.56 1.54 1.52 1.51 1.49 1.48 1.46 1.45 Ulna length 25.0 24.5 24.0 23.5 23.0 22.5 22.0 21.5 21.0 20.5 20.0 19.5 19.0 18.5 Women (< 65 years) 1.65 1.63 1.62 1.61 1.59 1.58 1.56 1.55 1.54 1.52 1.51 1.50 1.48 1.47 Women (> 65 years) 1.61 1.60 1.58 1.56 1.55 1.53 1.52 1.50 1.48 1.47 1.45 1.44 1.42 1.40 PF TIP 1.2 BOX 1.9 PHYSICAL ASSESSMENT DURING PULMONARY Always measure the patient’s height (without FUNCTION TESTING shoes) and weight. Height should be measured to the nearest centimeter and ● Breathing pattern within 1 decimal place. Self-reported heights ● Is the respiratory rate excessive? and weights are usually inaccurate. Arm span ● Are there any complaints of chest tightness or or other alternative measurements may be chest discomfort? used to estimate standing height for patients ● Are accessory muscles being used for breathing? who are unable to stand or who have ● Is the patient using pursed lips? significant spinal deformities. ● Breath sounds (with and without auscultation) ● Are there audible breath sounds? Are breath sounds distant or absent? ● Is there any wheezing? Over which lung fields? Physical Assessment ● Is there stridor, especially on inspiration? Physical assessment of patients referred for pul- ● Are there any other unusual breath sounds (e.g., crackles, rubs)? monary function studies may be needed to deter- ● Respiratory symptoms mine whether the individual can perform the test. ● Is there obvious shortness of breath (mild, Documentation concerning the physical assess- moderate, severe)? ment of the patient can also assist with the inter- ● Is the patient coughing? If so, is the cough pretation of test results. The physical assessment productive? should focus on breathing pattern, breath sounds ● Is there any cyanosis? ● Is the patient receiving supplemental oxygen? If (if necessary), and respiratory symptoms (Box 1.9). so, how much? These can be observed simply and noted as neces- ● What is the patient’s oxygen saturation (pulse sary. Assessment of the patient’s oxygen status us- oximetry reading)? ing pulse oximetry (see Chapter 6) may be required, especially if the subject presents to the laboratory using oxygen therapy. Some test modalities re- regarding the patient’s signs, symptoms, and ox- quire the patient to be off oxygen, and if the pa- ygenation status at the time of the test is a useful tient is intolerant, that portion of the test will not adjunct, especially if test performance is less than be performed. Documenting operator comments optimal. --- PAGE 46 --- 34 Ruppel’s Manual of Pulmonary Function Testing Pulmonary History function systems often allow history data to be stored Accurate interpretation of pulmonary function in a database along with the patient’s test results. studies—from simple screening spirometry to com- This is a useful feature but may limit the extent of plete cardiopulmonary evaluation—requires clinical the history that can be stored. In instances in which information related to possible pulmonary disease. the physician performs the test, such history may be An ordered array of questions that can be easily an- redundant if a medical history is available. swered by the patient provides the most useful his- Interpretation of PFTs is best made if the clinical tory. The interpreter of pulmonary function studies question asked of the test is considered. The clini- may have little clinical information other than that cian requesting the test should indicate the reason obtained at the time of testing. A pulmonary his- for the test. Examples of clinical questions asked tory should be taken routinely before pulmonary of pulmonary function studies include, “Does the function testing (Box 1.10). patient have airway obstruction?” or “Does the pa- Most of these questions can be answered with yes tient have hyperreactive airways?” The pulmonary or no or by circling an appropriate response. Space history, including the reason for the test, should be should be provided so that the patient or history used to decide what is normal or abnormal. Clinical taker can enter comments. Computerized p ulmonary information, as provided by the history, is especially BOX 1.10 PULMONARY HISTORY 1. Age, sex, standing height, weight, race 6. Smoking habits: Have you ever smoked the 2. Current diagnosis or reason for test following? 3. Family history: Did anyone in your immediate family ● Cigarettes (how many packs per day?) (mother, father, brother, or sister) ever have the _____________ following? ● Cigars (how many per day?) _____________ ● Tuberculosis ● Pipe (how many bowls per day?) _____________ ● Emphysema ● How long? _____________ years ● Chronic bronchitis ● Do you still smoke? Y/N If no, how long ago did ● Asthma you stop? _____________ years ● Hay fever or allergies ● Do you live with a smoker? Y/N ● Lung cancer 7. Cough: ● Other lung disorders ● On most days, do you have a cough? Y/N 4. Personal history: Have you ever had or been told ● How long have you had this cough? that you had the following? ● Is the cough productive or nonproductive? ● Tuberculosis 8. Dyspnea: Do you get short of breath at the ● Emphysema following times: ● Chronic bronchitis ● At rest? Y/N ● Asthma ● On exertion? If so, what causes it? _____________ ● Recurrent lung infections ● At night? Y/N ● Pneumonia or pleurisy 9. Current medications (for heart, lung, blood ● Allergies or hay fever pressure, other) ● Chest injury (if so, what kind?) _____________ Medication Last Taken ● Chest surgery (if so, what kind?) _____________ 5. Occupational/environmental exposure: ● What is or was your occupation? _____________ ● Have you ever been exposed to gases, dusts, or fumes that caused breathing problems? If so, what were they? _______________ ● Do you have hobbies or other activities that cause breathing problems? If so, what are they? _____________ --- PAGE 47 --- Indications for Pulmonary Function Testing • Chapter 1 35 important when the patient’s PFTs are near the studies to establish a diagnosis. For example, a lower or upper limits of normal. For example, an patient may be referred with a diagnosis listed as FEV near the LLN would be interpreted differently “asthma.” The clinical question is, “Does the pa- 1 in a healthy patient tested as part of a routine phys- tient have asthma?” Pulmonary function studies ical than it would be in a smoker who complained may be able to help answer this question, but the of increasing dyspnea. exact tests to be performed may not be defined. In this example, spirometry is indicated. Using an adaptive protocol, spirometry can be performed, PF TIP 1.3 and based on the results, appropriate additional A brief pulmonary history with the completion tests can be selected (Fig. 1.10). Bronchial challenge of a brief questionnaire can add significantly tests may be performed if spirometry results are to the data provided by pulmonary function normal. Alternatively, additional tests such as lung testing. Operators who are familiar with pulmonary pathophysiology can implement volumes or Dlco may be necessary. protocols that are appropriate for the purpose The correct sequence (and timing) for perform- of the test. ing tests is important. Many laboratories use a fixed order for component PFTs. This may include spi- rometry, followed by lung volumes and Dlco. In some instances, the order of tests may need to be TEST PERFORMANCE AND altered. The methodology used for some tests has SEQUENCE definite effects on the results of subsequent proce- Pulmonary function laboratories should have writ- dures. For example, the multiple-breath N -washout 2 ten policies and procedures defining how each test to determine FRC has the patient inhale 100% test is performed (see Chapter 12). An excellent re- O for several minutes. If this test is performed im- 2 source is the ATS’s Pulmonary Function Laboratory mediately before a Dlco test, the elevated O 2 level in Management and Procedure Manual, 3rd edition (2016), which is available on the ATS website. Indications for performing a specific test should be History and physical Get more related to the clinical question to be answered or to consistent with asthma? No information the patient’s diagnosis. Testing protocols that can be modified for individual patients are usually the Yes most cost-effective means of obtaining the required data. When the required tests have been deter- Perform spirometry mined, the exact sequence of tests can be selected. The sequence in which tests are performed may FEV1/FVC No br A on d c m h i o n d is i t la e t r or normal? vary according to patient need and the test method used. For example, a patient with severe obstructive Yes lung disease may not be able to perform an accept- 2 F 0 E 0 V m 1 L im a p n r d o 1 ve 2 s % No a b b ee le n a D d l m co in m ist a e n re e d u . ver until a bronchodilator has FV no C r , m F a E l? V1 No Yes Yes Stop Technologist-Driven Protocols (Operator-Driven Protocols) Go to bronchial Go to Go to COPD challenge restriction As described previously, the basis for deciding protocol protocol protocol which PFTs are needed is related to the clinical question being asked. The clinical question is of- FIG. 1.10 Protocol-decision diagram used by a pulmonary function operator to select appropriate testing. The diagram ten inappropriately stated as a diagnosis. In fact, shows routes to appropriate tests based on the results of simple many patients are referred for pulmonary function spirometry. --- PAGE 48 --- 36 Ruppel’s Manual of Pulmonary Function Testing the lungs (as well as in the blood and tissues) may volume determinations. Instructions about main- reduce the measured Dlco. Similarly, before repeti- taining a good seal on the mouthpiece and con- tion of the Dlco maneuver or FRC determination tinuing normal breathing can help reduce leaks by gas-dilution techniques, sufficient time must be or interrupted tests. Some maneuvers are compli- allowed to wash out residual test gas. cated and may be difficult to describe to the pa- tient. The Dlco maneuver and panting in the body Patient Instruction plethysmograph both consist of several steps. For Many PFTs depend on patient effort. To obtain these tests, a combination of demonstration and valid data, patients must be instructed and coached practice may be the most efficient means of in- for each maneuver. Instruction and coaching are structing the patient. particularly important for the FVC maneuver. Even after adequate instruction and demon- Instruction should include a description of what stration, some patients may be unable to perform the patient is expected to do, such as “You will take a certain tests. This may be caused by a lack of coordi- deep breath in and then blow out as hard and as fast nation related to illness, pain because of their con- as possible.” In addition to a description of the test, dition, or an inability to follow instructions. For the maneuver should be demonstrated. During the example, a patient may experience uncontrollable actual test, vocal encouragement should be given so coughing when asked to inspire deeply for an FVC that the patient knows what is expected and contin- maneuver. If the coughing prevents obtaining valid ues for an appropriate interval. Any problems that spirometry results, the fact should be noted in the occur with the first few efforts should be explained operator’s comments (see Chapter 2). Suboptimal before the patient attempts the test again. For ex- effort by the patient can usually be detected as ample, “That was a particularly good effort, but you poorly repeatable results on effort-dependent tests stopped before blowing out for 6 seconds. Let us try (e.g., the FVC). Care should be taken that adequate that again, and keep blowing out until I signal you instructions are given, and enough efforts recorded, to relax.” This type of feedback is important be- before deciding that the patient did not give a maxi- cause patients may be uncertain of what is required. mal effort. If the patient cannot continue or refuses Patients should be instructed that some maneuvers to continue a test, the exact reason should be docu- will be repeated so that their best effort can be ob- mented in the operator’s comments. tained. They should be assured that repeating some tests is required and does not necessarily reflect a SUMMARY problem on their part. ● Tests are categorized as airway function tests (spirometry), lung volume tests, Dlco tests, PF TIP 1.4 blood gases and gas exchange tests, cardiopul- The most effective way to get good patient monary exercise tests, and other specialized effort is to demonstrate each maneuver. tests. Each of these groups contains a wide vari- For spirometry, this can be accomplished ety of tests and techniques. by using a mouthpiece and simulating the maneuver expected of the patient. Be sure to ● Indications are extremely important because show what is meant by a maximal effort and they help the practitioner select appropriate how long the effort should last. Instructions tests. The clinical question asked of the test such as “snap or blast” your air out after a must be related to a valid indication for the maximal inspiration may help the patient test. understand the initial effort required during the maneuver. ● The underlying pathology involved in common pulmonary diseases and the role of pulmonary function testing are discussed as they relate Patients should also be carefully instructed for to the diagnosis and assessment of various tests that require quiet breathing, such as lung diseases. --- PAGE 49 --- Indications for Pulmonary Function Testing • Chapter 1 37 ● Patient preparation for pulmonary function performed. Technologist-driven protocols are studies is covered in general terms. More detailed described. Algorithms for selecting only appro- information for specific tests is presented in sub- priate tests are becoming increasingly popular. sequent chapters. Many of the physical measure- Such tools improve the sensitivity of the tests to ments and assessments, as well as the pulmonary answer the clinical question, and they make tests history, are similar regardless of the tests being more cost-effective. CASE STUDY CASE 1.1 Reason for test: Does the subject have asthma? (This She has never smoked and has no history of unusual case should be evaluated in conjunction with the environmental exposure. protocol described in Fig. 1.10.) PULMONARY FUNCTION TESTING HISTORY Personal Data The subject is a 22-year-old physical therapy student Sex: Female referred by the student health center at her college. Age: 22 She complains of cough and shortness of breath after Height: 175 cm vigorous exercise such as playing soccer. She describes Weight: 55 kg a history of “sinus problems” and allergies. No one Ethnicity Caucasian in her family has a history of pulmonary disease. Spirometry Before Drug After Drug Predicted LLN Actual % Z Score Actual % % Change FVC (L) 4.50 3.60 3.98 88.4 –0.94 4.21 95 6 FEV (L) 3.88 3.12 2.71 69.8 –2.51 3.12 82 15 1 FEV /FVC 0.87 0.75 0.68 0.74 –2.43 1 LLN, Lower limit of normal. Technologist/Operator’s Comments 4. What treatment might be recommended based on All efforts met ATS/ERS criteria for acceptable these findings? spirometry. Subject had some coughing during prebronchodilator efforts. DISCUSSION Interpretation QUESTIONS All spirometric efforts were performed acceptably. 1. What is the interpretation of the following? Prebronchodilator spirometry reveals mild obstruction. a. Prebronchodilator spirometry There is a significant improvement following an inhaled b. Response to a bronchodilator bronchodilator. 2. What is the cause of the subject’s symptoms? Impression: Reversible airway obstruction with 3. What other tests might be indicated? significant response to a bronchodilator. --- PAGE 50 --- 38 Ruppel’s Manual of Pulmonary Function Testing Cause of Symptoms Other Tests This subject’s chief complaints of cough and shortness Using the sample protocol in Fig. 1.10, no additional of breath following exertion are consistent with exercise- tests are necessary to support the diagnosis of induced bronchospasm. The subject’s FVC was above reversible airway obstruction. Bronchial challenge is the LLN with a normal Z score, whereas her FEV not needed to document reversible obstruction. 1 and FEV/FVC Z scores were both greater than –2. 1 These findings are diagnostic of obstruction that Treatment is relatively mild. Posttesting following a β2 agonist The subject was treated with a combination of ICS bronchodilator produced a 0.41-L (15%) increase in her plus long-acting β2 agonist, which alleviated most FEV. This was a significant improvement in airflow. (The of her symptoms. She was also given a short-acting 1 ATS/ERS recommends a 12% and 200-mL improvement bronchodilator for premedication before vigorous as evidence of significant response to a bronchodilator.) exercise. SELF-ASSESSMENT QUESTIONS Entry-Level 5. A 60-year-old male complains of dyspnea on 1. Measurement of airway resistance using the exertion and when lying in bed; his FEV and FVC 1 body plethysmograph was first described by are within normal limits. These symptoms are a. Otis and McKerrow. most consistent with which of the following? b. Meneely and Kaltreider. a. Emphysema c. DuBois and Comroe. b. CHF d. August and Marie Krogh. c. Sarcoidosis 2. Indications for spirometry include which of the d. Interstitial pulmonary fibrosis following? 6. Which of the following diseases often results 1. Preoperative evaluation for in an obstructive pattern when spirometry is pneumonectomy performed? 2. Measurement of exercise capacity 1. Asthma 3. Determination of the beneficial effects of a 2. Emphysema bronchodilator 3. Bronchiolitis obliterans 4. Measurement of the effects of working in a 4. Silicosis dusty environment a. 1, 2, and 3 a. 1, 2, and 3 b. 1, 3, and 4 b. 1, 3, and 4 c. 2, 3, and 4 c. 2, 3, and 4 d. 2 and 4 only d. 2 and 4 only 7. The most effective treatment for mild or 3. Measurement of lung volumes (TLC) is indicated moderate asthma is a. to assess response to exercise training. a. β2 -agonist bronchodilators. b. whenever simple spirometry is performed. b. leukotriene receptor antagonists. c. to diagnose restrictive lung disease. c. ICSs. d. when hypoxemia is suspected. d. IgE blockers 4. Arterial blood gases would be indicated in 8. Which of the following should a pulmonary which of the following patients? function operator do before performing a. An adult with exercise-induced spirometry? bronchospasm a. Administer an anticholinergic b. An adult with a suspected shunt bronchodilator. c. An adolescent with myasthenia gravis b. Ask the patient his or her current height and d. An obese child weight. --- PAGE 51 --- Indications for Pulmonary Function Testing • Chapter 1 39 c. Demonstrate how to correctly perform the b. Standing height without shoes should be test maneuver. measured to the nearest decimal point in d. Explain that the patient will be required to centimeters. perform three maneuvers. c. Arm span instead of height should be measured in children under age 12. Advanced d. Sitting height × 1.32 may be used for 9. Which of the following would be indicated patients who cannot stand. for a patient who complains of dyspnea on 13. A 25-year-old patient with suspected asthma exertion and chest tightness? performs spirometry. Her FVC is 3.2 L, and a. Dlco her FEV 1 is 2.2 L. Which of the following b. Cardiopulmonary exercise test should the pulmonary function operator do c. Metabolic study next? d. eNO a. Administer a bronchodilator. 10. Which of the following diseases is characterized by b. Evaluate for a possible restrictive disorder. granulomatous changes and fibrosis in the lungs? c. Perform a bronchial challenge test. a. Asthma d. Check oxygen saturation by pulse oximetry. b. CF 14. A patient with COPD who is also a current c. Emphysema smoker states that he has smoked within 1 d. Sarcoidosis hour before his scheduled PFT. Which of the 11. Pulmonary function testing is usually following tests might produce inaccurate contraindicated in which of the following results because of this? conditions? 1. FRC by He dilution a. ALS 2. Dlco b. Eisenmenger syndrome 3. Pulse oximetry c. Myasthenia gravis 4. MIP and MEP d. Untreated pneumothorax a. 1, 2, and 3 12. Which of the following describes an b. 2 and 3 only appropriate physical measurement taken c. 2 and 4 only before pulmonary function testing? d. 3 and 4 only a. Actual body weight should be measured to calculate predicted values. Graham, B., Brusasco, V., Burgos, F., Cooper, B., et al. 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Annals of the American Official ATS/ERS/JRS/ALAT Statement: Diagnosis Thoracic Society, 17(11), 1343–1351. --- PAGE 53 --- 2 Chapter Spirometry CHAPTER OUTLINE Vital Capacity Peak Expiratory Flow Description Description Technique Technique Significance and Pathophysiology Significance and Pathophysiology Forced Vital Capacity, Forced Expiratory Volume, Maximum Voluntary Ventilation and Forced Expiratory Flow Description Description Technique Technique Significance and Pathophysiology Acceptability and Repeatability for Spirometry Bronchodilator Responsiveness Testing Results Description Significance and Pathophysiology Technique Flow-Volume Curve Significance and Pathophysiology Description Summary Technique Case Studies Significance and Pathophysiology LEARNING OBJECTIVES After studying the chapter and reviewing the figures, tables, and case studies, you should be able to do the following: Entry-level 1. Determine whether spirometry is acceptable, repeatable, and/or usable. 2. Identify airway obstruction using vital capacity (VC) and forced expiratory volume in 1 second (FEV ). 1 3. Differentiate between obstruction and restriction as causes of reduced VC. 4. Determine whether there is a significant response to bronchodilators. Advanced 1. Select the appropriate VC and FEV for reporting from a series of spirometry maneuvers. 1 2. Quantify the degree of obstruction according to American Thoracic Society–European Respiratory Society (ATS-ERS) criteria. 3. Describe the characteristics of an intrathoracic or extrathoracic obstruction pattern. 4. Evaluate flow-volume curves. KEY TERMS body temperature, pressure, FEF forced vital capacity (FVC) 25%–75% and saturation (BTPS) FEV /VC inspiratory capacity (IC) 1 expiratory reserve volume (ERV) forced expiratory volume (FEV ) isovolume correction T 41 --- PAGE 54 --- 42 Ruppel’s Manual of Pulmonary Function Testing maximal expiratory flow volume maximal voluntary ventilation start-of-test (MEFV) (MVV) transpulmonary pressure (Ptp) maximal inspiratory flow volume peak expiratory flow (PEF) (MIFV) peak flow meter The chapter begins with the measurement of the voluntary ventilation (MVV). Case studies and vital capacity (VC) using simple spirometry, fol- self-assessment questions are included at the end of lowed by the most widely used pulmonary function the chapter. test, the forced vital capacity (FVC) maneuver. Special emphasis is placed on the performance of each test. Criteria for judging the acceptability and VITAL CAPACITY repeatability of test data are provided based on the most recent guidelines published by the American Description Thoracic Society–European Respiratory Society The VC is the volume of gas measured from a slow (ATS-ERS) Task Force on Standardization of Lung complete expiration after a maximal inspiration with- Function Testing. Volume–time and flow-volume out forced or rapid effort (Fig. 2.1). Alternately, VC curves are described as the two most common may be recorded as a maximal inspiration after a presentations of spirometric data. Bronchodilator complete expiration. VC is normally recorded in ei- studies to determine the reversibility of airway ob- ther liters (L) or milliliters (mL) and reported at body struction are also presented. Other tests described temperature, pressure, and saturation (BTPS). include peak expiratory flow (PEF) and maximal VC is sometimes referred to as the slow vital capacity IRV IC VC V T TLC ERV FRC RV RV FIG. 2.1 Lung volumes and capacities. Diagrammatic representation of lung volumes and capacities based on a simple spirogram. Relationships between the subdivisions and relative sizes compared with TLC are shown (shaded areas). Resting expiratory level is used as a starting point for FRC determinations because it remains more stable than other identifiable points during repeated measurements. ERV, Expiratory reserve volume; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve volume; RV, residual volume; TLC, total lung capacity; VC, vital capacity; VT, tidal volume. (Modified from Comroe, J. H. Jr., Forster, R. E., Dubois, A. B., et al. [1962]. The lung: Clinical physiology and pulmonary function tests [2nd ed.]. St. Louis, MO: Mosby.) --- PAGE 55 --- Spirometry • Chapter 2 43 (SVC), distinguishing it from FVC. Inspiratory ca- IC is measured by having the patient breathe pacity (IC) and expiratory reserve volume (ERV) normally for three or four breaths and then inhale are subdivisions of the VC. IC is the largest volume of maximally. The volume inspired from the resting ex- gas that can be inspired from the resting expiratory piratory level is measured by the computer or from level (see Fig. 2.1). IC is sometimes further divided a spirogram. This is usually done as part of an SVC into the tidal volume (V ) and inspiratory reserve maneuver. IC may also be calculated by subtracting T volume (IRV). ERV is the largest volume of gas that the ERV from the SVC. ERV is measured by having can be expired from the resting end-expiratory level the patient breathe normally for three or four breaths (see Fig. 2.1). Both the IC and ERV are recorded in and then exhale maximally. The change in volume liters or milliliters corrected to BTPS. from the end-expiratory level to the maximal expi- ratory level is the ERV. ERV may also be calculated Technique by subtracting the IC from the SVC. IC and ERV are SVC is measured by having the patient inspire max- usually measured from the same VC maneuver. IC imally and then exhale completely into a spirom- and ERV should be reported as the average of at least eter. (See Chapter 11 for a complete discussion of three acceptable maneuvers, whereas VC is reported spirometers.) The patient is instructed to perform as the largest of at least three acceptable maneuvers. the maneuver slowly and completely. SVC can also The accuracy of the IC and ERV measurements be measured from maximal expiration to maximal depends on the stability of the end-expiratory level, inspiration. The spirometer does not need to pro- which should vary by less than 100 mL. Three or duce a graphic display if only SVC is to be measured. more tidal breaths should be recorded before the However, if IC and ERV are to be determined (see SVC maneuver is performed. If the end-expiratory Fig. 2.1), some means of recording volume change volume is not consistent, IC and/or ERV may be mea- is required. The graphic display may be a computer sured incorrectly (i.e., too large or too small). Even if screen or a recording device (see Chapter 11). A the end-expiratory level is constant, the V usually in- T graphic display allows the technologist to deter- creases when the patient breathes through a mouth- mine that the test is performed correctly (Criteria piece with a nose clip in place. This increase in V may T for Acceptability 2.1). A graphic display is also usu- change the IC or ERV, depending on the patient’s ally required for reimbursement purposes. breathing pattern. Erroneous estimates of ERV may affect the calculation of RV, as described in Chapter 4. CRITERIA FOR ACCEPTABILITY 2.1 Significance and Pathophysiology Slow Vital Capacity Spirometry is indicated in a variety of situations 1. End-expiratory volume varies by less than (see Chapter 1). According to the 2019 ATS-ERS 100 mL for three preceding breaths. technical statement, there are no absolute con- 2. Volume plateau is observed at maximal traindications to spirometry, but many relative inspiration and expiration. contraindications should be considered (Box 2.1). 