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Pulmonary Function Tests (PFT) — Complete MD Exam Answer

1. DEFINITION & OVERVIEW

Pulmonary function tests (PFTs) are a battery of tests that measure how well the lungs work, encompassing:

Respiratory mechanics — lung volumes, airflow rates, airway resistance
Gas exchange — diffusing capacity (DLCO)
Ventilatory muscle strength — maximal inspiratory/expiratory pressures (MIP/MEP)

PFTs are central to the definition of obstructive and restrictive disorders, and lung function is one of the most important predictors of all-cause mortality.

2. LUNG VOLUMES & CAPACITIES

Static Lung Volumes

Abbreviation	Name	Definition	Normal (approx.)
TLC	Total Lung Capacity	Volume at end of maximal inspiration	~6 L
FRC	Functional Residual Capacity	Volume at relaxation (inward lung pull = outward chest wall pull)	~2.5 L
RV	Residual Volume	Volume after maximal exhalation (FRC − ERV)	~1.2 L
ERV	Expiratory Reserve Volume	Volume expelled from FRC to RV	~1.2 L
IC	Inspiratory Capacity	Volume from FRC to TLC	~3.5 L
IRV	Inspiratory Reserve Volume	Volume above tidal breath to TLC	~3 L
TV	Tidal Volume	Volume of a normal quiet breath	~0.5 L
VC	Vital Capacity	TLC − RV	~4.8 L

Key relationship: TLC = VC + RV = IC + FRC

Why RV cannot be measured by simple spirometry

RV is the gas remaining after maximal exhalation — you cannot "blow it out." Therefore absolute lung volumes require:

Body plethysmography (most accurate; can overestimate in severe obstruction if panting is too rapid)
Inert gas dilution (helium equilibration; underestimates in bullous disease/poor communicating spaces)
Nitrogen washout (patient breathes 100% O₂ from FRC until N₂ plateau; also underestimates in poorly communicating spaces)

3. SPIROMETRY

FVC Maneuver

The patient inhales to TLC, then blasts out as hard and fast as possible to RV. Key parameters derived:

Parameter	Full Name	Clinical Significance
FVC	Forced Vital Capacity	Total volume forcefully expelled
FEV₁	Forced Expiratory Volume in 1 second	Most important single spirometric parameter
FEV₁/FVC	Tiffeneau index	Core ratio for obstructive vs. restrictive differentiation
FEF₂₅₋₇₅%	Forced expiratory flow 25–75%	Reflects small airway function; high variability (60–140% predicted normal)
PEF	Peak Expiratory Flow	Effort-dependent; used in asthma monitoring
FEV₃/FVC	—	More sensitive than FEV₁/FVC for mild obstruction (captures longer time constants)

Normal Values

FEV₁/FVC: ≥ 0.70 (or above the lower limit of normal, LLN)
FVC: ≥ 80% predicted
FEV₁: ≥ 80% predicted

ATS/ERS Standard: At least 3 acceptable spirograms; the 2 largest FVC and 2 largest FEV₁ values should be within 150 mL of each other (up to 8 efforts permitted).

Volume–Time Curve vs. Flow–Volume Loop

Volume–time curve: Volume on Y-axis vs. time on X-axis; plateau indicates maximal exhalation
Flow–volume loop: Flow (L/s) on Y-axis vs. volume (L) on X-axis; the expiratory limb descends from peak flow to zero

Flow-volume loop configurations — Normal, Obstructive, Restrictive, and Mixed

4. INTERPRETATION ALGORITHM

Step 1: Evaluate FEV₁/FVC ratio

5. PATTERNS IN DETAIL

A. Obstructive Ventilatory Defect

Diagnosis: FEV₁/FVC < LLN (or < 0.70 by fixed ratio — GOLD criteria)

Mechanism: Increased airway resistance → airflow limitation → air trapping → hyperinflation

Findings:

↓ FEV₁/FVC (hallmark)
↓ FEV₁ (reduced)
FVC: normal or reduced (due to air trapping)
↑ RV, ↑ FRC, ↑ TLC (hyperinflation/air trapping)
RV/TLC ratio elevated
Flow–volume curve: scooped-out concave expiratory limb (characteristic)

