Cystic Fibrosis

A 5 year old male child is brought to the pediatric clinic due to recurrent pulmonary infections and failure to thrive. His mother reports multiple hospitalizations for respiratory infections. He had meconium ileus shortly after birth, requiring surgical intervention. Despite a good appetite, he has poor weight gain. On examination, he appears thin, with digital clubbing and a barrel shaped chest. Lung auscultation reveals bilateral crackles and wheezing. Sputum culture grows Staphylococcus aureus. Chest x ray shows hyperinflation. Sweat chloride is ≥60 mmol/L on two occasions. Genetic testing reveals a CFTR mutation. Diagnosis?

Diagnosis is Cystic fibrosis.

1. Definition

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the CFTR gene, leading to abnormal chloride transport and viscous secretions affecting multiple organs.

2. Pathophysiology

1. Mutation in the CFTR gene on chromosome 7, most commonly ΔF508
2. The CFTR protein is a cAMP regulated chloride channel
3. Effects:
1. Lungs and GI tract
• Decreased chloride secretion
• Increased sodium and water absorption via ENaC
• Leads to thick, dehydrated mucus
2. Sweat glands
• Decreased chloride reabsorption
• Leads to increased chloride concentration in sweat

3. Clinical Features

3.1 Pulmonary

1. Recurrent respiratory infections
• Early: Staphylococcus aureus, Haemophilus influenzae
• Later: Pseudomonas aeruginosa
2. Chronic productive cough
3. Bronchiectasis
4. Wheezing and dyspnea
5. Digital clubbing
6. Chronic sinusitis and nasal polyps

3.2 Gastrointestinal

1. Meconium ileus in neonates
2. Pancreatic insufficiency
• Steatorrhea
• Fat soluble vitamin deficiency (A, D, E, K)
3. Failure to thrive
4. Distal intestinal obstruction syndrome
5. CF related diabetes mellitus
6. Hepatobiliary disease, including biliary cirrhosis

3.3 Other Features

1. Male infertility due to congenital bilateral absence of vas deferens
2. Salt loss leading to heat intolerance and dehydration

4. Diagnosis

1. Sweat chloride test
• ≥60 mmol/L on two separate occasions is diagnostic
2. Newborn screening
• Elevated immunoreactive trypsinogen
3. Genetic testing
• Confirms CFTR mutation
4. Sputum culture
• Common organisms: S aureus, Pseudomonas, H influenzae
5. Chest imaging
• Hyperinflation, bronchiectasis, atelectasis, scarring
6. Pulmonary function tests
• Obstructive pattern

5. Management

5.1 Airway Clearance

1. Chest physiotherapy
2. Inhaled hypertonic saline
3. Dornase alfa, reduces mucus viscosity

5.2 Pharmacologic Therapy

1. Bronchodilators such as albuterol
2. Antibiotics for acute and chronic infections
3. CFTR modulators (genotype specific)
• Ivacaftor, improves channel function
• Lumacaftor or tezacaftor, improve protein folding
• Elexacaftor tezacaftor ivacaftor combination, most effective for ΔF508 mutation

5.3 Nutritional Support

1. Pancreatic enzyme replacement therapy
2. Fat soluble vitamin supplementation (A, D, E, K)
3. High calorie diet

5.4 Preventive Care

1. Influenza and pneumococcal vaccination

5.5 Advanced Therapy

1. Lung transplantation in advanced disease

6. Key Clinical Insight

Child with recurrent pulmonary infections, failure to thrive, meconium ileus, and elevated sweat chloride strongly suggests cystic fibrosis

7. Exam Level Pearls

1. ΔF508 is the most common mutation
2. Meconium ileus is a classic neonatal presentation
3. Sweat chloride ≥60 mmol/L confirms diagnosis
4. Early infection with Staphylococcus, later Pseudomonas
5. Pancreatic insufficiency leads to fat soluble vitamin deficiency