RespiratoryTier 1Disease (DEADMAN)

Bronchiectasis

Description

  • Permanent, irreversible dilatation of bronchi with chronic cough, sputum and recurrent infection
    • Radiological + clinical: bronchial dilatation on CT alone is not bronchiectasis without symptoms
The vicious vortex (Cole's cycle, updated)

Impaired mucociliary clearance -> chronic bacterial infection -> neutrophilic inflammation -> airway wall destruction -> more impaired clearance

  • Neutrophil elastase is the dominant destructive mediator (the brensocatib target)
  • Each element can be entered from any point - this is why the treatment attacks all four simultaneously
Morphological patterns (Reid)
  • Cylindrical - mildest, tram-track/signet-ring
  • Varicose - beaded
  • Cystic/saccular - most severe, grape-like clusters, air-fluid levels
Distribution -> aetiology
DistributionThink
Upper lobeCF, ABPA, post-TB, sarcoid
Right middle lobe / lingulaNTM ("Lady Windermere" - elderly thin women, MAC), foreign body
Lower lobePost-infective, aspiration, immunodeficiency, PCD
Central/perihilarABPA (with mucus plugging), tracheobronchomegaly
Focal/unilateralObstruction - tumour, foreign body, node - CT and bronchoscope it

Epidemiology

  • Prevalence rising with CT use: ~0.5-1% of adults; >1% over age 70
  • F>M; median age at diagnosis ~60s
  • Aboriginal and Torres Strait Islander peoples: among the highest documented rates in the world - post-infective, from childhood pneumonia and chronic suppurative lung disease
    • Prevalence in some remote communities exceeds 1 in 70 children
  • Often diagnosed years after symptom onset, mislabelled as COPD or asthma
  • ~30-40% have no cause identified despite full workup

Aetiopathogenesis1 exam ›

Post-infective (~30%) - the commonest identified cause
  • Childhood pneumonia, pertussis, measles, adenovirus
  • Tuberculosis and NTM; NTM can be cause or consequence
  • Severe necrotising pneumonia (S. aureus, Klebsiella)
Airway/immune defects
  • Cystic fibrosis - test sweat chloride and CFTR genotype in any adult with unexplained bronchiectasis, especially upper lobe, pancreatic or fertility issues
  • Primary ciliary dyskinesia - AR, defective dynein arms (absent, shortened or normal-length but non-functional)
    • Neonatal respiratory distress, wet cough from infancy, chronic rhinosinusitis, frontal sinus agenesis, recurrent otitis media with conductive hearing loss, infertility
    • ~50% have situs inversus; Kartagener = bronchiectasis + sinusitis + situs inversus (complete ciliary immotility)
    • Screen: nasal nitric oxide (very low); confirm with high-speed video microscopy, electron microscopy, genetics
  • Immunodeficiency - CVID (the most important to find - IVIg is transformative), XLA, IgG subclass deficiency, specific antibody deficiency, HIV, secondary to haematological malignancy or rituximab
  • Alpha-1 antitrypsin deficiency
Immune-mediated / inflammatory
  • ABPA - central bronchiectasis with mucus plugging; total IgE >1000, Aspergillus-specific IgE
  • Rheumatoid arthritis - may precede the arthritis; associated with worse RA outcomes
  • IBD (esp. ulcerative colitis), Sjogren, SLE, relapsing polychondritis, ankylosing spondylitis
Obstruction and aspiration
  • Tumour, foreign body, lymph node, middle lobe syndrome
  • Chronic aspiration, GORD, achalasia, oesophageal dysmotility
Structural / congenital
  • Tracheobronchomegaly (Mounier-Kuhn), Williams-Campbell (cartilage deficiency)
  • Yellow nail syndrome - yellow nails + lymphoedema + pleural effusion
  • Marfan, Ehlers-Danlos, alpha-1 antitrypsin deficiency
Other
  • Post-transplant/GVHD (bronchiolitis obliterans), inhalational injury (ammonia, chlorine, smoke), radiation
  • Traction bronchiectasis in fibrotic ILD (a different entity - not suppurative)
Microbiology - drives prognosis
  • *Haemophilus influenzae* - commonest overall
  • *Pseudomonas aeruginosa - the key prognostic organism*: more exacerbations, faster FEV1 decline, worse quality of life, higher mortality
  • Moraxella, S. pneumoniae, S. aureus (consider CF or ABPA if MSSA), Enterobacteriaceae
  • NTM (MAC, M. abscessus) - screen before starting long-term macrolide
  • Aspergillus - colonisation, ABPA, aspergilloma

