About This Page
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.
The Bottom Line
- Autosomal recessive — CFTR gene mutation (ΔF508 most common, ~70% of UK alleles)
- Detected on newborn blood spot screening (immunoreactive trypsinogen — IRT)
- Diagnosis confirmed by sweat test: chloride ≥60 mmol/L is diagnostic
- Multidisciplinary management: chest physiotherapy, pancreatic enzyme replacement, high-calorie diet, prophylactic antibiotics
- CFTR modulator therapy (e.g. elexacaftor/tezacaftor/ivacaftor) has transformed prognosis for eligible genotypes
Overview
Cystic fibrosis (CF) is an autosomal recessive condition caused by mutations in the CFTR gene on chromosome 7. The defective CFTR protein leads to impaired chloride and water transport across epithelial surfaces, resulting in thick, viscid secretions in the lungs, pancreas, liver, intestines, and reproductive tract. Progressive bronchiectasis and respiratory failure remain the primary cause of morbidity and mortality, although life expectancy has improved dramatically with modern management.
Epidemiology
CF affects approximately 1 in 2,500 live births in the UK. Carrier frequency is approximately 1 in 25. The ΔF508 mutation accounts for around 70% of CF alleles in the UK population. Over 10,900 people live with CF in the UK. Median predicted survival has increased to over 50 years with current therapies, largely driven by the introduction of CFTR modulator drugs.
Clinical Features
Symptoms
Recurrent lower respiratory tract infections — often with Staphylococcus aureus and Pseudomonas aeruginosa
Chronic productive cough
Failure to thrive despite adequate caloric intake
Steatorrhoea — pale, greasy, foul-smelling stools due to pancreatic exocrine insufficiency
Recurrent abdominal pain or distal intestinal obstruction syndrome (DIOS)
Meconium ileus in neonates (presents in ~15% of CF patients)
Nasal polyps — unusual in children under 5 without CF
Rectal prolapse in young children
Male infertility (absent vas deferens — congenital bilateral absence)
Signs
Finger clubbing
Hyperinflated chest with Harrison sulci
Coarse crackles and wheeze on auscultation
Poor weight gain with reduced subcutaneous fat
Hepatomegaly (if CF-related liver disease)
Salty-tasting skin (parents may report this)
Investigations
First-line
Newborn blood spot screeningMeasures immunoreactive trypsinogen (IRT) — raised IRT triggers CFTR gene analysis
Sweat test (pilocarpine iontophoresis)Gold standard: chloride ≥60 mmol/L = diagnostic; 30–59 = borderline (repeat or genotype); <30 = CF unlikely
Second-line
CFTR genotypingIdentifies specific mutations — important for CFTR modulator eligibility
Faecal elastaseLow levels (<200 µg/g) confirm pancreatic exocrine insufficiency (~85% of CF patients)
Sputum cultureRegular surveillance — look for S. aureus, H. influenzae, Pseudomonas aeruginosa, Burkholderia cepacia
Specialist
CT chestAssess bronchiectasis severity — increasingly used as monitoring tool
Lung function testingSpirometry from age ~5 — FEV₁ tracks disease progression
Liver ultrasoundScreen for CF-related liver disease (focal biliary cirrhosis)
OGTTAnnual screening from age 10 for CF-related diabetes (CFRD)
DEXA scanBone density assessment — osteoporosis risk from malabsorption and chronic inflammation
1
Respiratory
- Twice-daily chest physiotherapy (active cycle of breathing techniques, positive expiratory pressure devices)
- Nebulised dornase alfa (DNase) — reduces sputum viscosity
- Nebulised hypertonic saline (7%) — improves mucociliary clearance
- Prophylactic flucloxacillin from diagnosis to prevent Staphylococcal infection (until at least age 3)
- Prompt IV antibiotics for exacerbations — typically 14-day course of two agents (e.g. ceftazidime + tobramycin for Pseudomonas)
- Long-term azithromycin for chronic Pseudomonas colonisation (anti-inflammatory properties)
2
Nutrition
- High-calorie, high-fat diet (120–150% of normal caloric requirements)
- Pancreatic enzyme replacement therapy (PERT) — Creon with all meals and snacks
- Fat-soluble vitamin supplements (A, D, E, K)
- Overnight NG/gastrostomy feeds if unable to maintain adequate growth
- Regular dietetic review
3
CFTR modulator therapy
- Elexacaftor/tezacaftor/ivacaftor (Kaftrio): now available for patients ≥6 years with at least one ΔF508 mutation — dramatically improves lung function, weight, and quality of life
- Ivacaftor (Kalydeco): for gating mutations (e.g. G551D)
- Monitor LFTs — hepatotoxicity is a recognised side effect
4
Monitoring and screening
- MDT clinic review every 1–3 months (specialist CF centre)
- Annual review: spirometry, sputum cultures, bloods, OGTT (from age 10), liver USS, DEXA
- Strict infection control: CF patients should not be in close proximity to each other (cross-infection risk, especially Burkholderia cepacia)
5
Advanced disease
- Lung transplantation for end-stage respiratory failure
- Non-invasive ventilation as bridge to transplant or palliative measure
Complications
- Bronchiectasis: Progressive and the main cause of morbidity — worse with Pseudomonas colonisation
- CF-related diabetes (CFRD): Develops in ~50% of adults — screen annually from age 10 with OGTT
- CF-related liver disease: Focal biliary cirrhosis, portal hypertension — ~5–10%
- DIOS (distal intestinal obstruction syndrome): Equivalent of meconium ileus in older patients — treat with gastrografin
- Allergic bronchopulmonary aspergillosis (ABPA): Consider if worsening lung function with raised IgE and eosinophilia
- Nasal polyps: Common — especially in adolescents
- Male infertility: >95% of males — congenital bilateral absence of the vas deferens (CBAVD)
- Osteoporosis: From malabsorption and chronic inflammation
UKMLA Exam Tips
- 1Meconium ileus in a neonate = think cystic fibrosis until proven otherwise
- 2Sweat test: ≥60 mmol/L chloride is diagnostic. Remember the value
- 3ΔF508 is the most common CFTR mutation in the UK (~70%)
- 4Pseudomonas aeruginosa colonisation is associated with accelerated lung decline
- 5Burkholderia cepacia complex = poor prognosis and strict segregation from other CF patients
- 6Newborn screening uses IRT (immunoreactive trypsinogen) — NOT sweat test
- 7CF is the most common cause of recurrent chest infections + failure to thrive + steatorrhoea in a child
- 8Male infertility in CF: CBAVD (congenital bilateral absence of vas deferens) — females have reduced fertility but can conceive
practicetest your knowledge on cystic fibrosis in childrenApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — paediatrics and beyond.
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