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Note: The book you're referring to is likely Dr. Archith Boloor's Exam Preparatory Manual for Undergraduates: Medicine, which is not in this library. The answer below is compiled from Harrison's 22E, Fishman's Pulmonary Diseases & Disorders, and Murray & Nadel - the same standard references used in that manual - structured in the exam-Q&A format Boloor follows.

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HEMOPTYSIS

Definition

• Harrison's 22E, p. 318

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Hemoptysis vs Hematemesis (Important Distinction)

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Classification by Volume

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Causes of Hemoptysis

Airway Causes

• Bronchitis (viral - most common in developed countries, often streak hemoptysis)
• Bronchiectasis (including cystic fibrosis) - recurrent, can be massive; airways dilated, inflamed, highly vascular
• Bronchogenic carcinoma (squamous cell and small cell - central, erode major vessels)
• Carcinoid tumor (vascular, proximal airways)
• Foreign body aspiration

Parenchymal / Infectious Causes

• Pulmonary tuberculosis - most common worldwide (especially developing countries); cavitary disease, Rasmussen's aneurysm (erosion of pulmonary artery aneurysm into TB cavity)
• Lung abscess / Necrotizing pneumonia (S. aureus, Klebsiella, oral anaerobes)
• Pneumonia (Strep. pneumoniae, H. influenzae, Moraxella catarrhalis)
• Aspergilloma (fungus ball in pre-existing cavity, neovascularization - important cause of massive hemoptysis)
• Endemic fungi (Histoplasma, Coccidioides), Nocardia, NTM
• Paragonimiasis (mimics TB; Southeast Asia/China; raw crayfish ingestion)

Vascular Causes

• Mitral stenosis (raised pulmonary venous pressure)
• Pulmonary embolism with infarction
• Left heart failure (pink frothy sputum)
• Arteriovenous malformation (AVM)
• Aortobronchial fistula (aneurysm/pseudoaneurysm - small bleeds then massive)
• Dieulafoy's disease of the bronchus (rare - submucosal fistula between bronchial and pulmonary arteries)

Diffuse Alveolar Hemorrhage (DAH)

• Granulomatosis with polyangiitis (GPA, formerly Wegener's) - "pulmonary-renal syndrome" (hemoptysis + hematuria)
• Anti-GBM disease (Goodpasture syndrome)
• SLE-associated capillaritis
• Cocaine/inhalant toxicity
• Stem cell transplantation
• Vaping-induced lung injury

Miscellaneous

• Coagulopathy / thrombocytopenia / anticoagulants
• Catamenial hemoptysis (pulmonary endometriosis - cyclical bleeding with menstruation)
• Iatrogenic: post-lung biopsy, pulmonary artery catheter rupture, pulmonary vein stenosis post-ablation
• COPD (unexplained, usually non-recurrent)
• Bevacizumab / ramucirumab (anti-VEGF agents) in squamous cell lung cancer

Exam tip: In patients < 40 years - think infection; in patients > 40-45 years or smokers - think bronchogenic carcinoma.

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Evaluation

History

• Pattern, severity, frequency, quantity
• Sputum description (streaks vs frank blood vs clots)
• Respiratory symptoms, weight loss, smoking, TB contact, travel history
• Anticoagulant use, menstrual cycle (catamenial)

Physical Examination

• Vital signs, O2 saturation
• Signs of chronic lung disease (clubbing, hyperinflation)
• Cardiovascular: mitral stenosis (opening snap, mid-diastolic murmur)
• ENT: to exclude nasal/oropharyngeal source

Investigations

1. Chest X-ray - first-line; identifies cavities, masses, consolidation, hilar lymphadenopathy
2. CBC - degree of anaemia, thrombocytopenia (contributing factor)
3. Coagulation studies (PT/INR, aPTT)
4. Sputum AFB smear + culture - rule out TB
5. CT chest (HRCT / multidetector CT angiography) - identifies source of bleeding, underlying pathology, bronchial and non-bronchial systemic arteries with high sensitivity
6. Bronchoscopy - direct visualization, localizes bleeding site, allows therapeutic intervention (rigid preferred in massive hemoptysis)
7. Urinalysis / renal function - if pulmonary-renal syndrome suspected (GPA, Goodpasture)
8. Echocardiography - if mitral stenosis suspected

Imaging Examples:

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Management

Non-Massive Hemoptysis

• Identify and treat underlying cause
• Suppress cough (antitussives)
• Treat infection (antibiotics as appropriate)
• Correct coagulopathy if present
• Outpatient management often feasible; monitor closely

Massive / Life-Threatening Hemoptysis

1. Airway - maintain patency; intubate if needed (large-bore ETT, preferably 8.0 mm)
2. Oxygenation - supplemental oxygen
3. Hemodynamic stabilization - IV access, fluids, blood products

Special Situations

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Rasmussen's Aneurysm (High-Yield)

• Erosion of a pulmonary artery aneurysm into a pre-existing TB cavity
• Rare but important cause of massive hemoptysis in TB
• Source: pulmonary circulation (not bronchial)

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Sources

• Harrison's Principles of Internal Medicine, 22E (2025) - pp. 318-319, 635
• Fishman's Pulmonary Diseases and Disorders, 2-Volume Set - pp. 443-444
• Murray & Nadel's Textbook of Respiratory Medicine

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PLEURAL EFFUSION

Definition

• Harrison's 22E, p. 2311; Robbins Pathology, p. 676

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Physiology of Pleural Fluid Formation

• Fluid enters the pleural space from capillaries in the parietal pleura
• Fluid is removed via lymphatics of the parietal pleura
• Fluid can also enter from: lung interstitial spaces (via visceral pleura) or peritoneal cavity (via small diaphragmatic holes)
• The lymphatics can absorb 20 times more fluid than is normally formed

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Mechanisms of Accumulation (Pathophysiology)

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Classification: Transudate vs Exudate

Light's Criteria (Exudate - meets >/= 1):

• Transudates meet none of the above criteria
• These criteria misidentify ~25% of transudates as exudates ("pseudoexudates") - often a diuresed transudate
• If pseudoexudate suspected: use Serum-Pleural fluid Protein Gradient (SPPG) > 3.1 g/dL or Serum-Pleural fluid Albumin Gradient (SPAG) > 1.2 g/dL - 100% sensitive for CHF, 99% for hepatic hydrothorax