3. Two acceptable VC maneuvers should be Testing personnel should be aware of these condi- obtained—volumes agree within 150 mL. tions and have policies in place that guide decisions on whether or not to test the subject. Obtaining a valid SVC is important. The sub- Normal SVC may vary as much as 20% above or divisions of the SVC (IC and ERV) are used in the below the predicted value in healthy individuals, but calculation of residual volume (RV) and total lung it must be above the bottom 5th percentile (lower capacity (TLC). An excessively large V or an irreg- limit of normal [LLN]; see Chapter 13) to be consid- T ular breathing pattern during the SVC maneuver ered normal. The ATS-ERS guidelines recommend may alter ERV or IC. If either ERV or IC is errone- the use of the Global Lung Initiative (GLI) reference ously recorded, other lung volumes may be incor- set. This predicted set has results from ages 3 to 95, rectly estimated (see Chapter 4). with significantly stronger numbers than previously --- PAGE 56 --- 44 Ruppel’s Manual of Pulmonary Function Testing in patients with diaphragmatic paralysis, neuro- BOX 2.1 RELATIVE CONTRAINDICATIONS muscular disease, or symptoms that occur in the TO SPIROMETRY supine position that are not explained by other PF Attributable to increases in myocardial demand or tests. Normal subjects typically have a decrease in changes in blood pressure VC of 3% to 8%, whereas subjects with diaphragm Acute myocardial infarction within 1 wk Systemic hypotension or severe hypertension dysfunction would have a decrease of greater than Significant atrial/ventricular arrhythmia 10%. Lechtzin and colleagues demonstrated that an Noncompensated heart failure FVC of less than 75% predicted was 100% sensitive Uncontrolled pulmonary hypertension and specific for predicting diaphragm weakness. Acute cor pulmonale Clinically unstable pulmonary embolism History of syncope related to forced expiration/cough Attributable to increases in intracranial/intraocular PF TIP 2.1 pressure Cerebral aneurysm Normal values for lung function parameters Brain surgery within 4 wk are obtained by studying healthy subjects. Recent concussion with continuing symptoms The predicted or reference value for VC is Eye surgery within 1 wk computed using an equation, such as the Attributable to increases in sinus and middle ear following: pressures Sinus surgery or middle ear surgery or infection VC=x(cid:31)Height(cid:30)-y(cid:31)Age(cid:30)-z within 1 wk Attributable to increases in intrathoracic and where x, y, and z are constants intraabdominal pressure Predicted values may be read from Presence of pneumothorax special diagrams called nomograms but Thoracic surgery within 4 wk are usually calculated by a computer. Abdominal surgery within 4 wk (See Chapter 13.) The LLN, representing Late-term pregnancy the lower 5th percentile of the normal Infection control issues distribution curve, is recommended as the Active or suspected transmissible respiratory or cutoff to judge normality. systemic infection, including tuberculosis Physical conditions predisposing to transmission of infections, such as hemoptysis, significant As Dr. Hutchinson originally noted (see Chapter 1), secretions, or oral lesions or oral bleeding a patient’s VC is directly related to survival, and Adapted from 2019 ATS-ERS Spirometry Update. numerous studies have since supported his conclu- sion. In a study published in 2011 using data on spi- published reference sets, which increased the statis- rometry and survival from the Atherosclerosis Risk tical power of the reference (see Chapter 13). in Communities (ARIC) data set, 7489 participants In adults, VC varies directly with height and in- with usable spirometry data were compared against versely with age; tall patients have larger VCs than measures of ventilatory function after controlling short patients. VC increases up to approximately age for many other factors likely to be associated with 20 and then decreases each year thereafter, with an survival. The study concluded that survival was average decrease of about 25 to 30 mL/yr. It is usu- strongly associated with the FVC over all other spi- ally smaller in women than in men because of dif- rometry parameters. ferences in body size. Recent evidence indicates that There are numerous causes of a decreased VC lung volumes may differ significantly according to (Box 2.2). In general, these fall into the categories ethnic origin. VC also varies in individuals, depend- of loss of distensible lung tissue (i.e., fibrosis), ing on body position or time of day. Interpretation obstructive lung disease, and reduced chest wall ex- of lung function should consider the key factors of pansion (i.e., neuromuscular, kyphosis). age, sex, height, and race (see Chapter 13). When the VC is reduced, additional pulmonary VC can also be measured in the supine or prone function measurements may be indicated. Forced position to characterize the effect the position has expiratory maneuvers (see the section Forced Vital --- PAGE 57 --- Spirometry • Chapter 2 45 IC and ERV are approximately 75% and 25% BOX 2.2 CAUSES OF REDUCED VITAL of the VC, respectively. Changes in IC or ERV CAPACITY usually parallel increases or decreases in the VC. Loss of Distensible Lung Tissue Increased V T caused by exertion or acid–base disor- ders (e.g., metabolic acidosis, respiratory alkalosis) Lung cancer Pulmonary vascular congestion, pulmonary edema may reduce IRV or ERV. This occurs because end- Pneumonia inspiratory and end-expiratory levels (see Fig. 2.1) Atelectasis are altered. A similar pattern is commonly seen Pulmonary fibrosis (e.g., from dust, drug toxicity, when patients breathe into a spirometer through a radiation, or idiopathic) mouthpiece with nose clips in place. Changes in IC Pleural effusion or pleural scarring Pneumothorax or ERV are of minimal diagnostic significance when Surgical removal (e.g., lobectomy) considered alone. Reduction of IC or ERV is con- sistent with restrictive defects. Obese patients typ- Obstructive Lung Disease (caused by gas trapping, resulting in elevated residual volume [RV] but ically show a decrease in ERV, usually resulting in normal total lung capacity [TLC]) a low VC. A reduced ERV is one of the earliest lung Reduced Chest Wall Excursion function changes in obese patients. Neuromuscular weakness (e.g., myasthenia gravis) Chest wall deformity (e.g., kyphoscoliosis) INTERPRETIVE STRATEGIES 2.1 Obesity, pregnancy, ascites Suboptimal patient effort (e.g., caused by pain, Slow Vital Capacity motivation) 1. Was the test performed acceptably? Is it repeatable? 2. Are reference values correct? Age? Sex? Height? Capacity in this chapter) can reveal whether the re- Ethnicity? 3. Is VC less than predicted? If so, to what extent? duced VC is caused by obstruction. Reduced VC with- Is it less than the LLN? out slowing of expiratory flow is a nonspecific finding. 4. How does SVC relate to the clinical question to Measurement of other lung volumes (see Chapter 4) be answered? Is SVC correlated to the history may be indicated to determine whether a restrictive and physical findings? defect is present. Measurement of muscle pressures 5. Are additional tests indicated? Lung volumes? FVC? may help determine whether there is a problem with neuromuscular weakness (see Chapter 10). In adults, VC less than the LLN (95% confidence FORCED VITAL CAPACITY, limits; see Chapter 13) may be considered abnor- FORCED EXPIRATORY VOLUME, mal. Interpretation of the measured VC in relation AND FORCED EXPIRATORY FLOW to the reference value should consider the clinical Description question to be answered (Interpretive Strategies 2.1). The clinical question is often revealed in the FVC is the maximum volume of gas that can be history and physical findings of the patient (see expired when the patient exhales as forcefully and Chapter 1). The terms mild, moderate, and severe may rapidly as possible after a maximal inspiration. This be used to qualify the extent of reduction of the VC procedure is often referred to as the FVC maneuver. in a manner similar to that described for FEV (see A similar maneuver, beginning at maximal expira- 1 the following section, Forced Expiratory Volume). tion and inspiring as forcefully as possible, is called Artificially low estimates of the VC may result from forced inspiratory vital capacity (FIVC). The FVC and poor patient effort. Similarly, inadequate patient in- FIVC maneuvers are often performed in sequence struction may affect the performance of the test ma- to provide a continuous flow-volume loop (see the neuver. These errors may be eliminated by applying later section Flow-Volume Curve). appropriate criteria (see Criteria for Acceptability The forced expiratory volume (FEV T ) is the 2.1). The values for at least two maneuvers should be volume of gas expired over a given time interval (T) reproducible within 150 mL. from the beginning of the FVC maneuver. The time --- PAGE 58 --- 46 Ruppel’s Manual of Pulmonary Function Testing interval is stated as a subscript of FEV. The FEV but not forced. There should be little, if any, pause 1 measurement is the most widely used. Other in- (< 1 or 2 seconds) at maximal inspiration; a pro- tervals in common use are FEV , FEV , and FEV . longed pause (4–6 seconds) may decrease flow 0.5 3 6 The FVC and FEV are both reported in liters cor- during the subsequent expiration. T rected to BTPS. FEV is the ratio of FEV to FVC The volume expired may be displayed as v olume– T% T expressed as a percentage, where T is the interval time tracing or (Fig. 2.2) flow-volume graph from the start of the FVC. The FEV (FEV /FVC (Fig. 2.3). These tracings are typically shown on a 1% 1 × 100) is by far the most widely used of the various computer monitor or small display screen. The com- FEV parameters. VC (slow vital capacity) may be puter analyzes the signal from the spirometer and T% used in place of FVC if the VC is significantly larger. then calculates and displays the FVC. A spirometer Because a low value for the ratio of FEV to FVC is that produces a graphic tracing (either volume–time 1 used to detect obstruction, using the largest value or flow volume) is essential for clinical laboratory obtained for vital capacity (either VC or FVC) for purposes to allow a visual inspection of the maneu- the denominator may be helpful and is currently ver (see Fig. 2.3). Devices providing only numeric recommended by the ATS-ERS guidelines. data may be helpful for simple screening. Whether Flows over specific intervals or at specific points used for diagnosis or monitoring, all spirometers in the FVC are expressed as FEF . The subscript must meet the calibration and operational criteria X X describes the point or interval in relation to the proposed by the ATS-ERS (see Chapter 12). The FVC FVC maneuver. The FEF25%–75% is the average maneuver depends on patient effort. Not all patients flow during the middle half (from the 25%–75% may be able to perform it acceptably (Criteria for points) of an FVC maneuver. FEF values are usu- Acceptability 2.2). X ally recorded in liters per second, BTPS. FEF 25%–75% was formerly designated the maximum midexpiratory flow rate (MMFR). Other measures of average flow include the FEF (200- to 1200-mL portion of 200–1200 the FVC) and the FEF . FEF is also used to 75%–85% X denote instantaneous flow at specific points in the FVC maneuver. Commonly reported flows are the FEF , FEF , and FEF . The subscript refers to 25% 50% 75% the percentage of FVC that has been expired. Technique FVC is measured by having the patient, after in- spiring maximally, expire as forcefully and rapidly as possible into a spirometer. The patient should inspire completely. The inhalation should be rapid Inspiration Time (sec) )L( emuloV 9 8 Expiration 7 6 5 FVC 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 PF TIP 2.2 The FVC maneuver is extremely effort dependent and requires active coaching on FIG. 2.2 Forced vital capacity (FVC). Typical spirogram plot- the part of the operator. Some operators clap ting volume against time as patient exhales forcefully. In this trac- their hands, stomp their foot, or snap their ing, expiration causes an upward deflection; in some systems, fingers along with active vocalization (“blast,” the tracing is inverted. The patient inspires to the maximal inspi- “snap,” or “blow”), but whatever method ratory level (dashed line), at which point lung volume is close to is chosen should convey the urgency of total lung capacity (TLC). The patient then expires as forcefully blasting the air out fast and forcefully. and rapidly as possible to the maximal expiratory level, at which point the lungs contain the residual volume (RV) only (see text). --- PAGE 59 --- Spirometry • Chapter 2 47 2 12 10 8 6 4 2 0 0 2 4 6 2 4 6 )s/L( wolF Volume/Time Flow/Volume )L( loV Vol (L) Time (sec) Test 1 Test 2 Test 3 FIG. 2.3 Three acceptable FVC maneuvers from a 10-year-old subject. Acceptability based on a fast start (no hesitation), a sharp peak flow, no cough or glottic closure in the first second, and meeting the end-of-test criteria. 2.1 How To … Perform an FVC Maneuver 1. Tasks common to all procedures: a. Calibrate and prepare equipment. b. Review order. c. Introduce yourself and identify patient according to institutional policies. d. Describe and demonstrate procedure. 2. Have the subject sit upright with feet flat on the floor. 3. Subject’s chin should be upright, with the neck slightly extended. 4. The mouthpiece should rest on top of the tongue, with the patient gently biting down with the teeth and sealing the lips firmly around the mouthpiece. Nose clips are recommended, but the maneuver can often be performed without one. 5. With the spirometer hose or flow sensor in his or her hand, have the subject breathe quietly for several breaths on the mouthpiece (closed-circuit technique) and then take a maximal inspiration, or alternatively, have the subject take a maximal inspiration (open-circuit technique) and immediately place the mouthpiece in the mouth once TLC is reached. Some type of active encouragement (be a good coach/cheerleader) by the technologist may be helpful in conveying the necessity of the subject to take his or her deepest breath (e.g., “in, in, in”/“up, up, up”; raising the arms). 6. Instruct the subject to blast the air out forcefully. The technologist may wish to choose an action (e.g., clap the hands, snap the fingers, or stomp the foot) or a word (e.g., “blast,” “snap”) to convey the urgency of the maneuver. 7. Encourage the subject to continue to blow (verbal cues, “keep blowing”/“blow, blow, blow”) until empty. 8. If performing a flow-volume loop, have the subject rapidly and forcefully inspire to TLC. The FIVC should match the FVC in volume as a quality indicator that the FVC maneuver began after a full inflation. 9. If the subject becomes lightheaded or complains of dizziness or shortness of breath, make sure to allow extra time between maneuvers. 10. Perform until acceptability and repeatability criteria are achieved (see Criteria for Acceptability 2.2). 11. Note comments related to test quality. --- PAGE 60 --- 48 Ruppel’s Manual of Pulmonary Function Testing FEV (and other FEV values) may be measured CRITERIA FOR ACCEPTABILITY AND 1 T REPEATABILITY 2.2 by timing the FVC maneuver over the described in- tervals. Historically, this was done by recording the FVC Maneuver FVC spirogram on graph paper moving at a fixed 1. Maximal effort; no cough in the first second; no speed. The FEV for any interval could then be read leaks or obstruction of the mouthpiece from the graph, as shown in Fig. 2.4. Most modern 2. Good start-of-test; back-extrapolated volume spirometers time the FVC maneuver using a com- less than 5% of FVC or 100 mL, whichever is greater, and a rise time from 10% to 90% of peak puter. The computer then calculates and displays flow ≤ 150 ms the FEV or other FEV intervals. The spirometer 1 T 3. No glottic closure in the first second (FEV 1 should provide a volume–time display of each ma- useable criteria) or after the first second neuver (Fig. 2.5). A graphic representation allows (acceptability criteria) the monitoring of patient effort at the beginning of 4. Must achieve one of these three indicators for the end of forced expiration (EOFE): the test. Accurate measurement of FEV 1 (and other 1. Expiratory plateau (< 0.025 L in the last 1 s FEV intervals) depends on the determination of T of expiration) the start-of-test (Fig. 2.6). Computerized spirom- 2. Expiratory time > 15 seconds eters detect the start-of-test as a change in flow or 3. FVC is within the repeatability tolerance of or volume above a certain threshold. The computer is greater than the largest prior observed FVC. 5. If the maximum inspiration after the EOFE is then stores volume and flow data points in memory greater than the FVC, then the FIVC – FVC must and calculates the FEV . 1 be ≤ 100 mL or 5% of the FVC, whichever is Open-circuit technique describes an FVC maneu- greater. ver where the subject inhales maximally, places Repeatability Criteria the mouthpiece or filter into the mouth, and then 1. In subjects > 6 years of age, the two largest forcefully exhales until empty. Using this tech- acceptable FVC and FEV 1 values must nique, the patient has to coordinate taking the deep be ≤ 150 mL. breath, holding the breath at TLC, and placing the 2. In subjects ≤ 6, the two largest acceptable FVC and FEV 1 values must be ≤ 100 mL or 10%, whichever is greater. 7 3. Report the highest FVC and highest FEV , even 1 if they come from separate maneuvers. The 6 FEV /FVC ratio is derived from these values. 1 5 Adapted from ATS-ERS 2019 Spirometry Technical Statement. 4 3 2 PF TIP 2.3 1 There are three key components to an FVC 0 maneuver: 0 1. Deep breath Time (sec) 2. Blast 3. Meeting the EOFE test criteria (“keep blowing, keep blowing, keep blowing”) All of these are important, but without the initial deep breath, the latter two are meaningless! This is why the 2019 ATS-ERS Spirometry Technical Statement added the FIVC as a quality check. )L( emuloV RV FEV1 FEV6 FVC TLC 10 FIG. 2.4 Determination of forced expiratory volume (FEV ) T values from a forced vital capacity (FVC) maneuver. Various FEV T values can be measured from the volume–time display of an FVC effort. FEV at intervals of 1 and 6 seconds, along with the FVC, are shown (arrows). FEV is the most commonly used index of 1 airflow. FEV is sometimes used as a surrogate for FVC in patients 6 with airway obstruction. Precise timing and acceptable start-of- test are required to determine FEV values accurately (Criteria for T Acceptability 2.2). --- PAGE 61 --- Spirometry • Chapter 2 49 1 liter Maximal Extrapolated volume inspiratory level Zero time 1 second 2 seconds Back- extrapolation FIG. 2.5 Back-extrapolation of a volume–time spirogram. Back-extrapolation is a method for correcting measurements made from a spirogram that does not show a sharp deflection from the maximal inspiratory level. This occurs when a patient does not begin forced exhalation rapidly enough or hesitates at Time (sec) the start-of-test. A straight line drawn through the steepest part of a volume–time tracing is extended to cross the volume base- line (maximum inspiration). The point of intersection is the back- extrapolated time zero. To accurately determine the new time zero, the display should include at least 0.25 seconds and preferably at least 1 second before the start of the exhalation. Timed volumes, such as the forced expiratory volume in the first second (FEV), 1 are measured from this point rather than from the initial deflec- tion from the baseline or from the point of maximal flow. The perpendicular distance from maximal inspiration to the volume– time tracing at time zero defines the back-extrapolated volume. To FEV accurately determine FEV 1 , the back-extrapolated volume should FEV 1% (cid:31) FVC 1(cid:30)100 be less than 5% of the forced vital capacity (FVC) or less than 150 mL, whichever is greater, and the rise time from 10% to 90% FEV is also commonly written as FEV /FVC. of peak flow should be ≤ 150 ms. FVC efforts with larger extrap- 1% 1 olated volumes should be considered unacceptable. Both ratios are expressed as percentages, and this percentage is then related to normative values as a percentage of predicted. FEV and FVC should be 1 mouthpiece correctly, which can be a challenge for reported as the maximal values obtained from at some subjects. Closed-circuit technique describes a ma- least three acceptable FVC maneuvers. The FEV / 1 neuver where the subject breathes tidally on the spi- FVC ratio based on these values may be different rometer, inhales maximally, forcefully exhales, and from the ratio obtained from any single maneu- then may be instructed to inhale forcefully to mea- ver. If both VC and FVC maneuvers have been per- sure the inspiratory flow and volume. Most comput- formed, it is preferable to use the largest VC in the erized spirometers correct for a slow start-of-test by calculation. Some computerized spirometers calcu- back-extrapolation (see Fig. 2.5). Visualization of the late only the ratio obtained from FVC maneuvers. volume–time spirogram is the best means of identi- The FEF is measured from an FVC 25%–75% fying poor initial effort. Some portable spirometers maneuver. The FEF is the average flow during 25%–75% report FEV without a spirogram. Such measure- the middle half (from 25%–75%) of the VC. A com- 1 ments should be used with caution because it may puterized measurement of the FEF requires 25%–75% be difficult to determine whether the maneuver was storage of flow and volume data points for the entire performed acceptably. maneuver. Calculation of the average flow over the The ratio of the FEV to FVC is expressed as middle portion of the exhalation is simply 50% of the 1 follows: volume expired divided by the time required to get )L( emuloV 9 8 C 7 B 6 A 5 75% 4 3 25% 2 1 0 1 2 3 4 5 6 7 8 9 10 FIG. 2.6 FEF . The slope of the line connecting 25% and 25%–75% 75% points is the average flow over the middle half of the forced vital capacity (FVC) maneuver. Alternatively, a line connecting these points may be drawn to intersect two timelines 1 second apart (points A and B). The flow in liters per second can be read as the vertical distance between the points of intersection (AC)—in this case, approximately 2 L/sec. --- PAGE 62 --- 50 Ruppel’s Manual of Pulmonary Function Testing from the 25% point to the 75% point. To manually Patients with severe obstruction can often times calculate the FEF , a volume–time spirogram is exhale well past 15 seconds; however, multiple 25%–75% used. The points at which 25% and 75% of the VC have prolonged exhalations are rarely justified and been expired are marked on the curve (see Fig. 2.6). may cause undue lightheadedness, and fatigue. A straight line connecting these points can be ex- Glottic closure will underestimate FVC; however, tended to intersect two timelines 1 second apart. The it may yield a “usable” FEV . In the event of glot- 1 flow (in liters per second) can then be read directly tis closure, reinforce the need to keep the chin as the vertical distance between the points of inter- elevated with the neck slightly extended. A sim- section. Instantaneous flows, such as the FEF or ple trick might be to have the subject focus on an 50% FEF , cannot be read directly from a volume–time object located high on a wall, or instruct them to 75% display but can be measured using a flow–volume blow the air out as if he or she were “blowing at curve (see the later section Flow-Volume Curve). the stars.” Another trick might be to have the sub- The FEF depends on the FVC. Large ject focus on relaxing the throat or neck after the 25%–75% FEF values may be derived from maneuvers initial blast. If all these tricks fail to remedy 25%–75% that produce small FVC measurements because the the glottis closure, the FEV can still be used 1 “middle half” of the volume is actually gas expired if the closure happened after the first second. at the beginning of expiration. This effect may be 2. The start-of-test should be abrupt and unhes- particularly evident if the patient terminates the itating. Each maneuver should have the back- FVC maneuver before exhaling completely. When extrapolated volume calculated. FEV and all other 1 the FEF is used for assessing the response to flows must be measured after back-e xtrapolation 25%–75% bronchodilator or bronchial challenge, the effect of (see Figs. 2.5 and Fig. 2.11C). The ATS-ERS guide- changes in the absolute lung volumes must be con- lines recommend that the volume–time tracing sidered. Measuring the FEF at the same lung must begin at least 0.25 seconds before the be- 25%–75% volumes in the comparison tests is called the isovol- ginning of the exhalation to be able to measure ume technique. Isovolume corrections are usually the back-extrapolated volume. If the volume of applied when the FVC changes by more than 10% back-extrapolation is greater than 5% of the FVC (indicating a change in TLC or RV). This technique or 100 mL (whichever is greater) and the rise time requires that lung volumes (see Chapter 4) be mea- from 10% to 90% of peak flow is > 150 ms, the ma- sured in conjunction with flows. The isovolume neuver is unacceptable and should be repeated. technique may also be used with other flow mea- The patient should be shown the correct technique surements that are dependent on FVC. for performing the maneuver. Demonstration by The largest FEF is not necessarily the value the technologist is often helpful. 25%–75% reported. The FEF is recorded from the ma- 3. Performing a flow-volume loop (i.e., an FIVC) once 25%–75% neuver with the largest sum of FVC and FEV . Flows the EOFE has been achieved is encouraged by the 1 must be corrected to BTPS. 2019 ATS-ERS Spirometry Technical Statement. A comparison of the FIVC to the FVC can then be Acceptability and Repeatability for used as a quality check on the completeness of the Spirometry Results initial inspiration. If the FIVC – FVC is > 100 mL 1. Criteria used to judge the acceptability of test or 5% of the FVC, whichever is greater, the maneu- results from the FVC maneuver include the fol- ver is unacceptable and should be repeated. lowing: The tracing should show one of three 4. Other variables that make an effort unacceptable indicators of EOFE: (1) There is less than 0.025 are leak, obstruction of the mouthpiece with the L volume over 1 second (a plateau). (2) The sub- tongue, maneuvers conducted with zero-flow er- ject has achieved a forced expiratory time of 15 rors (see Figs. 2.11D and E), or maneuvers with seconds. (3) The subject cannot blow out long an EOFE “sneak breath” (see Fig. 2.11F). enough to reach a plateau, but the FVC val- 5. A minimum of three acceptable efforts should ues are repeatable. This latter criterion is most be obtained. The test may be repeated multiple commonly seen in children or smaller adults. times, and although eight maneuvers is generally --- PAGE 63 --- Spirometry • Chapter 2 51 a reasonable upper limit in most adults, it may Bronchospasm or fatigue often affects repeatabil- take more attempts. Children may require more ity. Interpretation of the test should include com- than eight attempts because each maneuver may ments regarding repeatability or a lack of it. As a not be a complete maneuver. Regardless, the op- minimum, three acceptable satisfactory maneu- erator will need to be attentive to the child and vers should be saved for evaluation (see Fig. 2.3). his or her tolerance of the efforts being asked Data from all acceptable maneuvers should be ex- of him or her so as to not overwhelm the child. amined. The largest FVC and the largest FEV should 1 A grading system has been proposed for a spi- be reported, even if the two values are from differ- rometry testing session (Table 2.1). The medical ent test maneuvers. The reported FEV /FVC ratio is 1 director and laboratory manager should decide taken from these values. Flows that depend on the on a minimal grade achieved in order to post the FVC (e.g., the FEF ) should be taken from the 25%–75% results into the patient’s medical record. A grade single best test maneuver, which is the maneuver < D might result in reporting data that do not with the largest sum of FVC and FEV 1 (Table 2.2). represent the subject’s true lung function. The reported flow-volume curve is also taken 6. Ideally, the two largest values for both FVC and from the single best test maneuver. One caveat to se- FEV should be within 150 mL (for ages 2–6, lecting the largest FEV from any maneuver is when 1 1 within 100 mL or 10% of the largest). This is the peak flow is significantly less than that of an- achieved by taking the largest FVC and FEV and other maneuver or maneuvers. A suboptimal blast 1 simply subtracting the second-largest values to may actually overestimate the FEV in a subject with 1 determine repeatability. If the two largest FVC or dynamic airway compression (see Fig. 2.11F). FEV values are not within 150 mL, the maneu- A common problem may occur when using these 1 ver should be repeated up to a maximum of eight criteria to produce a spirometry report. If a single times or until the patient cannot or will not con- volume–time or flow-volume tracing is included in tinue. The repeatability criteria should be applied the final report, it may not contain the FVC or FEV 1 only after the maneuver has been judged as accept- that appears in the tabular data. It is advisable to able. Individual spirometric maneuvers should not maintain recordings or raw data for all acceptable be rejected solely because they are not repeatable. maneuvers. Other methods of selecting the best test TABLE 2.2 TABLE 2.1 Comparison of Spirometry Efforts ATS-ERS Grading Scheme for Spirometry Best Test Criteria for Adults and Older Children and for Test Trial 1 Trial 2 Trial 3 Reported Grade Children Aged 2–6 Years FVC (L) 5.20 5.30 5.35a 5.35 A > 3 acceptable tests with repeatability within 0.150 L; ages 2–6, 0.100 L, or 10% of highest FEV 1 (L) 4.41a 4.35 4.36a 4.41 value, whichever is greater. FEV /FVC (%) 85 82 82 82 1 B > 2 acceptable tests with repeatability within FEF (L/sec) 3.87 3.92 3.94 3.94 25%–75% 0.150 L; ages 2–6, 0.100 L, or 10% of highest FEF (L/sec) 3.99 3.95 3.41 3.41 value, whichever is greater 50% FEF (L/sec) 1.97 1.95 1.89 1.89 C > 2 acceptable tests with repeatability within 25% 0.200 L; ages 2–6, 0.150 L, or 10% of highest PEF (L/sec) 8.39 9.44 9.89 9.89 value, whichever is greater FEF, Forced expiratory flow; FEV, forced expiratory volume; FVC, D > 2 acceptable tests with repeatability within forced vital capacity; PEF, peak expiratory flow. 0.250 L; ages 2–6, 0.200 L, or 10% of highest a These values are keys to selecting the best test results. The FEV 1 value, whichever is greater is taken from Trial 1 and the FVC from Trial 3, even though the largest sum of FVC and FEV occurs in Trial 3. All FVC-dependent E One acceptable test 1 flows (average and instantaneous) come from Trial 3. The maximal F No acceptable tests expiratory flow-volume curve, if reported, would be the curve from Trial 3 as well. It should be noted that the FEV (FEV/FVC) is 1% 1 ATS-ERS, American Thoracic Society–European Respiratory Society. calculated from the FEV 1 of Trial 1 and the FVC of Trial 3. --- PAGE 64 --- 52 Ruppel’s Manual of Pulmonary Function Testing have been suggested and are sometimes used. PEF of a loss of tethering support of the airways. Large may be used to assess patient effort for an FVC ma- pressure gradients across the walls of the airways neuver. Selecting the effort with the largest PEF may during forced expiration collapse the terminal por- cause errors if FVC and FEV are not also evaluated. tions of the airways. Gas is trapped in the alveoli 1 Spirometry may be performed in either the sit- and cannot be expired. This causes the FVC to ap- ting or standing position for adults and children, pear smaller than the SVC. The FVC can appear although the sitting position is recommended for larger than the SVC if the patient exerts greater ef- safety, especially in adults. There is some evidence fort on the forced maneuver. that FEV may be larger in the standing position in 1 adults and in children younger than 12 years of age. INTERPRETIVE STRATEGIES 2.2 The position used for testing should be indicated in the final report. The patient should keep the head FVC Maneuver slightly elevated and keep false teeth in if they fit 1. Were at least three acceptable spirograms obtained? well. The use of nose clips is recommended for spiro- Are FVC and FEV repeatable (within 150 mL)? 1 metric measurements that require rebreathing, even 2. Are reference values appropriate? Age? Sex? if just for a few breaths. Spirometers that record only Height? Race? 3. Is FEV (ratio) less than predicted? If so, expiratory flow may require the patient to place the 1% obstruction is present. mouthpiece into the mouth after maximal inspira- a. Is FVC also reduced? If so, is it caused by tion. If this is the case, nose clips are usually unneces- obstruction or restriction? sary. Care should be taken, however, that the patient b. If FVC is less than the LLN, lung volumes may places the mouthpiece into the mouth before begin- be indicated. c. Is the obstruction reversible? Bronchodilators ning a forced expiration. Failure to do so may result may be indicated. in an undetectable loss of volume. It may be impos- 4. Is FEV equal to or greater than expected? 