AKT · Respiratory/Airways diseaselow yield

Cystic fibrosis

Autosomal recessive CFTR mutation (ΔF508) → defective chloride transport → thick secretions

Overview

An autosomal recessive multisystem disease (commonest CFTR mutation ΔF508) in which defective epithelial chloride transport produces thick, viscous secretions affecting the lungs, pancreas, gut and reproductive tract. It is diagnosed in childhood (newborn screening, sweat test) but its burden is increasingly an adult respiratory one — recurrent infections, bronchiectasis and progressive lung disease — with multidisciplinary care and, now, transformative CFTR-modulator therapy. (Paediatric diagnosis/screening detail is on the child_health page.)

Recognise

Respiratory: chronic productive cough, recurrent chest infections, bronchiectasis, breathlessness, clubbing; chronic colonisation with Staph. aureus then Pseudomonas aeruginosa (and Burkholderia cepacia — a transplant contraindication)
Pancreatic insufficiency (steatorrhoea, failure to thrive — needs enzyme replacement), CF-related diabetes; meconium ileus (neonate)/distal intestinal obstruction syndrome
Male infertility (congenital absence of the vas deferens), nasal polyps, fat-soluble vitamin deficiency; diagnosed by sweat test (high chloride) + genetics + newborn screening

Red flags

Massive haemoptysis or a pneumothorax (from bronchiectasis) → emergency
Burkholderia cepacia colonisation → strict infection control (cross-infection risk) and a transplant contraindication; CF-related diabetes/declining lung function → specialist escalation

Differentials & how to tell them apart

Primary ciliary dyskinesia (Kartagener)bronchiectasis + situs inversus + infertility; normal sweat test

Bronchiectasis of other causepost-infective/immunodeficiency/ABPA — CF is a leading cause; sweat test/genetics distinguish

Asthma/COPDno pancreatic/GI/fertility multisystem features or raised sweat chloride

Investigations

Sweat test (raised chloride — diagnostic) + CFTR genetics; newborn blood-spot screening (immunoreactive trypsinogen); sputum culture (Staph, Pseudomonas, Burkholderia); spirometry; faecal elastase (pancreatic insufficiency); glucose (CF-related diabetes); HRCT (bronchiectasis); fat-soluble vitamins.

Management

Airway clearance + mucoactive agents + prompt anti-infective therapy + pancreatic enzymes + CFTR modulators

1Diagnosed in childhood (newborn screening + sweat test/genetics). Manage in a specialist MDT: daily airway clearance and mucoactive agents, prompt aggressive treatment of infective exacerbations, pancreatic enzyme replacement with fat-soluble vitamins, and nutrition.Gate: Burkholderia cepacia colonisation → strict segregation/infection control (cross-infection) and is a lung-transplant contraindication; chronic Pseudomonas changes antibiotic choice.
2Mutation-specific CFTR modulators are transformative; manage CF-related diabetes; lung transplant for end-stage disease. Paediatric diagnosis/screening detail is on the child_health page.

Airway clearance physiotherapy + mucoactive agents (dornase alfa, hypertonic saline) — daily clearance is central; treat infective exacerbations promptly and aggressively (often anti-pseudomonal)

Pancreatic enzyme replacement (Creon) + fat-soluble vitamins (ADEK) + high-calorie diet — for pancreatic insufficiency; manage CF-related diabetes

CFTR modulators (e.g. lumacaftor/ivacaftor, elexacaftor combinations) — mutation-specific; transformative — improve lung function and reduce exacerbations

Infection control + vaccines; lung transplant for end-stage disease — segregate to prevent cross-infection (Burkholderia); MDT specialist care

Key points

Autosomal recessive CFTR defect (ΔF508) → thick secretions: recurrent infections + bronchiectasis + pancreatic insufficiency + male infertility, diagnosed by sweat test (high chloride). Airway clearance + mucoactives + prompt anti-pseudomonal antibiotics + pancreatic enzymes; CFTR modulators are transformative. Burkholderia = segregate + transplant contraindication.

Monitor & prognosis

Lung function/sputum colonisation, nutrition/weight, CF-related diabetes (annual OGTT), liver, fat-soluble vitamins.

Greatly improved survival (now often into adulthood); CFTR modulators are changing the trajectory.

Source: NICE NG78 (cystic fibrosis); cross-ref child_health (screening/paediatrics)