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Causes

TRANSUDATIVE Effusions

1. Congestive heart failure (most common cause overall)
2. Cirrhosis (hepatic hydrothorax)
3. Nephrotic syndrome
4. Peritoneal dialysis
5. Superior vena cava obstruction
6. Myxedema (hypothyroidism)
7. Urinothorax

EXUDATIVE Effusions

• Metastatic disease - lung carcinoma, breast carcinoma, lymphoma (cause 75% of malignant effusions)
• Mesothelioma (asbestos-related)

• Bacterial infections / Parapneumonic effusion (most common exudative cause in US; up to 50% of community-acquired pneumonia)
• Tuberculosis (most common cause in developing countries)
• Fungal, viral, parasitic infections

• Esophageal perforation (amylase-rich, left-sided)
• Pancreatic disease (amylase-rich)
• Intraabdominal abscesses
• Diaphragmatic hernia
• Post-abdominal surgery, endoscopic variceal sclerotherapy, post-liver transplant

• Rheumatoid pleuritis (very low glucose, low pH)
• SLE, drug-induced lupus
• Sjogren syndrome
• Granulomatosis with polyangiitis (Wegener's)
• Churg-Strauss syndrome

• Post-coronary artery bypass surgery (left-sided, bloody early then serous)
• Asbestos exposure
• Sarcoidosis
• Uremia
• Meigs' syndrome (ovarian fibroma + right-sided pleural effusion + ascites - resolves with tumor removal)
• Yellow nail syndrome
• Drug-induced (nitrofurantoin, dantrolene, methysergide, bromocriptine, amiodarone, dasatinib)
• Trapped lung
• Radiation therapy
• Post-cardiac injury syndrome (Dressler's)
• Hemothorax
• Iatrogenic injury
• Ovarian hyperstimulation syndrome
• Chylothorax (triglycerides > 110 mg/dL - disruption of thoracic duct)

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Diagnostic Algorithm

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Clinical Features

• Dyspnea (most common, often out of proportion to effusion size in malignancy)
• Pleuritic chest pain (dull, heavy, worse with breathing - from pleural inflammation)
• Dry cough

• Tracheal/mediastinal shift away from large effusion
• Stony dull percussion note (dullest of all percussion notes)
• Reduced / absent breath sounds
• Reduced tactile vocal fremitus
• Reduced chest expansion on affected side
• Aegophony (e-to-a change) at upper border of effusion
• Friction rub (if inflammatory, before fluid accumulates)

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Radiology

• Meniscus sign - fluid has concave upper margin, higher laterally than medially
• Subpulmonary effusion - appears as "high hemidiaphragm" with peak more laterally than usual
• Lateral decubitus film - detects even small effusions (as little as 50 mL)
• Supine (ICU) film - hazy opacity of lower thorax; costophrenic angles NOT obscured; vascular markings preserved through opacity

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Thoracentesis and Pleural Fluid Analysis

• New or undiagnosed effusion
• CHF effusion that is unilateral, unequal in size, febrile patient, or pleuritic chest pain

• Protein, LDH (for Light's criteria)
• Glucose, cell count and differential
• Gram stain and culture
• Cytology

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Specific Effusions - High Yield Points

Parapneumonic Effusion and Empyema

• PPE in up to 50% of community-acquired pneumonia
• Complicated PPE / Empyema requires drainage if ANY of:
  1. Loculated pleural fluid
  2. pH < 7.20
  3. Glucose < 3.3 mmol/L (< 60 mg/dL)
  4. Positive Gram stain or culture
  5. Gross pus in pleural space
  6. Pleural fluid LDH > 900 IU/L
• Treatment: chest tube + intrapleural tPA (10 mg) + DNase (5 mg) if loculated; thoracoscopy; surgical decortication if above fail

Malignant Pleural Effusion

• Three tumors cause 75%: lung, breast, lymphoma
• Poor prognosis (< 6-month survival)
• Dyspnea often out of proportion to effusion size
• Usually exudate; rarely transudate
• Low glucose if high tumor burden
• Diagnosis by cytology (positive in ~60%) or pleural biopsy
• Treatment: therapeutic thoracentesis, indwelling pleural catheter (IPC), pleurodesis (talc most effective)

Tuberculous Effusion

• Exudate with high ADA, lymphocyte-predominant
• Low glucose, low pH
• Culture positivity low (~25%); pleural biopsy more sensitive
• Treatment: standard anti-TB drugs; steroids may reduce residual pleural thickening

Hepatic Hydrothorax

• Complicates ~5-10% of cirrhosis patients
• Ascitic fluid passes through small diaphragmatic defects
• Usually right-sided (85%), transudative
• May occur without detectable ascites
• Treatment: sodium restriction + diuretics; TIPS (70-80% response); VATS repair of diaphragmatic defects + pleurodesis; liver transplantation

Chylothorax

• Triglycerides > 110 mg/dL (or chylomicrons on lipoprotein electrophoresis)
• Milky white fluid; lymphocyte-predominant
• Causes: thoracic duct trauma/surgery, lymphoma (most common malignant cause), lymphangioleiomyomatosis
• Treatment: low-fat diet (medium-chain triglycerides), octreotide, thoracic duct ligation

Meigs' Syndrome

• Ovarian fibroma (or other pelvic tumor) + ascites + pleural effusion (usually right-sided)
• Effusion is transudate
• All resolves with removal of the tumor

Rheumatoid Pleuritis

• Characteristically: very low glucose (< 30 mg/dL), very low pH - lower than any other non-infectious cause
• Cholesterol crystals may be seen in chronic effusions

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Management Principles

Transudative Effusion

• Treat the underlying cause (heart failure, cirrhosis, nephrotic syndrome)
• Thoracentesis for symptom relief if large
• Do NOT insert a chest tube for a transudative effusion

Exudative Effusion

• Identify and treat specific cause
• Drainage if complicated PPE/empyema criteria met
• Malignant: IPC or pleurodesis for palliation

Pleurodesis

• Goal: obliterate pleural space to prevent recurrence
• Agents: Talc (most effective), bleomycin, doxycycline, tetracycline
• Method: chemical pleurodesis via chest tube or thoracoscopy (VATS)
• Requires lung re-expansion (will not work in trapped lung)

Indwelling Pleural Catheter (IPC)

• For recurrent malignant effusion or hepatic hydrothorax as bridge to transplant
• Outpatient drainage; can lead to auto-pleurodesis in ~40% of malignant cases