1% sible to calculate the volume of back-extrapolation a. Are FVC and FEV both reduced 1 from a tracing that displays expiratory flow only. proportionately? If so, restriction may be present; lung volumes and/or muscle pressures may be indicated. PF TIP 2.4 b. Are FVC and FEV within normal limits? If so, 1 spirometry is likely normal. The largest FVC and FEV are reported, even 1 5. Are the spirometric findings consistent with the if they come from different efforts, as long as patient history and physical findings? Is bronchial the efforts are acceptable. Peak flow (PEF) is challenge indicated to reveal obstruction? always the largest value from an acceptable effort. All of the other flows (FEF , etc.) 25%–75% are taken from the acceptable effort with the largest sum of FVC and FEV , as is the flow- FVC can be reduced by mucus plugging and 1 volume loop. bronchiolar narrowing, as is common in chronic bronchitis, chronic or acute asthma, bronchiecta- sis, and cystic fibrosis. Reduced FVC is also present Significance and Pathophysiology in patients whose trachea or mainstem bronchi are Forced Vital Capacity obstructed. Tumors or diseases affecting the pa- See Interpretive Strategies 2.2. FVC usually equals tency of the large airways can produce this result. VC in healthy individuals. In patients without ob- Some obstructed patients have a relatively normal struction, FVC and SVC should be within 150 mL FVC in relation to their predicted values. However, of each other. FVC and SVC may differ if the pa- the time required to expire their FVC (forced expira- tient’s effort is variable or if significant airway ob- tory time [FET]) is usually prolonged. Healthy adults struction is present (i.e., FEV 1 /FVC < 0.70). FVC is can expire their FVC within 4 to 6 seconds. Normal often lower than SVC in patients with obstructive children, adolescents, and many smaller adults may diseases if forced expiration causes airway collapse. exhale their FVC in less than 4 seconds. Patients with This pattern is often seen in emphysema because severe obstruction (e.g., those with emphysema) may --- PAGE 65 --- Spirometry • Chapter 2 53 the FVC compared with the VC maneuver. Such dis- eases include neuromuscular disorders and chest wall mechanical abnormalities, such as kyphosco- liosis and obesity. A reduction in FVC when going from sitting to supine has been shown to be a good indicator of diaphragmatic weakness. Reduced FVC (or VC) is a nonspecific find- ing. Values below the 5th percentile are consid- ered abnormal (see Chapter 13). A low FVC may be caused by either obstruction or restriction (see Box 2.2). Interpretation of the FVC in obstructive diseases requires correlation with flows. An FVC sig- nificantly lower than SVC suggests airway collapse Time (sec) and gas trapping. In restrictive patterns, low FVC may indicate the need to assess other lung volumes, particularly TLC (see Chapter 4). Interpretation of FVC values close to the LLN depends on the clini- cal question to be answered. An FVC at the 5th per- centile would be interpreted differently in a healthy require 15 seconds or more to exhale completely patient with no symptoms than in a patient with a (Fig. 2.7). Accurate measurement of FVC in such history of cough or wheezing. An FVC much lower individuals may be limited by how long the spirom- than expected is often accompanied by the com- eter can collect exhaled volume. Some spirometers plaint of exertional dyspnea. allow only 15 seconds of volume recording. This is A low value for FVC may also occur if the patient’s usually long enough to diagnose airway obstruction. effort is suboptimal. Patients who stop exhaling be- However, the FVC and FEV may be inaccurate if 1% fore achieving an obvious plateau (on a volume–time the patient continues to exhale for a longer time. The display) or who fail to take a maximal inhalation will ATS-ERS recommends that spirometers measure typically have an underestimated FVC. These pa- FVC for at least 15 seconds (see Chapter 11). tients should be encouraged to inhale maximally at An alternative to measuring FVC in severely ob- the start of the maneuver and then exhale completely structed patients is to use FEV . Because normal 6 for 6 seconds (3 seconds for children aged < 10) or patients can exhale their FVC in 6 seconds, sub- until a plateau occurs. Premature termination of the stituting FEV for FVC allows the FEV /FEV to 6 1 6 FVC effort may cause the FEV to be overestimated, 1% be used as an index of obstruction. Using FEV in 6 masking the presence of obstruction. place of FVC eliminates the necessity of having the An important quality issue to recognize is that a patient try to exhale for a long interval. Predicted large FVC (and its derived parameters) derived from values for FEV and FEV /FEV have been calcu- 6 1 6 a flow sensor may result from improper zeroing or lated. Because FEV may underestimate FVC, the 6 contamination of the sensor by condensation or use of FEV /FEV instead of FEV /FVC may reduce 1 6 1 mucus. This problem can usually be recognized by the sensitivity of spirometry to detect airway ob- poor repeatability of measurements, characterized struction, especially in older patients and in those by progressively increasing test results within a sin- with mild obstruction. gle testing session. Decreased FVC is seen in the same circum- stances as described for reduced VC, discussed ear- Forced Expiratory Volume lier. However, the reduction in FVC may be more FEV measures the volume expired over the first 1 evident than that of the slow VC in diseases that second of an FVC maneuver. FEV is reported as a 1 affect the bellows function of the chest, which is a volume, although it measures flow over a specific key determinant of the force generation involved in interval. FEV , like FVC, may be reduced in either 1 )L( emuloV 6 5 4 3 2 1 0 0 2 4 6 8 10 12 FIG. 2.7 Volume–time forced vital capacity (FVC) tracing from a patient with severe airway obstruction. A tick mark notes the point at which the patient exhaled his forced expiratory volume in the first second (FEV). A significant volume is exhaled after the 1 first second, and the tracing does not show an obvious plateau. --- PAGE 66 --- 54 Ruppel’s Manual of Pulmonary Function Testing Mortality (likelihood of dying) caused by respiratory disease is similarly related to the degree of obstruc- tion as measured by FEV . Patients with markedly 1 reduced FEV values are much more likely to die 1 of chronic obstructive pulmonary disease (COPD), lung cancer, and even cardiovascular disease, in- cluding myocardial infarction and stroke. Although FEV correlates with the prognosis and severity of 1 symptoms in obstructive lung disease, outcomes for individual patients cannot be accurately predicted. Whereas the ratio of FEV /VC defines obstruction, 1 the severity of obstruction is defined by the degree to which the FEV is reduced. The ATS-ERS Task Force Time (sec) 1 suggests the following classifications of severity: Severity Z Score Mild FEV 1 > –1.65 - < –2.5 Moderate FEV 1 ≥ –2.5 and ≤ –4 Severe FEV 1 >4 obstructive or restrictive patterns (Fig. 2.8; see also The concept of grading severity based on FEV ap- 1 Fig. 2.7). FEV values may also be reduced because plies best when the VC is in the normal range. Once 1 of poor effort or cooperation by the patient. the VC is below normal, a concomitant restrictive de- An obstructive ventilatory defect is character- fect may also be present, and this can be determined ized by the reduction of maximal airflow at all only by further measurement of lung volumes, in lung v olumes (e.g., the classic concave shape to particular TLC. Because the FEV in restriction is 1 the flow-volume curve). Flow is limited by airway reduced, in part, by the restrictive process itself, the narrowing during forced expiration. Airway ob- decrement in FEV resulting from the obstructive 1 struction may be caused by mucus secretion, bron- component of disease can no longer be assumed to chospasm, and inflammation, such as in asthma or reflect the severity of obstruction only. Thus the se- bronchitis. Airflow limitation may also result from verity of obstruction in a combined restrictive and a loss of elastic support for the airways themselves, obstructive defect is typically overestimated when as in emphysema. The earliest changes in obstruc- basing severity solely on the reduction in FEV . 1 tive patterns may occur in the small airways (i.e., Restrictive processes, such as fibrosis, edema, those < 2 mm), which may or may not be detected space-occupying lesions, neuromuscular disorders, by changes in FEV . obesity, and chest wall deformities, may all cause 1 FEV may also be decreased in large airway ob- FEV to be decreased. A reduction in FEV occurs 1 1 1 struction (trachea and bronchi). Tumors or foreign in much the same way as a reduction in VC. Unlike bodies that limit airflow cause the FEV to be re- the pattern seen in obstructive disease, in which 1 duced. These defects can be identified by flow re- VC is preserved and FEV is reduced, in restriction 1 ductions across the entire forced expiration (see the VC and FEV , values are proportionately decreased. 1 later section Flow-Volume Curve). Some patients with moderate or severe restriction FEV and FEV /VC are the most standardized have an FEV nearly equal to the VC. The entire VC, 1 1 1 indices of obstructive disease. An obstructive defect because it is reduced, is exhaled almost completely is defined best by a reduced FEV /VC ratio. The se- in the first second. To distinguish between obstruc- 1 verity of obstructive disease may be gauged by the tive and restrictive causes of reduced FEV values, 1 extent to which FEV is reduced. The ability to work the FEV /VC ratio (FEV ) and other flow measure- 1 1 1% and function in daily life is related to FEV and VC. ments are useful. Further definition of obstruction 1 )L( emuloV 6 5 4 3 2 1 0 0 2 4 68 1 0 12 FIG. 2.8 All three maneuvers show relatively normal flows; most of the forced vital capacity (FVC) is expired in the first sec- ond. However, the FVC is much lower than the expected value of 3.5 L for the patient. Notice the delayed start to the effort with the highest FVC, for which determination of the back- extrapolated volume is necessary. --- PAGE 67 --- Spirometry • Chapter 2 55 versus restriction may require the measurement reduced FEV for each interval (1 second, 2 sec- T% of lung volumes (e.g., functional residual capacity onds, etc.). The FEV /VC ratio is the most import- 1 [FRC] and TLC). However, studies have shown that ant measurement for distinguishing an obstructive when the FVC and FEV /VC ratio are both normal, impairment. A decreased FEV /VC ratio is the hall- 1 1 restriction, as defined by a low TLC, is very unlikely. mark of an obstructive disease. As already men- FEV is the most widely used spirometric pa- tioned, the ratio decreases with age, so care should 1 rameter, particularly for the assessment of airway be taken in interpreting the FEV /VC ratio in abso- 1 obstruction. FEV is used in conjunction with VC lute terms. An absolute cutoff of 70% is considered 1 for simple screening, assessment of response to to distinguish between normal and airflow obstruc- bronchodilators, inhalation challenge studies, and tion in defining COPD by the Global Initiative for the detection of exercise-induced bronchospasm Chronic Obstructive Lung Disease (GOLD) and (see Chapter 9). FEV is the most robust pulmonary the ATS-ERS guidelines on COPD. However, this 1 function test, making it the measurement of choice value may actually underestimate the presence of in evaluating lung function in general. In fact, the obstruction in younger adults (false negative) and motto of the National Lung Health Education overestimate it in older individuals (false positive) Program (NLHEP) is “Test your lungs. Know your (see Chapter 13 for predicted values). numbers,” and these numbers are the FEV and FVC Diagnosis of an obstructive pattern based on 1 (or FEV ). The NLHEP advocates for the widespread spirometry should focus on three primary vari- 6 use of simple office spirometry to increase the aware- ables: VC, FEV , and FEV /VC. Measurements 1 1 ness and detection of COPD, in addition to other such as FEF should be considered only af- 25%–75% respiratory disorders. In particular, the NLHEP rec- ter the presence and severity of obstruction have ommends that all smokers age 45 years and older been determined using the primary variables. If the have spirometry done to detect airflow obstruction, FEV /VC is borderline abnormal, additional flow 1 even before the onset of clinical symptoms. measurements may suggest the presence of an ob- structive pattern. Care should be taken when inter- Forced Expiratory Volume Ratio preting the FEV /VC ratio in patients who have VC 1 Normal FEV ratios for healthy adults are as and FEV values greater than predicted. The FEV / T% 1 1 follows: VC ratio may appear to indicate an obstructive pat- tern because of the variability of the greater-than- FEV = 50% to 60% 0.5% normal VC and FEV values. FEV = 75% to 85% 1 1% Although a low FEV /VC ratio is the key to de- FEV = 90% to 95% 1 2% fining obstruction, the ATS-ERS guidelines also FEV = 95% to 98% 3% define obstruction in the subset of patients who FEV = 98% to 100% 6% have a normal FEV /VC ratio but a low VC and a 1 These ratios may be derived by dividing pre- normal TLC. This pattern has been hypothesized to dicted FEV by predicted VC. Some studies of nor- be the result of small airway disease with resulting T mal patients derive equations for the ratio itself. small airway closure and gas trapping. This is often The reported FEV 1 /VC ratio is calculated from the termed a parallel shift. highest FEV and the highest FVC. The FEV /VC 1 1 ratio decreases with increasing age, presumably be- PF TIP 2.5 cause of a gradual loss of lung elasticity. For exam- Look at the FEV /FVC ratio first; if the FEV / ple, healthy older adults may have FEV /VC ratios 1 1 1 FVC ratio is lower than expected (the LLN), in the 65% to 70% range. Thus the 5th percentile obstruction is present. If the ratio is normal should be taken as the LLN when interpreting the or elevated, check the percent predicted for FEV /VC, just as with the FEV and VC separately. FVC and FEV . If FVC and FEV are both 1 1 1 1 Patients with unobstructed airflow can usu- reduced compared with the expected values, restriction or muscle weakness may be ally exhale their entire FVC within 4 seconds. present. Conversely, patients with obstructive disease have --- PAGE 68 --- 56 Ruppel’s Manual of Pulmonary Function Testing Patients who have a restrictive disease (e.g., pul- This is assumed to be caused by a decrease in the monary fibrosis) often have normal or increased cross-sectional area of the small airways. FEF 25%–75% FEV values. Because airflow may be minimally depends somewhat on patient effort because it de- T% affected in restrictive diseases, FEV and VC are pends on the FVC exhaled. Patients who perform 1 usually reduced in equal proportion. If the restric- the FVC maneuver inadequately often show widely tion is severe, FEV may approach the VC value. varying midexpiratory flow rates. 1 In addition, the increased elastic recoil of fibrotic The FEF /FVC ratio is thought to reflect 25%–75% lungs may enhance expiratory airflow. As a result, relative airway size to lung size, and as such, it has FEV appears to be higher than normal. The FEV / been found to be significantly associated with air- 1% 1 VC ratio may be 100% if the VC is severely reduced. way hyperresponsiveness. The clinical importance The presence of a restrictive disorder may be sug- of this finding is unknown. gested by a reduced VC and a normal or increased The validity of FVC maneuvers depends largely FEV /VC ratio. Further studies (e.g., measurement on patient effort and cooperation. Equally im- 1 of TLC) should be used to confirm the diagnosis of portant are the instruction and coaching supplied restriction. by the technologist. Many patients need several attempts before performing the maneuver accept- Forced Expiratory Flow 25% to 75% ably. Demonstration of the proper technique by the FEF is measured from a segment of the FVC technologist helps the patient give maximal effort. 25%–75% that includes flow from medium and small airways. Placement of the mouthpiece behind the teeth and Typical values for healthy young adults average lips, maximal inspiration, little if any pause, and 4 to 5 L/sec. These values decrease with age. FEF maximal expiration should all be demonstrated. 25%–75% is quite variable even in normal patients, with 1 Emphasis should be placed on the initial burst standard deviation (SD) equal to approximately of air and on continuing expiration for at least 6 1 L/sec. Values as low as 50% of predicted may be seconds. The acceptability of each FVC maneuver statistically within normal limits. This variability should be evaluated according to specific criteria requires guarded interpretation of the FEF (see Criteria for Acceptability 2.2). The final report 25%–75%. The FEF may be indicative of the status of should include comments on the quality of the data 25%–75% the medium to small airways. Decreased flows are obtained (see Chapter 12). These comments may be common in the early stages of obstructive disease. provided by the operator, physician, or both. Abnormalities in these measurements, however, The validity of the FEV also depends on cooper- 1 are not specific for small airway disease. Although ation and effort. Adequate instruction and demon- FEF may suggest changes in the small air- stration of the maneuver by the technologist are 25%–75% ways, it should not be used to diagnose small air- essential. The target repeatability of FEV should 1 way disease in individual patients. In the presence be within 150 mL for the two best of at least three of a borderline value for FEV /VC, a low FEF acceptable maneuvers. Accurate measurement 1 25%–75% may help confirm airway obstruction. Assessment of FEV requires an acceptable spirometer (see 1 of FEF after bronchodilator use must con- Chapter 11), preferably one that allows inspection 25%–75% sider changes in FVC as well. If FVC increases mark- of the volume–time curve and back-extrapolation. edly, FEF may actually decrease. Likewise, The validity of the FEV also depends on patient 25%–75% 1% if the FVC decreases, the FEF may increase. effort and cooperation. Because the values used to 25%–75% Isovolume correction can be used to compare derive the ratio may be taken from separate maneu- FEF before and after bronchodilator therapy. vers, both FEV and FVC should be reproducible. 25%–75% 1 However, the inherent variability of FEF and Poor effort on an FVC test may result in an overes- 25%–75% its dependence on FVC make it less useful than the timate of FEV . If the patient stops prematurely, T% FEV for assessing bronchodilator response. the FVC (i.e., denominator of the ratio) will appear 1 Reduced FEF values are sometimes seen smaller than it actually is. The FEV will then ap- 25%–75% 1% in cases of moderate or severe restrictive patterns. pear larger than it actually is. Some clinicians prefer --- PAGE 69 --- Spirometry • Chapter 2 57 to use the VC to calculate the FEV . This may be PEF 1% useful if the VC is significantly larger than FVC be- cause of airway compression. Patients who have moderate or severe obstruc- tion may require longer than 10 seconds to com- pletely exhale. Although continuing to exhale Expiratory increases measured FVC, the diagnosis of ob- FEF struction can be made with less-than-complete 50% expiration. The FEV may be a useful surrogate 6 measurement in obstructed patients who have dif- ficulty with prolonged exhalation. In some cases, prolonged effort may be difficult for the patient. The large transpulmonary pressure generated by a forced expiratory maneuver often reduces cardiac FVC output. Patients may complain of dizziness, see- ing “spots,” ringing in the ears, or numbness of TLC RV the extremities. A patient may occasionally faint as a result of decreased cerebral blood flow (termed FVC-induced syncope). This complication may be se- rious if it causes the patient to fall from a standing or sitting position. FLOW-VOLUME CURVE Inspiratory Description The FVC graphs the flow generated during an FVC PIF maneuver against volume change. The FVC may be followed by an FIVC maneuver, plotted similarly. Flow is usually recorded in liters per second, and the volume is recorded in liters, BTPS. The max- imal expiratory flow-volume (MEFV) curve shows flow as the patient exhales from maximal inspiration (TLC) to maximal expiration (RV). The maximal inspiratory flow volume (MIFV) displays inspiratory flow plotted from RV to TLC. When MEFV and MIFV curves are plotted to- gether, the resulting figure is called a flow-volume (F-V) loop (Fig. 2.9). The reported F-V loop is taken from the single best test maneuver (highest sum of FEV and FVC). 1 Technique The patient performs an FVC maneuver, inspir- ing fully and then exhaling as rapidly as possible. To complete the loop, the patient inspires as rap- idly as possible from the maximal expiratory level )ces/L( wolF 8 6 4 2 0 −2 −4 −6 −8 1 2 3 4 Volume (L) FIG. 2.9 Flow-volume loop. A flow-volume recording in which a forced vital capacity (FVC) and a forced inspiratory vital ca- pacity (FIVC) maneuver are recorded in succession. Flow in liters per second is plotted on the vertical axis, and volume, in liters, is plotted on the horizontal axis. By convention, expiratory flow is plot- ted upward (positive), and inspiratory flow is plotted downward (negative). The maximal exhalation begins with the patient at to- tal lung capacity (TLC) and continues until residual volume (RV) is reached; a maximal inspiration then returns to TLC. The FVC can be read from the tracing as the maximal horizontal deflection along the zero-flow line. Peak flows for expiration and inspira- tion (PEF and PIF) can be read directly from the tracing as the maximal deflections on the flow axis (positive and negative). The instantaneous flow (forced expiratory flow [FEF]) at any point in the FVC can also be measured directly. Abnormalities, such as small or large airway obstruction, may show up as characteristic changes in the maximal flow rates. The flow-volume loop is a graphic display of the maximal expiratory flow-volume (MEFV) and maximal inspiratory flow-volume (MIFV) curves combined. --- PAGE 70 --- 58 Ruppel’s Manual of Pulmonary Function Testing back to maximal inspiration. Volume is plotted on the horizontal x-axis, and flow is plotted on the vertical y-axis. The F-V loop is usually displayed on a computer screen. Expired volume is usually plotted from left to right. Sometimes, when con- comitant lung volumes have also been measured, an absolute lung volume scale is used, usually with TLC on the left and RV on the right. Airflow should be recorded at 2 L/sec/unit distance on the y-axis. Volume should be recorded at 1 L/unit distance on the volume axis. Scale factors should be at least 5 mm/L/sec for flow and 10 mm/L for volume. These factors are required so that manual measurements can be made from a printed copy of the maneuver. This one-to-two flow-volume re- lationship also ensures that the visual perspective of the graphic data is consistent regardless of the size of the display. FVC, in addition to PEF and peak inspira- tory flow (PIF), can be read directly from the F-V loop. Instantaneous flow at any lung volume can be measured directly from the F-V loop. Maximal flow at 75%, 50%, and 25% of the FVC is commonly recommended. This allows a review of the test ses- reported as the Vmax , Vmax , and Vmax . The sion and the detection of bronchospasm or fatigue. 75 50 25 subscript in these terms refers to the portion of the Reproducible MEFV curves, particularly the FVC remaining. The same flows are also reported as PEF, are good indicators of adequate patient the FEF , FEF , and FEF , with the subscripts e ffort (Criteria for Acceptability 2.3). Assessing 25% 50% 75% referring to the percentage of FVC exhaled. This the start-of-test and determining whether exha- latter terminology is now preferred by the ATS-ERS lation lasted at least 6 seconds may be difficult guidelines. if only the F-V loop is displayed. Simultaneous F-V loop data, stored in computer memory, can be display of flow-volume and volume–time curves is easily manipulated. Multiple loops can be compared useful (Fig. 2.11). Although computerized systems by superimposing them with contrasting colors. calculate the back-extrapolated volume, a v olume– Bronchodilator or inhalation challenge F-V loops time tracing may be necessary to perform back- can be presented in a similar manner. A predicted extrapolation manually (see Fig. 2.5). Common MEFV curve can be plotted using points for PEF and technical problems with volume–time tracings maximal flows at 75%, 50%, and 25% of the FVC. A and F-V loops are shown in Fig. 2.11. These in- patient’s flow-volume curve can then be superim- clude cough in the first second (Fig. 2.11A); early posed directly over the expected values (Fig. 2.10). termination or glottic closure (Fig. 2.11B); exces- Superimpositions of multiple FVC maneuvers as sive back-extrapolated volume or “slow”/hesitative F-V loops can be used to assess the reproducibility start (Fig. 2.11C); negative flow sensor drift, which of the patient’s effort. Positioning loops side by side would underestimate volumes (Fig. 2.11 D); pos- or superimposing can also help detect decreasing itive flow sensor drift, which would overestimate flows with repeated efforts. This pattern may be volumes (Fig. 2.11E); a sneak breath at the end seen because FVC maneuvers can induce broncho- of exhalation (Fig. 2.11F); or a suboptimal blast, spasm (i.e., FVC-induced bronchospasm or FVC which might yield an overestimation of FEV 1 worsening). Storing tests in the order performed is (Fig. 2.11G). wolF F-V curves on absolute lung volumes Normal Restrictive Obstructive 10 9 8 7 6 5 4 3 2 1 0 Volume FIG. 2.10 Superimposed flow-volume loops on an absolute volume scale. --- PAGE 71 --- Spirometry • Chapter 2 59 2 12 10 8 6 4 2 0 0 2 4 6 2 4 6 8 FIG. 2.11 Common technical problems identified with flow-volume loops. (A) Cough during the first sec- ond of exhalation will interfere with proper measurement of forced expiratory volume in the first second (FEV). (B) Glottic closure results in an abrupt termination of expiration and will affect accurate measurement 1 of forced vital capacity (FVC). )s/L( wolF Volume/Time Flow/Volume )L( loV Vol (L) Time (sec) Test 1 Test 4 Test 2 Test 5 A Test 3 Test 6 8 6 4 2 2 0 2 4 (cid:31)2 (cid:31)4 0 2 4 6 8 )s/L( wolF Flow/Volume Volume/Time )L( loV Vol (L) Time (sec) Test 1 Test 2 B Test 3 --- PAGE 72 --- 60 Ruppel’s Manual of Pulmonary Function Testing 4 12 10 8 2 6 4 2 0 0 2 4 6 2 4 6 8 10 12 14 16 FIG. 2.11, CONT’D (C) Test 1 demonstrates excessive back-extrapolation volume secondary to a slow start. This will cause an overestimation of the FEV. Look for the maneuver to “hug” the y-axis or not lean (Test 1 is 1 a “leaning Tower of Pisa”) (D) Negative flow sensor drift (all maneuvers slope downward). )s/L( wolF Volume/Time Flow/Volume )L( loV Vol (L) Time (sec) Test 1 Test 3 C Test 2 Test 4 Volume/Time Volume/Time Volume (L) D )s/L( wolF Times (s) )L( emuloV Test 1 Test 2 Test 3 Test 4 Test 5 Test 1 Test 2 Test 3 Test 4 Test 5 8 4 7 6 3 5 4 3 2 2 1 0 1 0 1 2 3 4 -1 -2 0 -3 2 6 10 14 18 22 26 30 4 8 12 16 20 24 28 -4 --- PAGE 73 --- Spirometry • Chapter 2 61 Volume/Time Volume/Time Volume (L) E FIG. 2.11, CONT’D (E) Positive flow sensor drift (all maneuvers slope upward). (F) A sneak breath at the end of the exhalation. )s/L( wolF Times (s) )L( emuloV Test 1 Test 2 Test 3 Test 4 Test 5 Test 1 Test 2 Test 3 Test 4 Test 5 10 5 9 8 7 4 6 5 3 4 3 2 2 1 0 0 1 2 3 4 5 -1 1 -2 -3 -4 0 5 10 15 20 25 30 35 -5 Volume/Time Volume/Time Volume (L) F )s/L( wolF Times (s) )L( emuloV Test 1 Test 2 Test 3 Test 4 Test 1 Test 2 Test 3 Test 4 6 3 5 4 2 3 2 1 1 0 0 1 2 3 -1 -2 0 5 10 15 20 25 30 35 40 -3 --- PAGE 74 --- 62 Ruppel’s Manual of Pulmonary Function Testing Volume (L) 0 1 2 3 −2 0 −4 −6 )ces/L( wolF 6 6 4 5 2 4 3 2 1 0 2 4 6 Time (sec) )L( emuloV Flow/Volume Flow(l/s) 10 8 6 4 2 0 2 4 -2 -4 -6 Vol(l) -8 G FIG. 2.11, CONT’D (G) Maneuver with suboptimal blast (3L/sec less than the other maneuvers). 8 10 12 FIG. 2.12 Flow-volume loop and volume–time tracings from a patient with severe obstruction. The expira- tory flow-volume curve shows severely reduced flows at all lung volumes; inspiratory flows are also markedly reduced. Note that the tidal breathing loop (recorded immediately before the forced effort) shows higher flows than the maximal expiratory flow-volume curve. This is consistent with dynamic airway compression during forced exhalation. The expiratory volume-time tracing reveals reduced flow with no obvious plateau even after 12 seconds of exhalation. --- PAGE 75 --- Spirometry • Chapter 2 63 Bronchoconstriction and inflammation directly re- CRITERIA FOR ACCEPTABILITY 2.3 duce the lumen of the small airways (Fig. 2.12). Flow-Volume Loop 1. Rapid rise from maximal inspiration to PEF (rise INTERPRETIVE STRATEGIES 2.3 time of < 150 ms) 2. Maximal effort until flow returns to zero Flow-Volume Loop baseline; no glottic closure or abrupt end of flow 3. No cough or artifact in the first second 1. Were at least three acceptable F-V loops 4. Maximal inspiratory effort with return of volume obtained? Does the beginning of the expiratory to point of maximal inspiration. (Failure to curve show a sharp rise to PEF? If not, suspect close loop indicates that effort was not started patient effort or large airway obstruction. from maximal inspiration, inspiratory effort was 2. Are the PEF and PIF values consistent? Do PEF or submaximal, or spirometer error.) Comparison other expiratory flows fall with repeated efforts? of the FIVC – FVC is a recommended quality If so, suspect hyperreactive airways. check. The values should be less than 100 mL. 3. Does the expiratory curve from PEF to maximal 5. At least three acceptable loops recorded; exhalation appear concave? If so, suspect airway superimposed or side-by-side loops should be obstruction. repeatable unless bronchospasm occurs. 