How does lung disease originate in the pathogenesis of cystic fibrosis (CF)?

Updated: Oct 22, 2019
  • Author: Girish D Sharma, MD, FCCP, FAAP; Chief Editor: Kenan Haver, MD  more...
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Most deaths associated with cystic fibrosis result from progressive and end-stage lung disease. In individuals with cystic fibrosis, the lungs are normal in utero, at birth, and after birth, before the onset of infection and inflammation (except possibly for the presence of dilated submucosal gland ducts in the airways). Shortly after birth, many persons with cystic fibrosis acquire a lung infection, which incites an inflammatory response. Infection becomes established with a distinctive bacterial flora. A repeating cycle of infection and neutrophilic inflammation develops.

Cleavage of complement receptors CR1 and C3bi and immunoglobulin G (IgG) by neutrophil elastase (NE) results in failure of opsonophagocytosis, leading to bacterial persistence. NE also causes production of the neutrophil chemoattractant interleukin (IL)–8 from epithelial cells and elastin degradation and acts as secretogogue, thereby contributing to persistence of inflammation and infection, structural damage, impaired gas exchange, and, ultimately, end-stage lung disease and early death.

One study reported that exposure to secondhand smoke adversely affects both cross-sectional and longitudinal measures of lung function in individuals with cystic fibrosis. [8] Variations in CFTR and a cystic fibrosis–modifier gene (TGFβ1) amplify the negative effects of secondhand smoke exposure.

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