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Sources

• Harrison's Principles of Internal Medicine, 22E (2025) - pp. 2311-2313
• Robbins, Cotran & Kumar Pathologic Basis of Disease - p. 676
• Murray & Nadel's Textbook of Respiratory Medicine
• Grainger & Allison's Diagnostic Radiology - p. 62

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PLEURAL EFFUSION

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Definition

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Physiology of Normal Pleural Fluid

• Fluid enters from capillaries of the parietal pleura
• Fluid is removed by lymphatics of the parietal pleura
• Can also enter from lung interstitium (via visceral pleura) or peritoneum (via diaphragmatic holes)
• Lymphatics can absorb 20x more fluid than is normally formed

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Mechanisms of Accumulation

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Classification: Transudate vs Exudate

Light's Criteria - Exudate meets at least ONE:

• Transudates meet none
• ~25% of transudates misidentified as exudates ("pseudoexudates") - often a diuresed transudate
• If pseudoexudate suspected: SPPG > 3.1 g/dL or SPAG > 1.2 g/dL corrects this (100% sensitive for CHF, 99% for hepatic hydrothorax)

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Causes

TRANSUDATES (systemic factors altered)

1. Congestive heart failure - most common cause of pleural effusion overall
2. Cirrhosis / Hepatic hydrothorax
3. Nephrotic syndrome
4. Peritoneal dialysis
5. Superior vena cava obstruction
6. Myxedema (hypothyroidism)
7. Urinothorax

EXUDATES (local factors altered)

• Metastatic disease - lung, breast, lymphoma (cause 75% of malignant pleural effusions)
• Mesothelioma

• Parapneumonic effusion - most common exudative cause in US (up to 50% of community-acquired pneumonia)
• Tuberculosis - most common cause in developing countries
• Fungal, viral, parasitic infections

• Pulmonary embolism (exudate or transudate)

• Esophageal perforation (amylase-rich, left-sided)
• Pancreatic disease (amylase-rich, left-sided)
• Intraabdominal abscesses, diaphragmatic hernia
• Post-abdominal surgery, post-liver transplant, endoscopic variceal sclerotherapy

• Rheumatoid pleuritis (characteristically very low glucose < 30 mg/dL, very low pH)
• SLE, drug-induced lupus
• Sjogren syndrome, GPA (Wegener's), Churg-Strauss

• Post-CABG (left-sided, bloody then serous)
• Asbestos exposure
• Sarcoidosis
• Uremia
• Meigs' syndrome (ovarian fibroma + ascites + right-sided effusion - transudate; resolves with tumor removal)
• Yellow nail syndrome
• Drug-induced: nitrofurantoin, dantrolene, methysergide, bromocriptine, amiodarone, dasatinib
• Trapped lung
• Radiation therapy
• Post-cardiac injury syndrome (Dressler's)
• Hemothorax
• Ovarian hyperstimulation syndrome
• Chylothorax (triglycerides > 110 mg/dL)
• Iatrogenic

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Clinical Features

• Dyspnea (most common; often out of proportion to size in malignancy)
• Pleuritic chest pain (dull, heavy, worse on breathing)
• Dry cough

• Tracheal/mediastinal shift away from large effusion
• Reduced chest expansion on affected side
• Stony dull percussion (dullest of all - differentiates from consolidation which is dull)
• Reduced / absent breath sounds
• Reduced tactile vocal fremitus (TVF)
• Aegophony at upper border of effusion
• Pleural friction rub (early, before fluid accumulates)

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Radiology

Chest X-ray (PA erect)

• Meniscus sign - concave upper border, higher laterally than medially
• Subpulmonary effusion - appears as "high hemidiaphragm" peaking more laterally; stomach bubble separated > 2 cm from lung (left-sided)
• Supine film (ICU) - hazy opacity of lower thorax; costophrenic angles NOT obscured; vascular markings visible through opacity (opposite to erect)
• Loculated effusion - lens-shaped, does not shift with position; "pseudotumour/vanishing tumour" in fissures

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Diagnostic Algorithm

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Thoracentesis and Pleural Fluid Analysis

• Protein + LDH (Light's criteria)
• Glucose, cell count + differential
• Gram stain + culture
• Cytology

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Specific Effusions - High Yield Points

Parapneumonic Effusion / Empyema

1. Loculated pleural fluid
2. pH < 7.20
3. Glucose < 60 mg/dL (< 3.3 mmol/L)
4. Positive Gram stain or culture
5. Gross pus in pleural space
6. LDH > 900 IU/L

• Chest tube drainage
• Intrapleural tPA 10 mg + DNase 5 mg if loculated
• Thoracoscopy (VATS) with breakdown of adhesions
• Surgical decortication if above fail

Malignant Pleural Effusion

• Lung + breast + lymphoma = 75% of all malignant effusions
• Poor prognosis (< 6-month median survival)
• Dyspnea out of proportion to size
• Low glucose if high tumor burden
• Treatment: therapeutic thoracentesis → indwelling pleural catheter (IPC) or pleurodesis (talc most effective)

Tuberculous Pleural Effusion

• Exudate; lymphocyte-predominant
• High ADA (> 40-45 U/L)
• Low glucose, low pH
• AFB culture positivity low (~25%); pleural biopsy + culture more sensitive
• Treatment: standard 4-drug anti-TB therapy; steroids reduce residual thickening

Hepatic Hydrothorax

• 5-10% of cirrhosis patients
• Ascitic fluid through diaphragmatic defects
• Usually right-sided (85%), transudate
• May occur without detectable ascites
• Treatment: Na restriction + diuretics → TIPS (70-80% response) → VATS pleurodesis → liver transplant

Chylothorax

• Milky white fluid; lymphocyte-predominant; triglycerides > 110 mg/dL
• Causes: thoracic duct trauma/surgery, lymphoma (most common malignant cause), LAM
• Treatment: low-fat diet (MCT oil), octreotide, thoracic duct ligation/embolization

Meigs' Syndrome

• Triad: Ovarian fibroma + ascites + right-sided pleural effusion
• Effusion is a transudate
• Resolves completely after tumor removal
• Must distinguish from Pseudo-Meigs' (other pelvic tumors)

Rheumatoid Pleuritis

• Characteristically: glucose < 30 mg/dL (lowest of all non-infective causes)
• Very low pH, high LDH
• Complement levels very low