4. Do either the expiratory or inspiratory portions 6. Report the F-V loop from the single best test of the curve show a “squared-off” pattern? If so, maneuver (highest sum of FEV and FVC). suspect large airway obstruction. If both, suspect 1 a fixed obstruction. 5. Is the inspiratory curve repeatable? If not, suspect variable extrathoracic obstruction or Significance and Pathophysiology suboptimal effort or fatigue. 6. Does the F-V loop show any other unusual See Interpretive Strategies 2.3. Maximal flow at any patterns (sudden changes in flow that are lung volume during forced expiration or forced in- reproducible or “sawtooth” pattern)? spiration can be easily measured from the F-V loop (see Fig. 2.9). Significant decreases in flow or volume are easily detected from a single graphic display. In healthy patients, flow (Vmax) over the effort- Many clinicians prefer to include the F-V loop or independent segment decreases linearly as lung MEFV curve as part of the patient’s medical record. volume decreases. Pressures around airways are bal- The shape of an MEFV curve from approximately anced by gas pressures in the airways so that flow 75% of FVC to maximal expiration is largely inde- is limited at an “equal pressure point.” As the lung pendent of patient effort. Flow over this segment empties, the equal pressure point moves upstream is determined by two properties of the lung: elastic into increasingly smaller airways and continues un- recoil and flow resistance. The lung is stretched by til small airways begin to close, trapping some gas maximal inspiration. Elastic recoil determines the in the alveoli (the RV). This pattern of airflow lim- pressure applied to gas in the lung during a forced itation in healthy lungs causes the MEFV curve to expiration. This pressure is determined by the recoil have a linear or slightly concave appearance. This of the lung and chest wall. Resistance to flow in the degree of concavity increases with age, presumably airways is the second factor affecting the shape of because of reduced flows secondary to loss of elas- the flow-volume curve. Flow limitation occurs in tic recoil with aging. the large and medium airways during the early part of a forced expiration. The site of flow limitation Flow-Volume Loops in Small Airway migrates “upstream” rapidly during forced expira- Obstruction tion. Resistance to flow in small (< 2 mm) airways Maximal flow is decreased in patients who have is determined primarily by the cross-sectional area. obstruction in small airways, particularly at low This cross-sectional area can be affected by a num- lung volumes. The effort-independent segment ber of factors. Destruction of alveolar walls, as in of the MEFV curve appears more concave or emphysema, reduces support of the small airways. “scooped out.” Values for Vmax and Vmax are 50 25 --- PAGE 76 --- 64 Ruppel’s Manual of Pulmonary Function Testing Flow-Volume Loops in Large Airway characteristically decreased. Decreases in Vmax 50 Obstruction correlate well with the reduction in FEF in 25%–75% patients with peripheral airway obstructive disease. Obstruction of the upper airway, trachea, or main- Because elastic recoil and resistance in small stem bronchi also shows characteristic patterns. airways determine the shape of the MEFV tracing, Both expiratory and inspiratory flow may be lim- different lung diseases can cause similar F-V pat- ited. The F-V loop is extremely useful in diagnos- terns. Emphysema destroys alveoli, with a loss of ing these large airway abnormalities (Fig. 2.13). elastic tissue and support for small airways. Flow Comparison of expiratory and inspiratory flows through small airways decreases because of col- at 50% of the FVC (FEF 50% and FIF 50% , respectively) lapse of the unsupported walls. In contrast, bron- may help determine the site of obstruction. In chitis, asthma, and similar inflammatory processes healthy patients, the ratio of FEF 50% to FIF 50% is increase resistance in the small airways. Increased approximately 1.0 or slightly less. Fixed large air- resistance is caused by edema, mucus production, way obstruction causes equally reduced flows at and smooth muscle constriction. Reduction in the 50% of the VC during inspiration and expiration cross-sectional area of the small airways reduces (see Fig. 2.13). Obstructive lesions that vary with flow. Emphysema and chronic bronchitis are often the phase of breathing also produce characteristic found in the same individual because of their com- patterns. Variable extrathoracic obstruction usu- mon cause—cigarette smoking. The MEFV curve ally shows normal expiratory flow but dimin- thus presents a picture of the extent of obstruction ished inspiratory flow. The FEF 50% /FIF 50% is often without identifying its cause. greater than 1.0 because the obstructive process Asthma 5 L Variable intrathoracic obstruction )ces/L( wolF Emphysema Restriction +5 −5 +5 −5 Variable Fixed obstruction extrathoracic obstruction FIG. 2.13 Abnormal flow-volume loop patterns. Six curves are shown, plotting flow in liters per second against the forced vital capacity (FVC) on an absolute volume scale, with the expected curve shown as dashed lines. In patients who have asthma or emphysema, the expiratory curve is characteristically concave. The total lung capacity (TLC) and residual volume (RV) points are consistent with hyperinflation and/or air trapping. In patients with lung or chest wall restriction, the shape of the loop is preserved, but the FVC is decreased. The TLC and RV are displaced toward lower lung volume. The bottom three examples depict types of large airway obstructions. Variable intrathoracic obstruction shows reduced flows on expiration (“what’s in is out”) despite near-normal flows on inspiration. Variable extrathoracic obstruction shows an opposite pattern. Inspiratory flow is reduced, whereas expiratory flow is relatively normal (“what’s out is in”). Fixed large airway obstruction is characterized by equally reduced inspiratory and expiratory flows. --- PAGE 77 --- Spirometry • Chapter 2 65 is outside of the thorax; the MEFV portion of the Expiratory flow remains constant until the site of curve appears as it would in a healthy individual, flow limitation reaches the smaller airways. This but the inspiratory portion of the loop is flattened. gives the expiratory limb a “squared-off” appear- Inspiratory flow depends on how much obstruction ance (see Fig. 2.13). The inspiratory portion of the is present. A common cause of variable extratho- loop may be completely normal. The FEF /FIF 50% 50% racic obstruction, resulting in truncated inspira- will typically be much less than 1.0, depending on tory flow, is paradoxical vocal cord closure during the severity of obstruction. In patients with trunca- inspiration, also known as vocal cord dysfunction. In tion of both the inspiratory and expiratory loops, a variable intrathoracic obstruction, PEF is reduced. fixed obstruction may be present. PF TIP 2.6 The classic analogy for an emphysematous lung is a balloon that has been blown up for several days and the air has escaped. The balloon (B), much like the emphysematous lung, is distended and floppy. It has lost its elastic recoil and is very compliant. The neck of the balloon is also affected and is collapsed. This gives the maximal expiratory flow-volume curve its characteristic obstructive concave or “scooped” appearance (A, C). )s/L( wolF 8 6 4 Peak expiratory flow 2 0 0 1 2 3 4 A Volume (L) B Predicted curve Low PEF Scooped out flow-volume curve Volume (L) C Normal inspiratory flow )s/L( wolF --- PAGE 78 --- 66 Ruppel’s Manual of Pulmonary Function Testing Flow-Volume Loops in Restrictive PF TIP 2.7 Disease A simple mnemonic for determining variable Restrictive disease processes may show normal or obstruction: “What’s in is out, what’s out is greater-than-normal peak flows with linear de- in.” In other words, a variable inspiratory obstruction affects the expiratory portion of the creases in flow versus volume. The lung volume dis- F-V curve, and a variable expiratory obstruction played on the x-axis is decreased. Moderate or severe affects the inspiratory portion of the F-V curve. Airway obstruction associated with abnormal- PF TIP 2.8 ity of the muscular control of the posterior phar- The restrictive flow-volume loop pattern (A) ynx and larynx sometimes produces a “sawtooth” is often compared with a very small balloon: pattern visible on the inspiratory and expiratory it takes high pressure to flow up the balloon, limbs of the MEFV curve (Fig. 2.14). This pattern the balloon does not get big (B), yet the air comes out very fast. Another analogy is the is neither sensitive nor specific for patients with “anthill” or “witch’s hat” (C), with very steep sleep apnea but is sometimes observed in this pa- flows secondary to high elastic recoil but tient population. If this pattern is observed on the decreased volumes. F-V curve and the subject complains of daytime hy- persomnolence, a referral to a sleep center may be warranted. The interpretation of this noise is some- times termed redundant tissue of the upper airway. Peak inspiratory flow and the pattern of flow during inspiration are largely effort dependent. Poor patient effort may result in inspiratory flow pat- terns similar to variable extrathoracic obstruction. Instruction by the technologist should emphasize maximal effort during inspiration and expiration. If repeated efforts produce reduced inspiratory flows, an obstructive process should be suspected. 8 6 4 2 Volume (Liters) 0 0 1 2 3 4 5 EXPIRED VOLUME, LITERS FIG. 2.14 The “sawtooth” pattern, sometimes termed redun- dant tissue of the airway, is sometimes seen in subjects with obstruc- tive sleep apnea. )s/L( etar wolF 8 Expiration 4 0 4 Inspiration B C )dnoces rep sretil( wolF A --- PAGE 79 --- Spirometry • Chapter 2 67 restriction demonstrates equally reduced flows at all liters per second, BTPS. When performed alone us- lung volumes. Reduced flows are primarily caused ing a peak flow meter, PEF is usually reported in by the decreased cross-sectional area of the small liters per minute, BTPS. airways at low lung volumes. Simple restriction causes the F-V loop to appear as a miniature of the Technique normal curve (see Fig. 2.10), often with supranormal PEF can be easily measured from a flow-volume flow, as evidenced by elevated FEV /VC. 1 curve (MEFV). PEF may also be measured by using In Bronchodilator Responsiveness Testing the F-V devices that sense flow directly (see Chapter 11) loops can be superimposed to measure changes in or by using volume-displacement spirometers and flow at specific lung volumes. The curves are usually deriving the rate of volume change. Many portable positioned by superimposing at maximal inspiration. devices (i.e., peak flow meters) are available to mea- This method assumes that any increase in FVC occurs sure maximal flow during forced expiration. Most while TLC remains constant. If postbronchodilator sense flow as movement of air against a turbine or lung volume tests are performed, the curves may be through an orifice. PEF done in conjunction with superimposed on an absolute volume scale (i.e., isovol- spirometry is performed as described for F-V loops. ume correction). This method shows bronchodilator- Measuring PEF with a peak flow meter may be induced changes in lung volumes and flows. done at the bedside, in the emergency department, Sometimes, lung volumes will change after bronchodi- in the clinic setting, or at home. In each setting, lator without any change in FEV. Inhalation challenge 1 the individual performing the measurement must studies (see Chapter 9) can be displayed similarly to know how to operate the specific peak flow meter. assess the reduction in flows at specific lung volumes. The maneuver should be demonstrated to the pa- Tidal breathing curves or MVV curves can also be tient. A return demonstration is essential when the superimposed on the F-V loop. The patient’s venti- patient is being trained to use the peak flow meter latory reserve can be assessed by comparing the ar- at home. eas enclosed under each of the curves. Patients who The peak flow meter should be set or zeroed, as have obstructive lung disease may generate F-V loops required. When performed at home with a portable only slightly larger than their tidal breathing curves. device as part of ambulatory monitoring, the stand- In severe obstruction, flow during tidal breathing ing position is usually recommended (if performed may actually exceed flow during a forced expiration. as part of a spirometry maneuver in the office or Dynamic compression of small airways during forced hospital setting, the patient should be sitting). The expiration causes airway collapse, whereas tidal patient should inhale maximally; the inhalation breathing may not. These patients have limited ven- should be rapid but not forced. The patient then tilatory reserve and shortness of breath with exertion. exhales with maximal effort as soon as the teeth F-V loops may also be measured during exercise and lips are placed around the mouthpiece. The (see Chapter 7). By superimposing a flow-volume neck should be in a neutral position to avoid tra- curve during exercise over the maximal F-V loop, spe- cheal compression with neck flexion or extension cific patterns of ventilatory response can be assessed. because these will reduce PEF. As in the FVC ma- Patients who have airflow limitation are typically neuver, a long pause (4–6 seconds) at maximal in- unable to increase ventilation during exercise when spiration may decrease the PEF; there should be no expiratory flow equals maximal flow. Exercise F-V more than 1 second of hesitation. The expiratory curves can be used to demonstrate this phenomenon. effort needs to be only 1 to 2 seconds to record PEF. At least three maneuvers should be performed PEAK EXPIRATORY FLOW and recorded, along with the order in which the values were obtained. All readings are recorded to Description detect effort-induced bronchospasm. The largest PEF is the maximum flow attained during an FVC PEF obtained should be reported. The PEF is effort maneuver. When reported in conjunction with dependent and variable. It may be particularly vari- other spirometric variables, PEF is expressed in able in patients with hyperreactive airways (Criteria --- PAGE 80 --- 68 Ruppel’s Manual of Pulmonary Function Testing for Acceptability 2.4). Up to five attempts should be may be limited. Peak flow is effort dependent. It made to achieve adequate repeatability, defined as primarily measures large airway function and mus- a difference of no more than 0.67 L/sec (40 L/min) cular effort. Decreased PEF values should be eval- between the largest of two out of three acceptable uated for consistent patient effort. PEF values for efforts. patients without hyperreactive airways are usually When PEF is used to monitor patients with similar with repeated efforts. Patients with asthma asthma, it is important to establish each person’s often have a pattern of decreasing PEF with repeated best PEF (i.e., the largest PEF achieved). Best values trials. Widely varying peak flows without a pattern can be obtained over 2 to 3 weeks. PEF should be of induced bronchospasm suggest poor effort or measured twice daily (morning and evening). The cooperation. However, PEF measurements alone personal best is usually observed in the evening af- are not sufficient to make a diagnosis of asthma. ter a period of maximum therapy. Daily measure- Spirometry, lung volumes, diffusing capacity, and ments are then compared with the personal best. airway resistance measurements may be required The personal best PEF should be reevaluated annu- for a full evaluation of the associated physiologic ally. This allows PEF to be adjusted for growth in impairment. children or for progression of disease. PEF should The effort dependence of PEF makes it a good be periodically compared with regular spirometry indicator of patient effort during spirometry. results (FEV ). Maximal transpulmonary pressures (Ptp) cor- 1 Portable peak flow meters need to be precise relate well with maximal PEF. Patients who exert (low variability in the same instrument). Precision variable effort during FVC maneuvers are seldom is more important than accuracy for detecting able to reproduce their PEF. Some clinicians use changes from serial measurements. Peak flow me- PEF in addition to the FVC and FEV to gauge max- 1 ters should have ranges of 60 to 400 L/min for chil- imal effort during spirometry. PEF measurements, dren and 100 to 850 L/min for adults. Standards when performed with a good effort, correlate well for peak flow monitoring devices have been pub- with the FEV as measured by spirometry. 1 lished by the ATS-ERS (see Chapter 11). INTERPRETIVE STRATEGIES 2.4 CRITERIA FOR ACCEPTABILITY 2.4 Peak Flow Peak Flow 1. What is the patient’s personal best PEF? 1. Patient was standing or sitting up straight. 2. Is the current PEF the best of three trials? Was it 2. Patient inhaled maximally (rapid but not forced) obtained in the morning or evening? Was it obtained and exhaled maximally without holding his or before or after inhaled bronchodilator therapy? her breath. 3. Zone systema: 3. At least three efforts were performed and Green: 80% to 100% of personal best recorded in order. Signals good control. Take your medications as usual. 4. The largest two out of three efforts were Yellow: 50% to 79% of personal best repeatable within 0.67 L/s (40 L/min). Signals caution. Your asthma may not be under 5. Largest PEF obtained is reported. good control. Take your medicine as directed by your physician and follow your asthma plan, From ATS-ERS Task Force, 2005. and/or ask your doctor whether you need to change or increase your daily medicines. Red: < 50% of personal best Signals a medical alert. You must take an inhaled Significance and Pathophysiology short-acting β2 agonist right away. Call your doctor or emergency room (ER) and ask what See Interpretive Strategies 2.4. The PEF attainable to do or go directly to the ER. by healthy young adults may exceed 10 L/sec or 600 L/min, BTPS. Even when an accurate pneumota- a From National Asthma Education and Prevention Program, EPR-3, 2007. chometer is used, the value of PEF measurements --- PAGE 81 --- Spirometry • Chapter 2 69 250 Green 200 Yellow 130 Red FIG. 2.15 Peak flow trend in a subject with asthma. The middle section of the trend data demonstrates an asthma exacerbation with a reduction in peak expiratory flow (PEF) that then responds to treatment. Patients with early small airway obstruction may cation immediately according to their physicians’ initially develop high flows during an FVC maneu- orders. Red (< 50% of the personal best PEF) indi- ver. Despite obstruction, these individuals show cates that an acute change has occurred. Immediate relatively normal PEF values. When small airway treatment is required, and the clinician should be obstruction becomes severe, PEF also decreases. The notified, or after taking their medication, the pa- reduction in PEF is often less than the decrease in tient should go to the ER. This approach dramati- FEF or FEF in patients with severe obstruction. cally improves the patient’s ability to communicate 50% 75% PEF measurements are particularly useful for symptomatic changes to the clinician (Fig. 2.15). monitoring patients with asthma at home. Daily Uniformly decreased PEF is often associated monitoring of PEF can provide early detection of with upper airway obstruction but is nonspecific. asthmatic episodes. It can be used to detect day– PEF assessed from F-V loops (along with PIF) helps night patterns (circadian rhythms) related to airway define both the severity and site of large airway reactivity. PEF monitoring provides objective criteria obstruction. for treatment. It can help determine specific triggers (e.g., allergens) or workplace exposures that cause symptoms. Daily morning and evening readings are MAXIMUM VOLUNTARY recommended. For patients taking inhaled broncho- VENTILATION dilators, PEF may be measured before and after treat- ment. Significant variation from the personal best or Description from one reading to the next should be emphasized. MVV is the volume of air exhaled in a specific in- The NAEPP suggests a “zone” system based on terval during rapid forced breathing. The maneuver the individual’s personal best or predicted PEF (see should last at least 12 seconds. It is recorded in li- Interpretive Strategy 2.4). The zone system uses ters per minute, BTPS, by extrapolating the volume green, yellow, and red as indicators for maintaining to 1 minute. or altering therapy. Green (80%–100% of the per- sonal best PEF) indicates a continuation of routine Technique therapy. Yellow (50%–79% of the personal best PEF) MVV is measured by having the patient breathe indicates that an acute episode may be starting. deeply and rapidly for a 12 to 15 seconds. Patients Patients should be instructed to take their medi- should set the rate but breathe rapidly and deeply. --- PAGE 82 --- 70 Ruppel’s Manual of Pulmonary Function Testing The volume breathed should be greater than the V 5 T but less than the VC. Instruct the patient to move 4 as much air as possible into and out of the spirome- 3 ter. The technologist should encourage the patient throughout the maneuver. An ideal rate is 90 to 2 110 breaths per minute, and an ideal V is approxi- 1 T mately 50% of the VC. 0 0 1 2 3 4 5 6 MVV is continued for at least 12 seconds but Time (sec) no more than 15 seconds. The patient is hyper- ventilating, so efforts longer than 15 seconds may exaggerate the sensation of lightheadedness. Even the 12-second interval may produce dizziness or syncope. The test may be performed with the pa- tient in either a sitting or standing position. If done while standing, a chair should be available in case of dizziness. Some automated spirometers allow MVV to be terminated before 12 seconds. This accom- The volume expired is measured by a spirometer. modates patients who cannot continue because The spirometer must have an adequate frequency of coughing or lightheadedness. If MVV does not response over a wide range of flows (see Chapter last 12 seconds, it should be noted in the technolo- 11). Historically, the volume of each breath was read gist’s comments (see Chapter 12). At least two MVV from a volume–time spirogram or from a recording maneuvers should be performed. The two largest of accumulated volume (Fig. 2.16). Now volume data should be within 20% of each other. The largest from each breath are summed by a computer for the value is reported (Criteria for Acceptability 2.5). interval measured. The MVV (for a 12-second test) is calculated as flow in liters per minute, as follows: 60 MVV(cid:31)Vol (cid:30) 12 12 where: Vol = volume in liters expired in 12 seconds 12 60 = factor for extrapolation from seconds to minutes For other intervals, the MVV is calculated simi- larly. The MVV must be corrected to BTPS. Significance and Pathophysiology See Interpretive Strategies 2.5. MVV tests the overall function of the respiratory system. It is influenced by airway resistance, respiratory muscles, compli- ance of the lung and/or chest wall, and ventilatory control mechanisms. Values in healthy young men average between 150 and 200 L/min. Values are slightly lower in healthy women. MVV decreases with age in both men and women and varies con- siderably in healthy patients. Only large reductions in MVV (25% or more) are considered significant. )L( emuloV 7 8 9 10 11 12 )L( emulov latoT 16 14 12 10 8 6 4 2 0 FIG. 2.16 Maximum voluntary ventilation (MVV). A composite MVV spirogram on which breath-by-breath volume change and accumulated volume are plotted against time. The undulating line shows the tidal volume (approximately 1 L in this test) moved during each breath over a 12-second interval. To calculate MVV, the volumes of individual breaths can be added and multiplied by a factor of 5 (i.e., 60 seconds/12 seconds = 5) because the MVV is reported in liters per minute. PF TIP 2.9 You can quickly check the validity of the MVV by comparing it with the patient’s FEV 1 multiplied by 40. If the MVV is significantly lower than FEV 1 × 40, patient effort may be the cause. Neuromuscular disease may also cause a reduced MVV in relation to FEV . 1 CRITERIA FOR ACCEPTABILITY 2.5 MVV 1. Volume–time tracing shows continuous rhythmic effort for at least 12 seconds. 2. Volume is approximately 50% of VC, and the rate is 90 to 110 breaths per minute. 3. Two acceptable maneuvers are obtained; MVV values are within 20%. 4. Report the highest acceptable MVV and breathing rate. From ATS-ERS Task Force, 2005. --- PAGE 83 --- Spirometry • Chapter 2 71 who have an MVV of less than 50 L/min often have a INTERPRETIVE STRATEGIES 2.5 ventilatory limitation to exercise. Maximal exercise MVV ventilation in healthy patients is usually less than 1. Was the MVV test performed acceptably? At 70% of their MVV. In airway-obstructed patients, least 12 seconds? maximal ventilation during exercise approaches or 2. Does MVV approximate FEV 1 × 40? If not, even exceeds their MVV. This pattern occurs partly suspect suboptimal effort, neuromuscular because the MVV itself is reduced in obstruction. weakness, or variable extrathoracic obstruction. 3. Is MVV less than 75% of predicted? If so, Highly conditioned healthy patients may also reach correlate with obstruction (FEV ). their MVV during maximal exercise (see Chapter 7). 1% 4. If no obstruction, look for clinical correlation MVV may be normal in patients who have restric- for reduced MVV. Consider testing maximal tive pulmonary disease. Diseases that limit lung or respiratory pressures. chest wall expansion may not interfere significantly with airflow. Patients who have restrictive disease MVV is decreased in patients with moderate or se- can compensate by performing the MVV maneuver vere obstructive disease. This may be the result of the with low V and high breathing rates. T increased airway resistance caused by bronchospasm The MVV maneuver depends on patient effort or mucus secretion. Reduction of MVV may also oc- and cooperation. Low MVV values may indicate ob- cur because of airway collapse and hyperinflation, struction, muscular weakness, defective ventilatory as in emphysema. The MVV maneuver exaggerates control, or poor patient performance. air trapping and airflow limitation. Volume–time Patient effort during the MVV maneuver may MVV tracings may show a shift if gas trapping oc- be estimated by multiplying the FEV by 40. For 1 curs during the test. A slight shift is usually noted example, a patient with an FEV of 2.0 L might be 1 during the first few breaths, even in healthy patients. expected to ventilate approximately 80 L/min (40 × The patient adjusts to a lung volume that allows 2.0 L) during the MVV test. If the measured MVV maximal airflow. These first few breaths are usually is less than 80% of (FEV 1 × 40), poor patient effort excluded from the MVV calculation. or neuromuscular weakness may be suspected. If The MVV maneuver also places a load on the re- the MVV exceeds (FEV 1 × 40) by a large volume, the spiratory muscles. Both inspiratory and expiratory FEV may be erroneous. 1 muscles are used in the MVV maneuver. Weakness or decreased endurance of either system may result in low MVV values. Poor coordination of the respi- BRONCHODILATOR ratory muscles caused by a neurologic deficit may RESPONSIVENESS TESTING also cause a low MVV. Disorders such as paralysis Description or nerve damage reduce MVV as well. A markedly reduced MVV correlates with post- Spirometry can be performed before and after bron- operative risk for patients having abdominal or chodilator administration to determine the revers- thoracic surgery. Patients who have low preoper- ibility of airway obstruction. An FEV of less than 1% ative MVV values show an increased incidence of predicted is a good indication for bronchodilator complications. Reduced strength or endurance of studies. Patients whose FEV and VC are within 1 the respiratory muscles may be the factor that al- normal limits may have a low FEV . This happens 1% lows MVV to predict postoperative problems. when the VC is greater than 100% of predicted while The MVV value may be helpful in estimating the FEV is slightly reduced. Even if the FEV and 1 1 ventilation during exercise. Note, however, that the FEV are normal, one may still test for a broncho- 1% MVV maneuver does not mimic the true respiratory dilator response in patients for whom there is a high pattern during maximal exercise and thus is only clinical suspicion of airflow obstruction because the an estimate of maximal breathing capacity during normal range is defined for a population, not any exercise (see Chapter 7). Airway-obstructed patients one individual. In addition, airflow obstruction may --- PAGE 84 --- 72 Ruppel’s Manual of Pulmonary Function Testing not be reflected in the FEV and FEV . Although Inhaled bronchodilators can be administered by 1 1% any pulmonary function parameter may be mea- a metered-dose inhaler (MDI) or a small-v olume sured before and after bronchodilator therapy, FEV nebulizer. An MDI provides a reproducible means 1 and specific airway resistance or conductance (sRaw, of administering the bronchodilator. Some pa- sGaw) are usually evaluated. tients are unable to coordinate activation of the MDI with slow, deep inspiration. For these pa- Technique tients, the use of an aerosol reservoir, or spacer, may The patient may perform an array of tests, includ- provide a more consistent delivery of medication. ing spirometry, lung volumes, and diffusing capac- If the patient is unfamiliar with the MDI, the tech- ity (Dlco). Lung volumes should be recorded before nologist may need to activate the device (How To … bronchodilator administration. This provides a 2.2). Small-volume, jet-powered nebulizers may be baseline for comparing lung volume changes after used to administer more bronchodilator over a lon- bronchodilator therapy. Even though indices of ger interval. Single-patient-use nebulizers (i.e., dis- flow (FEV , FEF , and sGaw) usually show the posable nebulizers) are preferred and should never 1 25%–75% greatest change, lung volumes and Dlco may also be reused. respond to bronchodilator therapy. β2 -agonist aerosols, such as albuterol, are most Patients referred for spirometry testing should commonly used. Each of these drugs has a rapid on- withhold routine bronchodilator therapy before the set of action, usually within 5 minutes. Maximum procedure (Table 2.3). Some patients may be unable to bronchodilatation usually takes longer. An interval manage their symptoms if bronchodilators are with- of 10 to 15 minutes between administration and held. These patients should be instructed to take their repeat testing is recommended for short-acting bronchodilator medication as needed. In these in- β2 agonists and 30 minutes later for ipratropium stances, the time when the medication was last taken bromide. should be noted. Some patients who use bronchodila- The ATS-ERS guidelines recommend a relatively tors shortly before testing (within 4 hours) still show high dose of bronchodilator be used to ensure significant improvement after a repeated dose. that if a bronchodilator response exists, it will be seen. Thus the recommended dose of albuterol is 400 mcg delivered as four inhalations of 100 mcg TABLE 2.3 each by MDI, separated by 30-second intervals. Medication Withholding Schedule For ipratropium bromide, the recommended dose Medication Time to Withhold is 160 mcg delivered as four inhalations of 40 mcg Short-acting β2 agonist (SABA; 4–6 hours each by MDI. e.g., albuterol or salbutamol) Bronchodilator administration often causes side Long-acting β2 agonist (LABA; 24 hours effects. The most common side effect of β2 -agonist e.g., formoterol or salmeterol use is tachycardia. Increased blood pressure, flush- Ultra-LABA e.g., indacaterol, 36 hours ing, dizziness, or lightheadedness is not unusual. vilanterol, or olodaterol Monitoring of pulse rate and possibly blood pres- Short-acting muscarinic antagonist 12 hours sure may be recommended for susceptible patients. (SAMA; e.g., ipratropium bromide This includes patients with known cardiac arrhyth- Long-acting muscarinic antagonist 36–48 hours mias or elevated blood pressure. Marked changes in (LAMA; e.g., tiotropium, heart rate, rhythm, or blood pressure or symptoms umeclidinium, aclidinium, or such as chest pain indicate a need to stabilize the pa- glycopyrronium) tient. The test should be stopped and the referring Adapted Table 8 from the American Thoracic Society/European physician or laboratory medical director should be Respiratory Society Standardization of Spirometry 2019 Update An notified immediately. Management of the patient’s Official American Thoracic Society and European Respiratory Society symptoms and continuation of testing are the deci- Technical Statement Graham BL, Steenbruggen I, Miller MR et al. Am J Respir Crit Care Med Vol 200, Iss 8, pp e70–e88, Oct 15, 2019. sion of the physician. --- PAGE 85 --- Spirometry • Chapter 2 73 2.2 How To … Use an MDI 1. Shake the MDI; activate once to prime and check contents. If empty, replace. 