Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in the CFTR gene. CFTR encodes an epithelial chloride channel. When the channel does not function adequately, chloride and water movement across epithelial surfaces is disrupted, so secretions become unusually concentrated, thick, and difficult to clear. The consequence depends on where those secretions collect. In the bronchi, tenacious mucus obstructs airflow and provides a medium in which bacteria persist, leading to recurrent infection and progressive airway injury. In the pancreas, obstructed ducts prevent digestive enzymes from reaching the intestine, producing malabsorption and poor weight gain. Similar obstruction affects the sinuses, biliary system, and reproductive tract. The common F508del variant deletes one amino acid at position 508. The altered protein is usually degraded before reaching the cell membrane, leaving essentially no functional channel at the apical surface. Other CFTR variants impair the channel in different ways, which is why genetic responsiveness affects the choice of CFTR modulator. CF is not simply “a child with chronic mucus.” It is a multisystem disorder in which pulmonary clearance, infection control, nutrition, glucose...