Cystic fibrosis is the major cause of severe chronic lung disease in children. It also is the principal reason for lung transplantation in this age group. Cystic fibrosis is an autosomal recessive disorder of exocrine glands caused by homozygous or compound heterozygous mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It results in high viscosity of mucoid secretions with plugging of ducts and organ damage. Although outcome has improved remarkably over the last few decades, pulmonary infection remains the most common cause of morbidity and mortality in these children (median survival is 32 years in the United States).

Chronic lung disease in these patients results from inspissation of mucus in airways, leading to bacterial colonization and chronic bronchocentric infection with bronchiectasis. Common organisms include Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa (particularly mucigenic strains), and Burkholderia cepacia. Fungal organisms, especially Candida and Aspergillus species, also infect approximately 20% of cystic fibrosis patients, and allergic bronchopulmonary aspergillosis is a feature in approximately 10%. Other life-threatening pulmonary complications include pneumothorax, massive hemoptysis, and cor pulmonale.

Pathologically, the lungs are characterized by mucus plugs beginning in infancy, followed by progressive infection, inflammation, and mucosal necrosis of the airways, resulting in severe bronchiectasis, which is the hallmark of cystic fibrosis. The areas of bronchiectasis are often most accentuated in the upper lobes and may extend nearly to the pleural surface, where they terminate in fibrous-walled cavities (bronchiectatic cysts). Grossly, the central airways contain thick tenacious yellow mucus, and there are often areas of surrounding parenchymal consolidation. Microscopically, the central airways contain adherent mucus material admixed with inflammatory cells and debris and may show squamous metaplasia or increased numbers of goblet cells. Characteristically, the submucosal glands show areas of hyperplasia associated with mucus-filled ducts alternating with areas of glandular atrophy. The mucosa of ectatic airways is frequently ulcerated and replaced by granulation tissue with a surrounding dense lymphoplasmacytic inflammatory infiltrate. Small airways are also affected, showing bronchiolar stenosis or obliteration. Hyperinflation and patchy bronchopneumonia are common parenchymal features.