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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Autosomal recessive — commonest life-limiting inherited disease in Caucasians; carrier frequency ~1 in 25
- CFTR gene mutation (F508del most common, ~70%) — defective chloride channel causing thick secretions in lungs, pancreas, and other organs
- Diagnosis: newborn screening (heel prick, day 5) + sweat test (sweat chloride ≥60 mmol/L = diagnostic) + genotyping
- Respiratory: progressive bronchiectasis, Pseudomonas colonisation, eventually respiratory failure
- CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor — Kaftrio) has transformed outcomes for eligible patients
Overview
Cystic fibrosis (CF) is an autosomal recessive condition caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene on chromosome 7. The CFTR protein is a chloride and bicarbonate channel in epithelial cells. Dysfunction leads to dehydrated, viscous secretions that obstruct airways, pancreatic ducts, bile ducts, vas deferens, and intestines. The lungs are the major site of morbidity and mortality — a cycle of mucus plugging, chronic infection (especially Pseudomonas aeruginosa and Staphylococcus aureus), and progressive bronchiectasis. More than 1,700 CFTR mutations have been identified; F508del (phenylalanine deletion at position 508) is present in approximately 70% of UK patients.
Epidemiology
CF affects approximately 10,800 people in the UK and approximately 1 in 2,500 live births in the Caucasian population. Carrier frequency is approximately 1 in 25. UK newborn screening (heel prick test at day 5) detects elevated immunoreactive trypsinogen (IRT), followed by genetic testing and sweat test for confirmation. Median predicted survival has improved dramatically from ~30 years in the early 2000s to over 50 years currently, driven by improvements in nutrition, airway clearance, antibiotics, and — most recently — CFTR modulator therapy.
Clinical Features
Symptoms
Chronic productive cough with thick, tenacious sputum
Recurrent lower respiratory tract infections (particularly Pseudomonas and Staphylococcus)
Malabsorption: steatorrhoea (pale, greasy, foul-smelling stools), failure to thrive in children
Nasal polyps and chronic sinusitis
Male infertility (bilateral absence of vas deferens — present in ~98%)
Meconium ileus in neonates (15–20%) — presents as bowel obstruction in the first days of life
Haemoptysis (from bronchiectasis)
Signs
Finger clubbing
Hyperinflated chest
Coarse crackles and wheeze
Poor growth and low BMI despite good appetite
Rectal prolapse (in children)
Signs of liver disease (hepatomegaly, jaundice) in advanced CF
Investigations
First-line
Newborn screening (IRT)UK heel prick test at day 5 — elevated IRT triggers further testing
Sweat test (quantitative pilocarpine iontophoresis)Gold standard for diagnosis — sweat chloride ≥60 mmol/L = diagnostic; 30–59 = borderline/equivocal
CFTR genotypingIdentifies specific mutations — essential for determining eligibility for CFTR modulator therapy
Second-line
Sputum cultureRegular surveillance for respiratory pathogens — Pseudomonas, S. aureus, Burkholderia cepacia complex, NTM
Spirometry (FEV1)Key measure of disease progression — monitored at every clinic visit
Faecal elastaseLow (<200 µg/g) confirms pancreatic exocrine insufficiency
OGTTAnnual screening for CF-related diabetes from age 10
Specialist
HRCT thoraxAssess bronchiectasis extent and progression
Liver ultrasoundScreen for CF-related liver disease (focal biliary cirrhosis)
DEXA scanOsteoporosis screening — increased risk from malabsorption, steroids, chronic inflammation
1
Respiratory management
- Airway clearance: daily physiotherapy (ACBT, PEP devices) — twice daily minimum
- Nebulised therapies: dornase alfa (DNase — reduces sputum viscosity), hypertonic saline
- Prompt treatment of exacerbations with IV antibiotics (typically 14 days)
- Pseudomonas eradication: first isolation — nebulised colistin or tobramycin for 3 months
- Chronic Pseudomonas: long-term nebulised antibiotics (alternating month tobramycin/colistin)
- Azithromycin prophylaxis for its anti-inflammatory properties
2
CFTR modulator therapy
- Elexacaftor/tezacaftor/ivacaftor (Kaftrio) — triple combination for patients with at least one F508del allele (~90% of UK patients eligible)
- Dramatically improves FEV1, reduces exacerbations, improves BMI and quality of life
- Monitor LFTs (hepatotoxicity risk) and for drug interactions
3
Nutritional management
- Pancreatic enzyme replacement therapy (PERT — Creon) with all meals and snacks
- High-calorie, high-fat diet (120–150% of normal caloric intake)
- Fat-soluble vitamin supplementation (A, D, E, K)
- Salt supplementation in hot weather
4
Other organ management
- CF-related diabetes: insulin (NOT metformin) is first-line
- CF-related liver disease: ursodeoxycholic acid
- Lung transplantation: consider when FEV1 <30% predicted or rapid decline despite optimal treatment
Complications
- Respiratory failure: Progressive bronchiectasis leading to end-stage lung disease — most common cause of death
- Pseudomonas colonisation: Associated with accelerated lung function decline
- CF-related diabetes: Develops in ~40–50% by age 30 — insulin-dependent
- Distal intestinal obstruction syndrome (DIOS): Equivalent of meconium ileus in older patients — treat with Gastrografin
- Allergic bronchopulmonary aspergillosis (ABPA): Common complication — treat with steroids + itraconazole
- Massive haemoptysis: From hypertrophied bronchial arteries
UKMLA Exam Tips
- 1Sweat chloride ≥60 mmol/L = diagnostic of CF. 30–59 = borderline. <30 = normal
- 2F508del is the most common CFTR mutation — present in ~70% of UK CF patients
- 3Meconium ileus in a neonate = think CF until proven otherwise
- 4Pseudomonas + S. aureus are the key respiratory pathogens — Burkholderia cepacia complex is an ominous sign (cross-infection risk)
- 5CF-related diabetes = insulin (NOT metformin, NOT diet alone — these patients need calories)
- 6Male infertility (congenital bilateral absence of vas deferens) is present in ~98% of CF males
- 7Kaftrio (triple CFTR modulator) has transformed outcomes — know it exists and that eligibility is mutation-dependent
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