2. Hold the MDI mouthpiece slightly away from the patient’s open mouth, or use a spacer or holding chamber (preferred method). The latter two should be attached when priming the MDI to eliminate the electrostatic properties of the device. 3. As the patient inspires slowly from the resting expiratory level, activate the MDI. 4. Have the patient continue slowly inhaling to maximal inspiration. 5. Have patient hold the breath for 5 to 10 seconds, followed by a slow exhalation. 6. Repeat inhalations as indicated (see text). Inhalations can be repeated at 30-second intervals. 7. Children may benefit from the use of a holding chamber and take up to 4 breaths after a single actuation of the MDI. Measurements of FEV , FVC, FEF , PEF, 1 25%–75% PF TIP 2.10 and sGaw are commonly made before and after bronchodilator administration. In each case, the Patients who have a reduced FEV 1 /FVC ratio may be candidates for a bronchodilator percentage of change is calculated as follows: study, even if they have taken their own medication within 4 hours. Many patients Postdrug(cid:30)Predrug %Change(cid:31) (cid:29)100, with a history of asthma or COPD may show Predicted value a significant improvement if they have been using their MDI incorrectly (see How To … where: 2.2). Alternatively, some patients may have a bronchodilator response even with a normal Postdrug = test parameter after administration baseline FEV or FEV /FVC ratio. Predrug = test parameter before administration 1 1 Predicted Value = GLI predicted value If the test value improves, the percentage of change will be positive. If the parameter worsens, Significance and Pathophysiology a negative percentage results. Small prebronchodi- See Interpretive Strategies 2.6. Reversibility of air- lator values (e.g., an FEV of 0.5 L) may show large way obstruction is considered significant for in- 1 changes even though the improvement is minimal. creases greater than 10% relative to the predicted FEV is the most commonly used test for quan- value for FEV or FVC (see Table 2.4). If the sGaw is 1 1 tifying bronchodilator response. If FEF or assessed, an increase of 30% to 40% is usually con- 25%–75% flows such as Vmax are used, they should be sidered significant. Some patients may show little 50 isovolume-corrected for changes in the FVC. If or no improvement in FEV but have a significant 1 FVC increases more than FEV after bronchodi- improvement in sGaw (see Chapter 4). Changes in 1 lator therapy, FEV may actually decrease. FEV FEF of 20% to 30% are sometimes consid- 1% 1% 25%–75% should not be used to judge bronchodilator re- ered significant. However, flows that depend on sponse. sGaw may show a marked increase after the FVC should be volume-corrected (Case Study bronchodilator therapy. Improved conductance 2.2). If not corrected, FEF may appear to de- 25%–75% may occur despite minimal change in FEV or crease, although FEV and FVC improve. Likewise, 1 1 conventional measures of flow. Spirometry or the FEF may appear to increase even though 25%–75% plethysmography after bronchodilator therapy there is no change in FEV . This tends to occur 1 should meet the usual criteria for acceptability when the postbronchodilator FVC falls from the and repeatability (i.e., three acceptable and two baseline value, often as a result of suboptimal tech- repeatable maneuvers). nique or effort. --- PAGE 86 --- 74 Ruppel’s Manual of Pulmonary Function Testing TABLE 2.4 Illustration of Bronchodilator Responsiveness Test Test Predicted Prebronchodilator Postbronchodilator Absolute (%) Change FVC (L) 3.30 2.80 3.25 + 0.45 (14) FEV 1 (L) 2.15 1.82 2.07 + 0.25 (12) FEV, Forced expiratory volume in the first second; FVC, forced vital capacity. 1 Diseases involving the bronchial smooth mus- sponse to another. The efficacy of a specific drug cle usually improve most from “before” to “after.” may require repeat testing after a trial on the medi- Increases greater than 50% in the FEV may occur in cation. Long-acting bronchodilators or inhaled cor- 1 patients with a clinical history of asthma. Patients ticosteroids may significantly improve a patient’s with chronic obstructive diseases may show little lung function, even if there is no acute response to improvement in flows. Poor bronchodilator re- an inhaled β2 agonist. sponse may be related to inadequate deposition of Some patients show a paradoxical response the inhaled drug because of poor inspiratory effort. to bronchodilator therapy. In these individuals, Failure to show a significant improvement after flows may actually decrease after the bronchodila- inhaled bronchodilator therapy does not exclude a tor therapy. Decreased flows after bronchodilator clinical trial. This is especially true if only the FEV therapy may also be related to fatigue from multi- 1 is being monitored. Changes in lung volumes, in ple FVC e fforts. Changes of less than 8% is within particular, may occur without substantial change the variability of measurement of FEV . Such small 1 in FEV , but this may not be evident during spirom- changes may occur just with testing and are un- 1 etry. Such changes may still result in significant likely to be significant. symptomatic improvement. Some patients have a significant response to one drug but little or no re- SUMMARY • The chapter describes spirometry—the most com- monly performed pulmonary function study. INTERPRETIVE STRATEGIES 2.6 • Various spirometry tests are identified. Bronchodilator Responsiveness Techniques for performing the tests and criteria Testing for acceptability are enumerated. 1. Are the prebronchodilator and • Simple spirometry, F-V loops, and bronchodila- postbronchodilator measurements tor studies are discussed. acceptable? Repeatable within 150 mL? If not, • Differentiation between obstructive and restric- postbronchodilator changes may be erroneous. tive disorders is made by explaining the patho- 2. Is there greater than 10% improvement in the percent predicted value for FEV and FVC? physiologies involved. 1 3. No significant improvement observed? • Other tests of respiratory mechanics related to Trial of bronchodilator therapy still may be airflow are discussed in related chapters (e.g., recommended, if clinically indicated. Chapters 4, 8, and 9). --- PAGE 87 --- Spirometry • Chapter 2 75 CASE STUDIES CASE 2.1 HISTORY There is no history of exposure to environmental The subject is a 21-year-old Caucasian male pollutants. in good health who plays college football. His chief complaint is shortness of breath after wind PULMONARY FUNCTION TESTING sprints and similar vigorous exercises. He denies Personal Data any other symptoms, including cough or sputum production. He has never smoked. His grandfather Sex: Male had lung problems, but there is no other history Age: 21 yr of pulmonary disease involving the family. He Height: 73 in. (185 cm) states that his brothers and sisters have hay fever. Weight: 180 lb (81.6 kg) Spirometry Predrug Pred LLN %Pred Postdrug %Pred %Change FVC (L) 6.85 6.08 4.93 113 6.73 111 − 2 FEV (L) 4.65 5.10 4.14 0.91 5.45 107 16 1 FEV /FVC 0.70 0.85 0.74 — 0.81 — 1 Pred, Predicted value. Reference set = GLI 2012. Technologist’s Comments Cause of Symptoms All FVC efforts were performed acceptably. All tests This subject has normal or slightly above-average values met ATS-ERS criteria. for most of his lung function parameters. The exception is his FEV/FVC which is below the expected value 1 , Interpretation and consistent with borderline obstruction. Simply All spirometry efforts before and after evaluating FVC and FEV compared with predicted 1 bronchodilator therapy were performed acceptably. values might give the impression that he is normal. Spirometry results are within normal limits except The FEV/FVC indicates that the subject, whose FVC is 1 for a decrease in the FEV 1% . There is a significant slightly larger than normal, expired a disproportionately increase in the FEV 1 after the administration of the small FEV 1 . This pattern of supranormal volumes with bronchodilator. lower-than-normal FEV/FVC is sometimes seen in 1 Impression: Borderline obstruction with significant healthy young adults. There is a 16% increase (0.8 L) response to a bronchodilator. Evaluation for exercise- in FEV after the administration of a bronchodilator 1 induced bronchospasm may be indicated. (see Spirometry results table % change column). This --- PAGE 88 --- 76 Ruppel’s Manual of Pulmonary Function Testing response is significant, in view of the subject’s complaint of shortness of breath after exercise. He appears to have FEV 1 reversible airway obstruction triggered by exercise. Pre Other Tests Further evaluation of the subject included an exercise Post test to demonstrate exercise-induced bronchospasm Pred (EIB). He jogged for 6 minutes on a treadmill at 85% of his predicted maximal heart rate. Upon completing the exercise, the subject’s FEV began to decrease. Five minutes 1 after stopping the test, his FEV decreased to 3.81 L, a 1 fall of 18% from the baseline value of 4.65 L. This extent of change (10% or greater fall in FEV) after exercise is 1 diagnostic of exercise-induced bronchospasm. Scattered wheezes were heard on auscultation. The obstruction was readily reversed by an inhaled bronchodilator. Inhalation- F-V curves are superimposed at TLC; challenge testing was deferred because the obstructive FEV 1 shows marked increase. defect was obvious after the exercise test. Treatment The subject was given a regimen of inhaled short-acting β2 agonist. He was given a portable peak flow meter to monitor his lung function. He reported a marked Volume (L) decrease in symptoms by pretreating himself with the inhaled medication 15 minutes before athletic activities. )ces/L( wolF 14 12 10 8 6 4 2 0 1 2 3 4 5 6 7 2 4 6 8 10 12 14 CASE STUDY 2.1 Flow-volume loops superimposed at total lung capacity (TLC). CASE 2.2 HISTORY extraordinary exposure to environmental dusts or The subject is a 47-year-old Caucasian carpenter fumes. whose chief complaint is shortness of breath on exertion. His dyspnea, although worse recently, has been present for several years. He smoked 1½ PULMONARY FUNCTION TESTING Personal Data packs of cigarettes per day for 32 years (48 pack- years). He has a cough in the morning. He says that Sex: Male he produces a “small amount of grayish sputum.” Age: 47 yr The subject’s father had tuberculosis. A sister had Height: 70 in. (178 cm) asthma as a child and now as an adult. He denies any Weight: 190 lb (86.4 kg) Spirometry Predrug Pred LLN % Pred Postdrug % Pred % Change FVC (L) 4.01 5.09 4.00 79 4.49 90 9% FEV (L) 2.05 4.03 3.17 51 2.20 6 4% 1 FEV /FVC 0.51 0.74 0.69 — 0.49 — — 1 Pred, predicted value. Reference set = GLI 2012. --- PAGE 89 --- Spirometry • Chapter 2 77 Technologist’s Comments LLN and does increase with bronchodilator but does All tests met ATS-ERS criteria. not meet the criteria for a positive response. FEV does not improve significantly after QUESTIONS 1 bronchodilator therapy. The FEV /FVC actually 1. What is the interpretation of the following? 1 % decreases as a result of the greater increase in FVC. This a. Prebronchodilator spirometry pattern is not unusual in subjects with obstructive airway b. Response to bronchodilator disease. The improvement in FVC makes obstruction with 2. What is the cause of the subject’s symptoms? air trapping the most likely cause of his improvement 3. What other tests might be indicated? after a bronchodilator. The FV curves (Case Study 2.2 4. What treatment might be recommended, based figure) plotted at absolute lung volumes (measured in the on these findings? body box). Improvement in flow is evident by noting the DISCUSSION curves at any particular lung volume. Interpretation All spirometry efforts were acceptable. The subject has Other Tests a reduced FEV , and his FVC was just above the LLN. The lung function of this subject is common in 1 There is only a slight increase in FEV after inhaled emphysema and chronic bronchitis. Air trapping is 1 bronchodilator therapy. FVC does not meet the 10% consistent with emphysematous changes but may increase criteria. also be present in bronchitis and asthma. Further Impression: Moderately severe airway obstruction evaluation of the subject included the measurement without a significant improvement following inhaled of lung volumes, Dlco, and blood gas analysis. The bronchodilator. findings from each of these additional tests were consistent with the results of his spirometry. He had Cause of Symptoms some air trapping (elevated RV/TLC), which would The subject is a smoker who has developed moderately explain the improved FVC after bronchodilator severe airway obstruction. His spirometry results therapy. Blood gases and diffusing capacity were reveal the extent of the obstruction with an FEV that relatively normal, the latter finding making chronic 1 is 50% of predicted. The FVC is also just above the bronchitis, not emphysema, the likely diagnosis. 8 L/sec (Pretreatment ) (Posttreatment ) 6 Note improvement in flow at 4 the midpoint of the predrug loop. 2 0 6 4 2 0 (cid:31)2 (L) (cid:31)4 (cid:31)6 (cid:31)8 CASE STUDY 2.2 Flow-volume loops. --- PAGE 90 --- 78 Ruppel’s Manual of Pulmonary Function Testing Each loop is plotted at the absolute lung volume at to a counselor for smoking cessation and successfully which it was measured. The increase in FEF accurately quit smoking. His cough gradually subsided during a 50% describes the degree of bronchodilator response. 6-month period. He noted a marked improvement in his dyspnea. Treatment A combination of bronchodilators and inhaled steroids was prescribed. The subject was also referred CASE 2.3 HISTORY He claims that gasoline fumes sometimes bring on the The subject is a 27-year-old auto mechanic referred episodes of shortness of breath. to the pulmonary function laboratory by his private physician. His chief complaint is “breathing problems.” He describes breathlessness that occurs suddenly PULMONARY FUNCTION TESTS Personal Data and then subsides. He has no other symptoms and no history of lung disease. None of his immediate Sex: Male family has any lung disease. He has smoked one pack Age: 27 yr of cigarettes per day for the past 10 years (10 pack- Height: 68 in. (173 cm) years). He has no unusual environmental exposure. Weight: 150 lb (68.2 kg) Spirometry Before Drug Predicted LLN % Predicted FVC (L) 3.80 5.15 4.32 74 FEV (L) 3.70 4.13 3.55 90 1 FEV /FVC 0.97 0.80 0.73 — 1 FEF (L/sec) 4.62 4.49 2.94 103 25%–75% FEF (L/sec) 4.81 6.01 — 80 50% FEF (L/sec) 3.12 3.33 — 94 75% MVV (L/min) 77 146 — 53 Reference set = National Health and Nutrition Examination Survey (NHANES) III. Technologist’s Comments DISCUSSION None of the FVC maneuvers was acceptable; they Interpretation did meet the EOFE criteria. The best FVC value was All spirometry maneuvers are unacceptable because of also not repeatable (within 150 mL). In total, eight poor subject effort. The subject’s best effort shows a maneuvers were attempted. The subject had difficulty reduced FVC. The FEV 1 was still usable and is within completing all maneuvers. the normal limits. All other flows and the MVV are within normal limits. QUESTIONS Impression: Spirometry results are inconsistent. The 1. What is the interpretation of the following? FVC and FEV are not repeatable. Overall, inadequate 1 a. Spirometry subject effort or technical errors are present. The FEV 1 b. Variability of the subject’s efforts was deemed “usable” and was within the normal limits. 2. What is the cause of the subject’s symptoms? 3. What other tests might be indicated? Cause of Symptoms 4. What treatment might be recommended, based This test shows poor repeatability, especially for effort- on these findings? dependent measurements. The accompanying figure --- PAGE 91 --- Spirometry • Chapter 2 79 shows the variability for three FVC maneuvers. The at the end of the test data. The poor quality of the tracings show incomplete exhalations and variability. data makes it impossible to determine whether his The low FVC is secondary to not meeting the EOFE symptoms are real. He appears to be malingering— criteria. However, the FEV , determined to be usable, that is, not giving maximal effort on tests that are 1 is within the normal limits. If simple restriction effort dependent. Poor repeatability in a subject who were present, both FVC and FEV should be reduced is free of symptoms at the time of the test suggests 1 similarly. The subject’s other flows are normal. Flows poor effort or lack of cooperation. that depend on the FVC (e.g., the FEF ) might 25%–75% also be in error if the FVC is incorrect. The FEV and Other Tests 1 MVV do not depend on the FVC. The MVV is much Alternative tests for this subject should be independent less than 40 times the FEV , so the MVV is probably of the subject’s effort. A simple blood gas analysis was 1 inaccurate secondary to subject effort. performed. The results indicated normal oxygenation Examination of the volume–time spirograms and acid–base status. Testing of lung volumes and reveals that the subject terminated each FVC maneuver diffusing capacity was postponed because both of after approximately 2 seconds. The FVC values all these depend on subject effort and cooperation. varied by more than 150 mL, confirming poor subject A bronchial challenge test (see Chapter 9) might cooperation. However, a lack of repeatability of the have been indicated because he had asthma-like FVC maneuvers is not sufficient reason for discarding symptoms. However, bronchial challenge tests use the test results. This subject’s FVC maneuvers spirometry, which this subject was unable or unwilling lasted only 2 seconds, despite repeated coaching to perform acceptably. by the operator. The efforts did not meet the EOFE criteria. Failure to exhale completely is one of the Treatment most common errors in spirometry. This error may Before suggesting any treatment, the referring be caused by a lack of cooperation on the part of the physician contacted the subject’s employer to ask subject or the inability to continue exhalation because about possible environmental hazards that might of cough. It may also occur if the technologist does cause the symptoms. He learned that the subject was not adequately explain or demonstrate the maneuver. facing possible termination for excessive absence The operator performing this test repeated the from work. The subject’s supervisor revealed that FVC maneuver eight times. Only the three best efforts the subject claimed to have asthma, which caused his were recorded. Appropriate comments were added excessive absenteeism. None of the efforts shown lasted 6 seconds; all FVC and FEV 1 values vary markedly. Time (sec) )L( emuloV 7 6 5 4 3 2 1 0 0 10 CASE STUDY 2.3 Volume–time graphs showing the lack of reaching a plateau, superimposed at total lung capacity (TLC). --- PAGE 92 --- 80 Ruppel’s Manual of Pulmonary Function Testing SELF-ASSESSMENT QUESTIONS Entry-Level Which of the following is suggested by these 1. A patient performs three FVC maneuvers using values? a spirometer. The spirometer reports that all a. Normal spirometry for an elderly man maneuvers had a back-extrapolated volume b. Obstructive lung disease of less than 5% and 100 mL. The maneuvers c. Restrictive lung disease met all other criteria for acceptability and d. Erroneously measured FEV 1 repeatability. The technologist should do which 4. Which of the following best describes the flow- of the following? volume curve shown? a. Repeat all maneuvers. a. Normal forced expiratory flow pattern b. Correct the FEV and all other flows by the b. Variable intrathoracic obstruction 1 amount of the back-extrapolated volume. c. Variable extrathoracic obstruction c. Perform at least one more maneuver. d. Fixed large airway obstruction d. Report the average of the three FVC values. 2. A 58-year-old man who complains of increased 10 shortness of breath with exercise has the following spirometry results: 8 Measured Predicted LLN % Predicted 6 FVC (L) 5.11 4.93 4.19 104 4 FEV 1 (L) 2.57 3.95 3.38 65 2 These results are consistent with which of the 0 following? −2 a. Normal lung function −4 b. Restrictive lung disease c. Obstructive lung disease −6 d. Incorrect predicted values −8 3. An 81-year-old man performs three acceptable −10 spirometry efforts and records these results: 1 2 3 4 5 Measured Predicted LLN % Predicted Volume (L) FVC (L) 2.17 3.82 3.25 57 FEV (L) 1.71 2.41 2.05 71 1 )ces/L( wolF 6 7 5. A 20-year-old man complains of shortness of breath with exercise. The following results of spirometry are obtained: Measured Predicted LLN % Predicted After Bronchodilator % Change FVC (L) 4.98 5.83 4.96 85 5.98 17 FEV (L) 3.18 4.68 3.98 68 3.50 7 1 Which of the following statements best c. There is moderate obstruction without describes these findings? significant response to bronchodilators. a. Results are of normal spirometry. d. Results are inconsistent and must be b. There is moderate obstruction with repeated. significant response to bronchodilators. --- PAGE 93 --- Spirometry • Chapter 2 81 6. A 33-year-old woman complains of increasing Which of the following is most consistent with shortness of breath with exertion. Her these results? spirometry results are as follows: a. Moderate obstructive lung disease b. Normal spirometry c. Severe lung volume restriction Measured Predicted LLN % Predicted d. Muscle weakness or poor effort FVC (L) 2.25 3.09 2.62 73 7. How long should the pulmonary function FEV 1 (L) 1.84 2.62 2.23 70 operator wait after giving an inhaled β2 agonist PEF (L/s) 2.77 6.17 5.24 45 before conducting postbronchodilator testing? MVV 45 104 — 43 a. 5 min (L/min) b. 15 min c. 30 min d. 45 min 8. A 60-year-old woman complains of increasing shortness of breath with exertion. Her spirometry results are as follows: Trial 1 Trial 2 Trial 3 Best Predicted LLN % Predicted FVC (L) 2.25 2.30 2.28 2.30 2.96 2.23 78 FEV (L) 1.14 1.06 1.12 1.14 2.41 1.86 47 1 BE Vol (L) 0.230 0.145 0.09 Which of the following is most consistent with 10. A healthy, physically fit patient performs these results? spirometry, and the following values are a. Three acceptable and two repeatable recorded: maneuvers Trial 1 Trial 2 Trial 3 Trial 4 b. The need to perform more maneuvers c. Moderate obstructive disease FVC (L) 6.52 6.23 6.17 6.37 d. Severe obstructive lung disease FEV 1 (L) 5.01 5.22 5.13 5.19 Which values of FVC, FEV , and FEV should Advanced 1 1% be reported for this patient? Trial 1 Trial 2 Trial 3 a. FVC = 6.52 L, FEV 1 = 5.22 L, FEV 1% = 80% b. FVC = 6.23 L, FEV = 5.22 L, FEV = 84% FVC (L) 3.01 2.99 3.12 1 1% c. FVC = 6.52 L, FEV = 5.01 L, FEV = 77% FEV (L) 1.99 2.01 1.95 1 1% 1 d. FVC = 6.52 L, FEV = 5.22 L, FEV = 82% 1 1% 11. A patient whose chief complaints are cough 9. A 14-year-old male with cystic fibrosis performs and hoarseness performs a series of FVC three spirometry trials: efforts, and flow-volume curves are recorded The reported flow-volume loop should come as shown. Which of the following diagnoses from which data? seems most likely? a. Trial 1 a. Fixed airway obstruction b. Trial 2 b. Variable intrathoracic obstruction c. Trial 3 c. Variable extrathoracic obstruction d. Average of all three trials d. The patient was malingering --- PAGE 94 --- 82 Ruppel’s Manual of Pulmonary Function Testing Flow 12. A patient performs the following test: Trial 1 Trial 2 Trial 3 Trial 4 FVC (L) 4.50 4.22 4.13 4.30 FEV (L) 3.45 3.15 3.02 2.95 1 The data are consistent with which of the following? Volume a. Acceptable and repeatable spirometry b. FVC-induced bronchospasm c. Poor repeatability d. Muscle weakness Krowka, M. J., Enright, P. L., Rodarte, J. R., et al. (1987). SELECTED BIBLIOGRAPHY Effect of effort on measurement of forced expiratory volume in one second. American Review of Respiratory General References Disease, 136, 829. Ferguson, G. T., Enright, P. L., Buist, S. A., et al. (2000). Leuallen, E. C., & Fowler, W. S. (1955). Maximal Office spirometry for lung health assessment in midexpiratory flow. American Review of Tuberculosis, adults: A consensus statement from the National 72, 783. Lung Health Education Program. Chest, 117, Milanzi1, E. B., Koppelman, G. H., Oldenwening, M., 1146–1161. et al. (2019). Considerations in the use of different West, J. B. (2001). Pulmonary physiology and pathophysiology: spirometers in epidemiological studies. Environmental An integrated, case-based approach. Baltimore, MD: Health, 18, 39. Lippincott Williams & Wilkins. Quanjer, P. H., Stanojevic, S., et al. (2012). Multi- ethnic Reference Values for Spirometry for the Spirometry 3-95 Age Range: The Global Lung Function Balfe, D. L., Lewis, M., & Mohsenifar, Z. (2002). Grading 2012 Equations. European Respiratory Journal, 40, 1324–1343. the severity of obstruction in the presence of a Roberts, S. D., Farber, M. O., Knox, K. D., et al. (2006). restrictive ventilatory defect. Chest, 122, 1365–1369. FEV /FVC ratio of 70% misclassifies patients with Burney, P. G., & Hooper, R. (2011). Forced vital 1 capacity, airway obstruction and survival in a general obstruction at the extremes of age. Chest, 130, 200–206. population sample from the USA. Thorax, 66, 49–54. Stanojevic, S., Wade, A., Stocks, J., et al. (2008). Eaton, T., Withy, S., Garrett, J. E., et al. (1999). Reference ranges for spirometry across all ages. Spirometry in primary care practice: The importance of quality assurance and the impact of spirometry American Journal of Respiratory and Critical Care workshops. Chest, 116, 416–423. Medicine, 177, 253–260. Swanney, M. P., Beckert, L. E., Frampton, C. M., et al. Enright, P. L., Linn, W. S., Avol, E. L., et al. (2000). (2004). Validity of the American Thoracic Society and Quality of spirometry test performance in children other spirometric algorithms using FVC and forced and adolescents: Experience in a large field study. expiratory volume at 6s for predicting a reduced total Chest, 118, 665–671. Hankinson, J. L., Odencrantz, J. R., & Fedan, K. B. lung capacity. Chest, 126, 1861–1866. Townsend, M. C., Hankinson, J. L., Lindesmith, L. A., (1999). Spirometric reference values from a sample et al. (2004). Is my lung function really that good? of the general U.S. population. American Journal of Flow-type spirometer problems that elevate test Respiratory and Critical Care Medicine, 159, 179–187. Hansen, J. E., Sun, X. G., & Wasserman, K. (2006). results. Chest, 125, 1902–1909. Should forced expiratory volume in six seconds Peak Expiratory Flow replace forced vital capacity to detect airway obstruction? European Respiratory Journal, 27, Godfrey, S. (2001). Monitoring asthma severity and 1244–1250. response to treatment. Respiration, 68, 637–648. --- PAGE 95 --- Spirometry • Chapter 2 83 Hankinson, J. L. (2000). Beyond the peak flow Standards and Guidelines meter: Newer technologies for determining and American Thoracic Society/European Respiratory documenting changes in lung function in the Society Technical Standard on Interpretive workplace. Occupational Medicine, 15, 411–420. Strategies for Routine Lung Function Tests (2021) Kennedy, D. T. (1998). Selection of peak flow meters Stanojevic S, Kaminsky DA, Miller M, et al. In press in ambulatory asthma patients: A review of the Eur Respir. literature. Chest, 114, 587–592. American Thoracic Society/European Respiratory Pesola, G. R., O’Donnell, P., Pesola, G. R., Jr., Chinchilli, V. Society Standardization of Spirometry 2019 M., & Saari, A. F. (2009). Peak expiratory flow in normals: Update An Official American Thoracic Society and Comparison of the mini Wright versus spirometric European Respiratory Society Technical Statement predicted peak flows. Journal of Asthma, 46(8), 845. Graham BL, Steenbruggen I, Miller MR et al. Am Wensley, D., & Silverman, M. (2004). Peak flow monitoring J Respir Crit Care Med Vol 200, Iss 8, pp e70–e88, for guided self-management in childhood asthma: Oct 15, 2019. A randomized controlled trial. American Journal of American Thoracic Society/European Respiratory Respiratory and Critical Care Medicine, 170(6), 606. Society Task Force. (2005). Standardization of Lung Function Testing. Number 2: Standardization of Before- and After-Bronchodilator spirometry. European Respiratory Journal, 26, 319–338 Studies (MVV resource). Brocklebank, D., Ram, F., Wright, J., et al. (2001). American Thoracic Society/European Respiratory Comparison of the effectiveness of inhaler devices Society Task Force. (2005c). Standardization of Lung in asthma and chronic obstructive airways disease: A Function Testing. Number 5: Interpretative strategies systematic review of the literature. Health Technology for lung function tests. European Respiratory Journal, Assessment, 5, 1–149. 