Cystic fibrosis

Cystic fibrosis (CF) is a progressive, genetic disease that primarily affects the respiratory and digestive systems. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene provides instructions for making the CFTR protein, which functions as a channel across the membranes of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. In individuals with CF, mutations render this protein defective or absent, disrupting the normal transport of chloride ions and water. This disruption leads to the production of unusually thick, sticky mucus.

The consequences of this defective protein are multisystemic. In the lungs, the thick mucus clogs the airways, trapping bacteria and leading to chronic infections, persistent inflammation, and progressive lung damage, which is the most common cause of mortality. In the digestive system, the mucus blocks ducts in the pancreas, preventing digestive enzymes from reaching the small intestine. This results in malabsorption of nutrients, leading to poor growth, vitamin deficiencies, and greasy stools. Other affected organs can include the liver, which may develop cirrhosis, and the reproductive system, where nearly all men with CF are infertile due to the absence of the vas deferens.

Cystic fibrosis is classified as an autosomal recessive disorder, meaning an individual must inherit two copies of the mutated CFTR gene—one from each parent—to have the disease. Individuals who inherit only one copy are known as carriers; they typically do not show symptoms but can pass the mutated gene to their children. CF is most common among people of Northern European ancestry, but it occurs in all racial and ethnic groups. Historically, CF was considered a fatal disease of early childhood. However, the understanding of its pathophysiology and the development of comprehensive care strategies have transformed its prognosis.

The management of cystic fibrosis has evolved dramatically, significantly improving both the quality of life and life expectancy for patients, which now often extends into middle age and beyond. Treatment is complex and lifelong, requiring a multidisciplinary team of specialists. Key components of care include daily airway clearance techniques (such as chest physiotherapy) to loosen and remove mucus from the lungs, inhaled medications to open airways and thin mucus, and aggressive use of antibiotics to treat lung infections. For digestive issues, patients take pancreatic enzyme replacement therapy (PERT) with every meal to aid in nutrient absorption, alongside a high-calorie, high-fat diet and vitamin supplements. A major breakthrough in recent years has been the development of CFTR modulator therapies. Unlike treatments that only address symptoms, these drugs target the underlying defect in the CFTR protein, helping it function more effectively. These modulators have revolutionized care for a large percentage of patients with specific mutations, leading to substantial improvements in lung function and overall health. Newborn screening programs in many countries allow for early diagnosis, enabling prompt initiation of treatment to prevent irreversible organ damage and improve long-term outcomes.