Cystic Fibrosis — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disorder caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene on chromosome 7. CFTR encodes a chloride and bicarbonate channel — dysfunction causes abnormally thick, dehydrated mucus in the lungs, pancreas, liver, intestine, and reproductive organs. CF affects approximately 100,000 people worldwide, predominantly White European populations (1 in 2,500–3,500 live births). Over 2,000 CFTR mutations exist — F508del is the most common (present in 70% of CF alleles globally). Progressive obstructive lung disease is the primary cause of morbidity and mortality. The CF treatment landscape has been revolutionised by CFTR modulators — particularly elexacaftor-tezacaftor-ivacaftor (Trikafta/Kaftrio) — with median survival exceeding 50 years in high-income countries with access to these therapies.

CF requires two pathogenic CFTR allele mutations (autosomal recessive inheritance). Both parents must be carriers (1 in 25 White Europeans) for a 25% chance of an affected child. Mutation classes determine severity: Class I–III mutations cause more severe disease (F508del is Class II — protein misfolding and degradation); Class IV–V mutations cause milder phenotypes (residual CFTR function). F508del homozygosity is associated with severe disease. Modifier genes (TGFB1, MBL2) and environmental factors influence clinical course. CF is rare in Black African and Asian populations (1:15,000–1:90,000). Preimplantation genetic testing and prenatal diagnosis are available for families with known CFTR mutations. No environmental exposures cause CF — it is entirely genetic.

Pulmonary (dominant feature): chronic productive cough with thick, purulent sputum, recurrent pulmonary exacerbations with bacterial infections (Staphylococcus aureus initially; later chronic Pseudomonas aeruginosa — characteristic and associated with accelerated decline), progressive airflow obstruction, bronchiectasis, haemoptysis, and ultimately respiratory failure. Pancreatic insufficiency (85–90%): fat malabsorption causing steatorrhoea (oily, foul-smelling stools), poor weight gain, failure to thrive, and fat-soluble vitamin deficiency (A, D, E, K). CF-related diabetes (CFRD — affects 30–50% of adults with CF). Liver disease: focal biliary cirrhosis, portal hypertension. Intestinal: meconium ileus at birth (15–20% of CF babies), distal intestinal obstruction syndrome (DIOS — constipation with partial/complete bowel obstruction). Male infertility (99% — congenital absence of the vas deferens). Sinusitis, nasal polyps. Clubbing of fingers in advanced disease. Salt wasting (electrolyte imbalance in heat or illness — salty sweat is characteristic).

Newborn screening (blood spot test): immunoreactive trypsinogen (IRT) is elevated in CF — positive screen triggers CFTR mutation analysis. Sweat test (sweat chloride): sweat chloride ≥60 mmol/L confirms CF (reference standard); 30–59 mmol/L is equivocal — repeat or add CFTR mutation testing; <30 mmol/L is normal. CFTR mutation analysis: extended panel identifies 90–95% of CF-causing mutations; whole gene sequencing for remaining cases. Nasal potential difference (NPD) and intestinal current measurement (ICM) for equivocal cases. CF Registry enrolment for longitudinal monitoring. Pulmonary function: spirometry (FEV1/FVC ratio — airflow obstruction); FEV1 trajectory is the primary prognostic marker. Sputum microbiology: quarterly cultures in stable disease, at all exacerbations. Chest HRCT: bronchiectasis distribution and severity. Annual blood tests: LFTs, glucose tolerance test (OGTT for CFRD from age 10), fat-soluble vitamins, renal function.

CFTR modulators are the transformative treatment: elexacaftor-tezacaftor-ivacaftor (Trikafta/Kaftrio) — triple combination therapy approved for F508del/F508del or F508del/minimal function mutations (eligible for ~90% of CF patients) — increases CFTR function to approximately 20–50% of normal, dramatically improving FEV1 (+14% predicted), reducing pulmonary exacerbations by 63%, and improving BMI. Tezacaftor-ivacaftor and lumacaftor-ivacaftor are alternatives for specific genotypes. Ivacaftor alone for gating mutations (G551D — 4–5% of patients). Airway clearance therapy: twice-daily chest physiotherapy (active cycle of breathing, oscillating PEP devices, high-frequency chest wall oscillation vest) — essential lifelong. Inhaled therapies: nebulised hypertonic saline (7%) hydrates airway mucus; nebulised dornase alfa (DNase — reduces sputum viscosity) improves FEV1 by 5–8%. Azithromycin (250–500 mg 3x/week) — anti-inflammatory, reduces Pseudomonas exacerbations. Inhaled tobramycin or aztreonam (alternating months) for chronic Pseudomonas colonisation. Pulmonary exacerbations: IV antibiotics (anti-pseudomonal — tobramycin + beta-lactam) for 14 days when FEV1 declines ≥10% or symptoms worsen. Pancreatic enzyme replacement therapy (PERT — lipase 1,000–2,500 units/kg per meal). High-calorie, high-fat diet; gastrostomy feeding in malnourished patients. Lung transplantation for FEV1 <30% or rapidly declining — median survival post-transplant ~7 years; now less commonly required since Trikafta.

