Pulmonology · Genetic Disorders
The facts most likely to be tested
Press 1–5 to rate · ↑↓ to navigate
Cystic fibrosis is an autosomal recessive disorder caused by a mutation in the CFTR gene on chromosome 7, leading to defective chloride transport.
The gold standard for diagnosis is a sweat chloride test showing levels ≥60 mmol/L on two separate occasions.
Patients frequently present with meconium ileus in the neonatal period, which is a highly specific sign of cystic fibrosis.
Chronic pulmonary infections are most commonly caused by Staphylococcus aureus in early childhood and Pseudomonas aeruginosa in adulthood.
Pancreatic insufficiency results in malabsorption of fat-soluble vitamins (A, D, E, K) and steatorrhea.
Treatment for pulmonary exacerbations includes airway clearance techniques, inhaled dornase alfa, and inhaled tobramycin.
CFTR modulators such as elexacaftor/tezacaftor/ivacaftor are the cornerstone of therapy for patients with eligible mutations.
Vignette unlocked
A 14-year-old male presents to the clinic with a chronic, productive cough and frequent foul-smelling, bulky stools. He has a history of recurrent sinopulmonary infections and poor weight gain despite a voracious appetite. Physical examination reveals digital clubbing and coarse crackles on lung auscultation. A sweat chloride test is performed and returns a value of 72 mmol/L.
What is the most appropriate initial management to address the patient's nutritional deficiency?
Pancreatic enzyme replacement therapy
The patient's presentation of malabsorption and chronic respiratory symptoms is classic for cystic fibrosis, which causes pancreatic insufficiency requiring exogenous enzyme supplementation.
Full handout
High yield triage
Etiology / Epidemiology
Autosomal recessive mutation in the CFTR gene (chromosome 7); most common lethal genetic disease in Caucasian populations.
Clinical Manifestations
Recurrent sinopulmonary infections, meconium ileus, and pancreatic insufficiency (steatorrhea/malnutrition).
Diagnosis
Sweat chloride test (≥60 mmol/L on two occasions) is the gold standard.
Treatment
Airway clearance therapy and CFTR modulators (e.g., elexacaftor/tezacaftor/ivacaftor).
Prognosis
Median survival is ~50 years; death usually results from respiratory failure or cor pulmonale.
Full handout
Epidemiology & Etiology
Caused by a mutation in the CFTR protein, leading to defective chloride transport. It follows an autosomal recessive inheritance pattern. It is most prevalent in individuals of Northern European descent.
Pertinent Anatomy
Affects exocrine glands in the lungs, pancreas, liver, and reproductive tract. Thick, viscous secretions obstruct the bronchioles and pancreatic ducts.
Pathophysiology
Defective chloride transport leads to dehydrated, viscous mucus. This causes mucociliary clearance failure, leading to chronic bacterial colonization, specifically Pseudomonas aeruginosa. Pancreatic duct obstruction results in exocrine insufficiency and fat-soluble vitamin malabsorption.
Clinical Manifestations
Infants may present with meconium ileus (pathognomonic). Older children exhibit failure to thrive, chronic cough, and bronchiectasis. Hemoptysis and pneumothorax are late-stage red flags. Patients often develop nasal polyps and clubbing of the digits.
Diagnosis
The Sweat chloride test (pilocarpine iontophoresis) is the gold standard, with values ≥60 mmol/L diagnostic. Genetic testing for ΔF508 mutation confirms the diagnosis. Newborn screening via immunoreactive trypsinogen (IRT) is standard in the US.
Treatment
Management includes chest physiotherapy and inhaled dornase alfa to thin secretions. CFTR modulators are the cornerstone of modern therapy. Avoid dehydration as it exacerbates mucus viscosity. Pancreatic enzyme replacement is required for malabsorption.
Prognosis
Chronic colonization with Burkholderia cepacia or Pseudomonas significantly worsens outcomes. Lung transplantation is the definitive treatment for end-stage disease. Patients require lifelong monitoring for CF-related diabetes.
Differential Diagnosis
Primary ciliary dyskinesia: situs inversus (Kartagener syndrome)
Asthma: reversible airway obstruction
Shwachman-Diamond syndrome: pancreatic insufficiency without respiratory symptoms
Alpha-1 antitrypsin deficiency: panacinar emphysema
Celiac disease: malabsorption without pulmonary involvement