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Management Summary

Transudative Effusion

• Treat underlying cause (CHF → diuretics/ACEi; cirrhosis → Na restriction, diuretics, TIPS; nephrotic → steroids + treat cause)
• Therapeutic thoracentesis for symptomatic relief
• Do NOT insert chest tube for a simple transudate

Exudative Effusion

• Identify and treat underlying cause
• Drain if complicated PPE/empyema criteria met
• Malignant: IPC or chemical pleurodesis

Pleurodesis

• Talc - most effective agent
• Others: bleomycin, doxycycline, tetracycline
• Method: via chest tube (slurry) or thoracoscopy (poudrage)
• Will NOT work if lung is trapped (cannot re-expand)
• Trapped lung diagnosis: pleural manometry, pneumothorax ex vacuo on imaging post-thoracentesis, rapid recurrence

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Sources

• Harrison's Principles of Internal Medicine, 22E (2025) - pp. 2311-2313
• Robbins, Cotran & Kumar Pathologic Basis of Disease - p. 676
• Murray & Nadel's Textbook of Respiratory Medicine
• Grainger & Allison's Diagnostic Radiology - p. 62

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BRONCHIAL ASTHMA

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Definition

1. Airway hyperresponsiveness to a variety of stimuli
2. Reversible airway obstruction (spontaneously or with treatment)
3. Airway inflammation (predominantly eosinophilic)
4. Airway remodeling in chronic disease

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Epidemiology

• Affects ~300 million people worldwide
• More common in boys < girls in childhood; reverses by age 40 (women > men in adults)
• Occupational asthma accounts for 10-25% of adult-onset asthma

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Etiology / Risk Factors

Intrinsic (Endogenous) Factors

• Atopy (genetic predisposition to IgE-mediated sensitization) - strongest risk factor
• Genetic factors (multiple susceptibility genes including those on chromosomes 5, 6, 11, 12)
• Sex and hormonal factors (perimenstrual, perimenopause, pregnancy)
• Obesity
• Prematurity, caesarean delivery, neonatal jaundice

Extrinsic (Environmental) Factors

• Allergen exposure (house dust mite, pollen, animal dander, mold, cockroach)
• Occupational exposures (flour, diisocyanates, formaldehyde - nursing and cleaning most common)
• Air pollution, tobacco (active and passive)
• Respiratory infections (rhinovirus, RSV, Mycoplasma pneumoniae)
• Diet (vitamin D deficiency, maternal polyunsaturated fatty acids)

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Triggers of Acute Attacks

1. Allergens (inhaled)
2. Irritants (smoke, dust, fumes, strong smells)
3. Viral respiratory infections (most common trigger in children)
4. Exercise and cold, dry air
5. Air pollution
6. Drugs: Aspirin / NSAIDs (aspirin-exacerbated respiratory disease - AERD), beta-blockers (most dangerous), ACE inhibitors (cough)
7. Occupational exposures
8. Hormonal changes / pregnancy
9. Emotional stress
10. GERD (independent predictor of exacerbations)

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Pathophysiology

Three Core Mechanisms

• Hallmark of asthma
• Exaggerated narrowing response to stimuli harmless to normal individuals
• Due to: smooth muscle hyperresponsiveness (direct) + inflammatory cell mediator release (indirect) + structural changes (airway wall thickening)

• Usually eosinophilic (Type 2 inflammation) - most common
• Neutrophilic in severe asthma and occupational asthma
• Mixed eosinophilic + neutrophilic = most severe phenotype
• Key cells: mast cells (early phase), eosinophils, T helper 2 (Th2) cells, basophils

• Smooth muscle hypertrophy and hyperplasia
• Subepithelial collagen deposition and basement membrane thickening
• Goblet cell hyperplasia, mucus hypersecretion
• Epithelial denudation and shedding
• Vascular proliferation
• Neuronal proliferation

Biphasic Response (Early and Late)

Key Mediators in Asthma

• Histamine - bronchoconstriction, mucus secretion
• Leukotrienes (LTC4, LTD4, LTE4) - potent bronchoconstriction, mucus secretion, edema (1000x more potent than histamine)
• IL-4, IL-13 - IgE production, goblet cell metaplasia
• IL-5 - eosinophil differentiation and survival
• IL-33, TSLP - alarmins from epithelium initiating type 2 inflammation
• PAF (platelet activating factor) - bronchoconstriction, eosinophil recruitment

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Classification

GINA Classification by Symptom Frequency (before treatment)

Classification of Asthma by Type/Endotype

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Clinical Features

Symptoms (Classic Triad)

• Wheeze (high-pitched, expiratory > inspiratory)
• Breathlessness (dyspnea)
• Cough (dry, non-productive; nocturnal cough is classic)
• Chest tightness
• Typically worse at night and early morning
• Episodic with symptom-free intervals

Signs in Acute Attack

• Tachypnea, tachycardia
• Hyperinflated chest (barrel chest in chronic)
• Prolonged expiration with expiratory wheeze
• Use of accessory muscles (sternocleidomastoid, scalenes)
• Intercostal / subcostal retractions
• Pulsus paradoxus > 10 mmHg (indicates severe attack)
• Hyperresonant percussion
• Reduced air entry bilaterally

Signs of Severe / Life-Threatening Attack

• Silent chest (no wheeze = no airflow = ominous)
• Cyanosis
• Inability to complete sentences
• SpO2 < 92%
• Bradycardia / hypotension
• Confusion / exhaustion
• PaCO2 rising (normal or elevated CO2 in asthma = impending respiratory failure)

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Investigations

Spirometry (Most Important)

• Obstructive pattern: FEV1 reduced, FVC reduced/normal, FEV1/FVC ratio < 0.70
• Reversibility: >/= 12% AND >/= 200 mL increase in FEV1 after SABA - confirms asthma
• Bronchial provocation test (methacholine/histamine challenge): if spirometry normal; PC20 < 8 mg/mL = positive (hyperresponsiveness)

Peak Expiratory Flow Rate (PEFR)

• Reduced during attacks
• Diurnal variation > 20% (morning dip) is characteristic of asthma
• Used for monitoring and guiding therapy (personal best PEFR)

ABG (in acute severe attack)

• Mild/Moderate: Respiratory alkalosis (hyperventilation - low PaCO2, high pH)
• Normal or rising PaCO2 = danger sign = impending respiratory failure
• Hypoxemia (low PaO2)

