Bronchiectasis

Definition

• Robbins & Kumar Basic Pathology, p. 455
• Grainger & Allison's Diagnostic Radiology, p. 155

Etiology and Predisposing Conditions

• Cystic fibrosis - most common hereditary cause; viscid mucus causes obstruction and chronic infection
• Primary ciliary dyskinesia (Kartagener syndrome) - autosomal recessive; abnormal cilia impair mucociliary clearance; triad of bronchiectasis + sinusitis + situs inversus; associated with male infertility
• Immunodeficiency states - especially immunoglobulin deficiencies (hypogammaglobulinemia), leading to recurrent bacterial infections
• Alpha-1-antitrypsin deficiency

• Necrotizing/suppurative pneumonia (Staphylococcus aureus, Klebsiella spp.)
• Tuberculosis - post-TB bronchiectasis is a major cause in endemic regions
• Post-COVID-19 pneumonia (SARS-CoV-2)

• Tumors, foreign bodies, mucus impaction

• Rheumatic disorders, inflammatory bowel disease
• Chronic aspiration, GERD
• Atopic asthma, chronic bronchitis

Pathogenesis

1. Obstruction (e.g., foreign body) → impaired secretion clearance → superimposed infection
2. Infection → inflammatory damage to bronchial walls + accumulating exudate → further airway distension
3. Alternatively: persistent necrotizing infection → poor secretion clearance → obstruction → peribronchial fibrosis → traction dilation

Morphology and Classification

Clinical Features

• Chronic productive cough - daily, copious mucopurulent sputum (typically >30 mL/day; may range 10-150+ mL)
• Hemoptysis - from chronically inflamed, friable mucosa; massive bleeding can occur from hypertrophied bronchial arteries
• Dyspnea - progressive exertional then resting dyspnea
• Fever, weight loss, fatigue during exacerbations
• Associated rhinosinusitis and postnasal drip common
• "Dry bronchitis" variant: minimal sputum, often upper lobe involvement

• Haemophilus influenzae
• Staphylococcus aureus
• Pseudomonas aeruginosa (especially in advanced/CF-related disease)
• Nontuberculous mycobacteria (NTM) - must always be screened with AFB smear/culture

Diagnosis

Chest X-Ray

Chest radiograph showing tramlines (parallel lines) and ring opacities reflecting dilated, wall-thickened bronchi - Grainger & Allison's Diagnostic Radiology, p. 155

HRCT (Gold Standard)

Post-infectious bronchiectasis on HRCT: bilateral cylindrical bronchiectasis involving right upper and lower lobes with bronchial wall thickening and mucoid impactions - Grainger & Allison's Diagnostic Radiology, p. 157

• Lack of tapering of bronchial lumina (cardinal sign)
• Signet ring sign - bronchial internal diameter > adjacent pulmonary artery diameter
• Bronchi visible within 1 cm of the costal pleura or abutting mediastinal pleura
• Mucus-filled dilated bronchi (glove-finger, V- or Y-shaped densities)
• Tree-in-bud sign - small centrilobular nodular/branching opacities reflecting infectious bronchiolitis (~70% of cases)
• Mosaic perfusion and expiratory air-trapping (obliterative bronchiolitis component)

Functional Assessment

• Spirometry: obstructive pattern (reduced FEV1)
• Sputum cultures including AFB
• Immunoglobulin levels, sweat chloride/CFTR testing, ciliary biopsy as indicated

Management

Underlying Cause

Airway Clearance (Cornerstone of Therapy)

• Chest physiotherapy with postural drainage, percussion, and vibration
• Oscillatory positive expiratory pressure devices (e.g., Acapella, flutter valve) - twice-daily use improves sputum volume and quality of life
• High-frequency chest wall oscillation vests
• Nebulized hypertonic saline (3-7%) - enhances mucociliary clearance, reduces exacerbations, improves FEV1 and quality of life; 7% NaCl produces ~15% FEV1 improvement vs. isotonic saline
• Pulmonary rehabilitation and exercise

Note: Recombinant human DNase (dornase alfa), effective in cystic fibrosis, has deleterious effects in non-CF bronchiectasis and should NOT be used.

