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Cystic fibrosis: Clinical manifestations of pulmonary disease

Julie P Katkin, MD
Section Editor
George B Mallory, MD
Deputy Editor
Alison G Hoppin, MD


Cystic fibrosis (CF) is a multisystem disease affecting the lungs, digestive system, sweat glands, and the reproductive tract. Patients with CF have abnormal transport of chloride and sodium across secretory epithelia, resulting in thickened, viscous secretions in the bronchi, biliary tract, pancreas, intestines and reproductive system [1,2].

Although the disease is systemic, progressive lung disease continues to be the major cause of morbidity and mortality for most patients. Over a variable time course, ranging from months to decades after birth, individuals eventually develop chronic infection of the respiratory tract with a characteristic array of bacterial flora, leading to progressive respiratory insufficiency and eventual respiratory failure [3]. The rate of progression varies widely, depending in part on genotype (including gene modifiers) as well as environmental factors. Registry data from CF Centers in the United States, Canada, and Europe indicate a median survival of about 40 years (figure 1) [4]. Females with CF appear to have higher morbidity and mortality than males [5]. This "gender gap" is modest but consistent across many populations and is hypothesized to be due to the pro-inflammatory effects of estrogens. (See "Cystic fibrosis: Genetics and pathogenesis".)

Treatment of CF associated-lung disease is undertaken with a variety of modalities, including mechanical airway clearance, antimicrobials, bronchodilators, supplemental oxygen, mucolytics, and a variety of other novel treatments in clinical trials. (See "Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection" and "Cystic fibrosis: Investigational therapies".)


Cystic fibrosis (CF) is caused by mutations in a single large gene on chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein [6-8]. CFTR has been shown to function as a regulated chloride channel, which in turn may regulate the activity of other chloride and sodium channels at the cell surface. The net result of these changes is an alteration in the rheology of airway secretions, which become thick and difficult to clear [9]. (See "Cystic fibrosis: Genetics and pathogenesis".)

Pathogens — The chronic airway obstruction caused by viscous secretions is soon followed by colonization with pathogenic bacteria, including Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex species. Methicillin-resistant S. aureus is encountered with increasing frequency in many regions. Other organisms frequently encountered in the CF airways include Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Klebsiella spp, although the contribution of these pathogens to the development of bronchial disease is not always clear. Chronic bacterial infection within the airways occurs in most patients with CF (table 1), and the prevalence of each bacterial type varies with the age of the patient (figure 2). Even among asymptomatic infants identified by newborn screening, there is evidence of subclinical lung disease within the first few months of life [10-12] (see 'Pulmonary function' below). Infection with S. aureus and P. aeruginosa are common even in young children with CF. The presence of P. aeruginosa with a mucoid phenotype is particularly suggestive of CF. Nontuberculous mycobacteria and fungal species such as Aspergillus also contribute to clinical disease in some patients. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Pathogens'.)

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Literature review current through: Nov 2017. | This topic last updated: Oct 12, 2016.
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