Other Investigations

• Chest X-ray: Hyperinflation (during attack); may show mucus plugging; rule out pneumothorax or pneumonia; usually normal between attacks
• CBC: Eosinophilia (blood eosinophils ≥ 150-300 cells/μL suggests type 2 asthma)
• Total serum IgE + specific IgE / skin prick test - for allergen identification
• Exhaled Nitric Oxide (FeNO): > 25 ppb suggests eosinophilic airway inflammation; predicts ICS response
• Sputum analysis: Eosinophils, Charcot-Leyden crystals, Curschmann's spirals, Creola bodies (shed epithelial clusters)

Classic Sputum Findings in Asthma

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Management

Goals of Therapy (GINA / NAEPP)

1. Symptoms ≤ 2 times/week
2. Night awakenings ≤ 2 times/month
3. Reliever use ≤ 2 times/week (except pre-exercise)
4. No more than 1 exacerbation/year
5. Optimize lung function
6. Maintain normal daily activities
7. Minimal or no side effects

Step-Up / Step-Down Approach

Key change (GINA): ICS/formoterol as-needed is now preferred at ALL steps including step 1. SABA monotherapy is no longer recommended as reliever due to increased asthma mortality.

Drug Classes

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Management of Acute Severe Asthma / Status Asthmaticus

Definition

Immediate Assessment - Features of Severe/Life-Threatening Attack

Treatment Protocol

1. Oxygen - high flow (target SpO2 94-98%)
2. Nebulized SABA (salbutamol 2.5-5 mg) - repeated every 15-20 min or continuous nebulization
3. Ipratropium bromide added to SABA (reduces hospitalizations in severe attacks)
4. Systemic corticosteroids - oral prednisolone 40-50 mg OR IV hydrocortisone 100 mg 6-hourly; begin within 1 hour; continue 5-7 days
5. Position patient upright

• Sedatives / anxiolytics
• Chest physiotherapy during acute attack
• Beta-blockers (even topical for glaucoma)
• NSAIDs / Aspirin in AERD

Markers of Impending Respiratory Failure (ABG)

• Rising / normal PaCO2 (hypercapnia) - most important
• PaO2 < 60 mmHg on O2
• pH < 7.35
• Falling PEFR despite treatment

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Comorbidities that worsen Asthma

1. Chronic rhinosinusitis ± nasal polyposis
2. Obesity
3. GERD
4. Inducible laryngeal obstruction (vocal cord dysfunction)
5. COPD (asthma-COPD overlap)
6. Anxiety / depression
7. Obstructive sleep apnea

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Differential Diagnosis

• COPD (usually irreversible obstruction, older smoker)
• Cardiac asthma (left heart failure)
• Vocal cord dysfunction / inducible laryngeal obstruction
• Bronchiectasis
• Foreign body aspiration (children)
• Eosinophilic bronchitis
• Tracheobronchomalacia
• Alpha-1 antitrypsin deficiency

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Bronchial Thermoplasty

• Bronchoscopic procedure delivering controlled radiofrequency (RF) energy to airways
• Reduces airway smooth muscle mass
• Used in severe persistent asthma not controlled with maximal pharmacotherapy
• 3 sessions (right lower lobe, left lower lobe, both upper lobes)

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Key Exam Points

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Sources

• Harrison's Principles of Internal Medicine, 22E (2025) - pp. 2260-2270
• Murray & Nadel's Textbook of Respiratory Medicine
• Fishman's Pulmonary Diseases and Disorders

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CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

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Definition

1. Emphysema - destruction of alveolar walls with air space enlargement (anatomic definition)
2. Chronic bronchitis - chronic cough and phlegm production for at least 3 months in each of 2 consecutive years (clinical definition)
3. Small airway disease - narrowing and reduced number of small bronchioles (< 2 mm)

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Epidemiology

• 4th leading cause of death in the United States
• Affects > 15 million persons in the US; ~480 million globally (projected 592 million by 2050)
• COPD is more common in males historically, but gender gap is narrowing

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Etiology / Risk Factors

Primary Cause

• Cigarette smoking - most important cause in developed countries (accounts for ~80-90%)
• Not all smokers develop COPD (genetic susceptibility determines who develops it)
• Biomass fuel combustion (wood, cow dung, crop residue) - major cause in developing countries
• Vaping and inhaled cannabis - increasingly recognized, especially in adolescents

Other Risk Factors

• Alpha-1 antitrypsin (AAT) deficiency - most important genetic cause; autosomal recessive; PiZZ phenotype; presents as panacinar emphysema, predominantly in lower lobes, in young non-smokers (age 30-40)
• Occupational exposures: VGDF (vapors, gas, dust, fumes); coal mining, gold mining, cotton textile dust
• Air pollution (fine/ultrafine particulate matter)
• Respiratory infections: childhood pneumonia; tuberculosis (tuberculosis-associated COPD - both emphysematous and fibrotic changes + extensive airway remodeling)
• HIV infection (increased risk, especially with low CD4 count)
• Asthma and airway hyperresponsiveness
• Abnormal lung development / low birth weight
• Poor socioeconomic status

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Pathology and Pathogenesis

Three Pathological Sites

• Mucus gland enlargement (Reid index - mucus gland thickness / bronchial wall thickness; normal < 0.4; in chronic bronchitis > 0.5)
• Goblet cell hyperplasia and metaplasia
• Squamous metaplasia (predisposes to carcinogenesis)
• Neutrophil influx → purulent sputum (elastase is potent secretagogue)

• Major site of increased airflow resistance in COPD
• Goblet cell metaplasia, mucus plugging
• Peribronchial fibrosis, smooth muscle hypertrophy
• Inflammatory cell infiltration (macrophages, CD8+ T cells)

Protease-Antiprotease Imbalance (Key Mechanism)

• Smoking activates macrophages and neutrophils → release elastase, MMP-9, MMP-12
• These proteases destroy connective tissue (elastin, collagen) of alveolar walls
• Normally balanced by alpha-1 antitrypsin (AAT) and SLPI
• Smoking also oxidatively inactivates AAT - double hit
• AAT deficiency severely reduces this protection → premature, severe emphysema

Oxidative Stress

• Cigarette smoke contains enormous amounts of oxidants
• Activates inflammatory transcription factors (NF-κB)
• Inactivates antiproteases
• Causes direct cellular and DNA damage