Pulmonary complications are the principal cause of morbidity and mortality in cystic fibrosis — progressive bronchiectasis and chronic infection with mucoid Pseudomonas aeruginosa (the hallmark CF pathogen, colonising airways in approximately 80% of CF patients by adulthood) cause relentless decline in FEV1, punctuated by infective exacerbations requiring IV antibiotic courses. Pulmonary exacerbations (acute deterioration in respiratory symptoms requiring intensified treatment) occur at a rate of 1–2 per year in typical adult CF patients and each episode is associated with a mean FEV1 loss of 2–5%, accelerating the lung function trajectory toward respiratory failure and the need for lung transplantation. Chronic respiratory failure requiring non-invasive ventilation (NIV) and ultimately bilateral sequential lung transplantation (the only curative option for end-stage CF lung disease — median survival post-transplant 6–8 years) is the eventual trajectory for many patients without CFTR modulator access. CF-related diabetes (CFRD) is the most common non-pulmonary complication — present in 40–50% of adults with CF (compared to less than 5% of children); caused by progressive loss of insulin-secreting beta cells from pancreatic exocrine damage and fibro-fatty replacement; CFRD worsens pulmonary outcomes and requires insulin therapy (oral hypoglycaemics are generally not recommended). Chronic liver disease (CF-associated liver disease — CFLD): cirrhosis from biliary obstruction develops in approximately 5–10% of patients, typically by late adolescence; portal hypertension with oesophageal varices is the most serious hepatic complication; ursodeoxycholic acid (UDCA) is used to protect bile flow. Osteoporosis: prevalent in approximately 50–75% of adults with CF from malabsorption of fat-soluble vitamin D and calcium, systemic inflammation, physical inactivity, and glucocorticoid use; bone mineral density below the fracture threshold is a significant cause of morbidity. Male infertility: over 95% of CF males are infertile from congenital bilateral absence of the vas deferens (CBAVD) — due to CFTR protein dysfunction in the vas deferens development; ICSI using surgically retrieved sperm from the epididymis or testes (MESA/TESA) enables biological parenthood; females have reduced fertility from thick cervical mucus. Pneumothorax (collapsed lung from rupture of a bullae) and haemoptysis (coughing blood — from bronchial artery hypertrophy in chronic bronchiectasis, potentially massive and life-threatening) are acute pulmonary complications.

CF cannot be prevented; however, carrier screening before or during pregnancy identifies at-risk couples (both carriers) who may opt for preimplantation genetic testing (PGT-M with IVF) to select unaffected embryos, or prenatal diagnosis (CVS or amniocentesis) with the option of termination. Carrier testing is available for partners of known carriers and for the general population in countries with established screening programmes. For people living with CF: strict infection control (CF patients should not have close contact with each other — cross-infection prevention); influenza and COVID-19 vaccination annually; pneumococcal vaccination; maintain physical activity — high aerobic fitness is the strongest predictor of survival; smoking cessation and avoidance of second-hand smoke; and strict adherence to inhaled and CFTR modulator therapies.

Go to hospital immediately for: severe respiratory distress with oxygen saturation below 90%, significant haemoptysis (coughing blood exceeding a teaspoon), pneumothorax (sudden sharp chest pain with worsening breathlessness), or acute bowel obstruction symptoms (severe abdominal pain, vomiting, no bowel movements — DIOS). Contact your CF team same-day for: new fever with increased cough and sputum production (pulmonary exacerbation requiring early IV antibiotics); FEV1 drop of more than 10% from personal best; or rapidly worsening breathlessness. All CF patients should have regular multidisciplinary CF centre reviews every 3 months to monitor lung function, nutritional status, microbiology, and optimise CFTR modulator dosing.