Severity grading by FEV₁ (% predicted):

Severity	FEV₁ % predicted
Mild	≥ 70%
Moderate	60–69%
Moderately severe	50–59%
Severe	35–49%
Very severe	< 35%

Causes: Asthma, COPD (chronic bronchitis, emphysema), bronchiectasis, cystic fibrosis, obliterative bronchiolitis

DLCO in obstruction:

Emphysema → ↓↓ DLCO (destruction of alveolar walls = ↓ surface area)
Chronic bronchitis/asthma → DLCO normal or mildly reduced

B. Restrictive Ventilatory Defect

Diagnosis: FVC reduced + FEV₁/FVC normal or elevated + TLC < LLN (TLC is mandatory to confirm restriction)

Mechanism: Reduced lung compliance or chest wall restriction → small lung volumes → proportional decrease in FVC and FEV₁

Findings:

↓ FVC
↓ FEV₁ (proportionally reduced)
FEV₁/FVC: normal or ↑ (≥ 0.70)
↓ TLC (confirmatory — MUST have TLC < LLN)
RV may be normal or reduced
Flow–volume curve: narrow, tall loop (reduced volume, preserved flows)

Spirogram tracings — Normal, Obstructive, Restrictive

Causes:

Intrinsic (parenchymal)	Extrinsic (chest wall/neuromuscular)
IPF, sarcoidosis, asbestosis, silicosis	Kyphoscoliosis, ankylosing spondylitis
Radiation pneumonitis	Obesity
Hypersensitivity pneumonitis	Neuromuscular: MG, GBS, ALS, phrenic nerve palsy
Pneumonectomy/lobectomy	Pleural effusion, mesothelioma

DLCO:

Parenchymal ILD → ↓ DLCO (thickened alveolar membrane)
Chest wall/neuromuscular → Normal DLCO (intrinsic gas exchange intact)

C. Mixed Obstructive-Restrictive Defect

Diagnosis: FEV₁/FVC < LLN AND TLC < LLN

Findings: Features of both obstruction and restriction coexist. Requires TLC measurement to diagnose.

Causes: Sarcoidosis with airway involvement, cystic fibrosis (late), combined ILD + emphysema

D. Nonspecific Ventilatory Pattern

Diagnosis: FEV₁/FVC normal + FVC ↓ (or FEV₁ ↓) + TLC normal

Significance: Does not fit classic obstructive or restrictive definition. May represent:

Early restriction (TLC at lower end of normal)
Mixed obstructive disease with air trapping masking reduced FVC
Small airway disease

6. DIFFUSING CAPACITY (DLCO / TLCO / Transfer Factor)

Principle

Patient exhales to RV → rapidly inhales a mixture of CO + inert tracer gas (He or CH₄) to TLC → breath-hold for 10 seconds → exhale
CO is measured before and after; the inert gas measures alveolar volume (VA)
DLCO = rate of CO uptake / driving pressure

Transfer coefficient: Kco = DLCO / VA (corrects for lung volume)

Normal DLCO

≥ 75% predicted (LLN: typically ~70% predicted)
Corrected for hemoglobin (anemia → falsely low; polycythemia → falsely high)
Corrected for COHb (smokers)
Altitude: lower PIO₂ → DLCO appears increased

Interpretation of DLCO Changes

DLCO	Pattern	Causes
↓↓ DLCO	Obstructive pattern	Emphysema (destruction of alveolar surface area)
↓ DLCO	Restrictive + parenchymal	ILD, sarcoidosis, asbestosis, pulmonary edema
Normal DLCO	Restrictive, extrapulmonary	Chest wall disease, neuromuscular disease, obesity
Normal DLCO	Obstructive	Asthma, chronic bronchitis (no parenchymal loss)
↑ DLCO	—	Pulmonary hemorrhage (Hb in alveoli binds CO), polycythemia, left-to-right shunts, exercise
↓ DLCO isolated	Normal spirometry + normal TLC	Pulmonary vascular disease (PE, pulmonary HTN), mild parenchymal disease

7. FLOW-VOLUME LOOP PATTERNS IN SPECIFIC CONDITIONS

Upper Airway Obstruction (UAO)

