Cystic fibrosis

Overview

•Most common life-limiting autosomal recessive condition in the UK - 1 in 2,500 live births

•CFTR gene mutation on chromosome 7 - most common UK mutation is ΔF508

•CFTR dysfunction → reduced chloride secretion → thick viscid secretions across multiple organs

Diagnosis

•Newborn screening - heel prick test (IRT); confirmed with genetic testing

•Sweat test - chloride >60 mmol/L on two separate occasions is diagnostic (98% sensitive); chloride, not sodium, is the diagnostic analyte

Management

•Airway clearance: physiotherapy (active cycle of breathing, oscillating PEP) - daily, lifelong

•Mucolytics: dornase alfa (DNase) - inhaled, ≥5 years with FEV1 >40%; hypertonic saline (6-7%) second-line

•Pseudomonas eradication (first isolation): inhaled tobramycin or colistimethate sodium ± oral ciprofloxacin

•Pulmonary exacerbation: IV tobramycin + piperacillin-tazobactam or meropenem (guided by sensitivities)

•CFTR modulator (ΔF508, ≥2 years): elexacaftor/tezacaftor/ivacaftor (Kaftrio) - most significant advance; dramatically improves FEV1 and reduces exacerbations

•Pancreatic enzyme replacement: Creon with all meals and snacks

•Nutrition: fat-soluble vitamin supplementation (A, D, E, K); high-calorie high-fat diet (~120-150% standard requirements)

•CFRD: managed with insulin

•End-stage respiratory failure: bilateral lung transplantation (FEV1 <~30% predicted); Burkholderia cepacia complex is a relative contraindication

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FEV1 is the key prognostic marker. Chronic Pseudomonas aeruginosa colonisation and Burkholderia cepacia infection are associated with accelerated decline.

Complications

•Cystic fibrosis-related diabetes (CFRD) - thick mucus damages pancreas → islet cell destruction → insulin deficiency; NOT type 1 or type 2 DM

•Meconium ileus - intestinal obstruction by thick meconium in neonates (~10-20% of CF neonates)

•Bronchiectasis - upper lobe predominant; progressive

•Male infertility - congenital bilateral absence of vas deferens (CBAVD) → obstructive azoospermia

•Pancreatic exocrine insufficiency - fat malabsorption, steatorrhoea, failure to thrive

•Nasal polyps - in children, almost pathognomonic for CF

•Recurrent respiratory infections - Haemophilus influenzae (early), Staphylococcus aureus, Pseudomonas aeruginosa (most important chronic pathogen), Burkholderia cepacia (poor prognosis)

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CFRD is distinct from type 1 and type 2 DM. It results from progressive destruction of pancreatic islet cells by fibrosis. Treatment is with insulin, not metformin or oral hypoglycaemics. Screening starts at age 10 with annual OGTT.