Diagnosis1 exam ›

Clinical
  • Chronic productive cough with daily mucopurulent sputum - the cardinal symptom; quantify volume and colour
  • Recurrent chest infections, dyspnoea, haemoptysis (~25-50%), pleuritic pain, fatigue, sinusitis
  • Coarse inspiratory crackles that change with coughing, wheeze, clubbing (~3-10%, less common than taught)
  • Consider it in: "COPD" in a never-smoker, recurrent pneumonia in the same lobe, chronic productive cough >8 weeks, unexplained haemoptysis
Diagnosis
  • HRCT chest is diagnostic
    • Bronchoarterial ratio >1 (signet ring sign)
    • Lack of normal tapering toward the periphery
    • Airway visible within 1 cm of the pleura
    • Supporting: bronchial wall thickening, mucus plugging, tree-in-bud, mosaic attenuation/air trapping
Aetiological workup - do it once, properly

Minimum in everyone

  • FBC with differential, immunoglobulins (IgG, IgA, IgM), serum electrophoresis
  • Total IgE + Aspergillus-specific IgE/precipitins (ABPA)
  • Sputum culture (bacterial, mycobacterial, fungal)
  • Spirometry with reversibility

Targeted

  • CF: sweat chloride + CFTR genotype - low threshold under 40, upper lobe disease, S. aureus, malabsorption, infertility
  • PCD: nasal NO, ciliary studies - lifelong symptoms from infancy, situs inversus, otitis media, infertility
  • Alpha-1 antitrypsin
  • RF, anti-CCP, ANA/ENA - CTD
  • Specific antibody responses to pneumococcal/Hib vaccine if immunoglobulins borderline
  • HIV serology; bronchoscopy if focal disease (exclude obstruction)
Assessing severity and future risk
  • Bronchiectasis Severity Index (BSI) and FACED score
    • Components: *age, BMI, FEV1, hospitalisation, exacerbations, MRC dyspnoea, Pseudomonas colonisation, radiological extent*
  • *The dominant predictors of future exacerbation are: prior exacerbations, Pseudomonas infection, and radiological extent*
Sputum monitoring
  • Culture at diagnosis, at exacerbation, and periodically when stable
  • Repeated NTM screening - especially before and during long-term macrolide

Management

Four parallel axes, all pursued at once: treat the cause, clear the airway, control infection, control inflammation.

1. Treat the underlying cause where one exists
  • CVID -> immunoglobulin replacement (the single most disease-altering intervention when it applies)
  • ABPA -> corticosteroid +/- itraconazole
  • CF -> CFTR modulators; NTM -> guideline-directed multidrug therapy
  • RA, IBD -> treat the systemic disease; GORD/aspiration -> treat
  • Obstruction -> remove it
2. Airway clearance - the foundation, in every patient
  • Daily physiotherapy: active cycle of breathing technique, autogenic drainage, PEP/oscillating PEP devices, postural drainage
  • Nebulised hypertonic saline (6-7%) or mannitol before clearance; pre-treat with a bronchodilator
  • *Dornase alfa is CONTRAINDICATED in non-CF bronchiectasis - it worsened outcomes in trials. This is the most examinable therapeutic contrast between CF and non-CF disease*
  • Pulmonary rehabilitation and regular exercise - strongly recommended
3. Infection control

### First isolation of Pseudomonas aeruginosa

  • Attempt eradication - oral ciprofloxacin +/- inhaled colistin or tobramycin (2-3 months)
    • ERS 2025 makes this a conditional recommendation - the evidence is weaker than in CF

### Chronic infection with >=3 exacerbations/yr

Long-term macrolide (azithromycin 250-500 mg 3x/week)Strongly recommended - reduces exacerbations (BAT, EMBRACE, BLESS). *Exclude NTM, check QTc and hearing first*
Long-term inhaled antibiotic*Strongly recommended for chronic P. aeruginosa*** - nebulised colistin, tobramycin, gentamicin, aztreonam