Key Inflammatory Cells in COPD

• Macrophages (central role - activated by cigarette smoke)
• CD8+ cytotoxic T lymphocytes (predominant T cell subtype - unlike asthma which is CD4+/Th2)
• Neutrophils (in airway lumen)
• Note: eosinophils are NOT the predominant cell (unlike asthma) - though blood eosinophils guide ICS use

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Clinical Features

History - Three Cardinal Symptoms

1. Chronic cough (often productive; sometimes dry)
2. Sputum production (usually mucoid; purulent during exacerbations)
3. Exertional dyspnea (progressive; initially on exertion, eventually at rest)
   • Patients date onset to an acute exacerbation, but symptoms predate this
   • Activities with significant arm work above shoulder level are particularly difficult
   • Activities that allow bracing the arms (pushing shopping cart, treadmill) are better tolerated

Physical Signs

• Barrel chest (increased AP diameter) due to hyperinflation
• Use of accessory muscles (sternocleidomastoid, scalenes)
• Tripod position (leaning forward on arms) to facilitate accessory muscle use
• Prolonged expiratory phase with audible wheeze
• Hyperresonant percussion (emphysema)
• Reduced breath sounds, reduced chest expansion
• Paradoxical inward movement of lower ribs on inspiration (Hoover's sign)

• Cyanosis (central)
• Cachexia and weight loss (elevated TNF-α - independent poor prognostic factor)
• Signs of cor pulmonale: elevated JVP, right ventricular heave, loud P2, peripheral edema

Important: Clubbing is NOT a feature of COPD. Its presence should prompt investigation for lung cancer or other causes.

Pink Puffer vs Blue Bloater (Classical Distinction)

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Investigations

Spirometry (Gold Standard for Diagnosis)

GOLD Grading (Severity of Airflow Obstruction)

GOLD ABE Classification (Guides Treatment)

Other PFT Findings

• Increased TLC, FRC, RV (air trapping and hyperinflation)
• Reduced DLCO (diffusing capacity) - hallmark of emphysema (alveolar destruction reduces gas exchange surface)
• RV/TLC ratio elevated (air trapping)
• Unlike asthma: < 12% reversibility after bronchodilator (not fully reversible)

Chest X-Ray

• Hyperinflation: flat hemidiaphragms, increased retrosternal air space, barrel-shaped thorax
• Increased AP diameter
• Bullae (emphysema - large lucent areas with thin walls)
• Attenuated vascular markings (emphysema)
• "Dirty chest" appearance (chronic bronchitis - increased bronchovascular markings)
• Enlarged pulmonary arteries (cor pulmonale)

HRCT Chest

• Most sensitive for emphysema detection
• Centrilobular emphysema: scattered lucencies, upper-lobe predominant
• Panacinar emphysema: uniform low attenuation, lower-lobe predominant (AAT deficiency)
• Air trapping on expiratory scans
• Airway wall thickening (chronic bronchitis)
• Mucus plugging (associated with increased mortality)

ABG

• Mild-Moderate: Normal or mild hypoxemia
• Severe: Type 2 respiratory failure (hypoxemia + hypercapnia - PaCO2 > 45 mmHg)
• Chronic hypercapnia: compensated respiratory acidosis (normal pH, elevated HCO3-)

Other Tests

• Alpha-1 antitrypsin level - screen if: early-onset (< 45 yrs), lower-lobe emphysema, non-smoker/minimal smoker, family history
• ECG / Echo - right heart strain, cor pulmonale
• CBC - polycythemia (secondary to chronic hypoxia), eosinophil count (guides ICS use)
• CRP, procalcitonin - during exacerbations

BODE Index (Predicts Mortality Better than FEV1 Alone)

• Higher score = worse prognosis
• BODE score ≥ 7 = candidates for lung transplantation evaluation

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Management

Three Interventions Proven to Improve Survival

1. Smoking cessation (most important)
2. Long-term oxygen therapy (LTOT) in chronically hypoxemic patients
3. Lung volume reduction surgery (LVRS) in selected emphysema patients

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Stable COPD Pharmacotherapy

Group A

• Short-acting bronchodilator as needed (SABA or SAMA)

Group B

• Long-acting bronchodilator (LAMA preferred) - start with single LABA or LAMA
• If symptoms persist: LABA + LAMA

Group E (High exacerbation risk)

• LABA + LAMA as initial treatment
• If blood eosinophils ≥ 300/μL: consider LABA + LAMA + ICS (triple therapy)
• Eosinophil count guides ICS use:
  • < 100/μL: ICS unlikely to benefit (do NOT add ICS)
  • 100-299/μL: consider ICS if exacerbations on LABA/LAMA
  • ≥ 300/μL: strong indication for triple therapy

Non-Pharmacological Management

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COPD Exacerbations

Definition

1. Increased dyspnea
2. Increased sputum volume
3. Increased sputum purulence

Precipitating Causes

• Viral infections > 50% (rhinovirus, influenza, parainfluenza, RSV)
• Bacterial infections: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae
• Air pollution, allergens
• Pulmonary embolism (always consider - incidence increased in COPD)
• Medication non-adherence
• No identifiable cause in a significant minority

Assessment of Severity

• Degree of dyspnea and change from baseline
• RR, HR, SpO2
• ABG: PaCO2 > 45 mmHg + pH ≤ 7.35 = respiratory acidosis → NIPPV
• CXR: rule out pneumonia, pneumothorax, cardiac failure (abnormal in ~25%)

• Respiratory acidosis (PaCO2 > 45 mmHg, pH ≤ 7.35)
• New or worsening hypoxemia
• Severe underlying COPD
• Significant comorbidities (heart failure)
• Inadequate home support

Treatment of Acute Exacerbation

• Target SpO2 88-92% (avoid over-oxygenation)
• High-flow O2 causes modest rise in PaCO2 (V/Q mismatch) - do not withhold O2 for hypoxemia

• Nebulized SABA (salbutamol 2.5-5 mg) + SAMA (ipratropium 500 mcg)
• Convert to MDI with spacer when improving

• Prednisolone 40 mg oral for 5 days (equivalent to IV hydrocortisone 100 mg 8-hourly)
• Reduces length of stay, hastens recovery, reduces relapse
• Hyperglycemia is most common complication (especially in diabetics)