26, 948–968. Association of Respiratory Technology and Physiology Flow-Volume Curves (ARTP) statement on pulmonary function. testing Hyatt, R. E., & Black, L. F. (1973). The flow volume 2020 Sylvester KP, Clayton N, Cliff N, et al. 2020. curve. American Review of Respiratory Disease, 107, 191. BMJ Open Resp Res 7:e000575. Lunn, W. W., & Sheller, J. R. (1995). Flow volume loops National Asthma Education and Prevention Program. in the evaluation of upper airway obstruction. (2007). Expert Panel Report III: Guidelines for the diagnosis Otolaryngologic Clinics of North America, 28, 721–729. and management of asthma. Bethesda, MD: National Miller, R. D., & Hyatt, R. E. (1973). Evaluation of Heart, Lung, and Blood Institute (NIH publication obstructing lesions of the trachea and larynx by flow no. 08-4051). volume loops. American Review of Respiratory Disease, Spirometry in Occupational Health—2020 = Townsend 108, 475. M. JOEM _ Volume 62, Number 5, May 2020. --- PAGE 96 --- 3 Chapter Diffusing Capacity Tests CHAPTER OUTLINE Carbon Monoxide Diffusing Capacity Significance and Pathophysiology Description Summary Techniques Case Studies LEARNING OBJECTIVES After studying the chapter and reviewing the figures, tables, and case studies, you should be able to do the following: Entry-level 1. Identify the steps for performing the single-breath Dlco. 2. List at least two criteria for an acceptable single-breath Dlco test. 3. Describe why Dlco is often reduced in emphysema. Advanced 1. Describe at least two nonpulmonary causes for reduced Dlco. 2. Explain the significance of a reduced Dl/V A. 3. Compare diffusion limitation caused by membranes and pulmonary capillary blood volume. 4. Explain the significance of the relationship between total lung capacity (TLC) and V . A KEY TERMS alveolar sample Jones and Meade method standard temperature, pressure, alveolar volume Kco dry (STPD) alveolitis membrane resistance three-equation method breath hold Müller maneuver tracer gas classic “discrete sample” systems multigas analysis transfer factor (Tlco; however, will Dl/V A O 2 desaturation be referred to as Dlco) Dlco rapid gas analyzer (RGA) systems Valsalva maneuver intrabreath method rebreathing method washout volume 84 --- PAGE 97 --- Diffusing Capacity Tests • Chapter 3 85 The chapter describes measurement of diffusion Alveolar in the lungs. Diffusing capacity (also referred to as Alveolus basement Interstitial membrane transfer factor) is usually measured using small Alveolar space epithelium concentrations of carbon monoxide (CO) and is Capillary basement referred to as Dlco or Dco. Dlco is used to assess Alveolar membrane the gas-exchange ability of the lungs—specifically, fluid 104 mm Hg oxygenation of mixed venous blood. Various meth- Capillary 40 mm Hg endothelium ods, all of which use CO, have been described. The Diffusion most-used method is the single-breath or breath- of CO 2 Diffusion hold technique. The single-breath method is also of O 2 the most widely standardized. The techniques sec- 40 mm Hg tion focuses on the single-breath method but also 45 mm Hg describes some of the other methods used for spe- Red blood cell cific applications. Capillary Dlco measurements are used in the diagnosis and management of most pulmonary disorders. FIG. 3.1 Diffusing capacity is performed to evaluate the alveo- The importance of standards and guidelines in the lar capillary interface where gas exchange occurs. performance of Dlco tests and in the overall in- terpretation of results is highlighted. Interpretive 1 1 1 = + D strategies are presented in a format like those in DLCO Dm θV C previous chapters. Diffusing capacity can be affected by factors that change the membrane component, as well as by al- CARBON MONOXIDE DIFFUSING terations in Hb and the capillary blood volume. CAPACITY A small amount of CO in inspired gas produces measurable changes in the concentration of inspired Description versus expired gas. Because little or no CO is normally Dlco measures the transfer of a diffusion-limited gas present in pulmonary capillary blood, the pressure (CO) across the alveolocapillary membranes. Dlco is gradient causing diffusion is basically the alveolar reported in milliliters of CO/minute/millimeter of pressure (P Aco). If the partial pressure of CO in the mercury at 0°C, 760 mm Hg, dry (i.e., standard tem- alveoli and the rate of uptake of the gas can be mea- perature, pressure, dry [STPD]). sured, the Dlco of the lung can be determined. There are several methods for determining Dlco (Table 3.1). Techniques All methods are based on the following equation: CO combines with hemoglobin (Hb) approximately V CO 210 times more readily than oxygen (O ). In the pres- DLCO= 2 P ACO–P CCO ence of normal amounts of Hb and normal ventila- tory function, the primary limiting factor to diffusion where: of CO is the status of the alveolocapillary membranes. This process of conductance across the membranes V CO = milliliters of CO transferred/minute (STPD) can be divided into two components: membrane con- P Aco = mean alveolar partial pressure of CO ductance (Dm) and the chemical reaction between P Cco = mean capillary partial pressure of CO, as- sumed to be zero CO and Hb (Fig. 3.1). Dm reflects the process of dif- fusion across the alveolocapillary membrane. Uptake Dlco is expressed in milliliters of gas/minute/unit of CO by Hb depends on the reaction rate (θ) and the of driving pressure at STPD conditions. It can also be pulmonary capillary blood volume (V ). These two expressed in SI units, mmol/min/kPal. The conver- C components occur in series, so the diffusion conduc- sion from Dlco SI units to mm Hg is 2.986. Example tance can be expressed as follows: Dlco 5.2 mmol/min/kPa = 15.5 mL/min/mm Hg. --- PAGE 98 --- 86 Ruppel’s Manual of Pulmonary Function Testing TABLE 3.1 Advantages and Disadvantages of Dlco Testing Methods Method Technique Advantages Disadvantages Applications Dlcosb (breath CO and tracer gas Easy calculations, simple, Sensitive to distribution Screening and hold) analysis relatively fast; highly standardized of ventilation clinical applications simple; 10-sec and automated; minimal and matching; breath hold COHb back-pressure “nonphysiologic”; not effect; also utilized in practical for exercise Dlno technique testing Dlcorb Rapid analysis Less sensitive to V A than Complex calculations Clinical and research (rebreathing) of CO and tracer Dlcosb; less sensitive to (computerized); rapidly applications; gas required; V/Q abnormalities; can responding analyzers provides most rebreathing must be be used to measure Dlno required; sensitive to accurate Dlco controlled COHb back-pressure Dlcoib Rapid analysis Breath holding not Complex calculations Screening and (intrabreath) of CO and required; can be used (computerized); flow clinical applications; tracer gas during during exercise must be controlled; may be useful in single controlled sensitive to uneven; not patients who cannot exhalation standardized hold the breath 1/Dm + 1/θVc Dlcosb repeated at Differentiates membrane Complex calculations; Research with (membrane two different levels transfer resistance from estimates of alveolar limited clinical diffusing capacity) of alveolar Po2 red cell uptake Po2 are critical applications 3.1 How To … Perform a Dlcosb Maneuver 1. Tasks common to all procedures: a. Calibrate and prepare equipment. b. Review order. c. Introduce yourself and identify patient according to institutional policies. d. Describe and demonstrate procedure. 2. Review spirometry data and adjust expired volume criteria if appropriate (V C < 2 L), if using a classic “discrete sample” system. 3. Enter recent Hgb and adjust for COHb if available. 4. Have the subject sit upright with feet flat on the floor and adjust the mouthpiece to the proper height. 5. The mouthpiece should rest on top of the tongue. Have the subject gently bite down with his or her teeth and seal lips firmly around the mouthpiece. Emphasize the need for tight lips without a leak. Place the nose clip securely. 6. Have the subject breathe quietly for several breaths and then empty completely to residual volume (RV; verbal cues such as “keep blowing until empty” are helpful; however, coaching subjects until “they are blue” is not necessary). 7. Once empty, have subject inhale rapidly as much as possible (verbal cues, “up, up, up”) and hold the breath (verbal cues, “keep holding” or “hold it”). Counting down the last few seconds can be extremely helpful. 8. Have subject blow air out until empty or the system terminates the maneuver. 9. A wait period of 4 minutes is required between maneuvers. 10. Perform until acceptability and repeatability criteria are achieved or a maximum of five maneuvers. (See Criteria for Acceptability 3.1.) 11. Note comments related to test quality. --- PAGE 99 --- Diffusing Capacity Tests • Chapter 3 87 Single Breath-Hold Technique (approximately 500 mL or less) or by continually (Modified Krogh’s Technique) aspirating a sample of the exhaled gas. In rapid gas The patient exhales to RV and then inspires a vital analyzer (RGA) systems, which have a 0% to 90% capacity breath (referred to as the IVC or VI) from a response time of ≤ 150 ms, continuous gas analysis system such as that in Fig. 3.2. A special diffusion occurs, and a fixed washout or sample volume is gas mixture is delivered either from a spirometer, not required. a reservoir bag, or by means of a demand valve. Regardless of the specimen technology used, The diffusion mixture usually contains 0.3% CO, the sample is analyzed to obtain the fractional a “tracer” gas, 21% O , and the balance is N . The CO and tracer gas concentrations in alveolar gas, 2 2 tracer gas is usually an insoluble inert gas such F AcoT (where T is the time of the breath hold), and as helium (He), methane (CH 4 ), or neon (Ne). The F A tracer, respectively. The concentration of CO in tracer used depends on the type of analyzer imple- the alveoli at the beginning of the breath hold mented to analyze the exhaled gas. The traditional (F Aco0 ) must be determined as well. It is calculated method uses He (usually about 10%) as the tracer as follows: gas. Rapidly responding infrared analyzers (see F tracer Chapter 11) have been used for continuous analysis F CO =FCO× A A 0 1 Ftracer of the small changes in CO. The same type of infra- 1 red analyzer can use CH as the tracer gas, allowing 4 where: a single analyzer can rapidly detect changes in both CO and the tracer. F Aco0 = fraction of CO in alveolar gas at beginning After inspiring the vital capacity (VC) breath, of breath hold (time = 0) the patient holds the breath at total lung capacity F Ico = fraction of CO in reservoir (usually 0.003) (TLC) for approximately 10 seconds. The patient F A tracer = fraction of tracer in alveolar gas sample then exhales. In a “classic system,” a discrete sample F I tracer = fraction of tracer in inspired gas (varies of alveolar gas is collected after a suitable washout with tracer gas used) volume (750–1000 mL) has been discarded. The The change in tracer gas concentration reflects alveolar sample may be collected in a small bag the dilution of the inspired gas by the gas remain- ing in the lungs (i.e., RV). This change is used to determine the CO concentration at the beginning an H a e l / y C z O ers 0.3% CO of the breath hold before diffusion from the alveoli 10% He into the pulmonary capillaries. The Dlcosb (single Spirometer 21% O2 breath) is then calculated as follows: Balance N2 V ×60 F CO DLCOsb= A ×Ln A 0 End-tidal (P –47)×(T) F CO sampler B A T where: V = alveolar volume, mL (STPD) A Automatic valve 60 = correction from seconds to minutes P = barometric pressure, mm Hg B 47 = water vapor pressure at 37°C, mm Hg FIG. 3.2 Dlco apparatus. Basic equipment for performing a T = breath-hold interval, seconds Dlco test (specifically the Dlcosb). Gas is delivered to the au- tomated valve from either a reservoir bag, spirometer, or a de- Ln = natural logarithm mand valve (not shown). The automated valve allows the patient F Aco0 = fraction of CO in alveolar gas at beginning to inhale the test gas rapidly. A computer usually displays a of breath hold volume– time tracing, along with signals from the gas analyzer(s) (see Figs. 3.3, 3.4, and 3.5). Timing of the maneuver is usually F AcoT = fraction of CO in alveolar gas at end of performed by the computer. breath hold --- PAGE 100 --- 88 Ruppel’s Manual of Pulmonary Function Testing V A may be calculated from the single-breath di- volume (V A ). Kco expressed per mm Hg multiplied lution of the tracer gas: by V A equals Dlco, thus Dlco divided by V A (Dlco/ V A ), is also termed Kco. It is the constant rate slope Ftracer of the CO uptake during the breath-hold time (BHT; V =(V −V )× I ×STPD correction factor A I D F A tracer log [F Aco0 / F AcoT ]/BHT; Fig. 3.4). The misinterpre- tation that Dlco/V A “corrects” Dlco for reduced V A where: is physiologically incorrect because Dlco/V A is not constant as V A changes; thus the term Kco reflects V = volume of test gas inspired, mL (Fig. 3.3) the physiology more appropriately. The American I V = dead space volume (anatomic and instrumen- Thoracic Society–European Respiratory Society D tal), mL (ATS-ERS) Standardized Pulmonary Function F tracer = fraction of tracer in alveolar gas sample A Ftracer = fraction of tracer in inspired gas (depends I on tracer used) Note that the V , usually expressed in body tem- A perature, pressure, and saturation (BTPS) units, must be converted to STPD for the single-breath calculation. The dilution of tracer gas is used twice—to determine the CO concentration at the beginning of the breath hold and to determine the lung volume (i.e., V ) at which the breath hold A occurred. Kco is the rate constant for carbon monoxide up- take from alveolar gas and the “measured” alveolar Inspiration Breath holding Expiration TI TLC Dead space washout Sample collection VI Breath-hold time (Jones) 0.3 TI RV )L( emuloV 0.3 0.1 5 10 6 BHTs 4 5 2 4 3 5 10 Time 2 1 0 0 2 4 6 8 10 Time (sec) FIG. 3.3 Dlcosb maneuver tracing. Tracing of a single-breath Dlco maneuver proceeding from left to right (heavy line). After exhaling to residual volume (RV; 0 L on the volume axis), the patient rapidly inspires a vital capacity breath (V) of the test I gas and then holds the breath at total lung capacity (TLC) for approximately 10 seconds. At the end of the breath hold, the patient exhales rapidly. The dead-space washout volume is dis- carded, and an alveolar gas sample is analyzed. The breath-hold timing method used is Jones and Meade. )%( saG emuloV CH 0.207 4 CO 150 KCO slope Alveolar sample Discard Vol 1.04 Collection Vol 0.79 DLCO 10.6 VA 4.18 85% VC IVC BHTe FIG. 3.4 Dlcosb maneuver using continuous gas analysis. The top graph shows the slope of the constant uptake of CO (Kco) during the breath hold maneuver. Changes in gas concentrations are shown (top). Test gases (CO and CH) rise rapidly to their 4 initial values of 0.3% during the breath hold. During exhalation, both gas concentrations fall as dead space is washed out. The tracer gas, CH, shows a plateau as alveolar gas is exhaled. CO 4 shows a similar pattern, but with a lower concentration because of uptake (diffusion). Gas concentration measurements are made from an alveolar window (gray lines) that can be adjusted. Simultaneous changes in lung volumes are shown on the bottom tracing. IVC indicates inspiratory volume (V). In this test, the I patient failed to inspire at least 85% of the VC (dashed gray line). Breath hold time start (BHTs) and breath hold time end (BHTe) indicate the breath-hold timing scheme. Calculated Dlco and related measurements are displayed, allowing for inspection of changes as the alveolar sample “window” is adjusted.(Courtesy Vyaire, Mettawa IL.) --- PAGE 101 --- Diffusing Capacity Tests • Chapter 3 89 Reporting statement recommends reporting Kco specialized infrared analyzers capable of detecting versus Dlco/V A to avoid any misinterpretation. several gases simultaneously. These systems use A simplification of the single-breath method de- methane (CH ) as a tracer gas. One advantage of 4 scribed earlier is widely used. The tracer gas and CO multigas analysis is that CO and CH are measured 4 analyzers may be calibrated to read full scale (100% rapidly and continuously (see Fig. 3.4) so that the or 1.000) when sampling the diffusion mixture calculated Dlco is available as soon as the exhala- and to read zero when sampling air (no tracer or tion has been completed. Gas chromatography (see CO). If the analyzers have a linear response to each Chapter 11) can also be used for Dlco gas analysis. other, the fractional concentration of the tracer gas Neon is used as the tracer gas (Fig. 3.5). Helium is in the alveolar sample is equal to the F Aco0 . This used as a “carrier” gas for the chromatograph. technique assumes that both the tracer gas and CO The resistance of the breathing circuit should are diluted equally during inspiration. Because no be less than 1.5 cm H O/L/sec, at a flow of 6 L/sec. 2 tracer gas leaves the lung during the breath hold, its This is important in allowing the patient to inspire concentration in the alveolar sample approximates rapidly from RV to TLC. A demand valve may be that of the CO before any diffusion occurred. The used instead of a reservoir bag for the test gas. In exponential rate of CO diffusion from the alveoli a demand-flow system, the maximal inspiratory can then be expressed as follows: pressure to maintain a flow of 6 L/sec should be less than 10 cm H O. Increased resistance, in either 2 F tracer a reservoir or a demand-valve system, may cause the Ln A   F CO  patient to produce large subatmospheric pressures A T during inspiration. This has the effect of increasing where: pulmonary capillary blood volume and may falsely increase Dlco. F tracer = fraction of tracer in alveolar gas, equal A The timing device for the maneuver should be to F Aco0 accurate to within 100 msec over a 10-second in- F AcoT = fraction of CO in alveolar gas at end of terval (1%). Most computerized systems time the breath hold maneuver automatically. However, a means of Ln = natural logarithm of the ratio verifying the accuracy of the BHT should be avail- This technique avoids the necessity of analyz- able. The Jones and Meade method of timing the ing the absolute concentrations of the two gases. breath hold should be used (see Fig. 3.5). The Jones However, it requires that the analyzers be linear with and Meade method measures BHT from 0.3 of the respect to each other. Analysis of CO is often done inspiratory time (i.e., 0.7 of the inspiratory time) to using infrared analyzers (see Chapter 11), and their the midpoint of the alveolar sample collection. output is nonlinear. Care must be taken to ensure Corrections must be made for the patient’s that corrected CO readings are used in the compu- anatomic dead space (V ) and for dead space in D tation. These corrections are easily accomplished the valve (and sample bag, if used). Anatomic V D either electronically or via software in computer- should be calculated as 2.2 mL/kg (1 mL/lb) of ized systems. Systems that use the same detector for ideal body weight. The equipment manufacturer both CO and the tracer gas (e.g., infrared, gas chro- should specify instrument V . Instrument V D D matography) also need to provide linear output. should not exceed 350 mL for adult subjects, in- The linearity of the system should be within 0.5% of cluding mouthpiece and any filters that might be full scale. This means that any drift or nonlinearity used. Smaller-instrument V may be necessary for D should cause no more than a 0.5% error when ana- pediatric patients. Anatomic and instrument V D lyzing a known gas concentration (see Chapter 12). are subtracted from inspired volume (V) before the I Dlco gas analysis is commonly performed with alveolar volume (V A ) is calculated. either a rapidly responding multigas analyzer All gas volumes must be corrected from ambi- or gas chromatography. Multigas analysis uses ent temperature, ambient pressure, and saturated --- PAGE 102 --- 90 Ruppel’s Manual of Pulmonary Function Testing 10 9 8 7 6 5 4 3 2 1 0 0 10 20 30 40 FIG. 3.5 (A) Dlcosb test using gas chromatography. (B) Rapid gas analyzer (RGA). (A) Volume–time tracing with inspiration, breath hold, and alveolar sampling is shown (left graph). In this scheme, inspiration causes a downward deflection. The output of the gas chromatograph is shown (right graph). Neon (the tracer gas, N) and CO show distinct peaks on the gas chromatograph tracing. The alveolar sample is superimposed e over a preanalysis (calibration) curve of the test gas. NeI is the initial tracer concentration, and Ne is the A concentration after the breath hold. CO concentrations of the undiluted test gas (CO) and end of the breath 0 hold (CO T ) are superimposed. Calculated Dlco and related values for multiple efforts are shown at the top. (B) Volume–time tracing with inspiration, breath hold, and alveolar sampling using an RGA. Note that the inspiratory vital capacity (IVC) did not meet the 90% target. The maneuver would still be considered usable if the calculated V is within 200 mL or 5% of the largest V from acceptable maneuvers in the same test session. A A (Courtesy MGC Diagnostics, Inc., St. Paul, MN.) with water vapor (ATPS) to STPD for the Dlco accuracy to be within 2% of expected. Using a 3-L calculations. However, when the V A is used to cal- calibration syringe (with ± 0.5% tolerance), vol- culate the ratio of Dlco to lung volume (Dl/V A ), ume must be between 2.925 and 3.075 L. Volume- it is normally expressed in BTPS units. The new based spirometer systems must also be free from ATS-ERS specifically requires flow and volume leaks. emuloV 10 2.5 8 2.0 6 1.5 4 1.0 2 0.5 Inspiration 0 0.0 10 20 30 40 Breath hold −2 −0.5 A Time (sec) stloV Ne I Ne A CO 0 Alveolar CO T sample 50 60 70 Time (sec) 88% Target 5 15 Time (Sec) )L( emuloV )%( saG 4.0 0.30 3.0 0.25 0.20 2.0 0.15 1.0 0.10 CH4 CO 0.05 Volume 0.0 0.00 0 10 20 --- PAGE 103 --- Diffusing Capacity Tests • Chapter 3 91 Gas analyzers affected by carbon dioxide (CO 2 ) in a lower Dlco. The breath hold should be re- or water vapor require appropriate absorbers. laxed, against either the closed glottis or a closed Absorption of CO is usually accomplished with valve. The patient should avoid excessive positive 2 a chemical absorber using Ba(OH) (baralyme) or intrathoracic pressure (Valsalva maneuver) or ex- 2 NaOH (sodium hydroxide, soda lye). Each of these cessive negative intrathoracic pressure (Müller ma- reactions produces water vapor. Therefore CO neuver). A Valsalva maneuver reduces pulmonary 2 absorbers should be placed upstream of an H O capillary blood volume and may produce a falsely 2 absorber. Anhydrous CaSO 4 is commonly used low Dlco. A Müller maneuver increases pulmonary to remove water vapor. Selectively permeable tub- capillary blood volume and may falsely increase ing (PERMA PURE) can also be used to establish Dlco. Expiration after the breath hold should be a known water vapor content. Gas-conditioning smooth and uninterrupted. Exhalation should devices must be routinely checked to ensure accu- take less than 4 seconds, and alveolar gas sampling rate gas analysis. Chemical absorbers typically add should occur in less than 3 seconds (again because an indicator that changes color as the absorber be- the calculations assume instantaneous emptying comes exhausted. of the lung). Patients who have moderate or severe airway obstruction may have difficulty achieving these criteria. The BHT, measured using the Jones PF TIP 3.1 and Meade method (see Fig. 3.3), should be 10 Watch the patient carefully during the seconds ± 2 seconds. Prolonged inspiratory or ex- Dlcosb effort to detect either a Valsalva or piratory times may result in BHTs greater than 12 Müller maneuver. Widely varying results in two or more Dlco measurements are often seconds. Adjustment of the shutter or valve closure caused by the patient failing to relax during time may be required to have the total BHT within the breath hold. Some pulmonary function the required time window. systems provide a pressure monitor to detect large positive or negative pressures during the breath hold. CRITERIA FOR ACCEPTABILITY 3.1 Dlcosb Dlcosb maneuvers should be performed after 1. System has passed calibration and quality the patient has been seated for at least 5 minutes. control procedures. The patient should refrain from exertion immedi- 2. Inspiration from RV to TLC should be rapid and ately before the test; exercise increases cardiac out- should occur in less than 4 seconds. put, which increases Dlco. The patient should be 3. V I ≥ 90% of largest VC in the same test session instructed about the requirements of the maneuver ● OR V I ≥ 85% of largest VC in the same test session and V within 200 mL or 5% (whichever is greater) and the technique demonstrated. Expiration to RV A of largest VA from other acceptable maneuvers should be of a reasonable duration, usually 6 sec- 4. BHT should be between 8 and 12 seconds, with no onds or less. Patients who have airway obstruction evidence of leaks or of Valsalva or Müller maneuver. may have difficulty exhaling completely in this in- 5. Exhalation should be rapid, with total exhalation lasting 4 seconds or less, with appropriate clearance terval. Inspiration to TLC should be rapid but not of Vd and proper sampling/analysis of alveolar gas. forced. Healthy subjects and patients with airway 6. An interval of at least 4 minutes should elapse obstruction should be able to inspire 90% of their between repeated tests. No more than five largest VC in the same test session or ≥ 85% of the single-breath maneuvers should be performed. largest VC in the same test session and have a V A 7. The V A is consistent with the clinical presentation. In a normal subject, the TLC–V within 200 mL or 5% (whichever is greater) of the A relationship should be remarkably close, if not largest V from other acceptable maneuvers (see A the same, and TLC performed by any method in Criteria for Acceptability 3.1). The single-breath cal- any disease state should be larger than V . A culation assumes instantaneous filling of the lung. 8. The average of two or more acceptable tests should Prolonged inspiratory times will decrease the actual be reported. Duplicate determinations should be within 2 mL/min/mm Hg (0.67 mmol/min/kPa). time of breath holding at TLC, typically resulting --- PAGE 104 --- 92 Ruppel’s Manual of Pulmonary Function Testing because of the effect of increasing carboxyhemoglo- PF TIP 3.2 bin (COHb) from inhalation of the test gas. There One of the most common problems should be a 4-minute delay between repeated ma- encountered when performing the Dlcosb neuvers to allow for washout of the tracer gas from maneuver is a failure of the subjects the lungs. to inspire at least 85% to 90% of their previously measured VC. Careful instruction The ATS-ERS Dlco technical statement de- or reinstruction of the subject usually helps scribes a grading system (Table 3.2) that can be used eliminate the problem, including making sure in assessing the reliability of the results. This sug- the subject expires completely before taking gested grading system has not been validated, so its the maximal inhalation of test gas. Patients utility and impact have yet to be defined. who have airway obstruction may have difficulty inspiring maximally after exhalation to residual volume (RV). Hemoglobin Correction/Adjustment Corrections for abnormal Hb concentrations should be applied with a current Hb value. The pre- To obtain an alveolar sample, dead space gas dicted Dlco should be corrected so that it reflects needs to be washed out (i.e., discarded). A washout of the Dlco at an Hb value of 14.6 g% for adult and 0.75 to 1.0 L is usually sufficient to clear the patient adolescent males and to an Hb value of 13.4 g% for and sampling device dead space. For patients with women and children of either sex younger than small vital capacities (> 2.0 L), the washout volume 15 years of age. The Hb-corrected predicted value may be reduced to 0.5 L. A sample volume of 0.5 to for males may be calculated as follows: 1.0 L should be collected, but a smaller sample may (1.7×Hb) be necessary in patients whose VC is less than 1 L. In DLCO (predicted forHb)=DLCO (predicted)× Dlcosb systems that use RGA technology to analyze 10.22+Hb) expired gas continuously (see Fig. 3.4), inspection of Similarly, Hb correction of the predicted values the washout of the tracer gas may be used to select for women and children younger than 15 years is an appropriate alveolar sample. Rapidly RGAs that calculated as follows: measure the CO and tracer gas simultaneously allow adjustment of washout volume (i.e., dead space) and (1.7×Hb) sample volume after completion of the maneuver. DLCO (predicted forHb)=DLCO (predicted)× (9.38+Hb) These adjustments may be particularly useful in subjects who have small vital capacities (e.g., pediat- Note that this scheme corrects the predicted value ric patients or adults with severe restrictive disease). rather than the patient’s measured value. For example, Such adjustments assume that both the CO and in an adult male patient with an Hb of 9.0 g/dL and tracer gas concentrations reflect changes occurring a predicted Dlco of 25 mL/min/mm Hg, a measured at the mouth. Alveolar sampling may be adjusted to begin at the point where the tracer gas and CO indi- cate an “alveolar plateau” (see Fig. 3.4). In patients TABLE 3.2 who have uneven mixing or emptying of the lungs, Dlco Grading System there may not be a clear demarcation between dead Sample Collection space and alveolar gas. Adjustments to either wash- Grade IVC/VC BHT (seconds) Time (seconds) out (dead space) volume or sample volume should A > 90% 8–12 < 4 be noted on the report. B > 85 8–12 < 4 Two or more acceptable Dlcosb maneuvers (see C > 80 8–12 < 5 Criteria for Acceptability 3.1) should be averaged. Duplicate determinations should be within 2 mL D < 80 < 8 or > 12 < 5 CO/min/mm Hg (0.67 mmol/min/kPa) of each F < 80 < 8 or > 12 > 5 other, obtained from acceptable efforts. No more BHT, Breath-hold time; IVC, inspiratory vital capacity; VC, vital than five repeated maneuvers should be performed capacity. --- PAGE 105 --- Diffusing Capacity Tests • Chapter 3 93 TABLE 3.3 Altitude Correction/Adjustment Patient Results With and Without Dlco varies inversely with changes in alveolar oxy- Hemoglobin Correction gen pressure (Pao2 ). Pao2 changes as a function of Actual Predicted % altitude, as well as with the partial pressure of ox- Dlco mL/min/mm Hg 19.0 25.0 76 ygen in the test gas. Dlco increases approximately 0.35% for each mm Hg decrease in Pao2 , or about D m l L c / o m ( i H n/ b m c m or r H e g cted) 19.0 19.9 95 0.31% for each mm Hg decrease in Pio2 . When test gas mixtures that produce an inspired O pressure 2 of 150 mm Hg (i.e., 21% at sea level) are used, Dlco Dlco of 19 mL/min/mm Hg would be reported as values will be equivalent to those measured at sea shown in Table 3.3. level. Alternatively, standard test gas (Fio2 = 0.21 Both uncorrected and corrected predicted Dlco is typical) can be used and the predicted Dlco cor- values and the resulting percentages should be re- rected by adjusting Pio2 . For a gas with a Pio2 of ported, along with the Hb value used for correction. 