Cystic Fibrosis ✅

Related Subjects: |Cystic Fibrosis |Sweat Test |Osteoporosis |Malabsorption |Bronchiectasis |Pseudomonas infection (Pseudomonas aeruginosa) |Autosomal Recessive |Genetic Mutations |Clustered Regularly Interspaced Short Palindromic Repeats CRISPR

⚠️ Cystic Fibrosis (CF) is an autosomal recessive CFTR channel disorder causing impaired chloride transport → dehydrated secretions → impaired mucociliary clearance → chronic infection and inflammation. ✅ Diagnosis is based on clinical features and/or newborn screening plus evidence of CFTR dysfunction (for example, sweat chloride testing and genetic testing). 💡 With modern specialist care and CFTR modulators, median predicted survival in the UK now exceeds 50 years.

📖 About

• Inherited defect of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.
• Leads to abnormal salt and water transport across epithelial surfaces.
• Results in dehydrated, tenacious secretions causing airway obstruction, chronic infection, inflammation, and multisystem disease.
• Commonly affects the respiratory, gastrointestinal, endocrine, hepatobiliary, reproductive, and musculoskeletal systems.

🧬 Aetiology

• Autosomal recessive inheritance.
• CFTR gene is on chromosome 7q31.2.
• More than 2,000 CFTR variants have been described.
• F508del (ΔF508) is the most common pathogenic variant in the UK population.
• Genotype does not fully predict severity because phenotype is influenced by modifier genes, environment, infection burden, and treatment access.
• Incidence in the UK is approximately 1 in 2,500 live births; carrier frequency is around 1 in 25 in people of Northern European ancestry.

🧪 Gene Mutations & Effects

🔍 Diagnosis

• Often detected by newborn screening using raised immunoreactive trypsinogen (IRT), followed by confirmatory testing.
• Diagnosis is supported by clinical manifestations together with evidence of CFTR dysfunction.
• Sweat chloride ≥60 mmol/L is consistent with CF in the appropriate clinical context.
• 30–59 mmol/L is intermediate / borderline and needs further assessment.
• Genetic testing may identify 2 CF-causing CFTR variants.
• Additional physiological testing such as nasal potential difference or intestinal current measurement may be used in atypical or inconclusive cases.

🧪 Investigations

• Sweat chloride test: key diagnostic test; usually repeated or interpreted alongside genetics and clinical features.
• Genetic testing: mutation analysis helps confirm diagnosis and identify eligibility for CFTR modulator therapy.
• Pancreatic function: faecal elastase for pancreatic insufficiency.
• Respiratory assessment: spirometry, sputum or cough swab microbiology, chest imaging if indicated.
• Microbiology: monitor for Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and other pathogens.
• Endocrine screening: screen annually for CF-related diabetes; in children this is commonly with OGTT from age 10 years.
• Nutritional assessment: growth, BMI, fat-soluble vitamin status.
• Hepatobiliary review: LFTs and assessment for liver disease if indicated.
• Fertility assessment: semen analysis in adult males if needed; consider reproductive counselling.

🫁 Clinical Features (Respiratory)

• Persistent or recurrent cough.
• Recurrent chest infections.
• Wheeze and progressive airflow obstruction.
• Bronchiectasis due to chronic infection-inflammation cycles.
• Pseudomonas colonisation is associated with worse long-term lung outcomes.
• Chronic rhinosinusitis and nasal polyps are common.
• Complications include massive haemoptysis, pneumothorax, and respiratory failure.

🍽️ Clinical Features (Gastrointestinal / Nutritional)

• Meconium ileus in neonates.
• Pancreatic insufficiency causing malabsorption, steatorrhoea, abdominal distension, and failure to thrive.
• Distal intestinal obstruction syndrome (DIOS).
• Poor weight gain and fat-soluble vitamin deficiency.
• Hepatic steatosis, focal biliary cirrhosis, gallstones, and chronic liver disease may occur.
• CF-related diabetes (CFRD) becomes increasingly common with age.

🧍 Other System Features

• Clubbing.
• Low bone mineral density / osteoporosis.
• Arthropathy may occur.
• Male infertility is common, usually due to congenital bilateral absence of the vas deferens.
• Females may have reduced fertility, but many can conceive.
• Salty-tasting sweat is a classic clue.

📊 Summary of Testing

⚠️ Complications

• Chronic suppurative lung disease and bronchiectasis.
• Respiratory failure and need for transplant assessment in advanced disease.
• CFRD.
• Low bone mineral density / osteoporosis.
• Chronic liver disease and portal hypertension.
• Reduced fertility or infertility.
• Psychological burden, treatment fatigue, and reduced quality of life.

💊 Management

📚 References

• NICE guideline NG78: Cystic fibrosis: diagnosis and management
• Cystic Fibrosis Trust UK Registry reports and standards of care
• Specialist CF centre / MDT guidance for ongoing management