Bronchiectasis

Definition

• Robbins & Kumar Basic Pathology, p. 455
• Harrison's Principles of Internal Medicine 22E, p. 2286

Morphological (Radiographic) Classification

• Murray & Nadel's Respiratory Medicine, p. 1575

Pathogenesis

The Vicious Cycle Hypothesis

1. Impaired mucociliary clearance (from CF, ciliary dyskinesia, a single severe infection, etc.) → microbial colonization
2. Chronic infection (especially Pseudomonas aeruginosa, which colonizes damaged airways and evades host defenses) → persistent inflammation
3. Neutrophil-driven damage: neutrophils release elastase, reactive oxygen species, and proteolytic enzymes → airway wall destruction (loss of elastin, smooth muscle, cartilage)
4. Destruction → further impaired clearance → more infection → worsening dilation

Three Mechanical Pathways to Dilation

• Bronchial obstruction → mucus stasis → superimposed infection → wall damage
• Direct bronchial wall damage from necrotizing infection/inflammation
• Traction bronchiectasis: parenchymal fibrosis (e.g., IPF, post-radiation) retracts and pulls open adjacent airways

"Two intertwined processes contribute to bronchiectasis: obstruction and chronic infection. Either may be the initiator." — Robbins & Kumar Basic Pathology, p. 455

Etiology & Predisposing Conditions

Postinfectious

• Childhood lower respiratory tract infections (pertussis, measles, adenovirus)
• Granulomatous infections: tuberculosis (a major cause in endemic regions); post-TB bronchiectasis remains an important cause of morbidity worldwide
• Necrotizing pneumonias (S. aureus, Klebsiella spp.)
• Post-SARS-CoV-2 pneumonia (advanced bronchiectasis reported)

Congenital / Hereditary

• Cystic fibrosis: most common cause in developed nations; viscid mucus → obstruction → severe bilateral bronchiectasis (upper lobe predominance)
• Primary ciliary dyskinesia (immobile cilia syndrome): autosomal recessive; inherited ciliary abnormalities → impaired mucociliary clearance → recurrent infections → bronchiectasis; associated with male sterility (Kartagener syndrome = PCD + situs inversus)
• Immunodeficiency states: hypogammaglobulinemia, IgG subclass deficiencies → recurrent bacterial infections
• α₁-antitrypsin deficiency: may be associated with bronchiectasis (especially ZZ genotype)

Immunological / Systemic

• ABPA (allergic bronchopulmonary aspergillosis): immune-mediated; characteristically causes central airway bronchiectasis
• Autoimmune diseases: rheumatoid arthritis, Sjögren's syndrome (immune-mediated wall damage)

Obstructive

• Tumors, foreign bodies, mucus impaction → localized bronchiectasis in the obstructed segment
• COPD and asthma (mild bronchiectasis is common; moderate-to-severe should trigger workup for underlying cause)

Anatomical Distribution Clues to Etiology

25–50% of referred cases remain idiopathic after workup. — Harrison's, p. 2286

Epidemiology

• Prevalence in the US is increasing, partly due to wider use of HRCT
• More common in women than men
• Incidence increases with age; NTM-associated bronchiectasis classically affects non-smoking women >50 years
• CF-related bronchiectasis presents in late adolescence/early adulthood
• Higher burden in developing nations (TB, malnutrition, immune dysfunction)

Pathology (Gross & Microscopic)

• Gross: Usually affects lower lobes bilaterally (most vertical airways); airways dilated up to 4× normal diameter, visible to within 1 cm of pleural surface (normally bronchioles cannot be followed beyond 2–3 cm from pleura); filled with purulent mucus
• Microscopy: Acute and chronic inflammatory infiltrate within bronchial walls; desquamation of lining epithelium; ulceration; mixed bacterial flora in sputum (Staphylococci, Streptococci, Pseudomonas aeruginosa, H. influenzae). In chronic disease: peribronchial fibrosis, loss of elastin and cartilage. Necrosis may produce abscess cavities.

(Robbins — Cut surface of CF lung showing dilated bronchi extending to sub-pleural regions)

Clinical Features

• Chronic productive cough — the dominant symptom; copious, thick, mucopurulent, sometimes foul-smelling sputum (can be massive in "wet" bronchiectasis)
• Dyspnea
• Hemoptysis — from mucosal vessel injury; can be massive and life-threatening
• Rhinosinusitis
• Crackles and wheezing on auscultation
• Digital clubbing in some patients
• Acute exacerbations: increased sputum volume and purulence; fever and new infiltrates may be absent

Diagnosis

Chest X-Ray

• Poor sensitivity; may be normal
• "Tram tracks" — parallel opaque lines representing thickened dilated bronchial walls seen longitudinally
• Tubular or ring shadows

HRCT (Imaging of Choice)

• Signet-ring sign: cross-section of dilated bronchus with diameter ≥1.5× that of the adjacent pulmonary artery (the bronchus is the "ring," the artery is the "signet")
• Tram-track sign: parallel lines representing longitudinal sections of dilated, thickened, non-tapering bronchi
• Bronchial wall thickening, failure of airways to taper, lack of bronchial disappearance at periphery
• Cystic lucencies (in saccular type); air-fluid levels; mucus plugging; tree-in-bud opacities

Pulmonary Function Tests

• Mild-to-moderate airflow obstruction (overlaps with COPD pattern)
• In severe disease: significant obstructive defect

Microbiological

• Sputum cultures: commonly yield H. influenzae, P. aeruginosa, S. aureus, NTM
• BAL if needed (especially for NTM diagnosis)

Workup for Underlying Etiology

• Sweat chloride / CFTR mutation testing (CF)
• Serum immunoglobulins and IgG subclasses (immunodeficiency)
• Ciliary electron microscopy / nasal NO / genetic testing (PCD)
• Serum IgE, Aspergillus-specific IgE/IgG, skin test (ABPA)
• ANA, RF, anti-CCP (autoimmune)
• HIV testing

Treatment

Airway Clearance (Cornerstone)

• Chest physiotherapy: postural drainage, percussion, oscillatory PEP devices, high-frequency chest wall oscillation vest
• Pulmonary rehabilitation and regular exercise
• Bronchodilators and hyperosmolar agents (e.g., hypertonic saline) by aerosol
• DNase (dornase alfa): recommended in CF-related bronchiectasis; not recommended in non-CF bronchiectasis (lacks efficacy, potential harm)

Antibiotics

• Acute exacerbations: targeted antibiotics (commonly H. influenzae and P. aeruginosa coverage) for 7–14 days
• Chronic macrolide therapy (e.g., azithromycin) has been shown to reduce exacerbation frequency in non-CF bronchiectasis
• NTM (MAC): macrolide + rifampin + ethambutol (only after meeting diagnostic criteria — two positive sputum cultures, or one positive BAL, or histopathology + one positive sputum)

Anti-Inflammatory Therapy

• Inhaled glucocorticoids: may reduce dyspnea and sputum; no proven effect on lung function or exacerbation rates; risks of immunosuppression
• Systemic glucocorticoids: important in ABPA and autoimmune-driven bronchiectasis
• Itraconazole: prolonged course for ABPA
• Neutrophil elastase inhibitors: emerging therapy (phase 2 data showing improved outcomes)

Surgery

• Resection of a focal area of disease in refractory cases
• Lung transplantation in advanced disease

Complications

Prognosis