150 mm Hg, the equation is as follows: Decreased Hb levels (anemia) will always reduce the predicted value, whereas elevated Hb (polycythe- DLCO predicted for altitude=DLCO predicted/ mia) will increase the predicted value. (1.0+0.0031[Pio −1150]) 2 Carboxyhemoglobin Correction/ where: Adjustment Pio =0.21(P −47) Correction for the presence of COHb in the pa- 2 B tient’s blood is also recommended. The predicted and P is the local barometric pressure (at altitude). Dlco may be adjusted as follows: If the B patient is breathing supplemental O and the 2 DLCO (predicted for COHb)=DLCO (predicted)× Pao2 is measured, the predicted Dlco can be ad- (102%−COHb%) justed, assuming a Pao2 of 100 mm Hg breathing air at sea level: PF TIP 3.3 DLCO predicted Dlco is affected by both Hb and COHb levels DLCO predicted forPAO 2 = (1.0+0.0035[P A −100]) in the patient’s blood. A low Hb (anemia) or high COHb reduces the measured Dlco. where: A high Hb (polycythemia) causes the Dlco to appear elevated. As a “rule of thumb,” Pao2 = measured or estimated alveolar oxygen a 10% COHb will reduce the measured partial pressure Dlco by 10%. Note that corrections for altitude or elevated alveolar oxygen tensions are made to the predicted The COHb% is the fraction of carboxyhemo- Dlco values. globin determined by hemoximetry expressed as Corrections for Hb, COHb, and altitude or ele- a percentage. This method assumes that the pre- vated Pao2 are recommended for all predicted Dlco dicted value already includes 2% COHb in healthy values when the conditions for the corrections are subjects. For subjects who have a COHb% greater known. Hb, COHb, and measured Pao2 may not be than 2%, the predicted value will always be reduced available for all patients; correction for altitude (Pio2 ) using this method. Patients should be asked to re- is easily performed for laboratories significantly frain from smoking for 24 hours before the test to above sea level. Previous guidelines recommended reduce the CO back-pressure in the blood. For pa- that corrections be applied to the patient’s measured tients who continue to smoke, the time of last expo- values rather than to the predicted values. Some lab- sure should be recorded. oratories may prefer to use the older method. --- PAGE 106 --- 94 Ruppel’s Manual of Pulmonary Function Testing In some instances, it may be appropriate to cor- 60 = correction from seconds to minutes rect the Dlco for the lung volume at which it is P B = barometric pressure, mm Hg measured. A common example would be when the 47 = water vapor pressure, mm Hg subject inhales a volume substantially less than his T2 − T1 = rebreathing interval, seconds or her known VC and breath holds at a V that is Ln = natural logarithm A less than expected. The Dlco may be corrected as F AcoT1 = fraction of CO in alveolar gas at beginning follows: of the rebreathing DLCO (atV Am )=DLCO ( atV Ap ) ×    0.58+0.42    V V Am       F Ac t o h T e 2 r = e b fr r a e c a t t i h o i n n g of CO in alveolar gas at the end of   Ap  The rebreathing method can also be imple- where: mented by using an RGA (for CO and tracer gas) and plotting the slope of the change in CO in re- V = measured alveolar volume Am lation to the slope of the tracer gas to estimate the V = predicted alveolar volume (i.e., TLC – V ) Ap D rate of CO uptake. The rebreathing method can be A similar correction can be applied to the Dl/V A : used during exercise. D L(atV )= D L( atV ) ×  0.42+0.58   V Am     V Am V Ap  V  A A   Ap  PF TIP 3.4 The V calculated from the single-breath These corrections are derived from healthy sub- A Dlco technique is essentially a “single- jects whose Dlco was measured at alveolar volumes breath” helium-dilution measurement of lung less than the expected value. Such corrections may volume and should never be larger than TLC not be applicable in all disease states because Dl calculated by any other method. If the V A is larger, there is a technical issue with the and V can be altered independently of one another A measurement of either TLC or Dlco, and the (see the section on Kco). In addition, some subjects results should be questioned. may not exhale completely to RV, with the subse- quent inspiration to TLC producing a V of less I than 85% of their VC. In such an instance, the sub- ject is actually breath holding at TLC, although the Slow Exhalation Single-Breath reduced V suggests otherwise. Intrabreath Method I The patient inspires a VC breath of test gas con- Rebreathing Technique taining 0.3% CO, 0.3% CH (methane), 21% O , and 4 2 The patient rebreathes from a reservoir containing the balance N . Then the patient exhales slowly and 2 a mixture of 0.3% CO, tracer gas, and air (or an O evenly at approximately 0.5 L/sec from TLC to RV. 2 mixture) for 30 to 60 seconds at a rate of approx- A rapidly responding infrared analyzer monitors imately 30 breaths/min. The final CO, tracer, and CO and CH gas concentrations. The exponential 4 O concentrations in the reservoir are measured rate of disappearance of CO can be calculated in 2 after this interval. An equation like that used for a manner similar to the rebreathing method. The the single-breath technique is used (see Criteria for change in V is calculated from the change in the A Acceptability 3.1): concentration of the CH tracer gas. CH is used as 4 4 the tracer gas because it can be rapidly measured us- V ×60 F co  DLCOrb= s ×Ln A T1 ing an infrared analyzer. Multiple estimates of Dlco (P B −47)(T2−T1) F A co T2  can be made during a single exhalation, recording Dlco as a function of lung volume. This is done us- where: ing an equation like that used for the single-breath V = volume of lung reservoir system (initial volume method. Instead of one estimate of V (equal to the S A × F I tracer/F A tracer) lung volume at breath hold), multiple increments --- PAGE 107 --- Diffusing Capacity Tests • Chapter 3 95 of V A are made, and Dlco is plotted against lung of the alveolocapillary membrane. Because NO volume. A single estimate of overall Dlco can also combines with Hb approximately 1500 times faster be obtained. The intrabreath method can also be than CO, the rate of NO uptake by the blood (θNO ) used during exercise. is large, although not infinite as previously under- stood. Therefore Dlno reflects the membrane re- Membrane Diffusion Coefficient and sistance to gas diffusion in the lungs. Dlno can be Capillary Blood Volume measured with either a single-breath or rebreathing The patient performs two Dlcosb tests, each at a technique. A small amount of NO is added to the different level of alveolar Po2 . The first Dlcosb diffusion mixture, and the uptake is measured us- test is performed as described previously. The pa- ing a chemiluminescence analyzer (see Chapter 11). tient then breathes an elevated concentration of O 2 The ATS-ERS technical standard for the Dlno will (balance N ) for approximately 5 minutes, exhales not be review in this chapter. 2 to RV, and performs the second Dlcosb maneuver. Dlco values are calculated for both the air- and Significance and Pathophysiology oxygen-breathing maneuvers. The total resistance See Interpretive Strategies 3.1. The average Dlco caused by the alveolocapillary membrane (Dm) and value for resting adult patients by the single-breath the resistance caused by the rate of chemical combi- method is approximately 25 mL CO/min/mm Hg nation with Hb and transfer into the red blood cell (STPD), with significant variability. Women have (θV C ) are calculated as follows: slightly lower normal values, presumably because of smaller normal lung volumes. The expected 1 1 1 = + Dlco value in a healthy patient varies directly with DLCO Dm θV C the patient’s lung volume. In some instances, it where: may be appropriate to adjust the predicted Dlco to account for decreased lung volume (see the sec- 1/Dlco = reciprocal of diffusing capacity or tion Techniques in this chapter). Dlco values can resistance increase two to three times in healthy individuals 1/Dm = alveolocapillary membrane resistance during exercise in response to increased pulmonary 1/ θV C = resistance of red blood cell membrane and capillary blood flow. rate of reaction with Hb Most reference equations use age, height, sex, θ = transfer rate of CO/milliliter of capillary blood and race to predict Dlco. Some reference equations V = capillary blood volume C use body surface area (BSA) to calculate expected Because CO and O compete for binding sites values. If the patient’s weight is used (i.e., to calcu- 2 on Hb, measurement of diffusion of CO at differ- late BSA), the ideal body weight is recommended. ent levels of alveolar Po2 can be used to distinguish Using the actual body weight in obese patients can resistance caused by the alveolocapillary mem- result in erroneously large predicted values unless brane from resistance caused by the red blood cell similar subjects are included in the reference popu- membrane and Hb reaction rate. V is presumed lation. Significant differences exist among reference C to remain the same for both tests, but θ varies in equations. These discrepancies result, in part, from response to changes in Po2 . Resistance caused by different methods used to measure Dlco in various the alveolocapillary membrane (1/Dm) can be cal- laboratories. Laboratories should check the ap- culated by plotting θ at two points against 1/Dlco propriateness of their reference equations by com- and extrapolating back to zero (as if no O were paring the results obtained from healthy subjects. 2 present). They should measure Dlco in a sample of healthy The membrane component of resistance to gas patients of each sex and compare the results using transfer can also be estimated by measuring the several reference equations. If the reference equa- rate of uptake of nitric oxide (NO). Dlno has been tions used are appropriate, the differences between suggested as a direct measure of the conductance the measured and expected values (i.e., residuals) for --- PAGE 108 --- 96 Ruppel’s Manual of Pulmonary Function Testing the healthy patients should be minimal. Predicted are also commonly associated with a reduction in values for Dlco and for Dl/V A should be taken Dlco. Inhalation of toxic gases or organic agents from the same reference set. Regression equations may cause inflammation of the alveoli (alveolitis) for the calculation of expected Dlco values are in- and decrease Dlco. These disease states are some- cluded in Chapter 13. times categorized as diffusion defects. The decrease in Dlco is probably more closely related to the loss of lung volume, alveolar surface area, or capillary INTERPRETIVE STRATEGIES 3.1 bed than to the thickening of the alveolocapillary Dlco membranes. Dlco also decreases when there is loss of lung tissue or replacement of normal paren- 1. Were the test maneuvers performed acceptably? Were the tests repeatable within 2 mL/min/mm chyma by space-occupying lesions such as tumors. Hg of each? Dlco may also be reduced in the presence of pul- 2. Were all appropriate corrections made to the monary edema. Disruption of alveolar ventilation, predicted values? Hb? COHb? Altitude? V ? A reduction of lung volume, and congestion of the 3. Are the reference values appropriate? Age? Height? Sex? (ATS-ERS guidelines recommend alveoli cause the reduction in Dlco in edema. In the Global Lung Initiative [GLI] standards.) early stages of congestive heart failure (CHF), Dlco 4. Is Dlco less than the lower limit of normal may be normal or slightly increased. As the left ven- (LLN) after appropriate corrections? If so, a gas tricle decompensates, pulmonary vessels become exchange abnormality likely exists. engorged. The increased blood volume can cause 5. Is the Kco within normal limits? If so, the reduced diffusing capacity is likely related to Dlco to increase until the congestion becomes ad- parenchymal changes, pulmonary vascular vanced. In most patients with heart failure, Dlco disease, or pulmonary hypertension. Consider is decreased because of the restrictive ventilatory clinical correlation (e.g., patient’s history, pattern. Dlco in patients who receive a heart trans- presentation, symptoms). plant for CHF does not return to normal, as might 6. Is the Kco reduced? If so, reduced diffusing be expected. capacity is likely related to airway obstruction (uneven distribution of ventilation, V/Q Dlco may also be decreased as a result of med- mismatch) or increased dead space. Compare V ical or surgical intervention for cardiopulmonary A and TLC; a large difference suggests an uneven disease. Lung resection for cancer or other reasons distribution of ventilation. Look for a clinical typically results in decreased Dlco. The extent of re- correlation. duction is usually directly proportional to the vol- 7. Is the Dlco increased after correction for Hb or altitude? If so, consider possible causes ume of lung removed. An exception to this pattern of increased pulmonary blood volume, occurs in lung volume reduction surgery (LVRS) hemorrhage, obesity, or left-to-right shunts. Also and in bullectomy. These surgical procedures typ- consider undiagnosed asthma. Look for clinical ically resect areas of the lung that have little or correlation. no blood flow. Lack of perfusion is documented 8. Is Dlco less than 60% of predicted? If so, consider additional tests (blood gases, exercise by a lung scan. Excision of tissue in such areas re- desaturation study). duces lung volume without necessarily reducing the surface area available for diffusion. Improved ventilation- perfusion matching in the remaining Dlco is often decreased in restrictive lung dis- lung often results in an improvement in Dlco. eases, particularly those associated with pulmonary Radiation therapy that involves the lungs usually fibrosis. Fibrotic changes in the lung parenchyma causes a decrease in Dlco. Radiation causes pneu- are associated with asbestosis, berylliosis, and sil- monitis that commonly results in fibrotic changes. icosis. Many other diseases caused by inhalation Drugs used in chemotherapy (e.g., bleomycin) and of dusts also result in fibrotic changes in lung tis- those used to suppress rejection in organ trans- sue. Idiopathic pulmonary fibrosis, sarcoidosis, plantation may cause reductions in Dlco. These systemic lupus erythematosus, and scleroderma drugs appear to directly affect the alveolocapillary --- PAGE 109 --- Diffusing Capacity Tests • Chapter 3 97 membranes. Some drugs used in the treatment of area, less gas can be transferred per minute even if cardiac arrhythmias (e.g., amiodarone) have been the remaining gas exchange units are structurally shown to decrease Dlco. For this reason, Dlco is normal. In addition to a loss of surface area for gas commonly used to monitor drug toxicity. exchange, the distance from the terminal bronchi- Dlco may also be helpful in evaluating disor- ole to the alveolocapillary membrane increases in ders, such as hepatopulmonary syndrome, in which emphysema. As alveoli break down, terminal lung gas exchange and pulmonary vascular defects co- units become larger. Gas must diffuse farther just exist. Diseases that affect the pulmonary vascular to reach the alveolocapillary surface. There is also bed also typically result in decreased Dlco. These a mismatching of ventilation and pulmonary capil- include pulmonary vasculitis and pulmonary hy- lary blood flow in emphysema. Disruption of alve- pertension. Pulmonary vascular disease often man- olar structures causes loss of support for terminal ifests itself as a reduced diffusing capacity with airways. Airway collapse and gas trapping result otherwise-normal pulmonary function. in ventilation-perfusion (V/Q ) abnormalities Dlco may be decreased in both acute and chronic (Fig. 3.6). obstructive lung disease. Dlco is decreased in em- Other obstructive diseases (e.g., chronic bron- physema for several reasons. Emphysematous lungs chitis, asthma) may not reduce Dlco unless they have a reduced surface area for gas exchange, with result in markedly abnormal V/Q patterns. Dlco the loss of both alveolar walls and their associated is sometimes used to differentiate among these capillary beds. As a result of the decreased surface obstructive patterns. Low Dlco in the presence of Normal Emphysema Anemia O O O 2 2 2 Red blood cell A B C Pulmonary emboli Volume loss (blood clot) Fibrosis/pneumonitis pneumonectomy/atelectasis O 2 O 2 O 2 D E F FIG. 3.6 Dlco and disease. Some of the more common disease disorders that affect gas exchange. (A) Depicts the normal alveolar capillary interface where gas exchange occurs. (B) Emphysema—destruction of the alveolar capillary interface and hyperinflation. (C) Anemia—reduction in oxygen-carrying capacity. (D) Pulmonary emboli and/or atrioventricular malformations affect oxygen transport. (E) Interstitial lung disease such as pulmonary fibrosis scars the alveolar membrane surface. (F) Alveolar volume loss from resection, alveolar collapse, or filling processes. --- PAGE 110 --- 98 Ruppel’s Manual of Pulmonary Function Testing obstruction is sometimes assumed to be evidence distribution of ventilation rather than loss of lung of emphysema. However, V/Q mismatching can volume. cause Dlco to appear to be decreased in asthma, In the presence of pulmonary disease, both chronic bronchitis, or emphysema. Some patients Dlco and V A may be affected. Dlco goes down as with asthma may have an increased Dlco, but the the lung empties but does so in a nonlinear fash- cause is not completely understood. ion. In obstruction, low Dlco without reduction in Dlco measurements at rest have been suggested V A results in a low ratio. In a purely restrictive pro- to estimate the probability of O2 desaturation cess, a decrease in Dlco reflects a loss of V A , and the during exercise. A large retrospective study demon- Kco is preserved. For example, a patient who has a strated that a Dlco of less than 60% correlated with Dlco of 12 mL CO/min/mm Hg (50% of predicted) O 2 desaturation during exercise (75% sensitivity and a V A of 3.0 L would have a Kco of 4. This re- and specificity). Patients with restrictive lung dis- duction in Dlco is roughly proportional to a loss ease and a low resting Dlco are at risk of O 2 desat- of lung volume. Some pulmonary conditions (e.g., uration even with low levels of exercise. Low resting pneumonectomy) may result in an increased Kco, Dlco may indicate the need for assessment of oxy- where gas exchange is preserved and lung volume genation during exercise. is decreased. Dlco is directly related to lung volume (V A ) in Dlco and Kco may also be affected if the pa- healthy individuals. The Dl/V A (also termed KCO) tient performs the breath-hold maneuver at a lung may be multiplied by the lung volume at which the volume of less than TLC. The predicted Dlco may measurement was obtained to express Dlco. This be corrected for the reduced V A as described pre- calculation is simple because V must be measured viously. There are important implications for the A to derive Dlco (see Fig. 3.5). In healthy subjects, and interpretation of diffusing capacity in the complex even in those with mild to moderate restriction, V A relationship between Dlco and Kco. Patients who approximates the TLC minus the assumed dead fail to inspire fully during the maneuver will have space (V D ). Analysis of this relationship can be use- a decreased Dlco, but the Kco may appear to in- ful to differentiate whether decreased Dlco is the crease. Correcting for V A does not correct for poor result of loss of lung volume (as in restriction) or inspiratory effort (< 85% of VC). In patients who from some other cause. In healthy individuals, al- have a low Dlco, a “normal” Kco should not be con- veolar volume and Dlco are proportional to body fused with normal gas exchange. size (height). Two patients of different heights will The Dlcosb is the most widely used method have different Dlco and V A values, but their Kco because it is relatively simple to perform, is nonin- values will be similar. In healthy adults, Kco is ap- vasive, and is more standardized than other meth- proximately 4 to 5 mL CO transferred/minute/liter ods. The rapidity with which repeated maneuvers of lung volume. can be performed also lends to its popularity. Most V A is measured by the dilution of the tracer gas automated systems use the Dlcosb, contributing a used (in the Dlcosb) and reflects the same volume certain degree of standardization to the methodol- into which CO is distributed and diffuses across ogy. Large differences in reported Dlco values exist the pulmonary capillary membranes. Mismatching among laboratories. This variability has been at- of ventilation and blood flow (as in obstructive tributed to different testing techniques, problems disease) can cause a significant portion of the lung in the gas analysis involved in the test, and differ- to not participate in gas exchange. This is usually ences in computations. Breath holding at TLC is characterized by a difference between the V mea- not a physiologic maneuver. This and the fact that A sured during the Dlco maneuver and the TLC mea- Dlco varies with lung volume cause some concerns sured by plethysmography or multiple-breath gas about Dlcosb as an accurate description of diffus- dilution. When the Dlco is reduced but the Kco ing capacity. Dlcosb is not practical for use during is normal or near normal, the decrement in gas ex- exercise. Some patients have difficulty expiring change can be assumed to be caused by an uneven fully, inspiring fully, or holding their breath. The --- PAGE 111 --- Diffusing Capacity Tests • Chapter 3 99 BOX 3.1 DlcoSB RECOMMENDATIONS A. Equipment 1. Volume accuracy same as for spirometry: ± 2.5% over 8-L range, all gases and flow conditions (includes syringe accuracy of 0.5%); checked daily. 2. Documented analyzer linearity from 0 to full span ± 0.5% with minimal drift over test interval; checked quarterly. 3. Circuit resistance less than 1.5 cm H O at 6 L/sec. 2 4. Demand valve sensitivity less than 10 cm H O to generate 6-L/sec flow. 2 5. Timing mechanism accurate to ± 1% over 10 sec; checked quarterly. 6. Instrument dead space (e.g., valves, filters) less than 0.200 L. 7. Perform a 3-L syringe Dlco weekly in patient testing mode 8. Perform a calibration syringe leak check monthly. 9. Validate system weekly by testing healthy nonsmokers (biologic controls; see Chapter 12). B. Patient preparation 1. The patient should be instructed to refrain from smoking on the day of the test; time of last cigarette should be noted. 2. Patient should be seated for Dlco maneuver. 3. Patients on supplemental O should be switched to breathing air for 10 minutes before testing, if clinically 2 acceptable. 4. The patient should be carefully instructed, and the procedure demonstrated. C. Technique (see How To ... Box 3.1) D. Calculations 1. Average at least two acceptable tests; duplicate determinations should be within 2 mL/min/mm Hg. 2. Use Jones and Meade method of timing the breath hold. 3. Alveolar volume should be determined by single-breath dilution of tracer gas. 4. Adjust for V volumes (instrument and patient). D 5. Determine inspired gas conditions (ATPS or ATPD). 6. Correct for CO and H O absorption. 2 2 7. Report Kco in mLCO (STPD)/min/mm Hg per L (BTPS). 8. Correct predicted value for Hb, COHb, and altitude (Pio2 ). 9. Consider adjusting predicted value for submaximal inspiration. 10. Use reference equations appropriate to the laboratory method and patient population (ATS-ERS guidelines recommend GLI as the preferred reference set). ATPD, ambient temperature, pressure, dry; ATPS, ambient temperature, pressure, and saturated with water vapor; ATS-ERS, American Thoracic Society–European Respiratory Society; BTPS, body temperature, pressure, and saturation; GLI, Global Lung Initiative; STPD, stan- dard temperature, pressure, dry. Adapted from 2017 ATS-ERS standards for single-breath carbon monoxide uptake in the lung. ATS-ERS guidelines aim to improve the standard- controlled. An additional advantage is that acet- ization of the single-breath maneuver (Box 3.1). ylene can be added to the diffusion mixture to The rebreathing method (Dlcorb) requires measure cardiac output simultaneously. Adding a somewhat complicated calculations but offers the small amount of nitric oxide (NO) to the diffusion advantages of a normal breathing pattern without mixture allows the Dlno to be measured during re- arterial puncture. Dlcorb is less sensitive to V/Q breathing as well. abnormalities and uneven ventilation distribution Measurement of Dlco by the intrabreath method than the Dlcosb. The rebreathing method is sensi- (Dlcoib) offers the advantage of not requiring a tive to the accumulation of COHb in the capillary breath hold at TLC. However, the patient must in- blood and the resultant back-pressure. Capillary spire a large enough volume of test gas so that the Pco is routinely assumed to be zero. The actual al- subsequent exhalation will clear the instrument veolocapillary CO gradient at the time of testing and anatomic V . In addition, the single-breath ex- D can be estimated, although with some difficulty. halation must be slow and even. In some systems, a The rebreathing method can be used during exer- flow restrictor may be necessary to limit expiratory cise, provided the rebreathing interval is carefully flow. The single-breath slow-exhalation method --- PAGE 112 --- 100 Ruppel’s Manual of Pulmonary Function Testing produces values similar to those obtained by the to equal the alveolar pressure of CO. In healthy breath-hold method in healthy patients when flow nonsmoking patients, little CO (usually < 2% is maintained at 0.5 L/sec. Uneven distribution of COHb) is present in pulmonary capillary blood. ventilation may produce intrabreath Dlco values When there is carboxyhemoglobinemia, dif- that are artificially elevated. Because the evenness fusion of CO is reduced because the gradient of ventilation distribution can be assessed from the across the membrane is reduced. COHb also washout of CH 4 , unacceptable Dlco values can be shifts the oxyhemoglobin dissociation curve, detected. Table 3.1 compares some advantages and further altering gas transfer. Each 1% increase in disadvantages of Dlco testing methods. COHb causes an approximate 1% decrease in the Measurement of membrane (Dm) and red blood measured Dlco. CO back-pressure corrections cell components (θV c ) of diffusion resistance in can also be made by estimating the partial pres- healthy patients reveals that each factor accounts sure of CO in the pulmonary capillaries. This for approximately half of the total resistance to gas pressure can be used to correct the F Aco0 and the exchange across the alveolocapillary membranes. F AcoT . More commonly, however, the predicted Difficulty in quantifying the partial pressure of O 2 Dlco is corrected for the presence of COHb in in the lungs (pulmonary capillaries) restricts the use excess of 2% (see the section Techniques in this of the membrane-diffusing capacity determination. chapter). Because the uptake of NO is limited almost entirely 3. Alveolar Pco2. Increased Pco2 elevates Dlco be- by the pulmonary capillary membranes, Dlno can cause the alveolar Po2 is necessarily decreased. be measured to assess membrane resistance. Significant increases in alveolar Pco2 (i.e., mod- Numerous other physiologic factors can influ- erate to severe hypoventilation) reduce the alveo- ence the observed Dlco: lar Po2 . 