CF is an autosomal recessive disorder resulting from mutations in a single gene, located on the long arm of chromosome 7. These mutations result in the absence of a functioning cystic fibrosis transmembrane conductance regulator (CFTR), which conducts chloride across cell membranes. CFTR is expressed in exocrine glands throughout the body. In the airways, it is predominantly expressed in the submucosal glands. Abnormal or absent CFTR function clogs the glands with mucous and changes the composition and mechanical properties of the airway secretions, initiating a pathophysiologic cascade that ultimately leads to progressive and chronic lung disease. Chronic endobronchial infection and the associated intense neutrophilic inflammatory response are pathognomonic for the disease.

Individuals with CF develop pulmonary infections with a unique set of bacterial pathogens, which are acquired in an age-dependent fashion. Initial infections occur shortly after birth and are typically caused by non–type-able Haemophilus influenzae and Staphylococcus aureus. Subsequent infections are caused by Pseudomonas aeruginosa, the most common virulent pathogen in patients with CF. Recent investigations have confirmed that infection with P. aeruginosa occurs earlier than previously believed. Up to 80% of children with CF will eventually be infected, with the initial infection occurring on average by age 2. Early strains of P. aeruginosa remain sensitive to antibiotics and can be eradicated with aggressive antimicrobial therapy. Persistent strains become mucoid, adapting to the local environment through the formation of macrocolonies and the production of an exopolysaccharide that confers resistance to phagocytosis and penetration by antibiotics. The acquisition of P. aeruginosa is associated with progression of lung disease and is a limiting factor in overall survival. The mucoid strains are associated with a more significant clinical deterioration. Late in the disease process, infections are caused by other opportunistic organisms, including Burkholderia cepacia complex, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, fungi, and nontuberculous mycobacterium. B. cepacia complex is a group of
closely related species that can cause a syndrome of high fever, bacteremia, severe necrotizing pneumonia, and possibly death.