Anti-inflammatory Therapy

• Long-term macrolide antibiotics (e.g., azithromycin): reduce exacerbations and improve lung function; inhibit cytokine release, neutrophil adhesion, Pseudomonas migration, and biofilm formation. Caveat: screen and exclude active NTM infection before starting macrolides, as they may drive resistance.
• Inhaled corticosteroids: medium-dose budesonide combined with formoterol is more effective than high-dose ICS alone
• Brensocatib (novel neutrophil elastase inhibitor, 10-25 mg orally daily): prolongs time to first exacerbation in non-CF bronchiectasis patients with ≥2 exacerbations/year - Goldman-Cecil Medicine, p. 917

Antimicrobial Therapy

• Acute exacerbations: 2-3 week course of broad-spectrum IV antibiotics tailored to culture/sensitivity, followed by oral regimen
• Inhaled antibiotics (tobramycin, colistin): improve bacterial clearance, may slow FEV1 decline; however, meta-analysis of 12 RCTs (n=1154) showed no reduction in exacerbation risk and no quality-of-life improvement
• Bronchodilators (inhaled β2-agonists): improve mucociliary clearance and reverse associated bronchoconstriction; no routine indication without confirmed airway reactivity

Surgical Options

Complications

• Progressive airflow obstruction (bronchiectasis in COPD is associated with increased mortality)
• Massive hemoptysis
• Lung abscess, empyema
• Cor pulmonale (right heart failure from chronic hypoxia)
• Amyloidosis (in longstanding disease)
• NTM superinfection

Recent Evidence (2024-2026)

• A 2026 systematic review and meta-analysis on mucoactive agents (PMID 42342264) in bronchiectasis is now published in European Respiratory Review
• A 2026 network meta-analysis in Chest on anti-inflammatory therapies in non-CF bronchiectasis (PMID 41534709) - reinforcing the role of macrolides and evaluating newer agents
• Obstructive sleep apnea has been identified as a significant comorbidity in bronchiectasis (PMID 41905893)

Three Types of Bronchiectasis

1. Cylindrical (Tubular) - Mild

• Airways are uniformly and symmetrically dilated with no tapering as they travel distally
• Bronchial walls are smooth and regular
• On HRCT: "tram-track sign" on longitudinal view; signet ring sign on cross-section (bronchus larger than adjacent pulmonary artery)
• Mildest form; best prognosis

2. Varicose - Moderate

• Irregular alternating dilation and constriction of the airway wall, resembling varicose veins
• Non-uniform, serpiginous (twisting) dilation with focal outpouchings
• On HRCT: beaded configuration of the bronchial lumen
• Intermediate severity

3. Cystic (Saccular) - Severe

• Balloon-like or grape-like peripheral sacs at the end of bronchi
• Distal airways destroyed and replaced by clusters of cysts
• On HRCT: string of cysts (bronchi cut along their length) or cluster of cysts (adjacent dilated bronchi); air-fluid levels common from retained secretions
• Most severe form; most common after bronchial obstruction or severe necrotizing infection
• Confluent cystic distortion produces bronchiectatic consolidation and volume loss

Severity increases: Cylindrical → Varicose → Cystic

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Cor Pulmonale

Definition

• Robbins & Kumar Basic Pathology, p. 363

Etiology - Causes of Underlying Pulmonary Hypertension

Pathophysiology

Fig. 59-1: Pathophysiology of cor pulmonale - Fuster & Hurst's The Heart, 15th Ed., p. 1799

Central illustration: Pulmonary hypertension in structural lung disease - Fuster & Hurst's The Heart, 15th Ed.

Key mechanisms raising pulmonary vascular resistance (PVR):

1. Alveolar hypoxia (dominant driver) - acute hypoxia causes vasoconstriction of small muscular pulmonary arteries (50-100 μm); chronic hypoxia causes vascular stiffness and remodeling
2. Loss of vascular cross-sectional area - destruction/obliteration from emphysema or fibrosis
3. Endothelial dysfunction - reduced NO and prostacyclin (vasodilators) + increased endothelin (vasoconstrictor), promoting vascular remodeling
4. Hypercapnia and acidosis - potentiates hypoxic vasoconstriction
5. Polycythemia - secondary erythrocytosis from chronic hypoxia increases blood viscosity and PVR
6. Hypervolemia and thromboembolism - contribute mechanically
7. Vascular inflammation - CD8+ T-cell infiltration of pulmonary arterial walls, intimal thickening, smooth muscle proliferation

