Cystic Fibrosis

Question · easy

A 28-year-old man has a 4-year history of daily productive cough, recurrent sinusitis, and three pneumonias in the past year. CT of the chest shows upper-lobe predominant bronchiectasis. A sweat chloride test returns 45 mmol/L. What is the most appropriate next step in evaluation?

Cystic fibrosis is excluded; evaluate for immunodeficiency only Repeat sweat chloride testing and obtain CFTR genetic analysis Start long-term azithromycin and defer further diagnostic testing Perform bronchoscopy with bronchoalveolar lavage

Question · medium

The F508del variant is the most common CFTR mutation. Which molecular mechanism best describes it?

Absent protein synthesis from a premature stop codon (class I) Defective channel gating at the cell surface (class III) Defective protein folding with endoplasmic reticulum arrest and proteasomal degradation (class II) Accelerated removal of CFTR from the cell surface (class VI)

Question · medium

Ivacaftor monotherapy produces marked clinical improvement — improved lung function, fewer hospitalizations, weight gain, and normalization of sweat chloride — in patients carrying which CFTR mutation?

G551D (class III gating defect) Two minimal-function alleles of any type G542X (class I nonsense mutation) Homozygous F508del

Question · hard

A 24-year-old woman with cystic fibrosis is admitted with increased purulent sputum, worsening dyspnea, and a fall in FEV1. Sputum culture grows mucoid Pseudomonas aeruginosa. Which is the most appropriate initial management?

Oral ciprofloxacin for 5 days Intravenous aminoglycoside plus an antipseudomonal β-lactam for ~14 days with frequent chest physiotherapy Inhaled tobramycin alone for 28 days Intravenous methylprednisolone and bronchodilators without antibiotics

Question · medium

A 30-year-old man with cystic fibrosis and his partner are unable to conceive. Semen analysis shows azoospermia. Which mechanism best explains infertility in men with CF?

Congenital bilateral absence of the vas deferens with preserved spermatogenesis Hypogonadotropic hypogonadism from chronic illness Primary testicular failure with absent spermatogenesis Retrograde ejaculation from autonomic neuropathy