1. Hemoglobin and hematocrit (Hct). Decreased Hb 4. Pulmonary capillary blood volume. Increased blood or Hct reduces Dlco, whereas increased Hb and volume in the lungs (V C ) causes increased Dlco. Hct elevate Dlco. Dlco may be corrected if the Increases in pulmonary capillary blood volume patient’s Hb is known. CO uptake varies approx- may result from increased cardiac output as oc- imately 7% for each gram of Hb. The predicted curs during exercise. Patients should be seated Dlco may be corrected so that the value reported and resting for several minutes before Dlco test- is compared with a standardized Hb level of ing is performed. Pulmonary hemorrhage and 14.6 g% for men and 13.4 g% for women and chil- left-to-right shunts may also cause an increase dren younger than 15 years. When this correction in blood volume in the lungs. In each of these is applied, the predicted Dlco will be reduced (and cases, the increase in Dlco is related to the in- the percentage of predicted increased) if the pa- creased volume of Hb available for gas transfer. tient’s Hb is less than the standard value (14.6 g% Excessive negative intrathoracic pressure during or 13.4 g%, respectively). Conversely, the predicted breath holding can increase pulmonary capillary Dlco increases (and the percentage of predicted volume and elevate the Dlco. Conversely, exces- decreases) if the Hb is greater than the standard sive positive intrathoracic pressure (Valsalva ma- value. Both corrected and uncorrected Dlco pre- neuver) can reduce pulmonary blood flow and dicted values should be reported, along with the decrease Dlco. Hb value used for adjustment. Care should be 5. Body position. The supine position increases Dlco. taken to use Hb values representative of the pa- Changes in body position affect the distribution tient’s actual Hb level at the time of the Dlco test. of capillary blood flow. 2. COHb. Increased COHb levels, often found in 6. Altitude above sea level. Dlco varies inversely with smokers, reduce Dlco. Smokers may have COHb changes in alveolar oxygen pressure (Pao2 ). At al- levels of 10% or greater, causing significant CO titudes significantly greater than sea level, Dlco back-pressure. The diffusion gradient for CO increases unless corrections are made (see the across alveolocapillary membranes is assumed section Techniques in this chapter). --- PAGE 113 --- Diffusing Capacity Tests • Chapter 3 101 7. Asthma and obesity. Asthma and obesity have been 2. Epidemiology Standardization Project (ESP) method: associated with an elevated Dlco in some stud- From the midpoint of inspiration (half of the V I ) ies. Increased pulmonary capillary blood volume to the beginning of alveolar sampling. may explain these observations, but the exact 3. Ogilvie method: From the beginning of inspiration physiology is unclear. (V) to the beginning of alveolar sampling. I Several additional technical considerations Theoretically, BHT is considered the time during may affect the measurement of Dlco (particu- which diffusion occurs. That is, the Dlco equa- larly Dlcosb). V A is calculated from the dilution tion assumes that the entire breath hold is at TLC. of a tracer gas during the single-breath maneuver. However, because some gas transfer takes place This technique typically underestimates lung vol- during inspiration and expiration, Dlco will be in- ume in patients who have moderate or severe ob- fluenced by the proportion of time spent in these struction. A low estimated V A results in low Dlco two phases. A three-equation method has been values. Some clinicians prefer to use a separately proposed that uses separate equations for the three determined lung volume to estimate V . RV, mea- phases of the maneuver (i.e., inspiration, breath hold, A sured independently by plethysmography or one expiration). This method has not been widely used, of the gas-dilution techniques, can be added to however. The timing method might become signifi- the inspired volume (V) to derive V . The V calcu- cant if the reference values used for comparison were I A A lated by this method is usually larger in patients generated by one of the other methods. The Jones with airway obstruction than the V calculated and Meade method is the method recommended by A from the single- breath dilution method. The re- the ATS-ERS guidelines (see Box 3.1). Rapid inspi- sulting estimate of Dlco is larger. The Dlco cal- ration from RV to TLC and rapid expiration to the culation, however, is based on the volume of gas alveolar sampling phase reduce differences resulting into which both the inspired CO and tracer gas from the timing methods (see Box 3.1). Conversely, are distributed but not the lung volume, in which patients who display prolonged inspiratory or expi- gas mixing is minimal. Some laboratories report ratory times may have reduced Dlco values. Dlco values calculated by both methods. The The volume of gas discarded before collect- ATS-ERS guidelines recommend the calculation ing the alveolar sample may affect the measured of V A using the single-breath tracer gas method. Dlco. Most classic discrete sampling systems al- Comparison of the single-breath V measured low the washout volume to be adjusted, with 0.75 A during the Dlco maneuver with lung volumes to 1.0 L most used. Washout volume may need to (i.e., TLC) measured by the standard methods is be reduced to 0.5 L if the patient’s VC is less than often helpful in elucidating the cause for a low 2.0 L. In patients who have obstructive disease, re- Dlco. ducing the washout volume may result in increased A simple method of evaluating the quality of the dead-space gas being added to the alveolar sample. test is to compare the TLC–V relationship; the V Because dead-space gas resembles the diffusion A A should never be larger than the measured TLC, re- mixture, Dlco may be underestimated. gardless of the TLC testing methodology. The alveolar sampling technique also affects RGAs allow for the calculation of anatomic dead Dlco measurement. Alveolar samples should be space using the Fowler technique. This measured collected within 4 seconds, including washout dead space (V ) can then be used in the calculation and alveolar sampling. A sample volume of 0.5 to D of V versus using an estimated V . 1.0 L is recommended. Patients with a small VC A D The method of timing of breath hold also influ- (i.e., < 2.0 L) may require a smaller volume, just as ences the calculation of Dlco (see Fig. 3.3). Most with the washout. When only a small sample is ob- systems measure BHT by one of three methods: tained, the gas may not accurately reflect alveolar 1. Jones and Meade method: Includes 0.7 of the in- concentrations of CO and tracer gas, particularly in spiratory time to the midpoint of the alveolar the presence of V/Q abnormalities. Continuous sample. analysis of the expired air using RGA technology --- PAGE 114 --- 102 Ruppel’s Manual of Pulmonary Function Testing allows identification of alveolar gas. Infrared an- easily to obtain multiple measurements. Many alyzers that can simultaneously analyze the tracer automated Dlcosb systems are common. gas and CO will allow the entire breath to be ana- • The ATS-ERS and others have published stan- lyzed. These instruments permit adjustment of the dardization guidelines for Dlcosb. Careful alveolar sampling window so that a representative attention to these standards can reduce the gas sample can be obtained (see Fig. 3.4). variability in Dlcosb measurements in different laboratories. SUMMARY • Dlco measurements are used diagnostically for a variety of diseases. Because Dlco assesses gas • The chapter addresses the measurement of exchange, it is useful in both obstructive and re- diffusing capacity (Dlco), also referred to as strictive disease patterns. transfer factor (T LCO ). Dlco can be measured by • Dlco measurements may be affected by a variety various techniques, including the single-breath, of factors, such as Hb level, COHb, or altitude. rebreathing, and intrabreath methods. Techniques for correcting Dlco for these factors • The single-breath method, or Dlcosb, is most include adjusting the predicted values used for used. Dlcosb is noninvasive and can be repeated interpretation. CASE STUDIES CASE 3.1 HISTORY β2 agonist but withheld it for 12 hours before the A 55-year-old woman is referred to the pulmonary test. function laboratory because of shortness of breath on exertion. She has a 38-pack-year smoking PULMONARY FUNCTION TESTING Personal Data history but stopped smoking 6 months ago. She Age: 55 still coughs each morning, but her sputum volume Height: 65 in. (165 cm) has decreased since she stopped smoking. She has Weight: 137 lb (62.3 kg) no significant environmental or family history of Race: African American pulmonary disease. She had been using an inhaled Spirometry Prebronchodilator Postbronchodilator Predicted LLN Actual % Predicted Actual % Predicted % Change FVC (L) 2.89 2.16 2.77 96 2.82 98 2 FEV (L) 2.30 1.67 1.91 83 2.01 87 5 1 FEV (%) 80 70 69 71 1% FEF (L/sec) 2.33 0.92 1.44 62 1.51 65 5 25%–75% PEF (L/min) 6.08 4.01 4.01 66 5.13 84 28 FEF, Forced expiratory volume; FEV, forced expiratory volume in the first second; PEF, peak expiratory flow. 1 --- PAGE 115 --- Diffusing Capacity Tests • Chapter 3 103 Lung Volumes change in FEV and FVC. Lung volumes reveal 1 Predicted LLN Actual % Predicted a slightly increased functional residual capacity and moderately increased RV. The RV/TLC ratio TLC (L) 4.39 3.42 4.97 113 is increased, consistent with air trapping. Dlco is FRC (L) 2.45 3.10 127 markedly decreased even after correction for Hb. Kco RV (L) 1.58 2.20 139 is decreased, consistent with an obstructive process. VC (L) 2.89 2.16 2.77 96 Impression: Mild obstruction with minimal IC (L) 1.94 1.87 96 response to bronchodilator; this should not preclude ERV (L) 0.87 0.90 103 a therapeutic trial if clinically indicated. Lung volumes RV/TLC (%) 36 44 suggest air trapping. Dlco is severely decreased, even when corrected for Hb. ERV, Expiratory reserve volume; FRC, fractional reserve capacity. Cause of Symptoms Diffusing Capacity This subject has symptoms characteristic of airway Predicted Actual % Predicted obstruction that has progressed to the point where dyspnea on exertion prompted a visit to the physician. Dlcosb (mL CO/ 19.7 10.0 51 Her obstruction appears mild. Her FEV is still above min/mm Hg) 1 the LLN for her age and height. Her response to Dlcosb corr 18.1 10.0 55 bronchodilator therapy seems to indicate obstruction (mL CO/min/ caused by inflammation rather than reversible mm Hg) bronchospasm. Lung volume testing confirms that V (L) 4.39 3.99 91 A the obstruction appears to have caused some air Kco 4.49 2.51 46 trapping. This pattern is not unusual for subjects with Hb (g/dL) 11.0 chronic bronchitis and emphysema. Her gas exchange, as measured by Dlco, is markedly Technologist’s Comments impaired. Emphysema reduces Dlco by reducing the Spirometry maneuvers met ATS-ERS criteria. Lung alveolocapillary surface area available for diffusion. volumes by body plethysmography were performed Chronic bronchitis can reduce Dlco by causing a acceptably and met ATS-ERS criteria. All Dlco ventilation-perfusion mismatch. The subject may have maneuvers met ATS-ERS criteria (two tests were both disease processes disrupting gas transfer. Her V A averaged). Dlco was corrected for an Hb of 11 g/dL. measured by the single-breath inhalation of tracer gas during the Dlco maneuver is about a liter less than QUESTIONS her TLC measured in the body plethysmograph. This 1. What is the interpretation of the following? discrepancy suggests poor distribution of inspired gas a. Prebronchodilator and postbronchodilator and is typical in subjects with some degree of airway spirometry obstruction. b. Lung volumes Subjects who have reduced Dlco values seldom c. Dlco have normal blood gases. Exertion or exercise often 2. How are the pulmonary function test results aggravates the gas exchange impairment. Many related to the subject’s symptoms? subjects with markedly reduced Dlco (< 50%–60% of 3. What other tests might be indicated? predicted) display exercise desaturation. That is, their 4. What treatment might be recommended based on Pao2 falls to levels of 55 mm Hg or less with exercise. these findings? The decrease in Dlco does not, however, accurately predict the degree of desaturation that will occur. DISCUSSION Interpretation Other Tests All maneuvers were performed acceptably. FVC and An obvious additional test for this subject would FEV are within normal limits, but the FEV is be measuring resting arterial blood gases while she 1 1% below the LLN, consistent with airway obstruction. breathes room air. Resting hypoxemia would explain After inhaled bronchodilator, there is only a minimal dyspnea on exertion. The subject returned to have a --- PAGE 116 --- 104 Ruppel’s Manual of Pulmonary Function Testing blood gas sample drawn. Her Pao2 while breathing Treatment air was 63 mm Hg, with a saturation of 91%. Because Based on the results of the exercise evaluation, this value did not qualify her for supplemental O , an supplemental O was prescribed for the subject 2 2 exercise test was performed with an arterial catheter to use during exertion. Because she showed little in place (see Chapter 7). At a low workload on the response to bronchodilators, her inhaled β2 agonist treadmill, her Pao2 decreased to 51 mm Hg. She was was discontinued. However, a trial of inhaled then retested while breathing O via nasal cannula steroids (beclomethasone) resulted in a noticeable 2 at 1 L/min. She then tolerated more exercise, and her improvement of symptoms. Pao2 never decreased below 68 mm Hg. CASE 3.2 HISTORY prescribed amiodarone. To monitor the effects of this The subject is a 63-year-old woman with a history medication, she was referred for tests before starting of cardiomyopathy, hypertension, and pernicious the drug and again after 3 months of therapy. anemia. She has had episodes of ventricular tachycardia that have been managed by means of an implantable PULMONARY FUNCTION TESTING Personal Data cardiac defibrillator (ICD). She has never smoked and Sex: Female denies cough or sputum production. She experiences Age: 63 shortness of breath with exertion. Her family history Height: 62 in. (157 cm) includes a sister who had asthma and chronic Weight: 131 lb (59.5 kg) bronchitis. She has no history of environmental toxin Race: Caucasian exposure. To manage her arrhythmias, her physician Spirometry Pretreatment 3 Months Predicted LLN Actual % Predicted Actual % Predicted FVC (L) 2.96 2.31 2.50 84 1.97 67 FEV (L) 2.27 1.72 2.09 92 1.81 80 1 FEV (%) 77 68 84 92 1% FEF (L/sec) 2.09 0.94 2.82 135 2.77 133 25%–75% FEF, forced expiratory flow. Lung Volumes (He Dilution) Pretreatment 3 Months Predicted LLN Actual % Predicted Actual % Predicted TLC (L) 4.88 3.66 3.92 87 3.50 78 FRC (L) 2.54 2.26 89 2.23 88 RV (L) 1.71 1.50 87 1.52 89 VC (L) 2.96 2.31 2.42 82 1.97 67 IC (L) 1.94 1.66 85 1.26 65 ERV (L) 0.83 0.76 91 0.71 85 RV/TLC (%) 38 38 44 --- PAGE 117 --- Diffusing Capacity Tests • Chapter 3 105 Diffusing Capacity (Dlcosb) Pretreatment 3 Months Predicted Actual % Predicted Actual % Predicted Dlco (mL/min/mm Hg) 18.0 12.6 69 9.7 54 Dlcosb corr (mL/min/mm Hg) 16.7 12.6 75 9.7 58 V (L) 4.48 3.26 72 3.31 95 A Kco 4.0 3.9 2.9 Hb (g/dL) 13.4 11.3 11.4 Technologist’s Comments history of anemia, her Hb level was checked. The Hb- Pretreatment: Spirometry and lung volumes by He adjusted Dlco was at the LLN (approximately 75% for dilution met ATS-ERS criteria. The inspiratory the reference equation used). Because amiodarone has volume during the Dlco maneuver was less than 85% been shown to cause changes to the lung parenchyma, of the VC. her cardiologist requested pulmonary function 3 Months: Spirometry, lung volumes, and Dlco all studies, including Dlco. met ATS-ERS criteria. On her return visit after 3 months of antiarrhythmic therapy, some significant changes had occurred. As QUESTIONS described in the interpretation of the 3-month follow- 1. What is the interpretation of the following? up, her FVC had decreased slightly. TLC also decreased a. Pretreatment spirometry, lung volumes by a similar volume (400–500 mL). Her other lung b. Dlco before treatment volumes (FRC, RV) remained largely unchanged. c. Dlco after 3 months of treatment These changes suggest that something happened that 2. What is the cause of change in the subject’s Dlco? primarily affected her VC. 3. What technical problems might have affected the The subject’s Dlco showed the greatest decrease interpretation of the Dlco before treatment? during the 3-month period. Her Dlco decreased by approximately 30%. The Hb-corrected percentage of DISCUSSION predicted fell from 75% to 58%. The Kco also decreased Interpretation slightly. The Kco is often preserved when Dlco Pretreatment, FVC is normal, as are FEV and FEV . 1 1% decreases simply because of loss of lung volume. When Lung volumes by He dilution are normal. The the Kco decreases in conjunction with a low Dlco, diffusing capacity was substandard in performance factors other than loss of lung volume are assumed because the subject could not inspire fully. The best to be responsible for the change. In this subject, it efforts show mildly reduced Dlco at the LLN after appears that drug therapy did affect Dlco. However, a correction for the subject’s Hb of 11.3. pattern of pneumonitis and fibrosis causing reduced After 3 months, FVC is decreased, but FEV is 1 lung volumes is not clear. Because of the changes in normal. This makes the FEV appear greater than 1% Dlco, amiodarone therapy was discontinued. expected. Lung volumes by He dilution show a TLC that is mildly decreased but with a normal FRC and RV. Dlco is moderately decreased even when corrected Technical Factors Influencing Dlco for an Hb of 11.4 g%. Since the previous test, the A second factor is that the subject’s pretreatment subject’s VC has decreased slightly, and the Dlco has Dlco tests did not meet established criteria for decreased significantly. acceptability. She was unable to inspire at least 85% of her VC in any of the maneuvers. This information Cause of Changes in Diffusing Capacity is documented in the technologist’s comments for the This case presents a good example of one application test. When the subject fails to inspire maximally, the of Dlco: monitoring drug therapy. The subject had breath hold may not occur at TLC. Therefore Dlco essentially normal lung function. Initially, her Dlco may appear low compared with predicted values. was slightly reduced. However, because she had a This technical difficulty may have influenced the --- PAGE 118 --- 106 Ruppel’s Manual of Pulmonary Function Testing pretreatment test results. The subject’s measured V A DLCO (atV )=14.8mL/min/mmHg (3.26 L) was significantly less than the TLC assessed Am (predictedatthe measuredV ) by He dilution (3.92 L). In this instance, it may be A appropriate to correct the predicted Dlco for the effect of the reduced lung volume using the equation  3.26 described previously: DLCO (atV Am )=16.7×  0.58+0.42   4.48    DLCO (atV )=DLCO ( atV ) ×  0.58+0.42   V Am     Am Ap    V Ap     When the subject’s measured Dlco of 12.6 mL/ min/mm Hg is compared with 14.8 mL/min/mm Hg Substituting the subject’s measured alveolar as the expected value, the percent predicted becomes volume (V ) and the predicted alveolar volume (V ) 85%. Correcting for Hb and the effect of a substandard Am Ap along with the Hb-corrected predicted Dlco (16.7 mL/ inspired volume suggests that the subject’s diffusing min/mm Hg, in this case) for the right-hand terms in capacity was well within normal limits before the equation gives the following: beginning the antiarrhythmic therapy. SELF-ASSESSMENT QUESTIONS Entry-Level 4. In which of the following conditions would an 1. Correct performance of the Dlcosb requires increased Dlco be expected? that the subject inspire at least 1. Pulmonary hemorrhage a. 90% of the VC. 2. Sarcoidosis b. 85% of the TLC. 3. Pneumonectomy c. 80% of the IC. 4. Polycythemia d. 2 to 3 times the V . a. 1 and 3 T 2. In which Dlco method does the patient perform b. 1 and 4 slow exhalation of the VC after inspiring? c. 2 and 3 a. Dlcorb (rebreathing) d. 2 and 4 b. Dlno (nitric oxide) 5. Dlco is often reduced in emphysema because of c. Dlcosb (single breath) which of the following? d. Dlcoib (intrabreath) 1. Fibrotic granulomas 3. A patient with a VC of 2.0 L performs several 2. Destruction of alveolar walls Dlcosb maneuvers, with the following 3. Anemia results: 4. Increased distance from the terminal bronchiole to alveolocapillary membrane Trial Dlco KCO V I a. 1 and 2 1 8.0 4.0 1.8 b. 1 and 3 2 7.4 3.8 1.4 c. 2 and 4 3 7.3 3.6 1.4 d. 3 and 4 4 6.9 4.0 1.0 Advanced The pulmonary function technologist should 6. A 52-year-old female patient has a Dlco of a. average the first two trials and report the 15.0 mL/min/mm Hg with a predicted value of result. 20.0. If her Hb is 9.5 g/dL, what is her corrected b. report the Dlco as 8.0. percentage of predicted diffusing capacity? c. average all trials and report the result. a. 64% d. perform one more trial. b. 75% c. 88% d. 91% --- PAGE 119 --- Diffusing Capacity Tests • Chapter 3 107 7. A 25-year-old male has an uncorrected Dlco of c. Reduced Dlco consistent with a restrictive 24.9 mL/min/mm Hg (69% of predicted) but defect no history of pulmonary disease. Which of the d. Reduced Dlco consistent with obesity following might explain these findings? 9. A healthy adult male has his Dlco measured 1. Left-to-right shunt at two different levels of inspired oxygen to 2. Carboxyhemoglobin estimate his membrane-diffusing capacity. 3. Congestive heart failure Which of the following results would be 4. Anemia expected in this subject? a. 1 and 2 only a. 1/Dm and 1/θV c approximately equal b. 3 and 4 only b. 1/Dm approximately 2 times larger than c. 1, 2, and 3 1/θV c d. 2, 3, and 4 c. 1/θV c approximately 2 times larger than 8. An adult patient whose TLC is 6.5 L (by 1/Dm plethysmography) performs two acceptable d. 1/Dm 5 to 10 times larger than 1/θV c Dlcosb maneuvers and records the following 10. A patient has a Dlcosb of 10.6 mL/min/mm results: Hg (STPD), which is 50% of his predicted Dlcosb 9.1 mL/min/mm Hg value. His Kco is 1.6. Which of the following is V 4.5 L most consistent with these values? A Which of the following interpretive statements a. Pulmonary hemorrhage is most consistent with these values? b. Pneumonectomy a. Normal diffusing capacity corrected for lung c. Pulmonary emphysema volume d. Obesity b. Reduced Dlco consistent with airway obstruction Saydain, G., Beck, K. C., Decker, P. A., et al. (2004). SELECTED BIBLIOGRAPHY Clinical significance of elevated diffusing capacity. Chest, 125, 446–452. General References Stam, H., Splinter, T. A. W., & Versprille, A. (2000). Crapo, R. O., Jensen, R. L., & Wanger, J. S. (2001). Single- Evaluation of diffusing capacity in patients with a breath carbon monoxide diffusing capacity. Clinics in restrictive lung disease. Chest, 117, 752–757. Chest Medicine, 22, 637–649. Hadeli, K. O., Siegel, E. M., Sherrill, D. L., et al. (2001). Predictors of oxygen desaturation during Dlcosb submaximal exercise in 8,000 patients. Chest, 120, Drummond, M. B., Schwartz, P. F., Duggan, W. T., 88–92. et al. (2008). Intersession variability in single-breath Hsia, C. W. (2006). Recruitment of lung diffusing diffusing capacity in diabetics without overt lung capacity. Chest, 1222, 1774–1783. disease. American Journal of Respiratory and Critical Care Jensen, R. L., & Crapo, R. O. (2003). Diffusing Medicine, 178, 225–232. capacity: How to get it right. Respiratory Care, 48, Hughes, J. M. B., & Pride, N. B. (2012). Examination of 777–782. the Carbon Monoxide Diffusing Capacity (DLCO) in Johnson, D. C. (2000). Importance of adjusting Relation to Its KCO and VA Components. American carbon monoxide diffusing capacity (Dlco) and Journal of Respiratory and Critical Care Medicine Vol, 186, carbon monoxide transfer coefficient (KCO) for 132–139. alveolar lung volume. Respiratory Medicine, 94, Jones, R. S., & Meade, F. (1961). A theoretical and 28–37. experimental analysis of anomalies in the estimation Plummer, A. L. (2008). The carbon monoxide diffusing of pulmonary diffusing capacity by the single breath capacity clinical implications, coding, and method. Quarterly Journal of Experimental Physiology documentation. Chest, 134, 663–667. and Cognate Medical Sciences, 46, 131–143. --- PAGE 120 --- 108 Ruppel’s Manual of Pulmonary Function Testing Mohsenifar, Z., & Tashkin, D. P. (1979). Effect of Dlcoib carboxyhemoglobin on the single breath diffusing Huang, Y. C., & MacIntyre, N. R. (1992). Real-time gas capacity: Derivation of an empirical correction factor. analysis improves the measurement of single-breath Respiration, 37, 185–188. diffusing capacity. American Review of Respiratory Punjabi, N. M., Shade, D., Patel, A. M., et al. (2003). Disease, 146, 946–950. Measurement variability in single breath diffusing Huang, Y. C., O’Brien, S. R., & MacIntyre, N. R. (2002). capacity of the lung. Chest, 123, 1082–1089. Intrabreath diffusing capacity of the lung in healthy Wise, R. A., Teeter, J. G., Jensen, R. L., et al. (2007). individuals at rest and during exercise. Chest, 122, 177–185. Standardization of the single-breath diffusing Wilson, A. F., Hearne, J., Brennan, M., et al. (1994). capacity in a multicenter clinical trial. Chest, 132, Measurement of transfer factor during constant 1191–1197. exhalation. Thorax, 49, 1121–1126. Dlcorb Standards and Guidelines Barazanji, K. W., Ramanathan, M., Johnson, R. L., Jr., Graham, B. L., Brusasco, V., Burgos, F., Cooper, B. G., et al. (1996). A modified rebreathing technique using Jensen, R., Kendrick, A., et al. (2017). ERS/ATS an infrared gas analyzer. Journal of Applied Physiology, standardisation of the single-breath carbon 80, 1258–1262. monoxide uptake in the lung. European Respiratory Hsia, C. C. W., McBrayer, D. G., & Ramanathan, M. Journal, Eur Respir J, 49. (1995). Reference values of pulmonary diffusing Zavorsky, G. L., Hsia, C. W., Hughes, M. B., Borland, C. D., & capacity during exercise by a rebreathing technique. Guénard, H., et al. (2017). Standardisation and American Journal of Respiratory and Critical Care application of the single-breath determination of Medicine, 152, 658–665. nitric oxide uptake in the lung. Eur Respir J, 49. --- PAGE 121 --- 4 Chapter Lung Volumes, Airway Resistance, and Gas Distribution Tests JEFFREY M. HAYNES, RRT, RPFT, FAARC CHAPTER OUTLINE Lung volumes: functional residual capacity, Gas Distribution Tests: Single-Breath Nitrogen residual volume, total lung capacity, Washout, Closing Volume, and Closing Capacity and residual volume/total lung capacity Description Ratio Technique Description Significance and Pathophysiology Technique Multiple-Breath Nitrogen Washout, Lung Significance and Pathophysiology Clearance Index, And Phase III Slope Analysis Airway Resistance and Conductance Description Description Technique Technique Significance and Pathophysiology Significance and Pathophysiology Summary Case Studies LEARNING OBJECTIVES After studying the chapter and reviewing the figures, tables, and case studies, you should be able to do the following: Entry-level 1. Describe the measurement of lung volumes using gas-dilution/washout methods. 2. Explain two advantages of measuring lung volumes using the body plethysmograph. 3. Calculate residual volume and total lung capacity from functional residual capacity (FRC) and the subdivisions of vital capacity (VC). 4. Identify a restricted disease process from measured lung volumes. 5. Describe the measurement of airway resistance using the body plethysmograph. Advanced 1. Calculate FRC using helium-dilution and nitrogen-washout methods. 2. Describe the correct technique for measuring thoracic gas volume using body plethysmography. 3. Identify air trapping and hyperinflation using measured lung volumes. 4. Describe the differences between Raw, sGaw, and sRaw. 5. Identify uneven distribution of gas in the lungs by either single- or multiple-breath techniques. KEY TERMS airway resistance (Raw) closed-circuit, multiple-breath closing capacity (CC) Boyle’s law helium dilution (FRC ) dilutional lung volumes He 109 --- PAGE 122 --- 110 Ruppel’s Manual of Pulmonary Function Testing distribution of ventilation open-circuit, multiple-breath nitrogen- specific airway conductance end-expiratory level washout technique (FRCN ) (sGaw) 2 FRC (FRC measured with the residual volume (RV) specific airway resistance pleth body plethysmograph) RV/TLC ratio (sRaw) functional residual capacity (FRC) single-breath nitrogen-washout “switch-in” error hyperinflation test (SBN ) thoracic gas volume (V ) 2 TG lung volume reduction surgery (LVRS) slope of phase III total lung capacity (TLC) The chapter introduces the measurement of abso- volume (RV) is the volume of gas remaining in the lute lung volumes beyond the inspired and expired lungs at the end of a maximal expiration, regardless lung volumes measured by spirometry. The gas vol- of the lung volume at which exhalation was started ume remaining in the lungs after the vital capacity (see Fig. 2.1). Total lung capacity (TLC) is the vol- (VC) has been exhaled must be measured indirectly. ume of gas contained in the lungs after maximal Several methods can accomplish this. Each method inspiration. FRC, TLC, and RV are reported in li- has its own advantages and disadvantages. Two ters (L) or milliliters (mL) corrected to body tem- methods—helium (He) dilution and nitrogen (N ) perature, pressure, and saturation (BTPS). The RV/ 2 washout—involve having the patient breathe gases TLC ratio defines the fraction of TLC that cannot or gas concentrations not normally present in the be exhaled (RV), expressed as a percentage. lungs: He or 100% oxygen (O ). These techniques are Thoracic gas volume (V ) is the absolute vol- 2 TG sometimes referred to as dilutional lung volumes. ume of gas in the thorax at any point in time and The gas-dilution techniques can also provide infor- any level of alveolar pressure. V is only mea- TG mation about the distribution of gas in the lungs. sured when using a body plethysmograph to mea- A third method uses the body plethysmograph sure lung volumes. V is usually measured at the TG to measure the thoracic gas volume (VTG). The end-expiratory level and is therefore usually close to use of the body plethysmograph also allows the the FRC. V is not a physiologic measure like FRC; TG measurement of airway resistance (Raw) and the it is simply the lung volume where closed-shutter volume-associated parameters of specific airway breathing is performed to calculate FRC. The V is TG conductance (sGaw) and specific airway resis- reported in liters or milliliters, BTPS. tance (sRaw). Conventional radiographs, nuclear medicine imaging of the lungs, computerized to- Technique mography (CT), and magnetic resonance imaging There are a variety of methods for measuring absolute (MRI) may also provide an estimate of lung vol- lung volumes (Table 4.1). FRC is measured directly umes, especially in patients with a limited ability to with the open-circuit multiple-breath N -washout, 2 cooperate. However, these methods are more com- closed-circuit multiple-breath He-dilution, and body plex, may involve radiation, can be quite costly, and plethysmographic techniques. Once FRC and VC at present are not used routinely in clinical care. have been measured, RV and TLC can be calculated. TLC can be estimated directly with the single-breath LUNG VOLUMES: FUNCTIONAL N 2 washout and single-breath He dilution as part of RESIDUAL CAPACITY, RESIDUAL the diffusing capacity (Dlco) test and by chest imag- VOLUME, TOTAL LUNG CAPACITY, ing techniques. RV can only be measured indirectly AND RESIDUAL VOLUME/TOTAL once FRC or TLC has been determined. LUNG CAPACITY RATIO Open-Circuit, Multiple-Breath Description Nitrogen Washout Functional residual capacity (FRC) is the volume Determination of FRC with the open-circuit of gas remaining in the lungs at the end of a quiet multiple-b reath nitrogen-washout technique breath. On a simple spirogram, this point is termed (FRCN ) is based on washing out the N from the 2 2 the end-expiratory level (see Fig. 2.1). Residual lungs while the patient breathes 100% O for several 2 [Command failed with exit code 137]