• Duration: 5-7 days (moderate-severe exacerbations)
• Choices: amoxicillin-clavulanate, doxycycline, azithromycin, or respiratory fluoroquinolone (levofloxacin)
• Based on local resistance patterns

• Indication: PaCO2 > 45 mmHg AND pH ≤ 7.35 (respiratory acidosis)
• Reduces mortality, need for intubation, hospital stay
• Contraindications: hemodynamic instability, altered consciousness, inability to cooperate, copious secretions, craniofacial abnormalities

• Indications: failed NIPPV, respiratory arrest, severe hypoxemia, hemodynamic instability, altered mental status
• Mortality 17-49% for that hospitalization
• Consider auto-PEEP (dynamic hyperinflation) - ensure adequate expiratory time

Post-Exacerbation Prognosis

• ~20% rehospitalized in 30 days; ~45% in 1 year
• ~20% mortality in the year following hospital discharge

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Cor Pulmonale

• Right heart failure due to COPD (pulmonary hypertension from hypoxic vasoconstriction)
• Signs: elevated JVP, right ventricular heave, loud P2, pansystolic murmur (TR), peripheral edema
• ECG: right axis deviation, P pulmonale (tall P in II > 2.5 mm), RV hypertrophy (R > S in V1)
• Echo: dilated RV, TR, raised RVSP
• Treatment: LTOT (most effective), diuretics for edema, vasodilators not generally effective

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Key Exam Points

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Sources

• Harrison's Principles of Internal Medicine, 22E (2025) - pp. 2293-2302
• Murray & Nadel's Textbook of Respiratory Medicine
• Fishman's Pulmonary Diseases and Disorders

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BRONCHIECTASIS

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Definition

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Morphological Types (Reid's Classification)

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Etiology

By Pattern of Lung Involvement

• Airway obstruction - extrinsic (lymphadenopathy, tumor mass) or intrinsic (foreign body, tumor, scar/stenosis)
• Congenital bronchial atresia

1. Infectious Causes (most common overall)

• Post-infectious (historically most common): whooping cough (Bordetella pertussis), measles (rubeola), influenza, adenovirus, Klebsiella, S. aureus
• Tuberculosis - most common cause in developing countries (cavitary disease + parenchymal destruction)
• Non-tuberculous mycobacteria (NTM) - especially MAC (M. avium-intracellulare complex)
• Granulomatous fungi: Histoplasma capsulatum
• Lung abscess, pneumonia

2. Congenital / Genetic Causes

• Cystic fibrosis (CF) - most common cause in young adults in developed countries; upper-lobe predominant
• Primary Ciliary Dyskinesia (PCD / Kartagener's syndrome) - autosomal recessive; defective dynein arms → immotile cilia → poor mucociliary clearance; Kartagener's triad = bronchiectasis + sinusitis + situs inversus
• Alpha-1 antitrypsin deficiency
• Hypogammaglobulinemia (primary immunodeficiencies: common variable immunodeficiency - CVID, X-linked agammaglobulinemia)
• Cartilage defects: Mounier-Kuhn syndrome (tracheobronchomegaly), Williams-Campbell syndrome (central airway bronchiectasis)
• Congenital cystic disease

3. Immunodeficiency

• Primary (hypogammaglobulinemia, CVID)
• Secondary (HIV, post-transplant bronchiolitis obliterans syndrome - BOS)

4. Autoimmune / Rheumatologic

• Rheumatoid arthritis
• Sjogren's syndrome
• Inflammatory bowel disease (IBD)
• SLE

5. Allergic / Immune-mediated

• Allergic Bronchopulmonary Aspergillosis (ABPA) - immune reaction to Aspergillus; central airway bronchiectasis; associated with refractory asthma; high IgE, eosinophilia, Aspergillus precipitins

6. Chronic Aspiration

• Esophageal motility disorders (scleroderma, achalasia)
• Gastro-oesophageal reflux
• Neuromuscular disorders
• Lower-lobe predominant

7. Miscellaneous

• Yellow nail syndrome (bronchiectasis + pleural effusion + yellow discoloured nails + lymphoedema)
• Traction bronchiectasis (from lung fibrosis - IPF, post-radiation)
• Sarcoidosis, PMF/silicosis
• Young's syndrome (obstructive azoospermia + sinusitis + bronchiectasis)

8. Idiopathic

• 25-50% of cases after workup

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Anatomic Distribution - Clue to Etiology

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Pathogenesis - "Vicious Cycle Hypothesis"

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Clinical Features

Symptoms

• Chronic productive cough - most common symptom; persistent; thick, tenacious, mucopurulent sputum
• Sputum classically described as three-layered on standing (frothy top + mucopurulent middle + thick sediment bottom) - Reid's 3-layer sign
• Haemoptysis - common; can be massive (bronchial arteries dilated and tortuous)
• Breathlessness / exertional dyspnea
• Recurrent chest infections / pneumonia (same lobe)
• Pleuritic chest pain
• Systemic features: fever, weight loss, fatigue (during exacerbations)

Signs

• Coarse crackles (crepitations) - most consistent sign; inspiratory, basal or localised
• Wheeze (bronchospasm)
• Clubbing of fingers (common in bronchiectasis - unlike COPD where clubbing should trigger cancer workup)
• Cyanosis (advanced disease)
• Signs of cor pulmonale (late)
• Signs of underlying disease (joint deformity in RA, nasal polyps in CF/ABPA, situs inversus in Kartagener's)

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Investigations

Imaging

• Often normal in early disease (insensitive)
• Tram-track shadows - dilated bronchi seen end-on as parallel lines ("tram tracks")
• Ring shadows / cystic spaces (cystic bronchiectasis)
• Peribronchial thickening (honeycombing appearance)
• Crowding of lung markings (from volume loss)
• CXR may show causal lesion (old TB, pleural scarring, lymphadenopathy)

1. Inner or outer airway-artery diameter ratio ≥ 1.5 (signet ring sign - bronchus bigger than accompanying vessel)
2. Lack of airway tapering (airways fail to narrow as they proceed distally)
3. Visibility of airways within 1 cm of the pleural surface (normal airways not visible this peripherally)
4. Bronchial wall thickening in dilated airways
5. Tree-in-bud pattern (mucus-filled bronchioles)
6. Cysts emanating from bronchial walls (cystic bronchiectasis)

Signet ring sign = cross-sectional bronchial diameter ≥ 1.5x the adjacent pulmonary artery (most characteristic CT finding)

