Bronchiectasis & Cystic Fibrosis in Adults

Bronchiectasis: presentation and imaging

A vicious cycle. Bronchiectasis is permanent, abnormal dilation of the bronchi. Impaired mucus clearance allows chronic bacterial infection, which recruits neutrophils whose elastase and other proteases damage the airway wall; the dilated airway then clears mucus even less well, and the cycle continues.

Presentation. Chronic cough with daily mucopurulent sputum, recurrent chest infections, hemoptysis, dyspnea, and fatigue. Examination shows coarse crackles, wheeze, and sometimes clubbing, and spirometry usually shows obstruction. Massive hemoptysis arises from hypertrophied bronchial arteries and is controlled with bronchial artery embolization.

Imaging. Noncontrast high-resolution CT is the diagnostic test. It shows a bronchoarterial ratio >1 (signet ring sign), loss of normal tapering (tram tracks), airways visible within 1 cm of the pleura, mucus plugging, and tree-in-bud opacities. The chest radiograph is often normal or shows only ring shadows and tram lines.

Finding the cause

Baseline tests for everyone. CBC with differential, serum IgG, IgA, and IgM, total IgE with Aspergillus-specific IgE, and sputum bacterial and mycobacterial cultures. Further tests follow the clues below. Many cases remain idiopathic, but finding a treatable cause changes management.

Cystic fibrosis in adults. Milder CFTR mutations can present late with bronchiectasis, pansinusitis or nasal polyps, recurrent pancreatitis, or male infertility. A sweat chloride ≥60 mmol/L (pilocarpine iontophoresis) confirms CF; 30–59 mmol/L is intermediate and calls for CFTR genotyping (two disease-causing mutations) or nasal potential difference testing.

CVID. Low IgG with low IgA and/or IgM and poor vaccine responses; lifelong IV or subcutaneous immunoglobulin replacement reduces infections and slows lung damage.

Primary ciliary dyskinesia. Autosomal recessive defects in ciliary dynein arms cause neonatal respiratory distress, a year-round wet cough from infancy, chronic sinusitis and otitis, middle- and lower-lobe bronchiectasis, immotile sperm, and a higher risk of ectopic pregnancy. About half of patients have situs inversus (Kartagener syndrome). Nasal nitric oxide is low; electron or high-speed video microscopy of cilia, or genetic testing, confirms it.

Managing non-CF bronchiectasis

Airway clearance. Daily clearance is the foundation: the active cycle of breathing technique, oscillating positive expiratory pressure devices, high-frequency chest wall oscillation, and exercise or pulmonary rehabilitation. Nebulized hypertonic saline hydrates secretions; give a bronchodilator first to prevent bronchospasm. Vaccinate against influenza and pneumococcus. Surgical resection is reserved for localized disease with uncontrolled symptoms or bleeding.

Dornase alfa helps CF but increased exacerbations and FEV1 decline in non-CF bronchiectasis; do not use it there.

Exacerbations. An exacerbation is at least 48 hours of worsening in three or more of cough, sputum volume, sputum purulence, dyspnea, fatigue, or hemoptysis, prompting a change in treatment. Send sputum for culture, then treat for 14 days guided by prior isolates. H. influenzae, the most common organism, is treated with amoxicillin or amoxicillin-clavulanate. Pseudomonas is treated with oral ciprofloxacin or levofloxacin, the only oral antipseudomonal drugs, or with an IV antipseudomonal β-lactam when the exacerbation is severe.

Pseudomonas aeruginosa. Chronic infection roughly triples mortality and increases exacerbations and admissions. At first isolation, attempt eradication with 2 weeks of ciprofloxacin (or IV therapy) followed by about 3 months of inhaled colistin, gentamicin, or tobramycin. Chronic infection with frequent exacerbations calls for long-term inhaled antibiotics.

Macrolides. Three or more exacerbations a year despite good airway clearance justifies long-term azithromycin or erythromycin, whose anti-inflammatory effect cuts exacerbations roughly in half. First exclude NTM with sputum mycobacterial cultures, because macrolide monotherapy selects macrolide-resistant MAC; also obtain a baseline ECG for QTc and a hearing assessment.

Brensocatib. This oral DPP1 inhibitor blocks neutrophil serine protease activation and, in the ASPEN trial, reduced exacerbations in non-CF bronchiectasis; it was FDA approved in 2025 for patients 12 years and older and is an option for frequent exacerbators.

Cystic fibrosis in adults

Disease basis. CF is autosomal recessive, caused by mutations in CFTR on chromosome 7; F508del, a misfolding mutation, is the most common. Defective chloride and bicarbonate secretion dehydrates secretions in the airways, pancreas, bowel, biliary tree, and reproductive tract. Most patients now live well into adulthood.

CFTR modulators. Elexacaftor-tezacaftor-ivacaftor pairs two correctors, which help misfolded CFTR reach the cell surface, with a potentiator that holds the channel open. It is indicated for patients with at least one F508del or other responsive mutation and raises FEV1 by about 10–14 percentage points, lowers sweat chloride, improves weight, and reduces exacerbations. Ivacaftor alone treats gating mutations such as G551D. Monitor liver enzymes; these CYP3A substrates require avoiding strong inducers (rifampin, St. John's wort) and dose reduction with strong inhibitors.

Other adult problems. Chronic sinusitis with polyps, CF liver disease, low bone density, and ABPA. Meconium ileus is the newborn counterpart of DIOS and usually signals CF.

Microbiology. Airway flora shifts with age: S. aureus and H. influenzae in childhood, then chronic mucoid Pseudomonas, then Burkholderia cepacia complex, MRSA, Stenotrophomonas, and M. abscessus in adults. B. cepacia complex is intrinsically resistant to polymyxins and aminoglycosides, spreads between patients (so patients with CF are segregated from each other), can cause a fatal necrotizing pneumonia with bacteremia called cepacia syndrome, and may exclude a patient from lung transplantation.