Morphology

(B) Chronic cor pulmonale - right ventricle (left side of image) markedly dilated and hypertrophied with thickened free wall and hypertrophied trabeculae. The enlarged RV distorts the shape and volume of the left ventricle. - Robbins & Kumar, p. 363

• Acute cor pulmonale (e.g., massive PE): right ventricle shows only dilation; may even be of normal size if sudden death occurs
• Chronic cor pulmonale: RV + often right atrial hypertrophy; in extreme cases the RV free wall thickness equals or exceeds that of the left ventricle; pulmonary arteries show abnormal intimal thickening

Clinical Features

• Dyspnea (progressive, exertional then at rest)
• Fatigue, reduced exercise tolerance
• Peripheral edema (ankle swelling)
• Syncope on exertion (in severe pulmonary hypertension)

• Jugular venous distension with prominent V wave (tricuspid regurgitation)
• Right ventricular heave (parasternal)
• Loud P2 (accentuated pulmonary component of S2)
• Graham Steell murmur - early diastolic murmur of pulmonary regurgitation (late finding)
• Hepatomegaly, ascites, peripheral edema (late - signs of RV volume overload)
• Cyanosis (from underlying lung disease and hypoxemia)

Why Edema Develops (Mechanism)

1. Chronic hypercapnia → renal compensatory sodium and bicarbonate retention → fluid retention
2. Reduced effective renal plasma flow → impaired urinary sodium excretion
3. Activation of the renin-angiotensin-aldosterone system

Investigations

ECG

• P pulmonale - peaked P waves >2.5 mm in lead II (right atrial enlargement)
• Right axis deviation (QRS axis >+90°)
• R/S ratio >1 in V1 (RV hypertrophy)
• S1Q3T3 pattern (acute cor pulmonale from PE)
• Incomplete or complete right bundle branch block
• ST depression and T-wave inversion in right precordial leads (V1-V4)

Echocardiography

• Dilated RV with reduced RV function
• RV free wall hypertrophy (>5 mm)
• Paradoxical interventricular septal motion ("D-shape" of LV on short axis)
• Doppler estimation of pulmonary artery systolic pressure via tricuspid regurgitation jet velocity
• Note: Doppler-estimated PA pressure correlates poorly with direct catheter measurements in severe disease

Chest X-Ray

• Prominent pulmonary arteries (central pulmonary artery dilation)
• Cardiomegaly with right heart enlargement
• Oligaemic peripheral lung fields
• Evidence of underlying lung disease

Right Heart Catheterization (Gold Standard)

• Directly measures pulmonary artery pressure (mean PAP >20 mmHg = pulmonary hypertension)
• Pulmonary capillary wedge pressure normal (rules out left heart cause)
• Used when noninvasive studies are inconclusive

Additional

• Pulmonary function tests, ABG, CT pulmonary angiography (to exclude PE)
• Cardiac MRI: most accurate assessment of RV volumes and function

Management

Primary Approach: Treat the Underlying Lung Disease

• Optimize bronchodilators, inhaled corticosteroids for COPD/asthma
• CPAP/BiPAP for OSA or hypoventilation syndromes
• Nocturnal noninvasive ventilation in stable chronic hypercapnia (neuromuscular disease, kyphoscoliosis)

Long-Term Oxygen Therapy (LTOT) - Cornerstone

• Indications: PaO2 <55 mmHg on room air, OR PaO2 <59 mmHg if edema, polycythemia, or P pulmonale on ECG are present
• Reduces hypoxic vasoconstriction, lowers PVR, reduces polycythemia
• Goal: SaO2 ≥90%; use ≥15 hours/day

Diuretics

• Reduce volume overload and edema; optimize preload
• Monitor electrolytes carefully; avoid over-diuresis (RV is preload-dependent)

Vasodilators

• Calcium channel blockers and other vasodilators can dilate the pulmonary circulation but may worsen hypoxemia - benefit not established in secondary cor pulmonale
• PAH-specific agents (sildenafil, endothelin receptor antagonists, prostacyclins) are used in idiopathic PAH but evidence is limited in cor pulmonale from structural lung disease

Polycythemia

• Traditionally treated with phlebotomy; recent cohort data suggest polycythemia is less common than expected and has uncertain effect on outcomes
• Hematocrit kept <55% if polycythemia present

Prognosis

• Once cor pulmonale is established, survival is significantly diminished
• If mean pulmonary artery pressure exceeds 25 mmHg, average 5-year survival is reduced by 50%