1. Cough most days of the week
2. Sputum production most days of the week
3. History of exacerbations

Pulmonary Function Tests

• Obstructive pattern most common (FEV1/FVC < 0.70)
• Sometimes mixed obstructive + restrictive
• FVC and FEV1 both reduced in severe disease
• Not fully reversible (unlike asthma)

Sputum

• Gram stain and culture (most important): common organisms:
  • Haemophilus influenzae (most common)
  • Pseudomonas aeruginosa (poor prognosis; in advanced/CF-related disease)
  • S. pneumoniae, Moraxella catarrhalis, S. aureus
  • NTM (MAC) - consider in nonsmoking women > 50 with mid-zone disease
• AFB stain + culture (TB / NTM)
• Fungal culture (ABPA)

Blood Tests

• CBC: eosinophilia (ABPA, parasites), neutrophilia (bacterial infection)
• Immunoglobulins (IgG, IgA, IgM) - screen for hypogammaglobulinemia
• Serum IgE (total and Aspergillus-specific), Aspergillus precipitins, skin prick test - for ABPA
• Sweat chloride test - screen for CF (Cl- > 60 mEq/L = positive)
• Alpha-1 antitrypsin levels
• Rheumatoid factor, ANA, ANCA - connective tissue diseases
• HIV testing
• Nasal nitric oxide (nNO) - reduced (< 77 nL/min) in Primary Ciliary Dyskinesia

Bronchoscopy

• Mandatory in focal bronchiectasis - exclude airway obstruction by mass or foreign body
• BAL for culture (including NTM, fungi)
• Biopsy for cilia ultrastructure (electron microscopy for PCD - absent dynein arms)

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Special Conditions

Kartagener's Syndrome (Primary Ciliary Dyskinesia)

• Autosomal recessive
• Triad: Bronchiectasis + Chronic sinusitis + Situs inversus (dextrocardia)
• Due to absent/abnormal dynein arms on cilia → immotile cilia
• Males: infertility (immotile sperm)
• Diagnosis: nasal NO < 77 nL/min + electron microscopy of cilia (absent dynein arms) + genetic testing

ABPA (Allergic Bronchopulmonary Aspergillosis)

• Hypersensitivity to Aspergillus fumigatus in asthmatics
• Central proximal bronchiectasis (pathognomonic)
• Criteria: refractory asthma + elevated total IgE > 1000 IU/mL + elevated Aspergillus-specific IgE + Aspergillus precipitins + eosinophilia
• CXR/CT: central bronchiectasis, "finger-in-glove" opacities (mucus plugging), consolidation (often fleeting)
• Treatment: oral corticosteroids + itraconazole/voriconazole

Young's Syndrome

• Males: obstructive azoospermia + chronic sinusitis + bronchiectasis
• Normal cilia ultrastructure (unlike PCD)
• Mechanism: abnormal mucus / epididymal obstruction

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Management

Goals

1. Control active infection - reduce microbial load
2. Improve secretion clearance (bronchial hygiene)
3. Treat underlying cause
4. Manage complications (haemoptysis, cor pulmonale)

Airway Clearance Techniques (Bronchial Hygiene) - Cornerstone

• Postural drainage - positioning to drain affected segments by gravity (historically: head-down position)
• Chest physiotherapy - manual percussion (hand clapping) or mechanical
• Oscillatory PEP devices (Flutter valve, Acapella) - positive expiratory pressure + oscillation loosens mucus
• High-frequency chest wall oscillation vest
• Huffing technique
• Hypertonic saline nebulisation - increases mucociliary clearance (reduces exacerbations)
• Nebulized bronchodilators (pre-clearance)
• Pulmonary rehabilitation + regular exercise - improves secretion clearance + exercise capacity

DNase (Dornase alfa): Recommended in CF-related bronchiectasis ONLY. NOT recommended in non-CF bronchiectasis (may cause harm - increased exacerbations in non-CF).

Antibiotic Therapy

• Duration: 7-14 days (minimum 7-10 days)
• Common pathogens: H. influenzae, Pseudomonas aeruginosa
• Oral: amoxicillin-clavulanate, ciprofloxacin (if Pseudomonas suspected)
• IV: for severe exacerbations, Pseudomonas-directed (piperacillin-tazobactam, ceftazidime, meropenem)
• Pseudomonas eradication protocol in newly colonized patients (intensive courses)

• Azithromycin 250 mg three times/week or 500 mg daily 3 days/week - reduces exacerbations; anti-inflammatory + antimicrobial properties; check QT interval and audiology
• Nebulized colistin or tobramycin - for chronic Pseudomonas colonization

• Macrolide (azithromycin/clarithromycin) + rifampicin + ethambutol - triple therapy
• Prolonged treatment (12-18 months or 12 months after negative culture)
• Check macrolide susceptibility

Anti-Inflammatory Therapy

• Inhaled corticosteroids (ICS): may reduce dyspnea and sputum; no significant effect on exacerbation rate or lung function; risk of immunosuppression in infected airways
• Oral corticosteroids: important for ABPA-associated bronchiectasis; not routine
• Statins: anti-inflammatory benefit under investigation
• Oral neutrophil elastase inhibitor (brensocatib): phase 2 trial showed reduced exacerbations (awaiting phase 3 confirmation)

Surgery

• Indications: focal bronchiectasis causing recurrent infections refractory to medical therapy; massive haemoptysis (segmentectomy/lobectomy)
• Not suitable for diffuse disease
• Bronchial artery embolization for massive haemoptysis (bridge to surgery or definitive in diffuse disease)

Lung Transplantation

• For end-stage bilateral diffuse bronchiectasis (especially CF)

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Complications

1. Massive haemoptysis (life-threatening; from dilated bronchial arteries)
2. Recurrent pneumonia / lung abscess
3. Empyema
4. Cor pulmonale (pulmonary hypertension → right heart failure)
5. Amyloidosis (AA type - rare complication of chronic infection)
6. Respiratory failure (hypoxaemia + hypercapnia)
7. Pneumothorax (uncommon)
8. Brain abscess (haematogenous spread in severe infection)

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Key Exam Points

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Sources

• Harrison's Principles of Internal Medicine, 22E (2025) - pp. 2286-2287
• Fishman's Pulmonary Diseases and Disorders - pp. 1579-1584
• Murray & Nadel's Textbook of Respiratory Medicine