Type	Location	Effect	Pattern on Loop
Fixed obstruction (tracheal stenosis, goiter)	Above or below thoracic inlet	Equal limitation in both phases	Plateau in both inspiratory AND expiratory limbs
Variable extrathoracic (vocal cord paralysis, tracheomalacia above inlet)	Above thoracic inlet	Worsens on inspiration (negative pressure collapses airway)	Plateau in inspiratory limb only
Variable intrathoracic (tracheomalacia below inlet)	Below thoracic inlet	Worsens on exhalation (positive pleural pressure compresses airway)	Plateau in expiratory limb only

Emphysema

Scooped-out expiratory limb
"Negative effort dependence" — tidal flow may exceed forced expiratory flow (highly collapsible airways collapse more during forced effort)
Increased RV, FRC, TLC

8. BRONCHODILATOR RESPONSE TESTING

Protocol

Administer SABA (salbutamol 400 mcg via MDI + spacer, or 2.5 mg nebulized); reassess after 15–20 minutes
OR LABA (salmeterol, formoterol); reassess after 30–60 minutes

Positive (Significant) Bronchodilator Response (ATS/ERS 2022):

≥ 10% increase in FEV₁ or FVC relative to predicted AND absolute increase ≥ 200 mL
(Older criteria: ≥ 12% AND ≥ 200 mL increase from baseline — still widely used for MD exams)

Clinical interpretation

Complete reversibility (FEV₁/FVC normalizes): suggests asthma
Partial/incomplete reversibility: COPD or incompletely controlled asthma
No reversibility: established COPD
Significant response does NOT exclude COPD; absence does NOT exclude asthma

9. BRONCHIAL CHALLENGE TESTING

Used when spirometry is normal but asthma is suspected (e.g., chronic cough, exercise-induced symptoms).

Methacholine Challenge

Principle: Inhalation of progressive concentrations of methacholine (muscarinic agonist)
Endpoint: PC₂₀ — concentration causing 20% fall in FEV₁
Interpretation:
- PC₂₀ < 1 mg/mL: moderate–severe hyperresponsiveness (asthma very likely)
- PC₂₀ 1–4 mg/mL: borderline
- PC₂₀ 4–16 mg/mL: mild hyperresponsiveness (possible asthma)
- PC₂₀ > 16 mg/mL: normal (asthma unlikely)

Other Stimuli

Exercise challenge (EIB diagnosis): ≥ 10–15% fall in FEV₁ after exercise = positive
Mannitol challenge: dry powder osmotic stimulus; high specificity for asthma
Eucapnic voluntary hyperpnoea (EVH): used in athletes

10. RESPIRATORY MUSCLE STRENGTH

Test	Measurement	Normal	Interpretation
MIP (PImax)	Maximal inspiratory pressure at RV	> −80 cmH₂O (men); > −70 cmH₂O (women)	↓ = diaphragm/inspiratory muscle weakness
MEP (PEmax)	Maximal expiratory pressure at TLC	> +80 cmH₂O	↓ = expiratory muscle weakness (↓ cough efficacy)
Sniff nasal inspiratory pressure (SNIP)	Diaphragm strength	—	Sensitive test; reduced in phrenic nerve palsy

Indications: Neuromuscular diseases (MG, GBS, ALS, Duchenne MD), unexplained dyspnea or hypercapnia with low spirometry but normal TLC

PFT pattern in neuromuscular disease:

Reduction in FVC (often supine FVC drops > 20% vs. erect → indicates diaphragm weakness)
Normal FEV₁/FVC
Normal DLCO
↓ MIP and MEP

11. FACTORS AFFECTING PFT RESULTS

Patient factors

Factor	Effect
Height	↑ height → ↑ all lung volumes
Age	TLC minimally changed; FVC and FEV₁ decrease (−21 to −33 mL/yr in men); RV increases
Sex	Men > women for most volumes
Ethnicity/Race	African-Americans and Asian subjects have ~10–15% lower lung volumes than White subjects at same height (controversial; ATS 2022 moving toward race-neutral equations)
Obesity	↓ FRC and ERV; restrictive-like pattern possible
Smoking	Accelerated decline in FEV₁ (~45 mL/yr vs. ~25 mL/yr in non-smokers)
Posture	Supine → ↓ FRC (especially in obesity/neuromuscular disease)

