⚠️ Cystic Fibrosis (CF) can present unexpectedly and severity varies widely. ✅ Elevated chloride in a pilocarpine-induced sweat test is diagnostic. 🦠 Interestingly, carriers have partial resistance to cholera as the toxin cannot open the chloride channels in the small intestine. 💡 With modern care, the UK median survival now exceeds 50 years.

📖 About

Inherited defect of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.
Results in production of thick, viscid mucus → obstruction and recurrent infection.
Multisystem disorder: respiratory, gastrointestinal, endocrine, reproductive, musculoskeletal.

🧬 Aetiology

Autosomal recessive inheritance;>800 mutations identified.
CFTR gene on chromosome 7q31.2.
Over 70% cases due to ΔF508 mutation (misfolded CFTR protein).
Genotype is a poor predictor of severity due to modifier genes and environment.
Incidence: ~1 in 2,500 live births in the UK; carrier frequency ~1 in 25.

🧪 Gene Mutations & Effects

🔍 Diagnosis

Detected on newborn screening (elevated immunoreactive trypsinogen → sweat/gene test confirmation).
Clinical manifestations + positive sweat chloride test (≥60 mmol/L).
Genetic confirmation (two pathogenic CFTR mutations).
Rarely, diagnosis made on clinical grounds if tests inconclusive but features typical.

🧪 Investigations

Sweat chloride test: Gold standard; ≥60 mmol/L diagnostic; 30–59 borderline.
Genetic testing: Mutation analysis; informs prognosis and CFTR modulator eligibility.
Pancreatic function: Faecal elastase (low = insufficiency).
Respiratory evaluation: Baseline spirometry, chest X-ray/CT for bronchiectasis.
Microbiology: Sputum cultures for Pseudomonas, Staphylococcus aureus, Haemophilus influenzae.
Endocrine: OGTT or HbA1c (screen for CF-related diabetes).
Fertility workup: Scrotal USS may show absent vas deferens; semen analysis in adults.

🫁 Clinical (Pulmonary)

Chronic cough, recurrent chest infections, bronchiectasis.
Pseudomonas colonisation → progressive decline.
Complications: pneumothorax, massive haemoptysis, chronic rhinosinusitis, nasal polyps.

🍽️ Clinical (Gastrointestinal)

Meconium ileus in neonates (10–20%).
Pancreatic insufficiency → malabsorption, steatorrhoea, failure to thrive.
Distal intestinal obstruction syndrome (DIOS).
Fatty liver, biliary cirrhosis, gallstones.
Secondary diabetes in up to 50% of adults.

🧍 Other Systems

Finger clubbing, osteoporosis, CF-related arthritis.
Male infertility (congenital bilateral absence of vas deferens).
Female subfertility due to thick cervical mucus.
Salty-tasting sweat (often first noticed by parents).

📊 Summary of Testing

Diagnostic Test	Description	Criteria
🧪 Sweat Chloride Test	Chloride concentration in sweat	≥60 mmol/L = diagnostic; 30–59 borderline; <30 unlikely
🧬 Genetic Testing	Identification of CFTR mutations	Two pathogenic variants confirms CF
⚡ Nasal Potential Difference	Assesses CFTR ion transport	Abnormal in atypical cases
👶 Newborn IRT	Raised immunoreactive trypsinogen	Triggers confirmatory testing

⚠️ Complications

Chronic respiratory failure, pulmonary hypertension, cor pulmonale.
Recurrent chest infections and bronchiectasis.
CFRD (cystic fibrosis–related diabetes).
Osteoporosis, delayed puberty, renal calculi.
Chronic liver disease, gallstones.
Reduced fertility/infertility.

💊 Management

Area	Interventions	Notes
Airway Clearance 🫁	Chest physiotherapy, oscillating PEP, nebulised hypertonic saline	Daily lifelong therapy
Mucolytics 💨	Dornase alfa (DNAse) inhalation	Improves FEV1, reduces exacerbations
Antibiotics 💊	Oral, inhaled, IV guided by cultures; inhaled tobramycin for chronic pseudomonas	Rotate to reduce resistance
Anti-inflammatory	Azithromycin long-term (anti-inflammatory + anti-Pseudomonas)	Evidence-based survival benefit
Nutrition 🍽️	Pancreatic enzyme replacement (PERT), fat-soluble vitamin supplements, high-calorie diet	Essential for growth and survival
CFTR Modulators 🧬	Ivacaftor, Lumacaftor/Ivacaftor, Tezacaftor/Ivacaftor, Elexacaftor/Tezacaftor/Ivacaftor (Trikafta/Kaftrio)	Genotype-specific, game-changing for eligible patients
Complication management	Treat CFRD, bone disease, liver disease	Regular screening essential
Transplant	Lung transplantation for advanced disease	Improves survival in end-stage CF
Psychosocial ❤️	Counselling, mental health, family support, CF charities	Quality of life focus

📚 References

NICE guidance on CF (NG78)
Ong T, et al. Cystic fibrosis in adults: management of respiratory disease. BMJ 2021.
Cystic Fibrosis Trust UK resources.

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Cystic Fibrosis