Cystic fibrosis | 0.6%–2.7% | Younger age (< 45 yr); history of malabsorption; history of pancreatitis; history of Pseudomonas aeruginosa infection, Staphylococcus aureus infection, nontuberculous mycobacterial infection; history of male infertility | Sweat chloride assessment; CFTR genetic analysis as per guidelines (specialist centre referral) |
Alpha1-antitrypsin deficiency | 0.6%–11.3% | Evidence of emphysema; obstructive pattern on spirometry; panniculitis | Serum alpha1-antitrypsin level; phenotyping in those with low serum levels |
Primary ciliary dyskinesia | 2.0%–10.3% | History of chronic upper respiratory tract problems, otitis media, male infertility; abnormal ciliary beat pattern ± frequency on nasal brushings | Measurement of nasal nitric oxide levels; ciliated epithelial biopsy (specialist centre referral) |
Allergic bronchopulmonary aspergillosis | 0.9%–7.8% | History of asthma; peripheral blood eosinophils > 500 cells/μL; positive Aspergillus fumigatus IgG or positive precipitins; sputum culture of A. fumigatus; fleeting infiltrates on chest radiograph or CT chest; proximal bronchiectasis on CT chest scan | Total IgE > 500 IU/mL; positive A. fumigatus–specific IgE or immediate reaction on skin-prick testing |
Autoimmune/connective tissue diseases (typically rheumatoid arthritis, SLE) | 1.8%–31.1% | History or clinical signs of connective tissue disease ± vasculitis | Rheumatoid factor; anti-CCP; other investigations pertinent to suspected diagnosis from clinical review |
Inflammatory bowel diseases | 1.0%–3.0% | History or clinical signs of ulcerative colitis or Crohn disease | Specialist gastrointestinal review; positive pathological features on colonoscopy |
Congenital malformations | 0.2%–0.6% | Williams–Campbell syndrome (bronchomalacia); Mounier-Kuhn syndrome (tracheobronchomegaly) and lung sequestration | Typically diagnosed on chest CT |
Aspiration | 0.2%–11.3% | History of reflux; history of aspiration | Various modalities available: video fluoroscopic swallow study; upper gastrointestinal endoscopy; ambulatory esophageal manometry; pH studies; flexible endoscopic evaluation of swallow |
Humoral immunodeficiency | 1.1%–16.0% | History of recurrent infections | Serum immunoglobulins levels (IgG, IgA and IgM); specific antibody responses to pneuomococcal, Haemophilus influenzae B and tetanus antigens |
Postinfectious* | 29.0%–42.0% | History or radiologic evidence of previous infection (e.g., frequently, pneumonia, Bordetella pertussis, Mycobacterium tuberculosis, nontuberculous mycobacteria) | |
Idiopathic* | 26.0%–53.0% | Other causes excluded | Other causes excluded |