Technical/analytical factors

Poor effort → falsely low FVC and FEV₁
Air leaks, calibration errors
Medication effects (bronchodilators must be withheld: SABA 4–6 hrs, LABA 12–24 hrs before testing if reversibility is being assessed)

12. SEVERITY CLASSIFICATION

GOLD Staging (Obstructive — post-bronchodilator):

GOLD Stage	FEV₁ % predicted
1 (Mild)	≥ 80%
2 (Moderate)	50–79%
3 (Severe)	30–49%
4 (Very Severe)	< 30%

Restrictive Disease Severity (ATS/ERS):

Severity	TLC or FVC % predicted
Mild	70–80%
Moderate	60–69%
Moderately severe	51–59%
Severe	41–50%
Very severe	≤ 40%

13. SPECIAL APPLICATIONS OF PFT

Clinical Scenario	PFT Role
Pre-operative assessment	FEV₁ < 40% predicted or ppoFEV₁ < 30% → ↑ post-op pulmonary complication risk; ppoFEV₁ < 40% → relative contraindication for pneumonectomy
Disability assessment	Objective functional impairment quantification
Asthma control monitoring	Serial FEV₁/PEF measurements
ILD monitoring	≥ 10% relative decline in FVC over 6–12 months = significant progression (predicts mortality in IPF)
Lung transplant listing	FVC < 50% in ILD; FEV₁ < 20% + DLCO < 20% or homogeneous emphysema → transplant evaluation
Lung volume reduction surgery (LVRS)	FEV₁ 20–45%, TLC > 100%, RV > 150%, upper lobe predominant emphysema
Monitoring after COVID-19	~70% of moderate-severe survivors have DLCO abnormalities at 6 weeks; ~25% obstructive, ~20% restrictive

14. SUMMARY TABLE — CLASSIC EXAM PATTERNS

Pattern	FEV₁/FVC	FEV₁	FVC	TLC	RV	DLCO
Normal	≥ 0.70	≥ 80%	≥ 80%	N	N	N
Obstructive (airway)	↓	↓	N or ↓	N or ↑	↑	N
Emphysema	↓	↓↓	↓	↑	↑↑	↓↓
Restrictive (ILD)	N or ↑	↓	↓↓	↓	↓	↓
Restrictive (chest wall/NMD)	N or ↑	↓	↓↓	↓	N or ↓	N
Mixed	↓	↓↓	↓↓	↓	variable	↓
Pulmonary HTN / vascular	N	N	N	N	N	↓↓
Pulmonary hemorrhage	N	N	N	N	N	↑↑
Neuromuscular	N or ↑	↓	↓	↓	N or ↑	N

15. KEY EXAM POINTS (HIGH-YIELD)

FEV₁/FVC < 0.70 (or < LLN) = obstructive; requires TLC to distinguish "obstruction with air trapping" from "mixed"
TLC < LLN is mandatory to confirm restriction — spirometry alone cannot diagnose restriction
DLCO ↑ = pulmonary hemorrhage, polycythemia, left-to-right shunt
DLCO ↓ in isolation (normal spirometry + normal TLC) = pulmonary vascular disease
Emphysema: FEV₁/FVC ↓ + RV ↑↑ + TLC ↑ + DLCO ↓↓
Asthma: FEV₁/FVC ↓ + significant reversibility (≥ 12% and ≥ 200 mL) + normal DLCO
Neuromuscular disease: reduced FVC and TLC, normal FEV₁/FVC, normal DLCO, ↓ MIP/MEP; supine FVC falls > 20% = diaphragm weakness
Fixed upper airway obstruction: plateau on BOTH inspiratory and expiratory limbs
FEF₂₅₋₇₅%: small airway marker; high variability — use with caution in isolation
Helium dilution underestimates TLC in emphysema (bullae don't communicate); body plethysmography is the gold standard

Sources: Murray & Nadel's Textbook of Respiratory Medicine; Goldman-Cecil Medicine; Fishman's Pulmonary Diseases & Disorders; Bailey & Love's Surgery; ATS/ERS Technical Standard on Lung Function Interpretation (PMID 40084848, 38999220)

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