### Exacerbation

  • 14 days of antibiotics, guided by the most recent sputum culture
    • Empirical: amoxicillin or doxycycline; *ciprofloxacin if Pseudomonas***
    • IV antipseudomonal combination if severe or failing oral therapy
  • Increase airway clearance intensity during exacerbations
4. Anti-inflammatory therapy - the new axis
  • Brensocatib - oral DPP-1 inhibitor; blocks activation of neutrophil serine proteases including neutrophil elastase
    • ASPEN: ~20% reduction in exacerbation rate at both doses; 25 mg attenuated FEV1 decline
    • First disease-modifying therapy approved for bronchiectasis (FDA Aug 2025); for frequent exacerbators
    • Adverse effects: hyperkeratosis, periodontal disease, cough; check Australian availability
  • *Inhaled corticosteroids are NOT indicated unless there is coexisting asthma or COPD* - no benefit, increases pneumonia and NTM risk
  • Bronchodilators only if demonstrable obstruction or symptomatic benefit
5. General
  • Vaccination - influenza, pneumococcal, COVID-19, pertussis, RSV
  • Smoking cessation; nutrition (low BMI is prognostic); treat sinus disease
  • Manage anxiety, cough and incontinence (often unreported and highly disabling)
  • Long-term oxygen if chronic hypoxaemia; NIV for chronic hypercapnia
6. Haemoptysis
  • Tranexamic acid (oral, IV or nebulised) - conditionally recommended
  • Massive haemoptysis: bleeding side down, secure airway, bronchial artery embolisation (bronchial arteries hypertrophy in bronchiectasis)
  • Surgery as a last resort
7. Surgery and transplant
  • Resection for localised disease with refractory symptoms or recurrent haemoptysis after maximal medical therapy
  • Bilateral lung transplantation for end-stage disease (single is contraindicated - suppurative)
8. Follow-up
  • Sputum culture, spirometry, exacerbation count, BSI at review
  • Re-screen for NTM annually and before macrolide initiation
  • Reassess the aetiological workup if the phenotype changes

Associations

  • COPD - overlap phenotype; worse exacerbations, higher mortality than either alone
  • Asthma and ABPA
  • Rheumatoid arthritis - may precede joint disease by years
  • Inflammatory bowel disease - especially ulcerative colitis, sometimes post-colectomy
  • Sjogren, SLE, ankylosing spondylitis, relapsing polychondritis, Marfan, Ehlers-Danlos
  • CVID and other primary immunodeficiency
  • CF, PCD, alpha-1 antitrypsin deficiency
  • Chronic rhinosinusitis - near-universal in PCD and CF
  • NTM lung disease - MAC in the "Lady Windermere" phenotype
  • GORD and aspiration
  • Yellow nail syndrome; Mounier-Kuhn (tracheobronchomegaly)
  • Osteoporosis, depression, urinary incontinence, sleep disturbance
  • Amyloidosis (AA) - chronic suppuration, now rare

Natural history & complications

  • Slowly progressive; FEV1 declines ~50-55 mL/yr, faster with Pseudomonas and frequent exacerbations
  • Exacerbations drive decline - each is associated with lung function loss, worse quality of life and higher mortality
  • Frequent-exacerbator phenotype (>=3/yr) is stable over time and identifies the group needing suppressive therapy
  • Mortality: ~10-30% at 5 years in severe disease (BSI high category); prognosis in mild disease is good
Poor prognostic markers
  • *Chronic Pseudomonas aeruginosa infection* - the strongest modifiable marker
  • Frequent exacerbations and hospitalisation
  • Low FEV1, low BMI, older age, extensive radiological involvement
  • Coexisting COPD, pulmonary hypertension, chronic hypoxaemia
  • High BSI or FACED score
Complications
  • Recurrent exacerbation and pneumonia
  • Haemoptysis - including massive from hypertrophied bronchial arteries
  • Chronic respiratory failure and cor pulmonale
  • NTM infection - increasingly common, particularly on long-term macrolide
  • Aspergilloma in a cavity
  • Empyema, lung abscess, pneumothorax
  • AA amyloidosis (rare)
  • Malnutrition, osteoporosis, depression, social isolation, urinary incontinence from cough
Monitor
  • Sputum volume/colour, exacerbation frequency, spirometry, BMI
  • Sputum culture including mycobacteria; QTc and audiometry on long-term macrolide
  • Oxygenation, symptoms of right heart failure

7 of 7 sections written · drafted 2026-09-04