Cigarette smoke and CFTR: implications in the pathogenesis of COPD

Am J Physiol Lung Cell Mol Physiol. 2013 Oct 15;305(8):L530-41. doi: 10.1152/ajplung.00039.2013. Epub 2013 Aug 9.

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder consisting of chronic bronchitis and/or emphysema. COPD patients suffer from chronic infections and display exaggerated inflammatory responses and a progressive decline in respiratory function. The respiratory symptoms of COPD are similar to those seen in cystic fibrosis (CF), although the molecular basis of the two disorders differs. CF is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a chloride and bicarbonate channel (CFTR), leading to CFTR dysfunction. The majority of COPD cases result from chronic oxidative insults such as cigarette smoke. Interestingly, environmental stresses including cigarette smoke, hypoxia, and chronic inflammation have also been implicated in reduced CFTR function, and this suggests a common mechanism that may contribute to both the CF and COPD. Therefore, improving CFTR function may offer an excellent opportunity for the development of a common treatment for CF and COPD. In this article, we review what is known about the CF respiratory phenotype and discuss how diminished CFTR expression-associated ion transport defects may contribute to some of the pathological changes seen in COPD.

Keywords: CFTR; COPD; calcium-activated chloride channel; cystic fibrosis; epithelial sodium channel (ENaC); mucus stasis; respiratory infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chronic Disease
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Inflammation
  • Ion Transport
  • Oxidative Stress*
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / therapy
  • Smoking / adverse effects*
  • Smoking / metabolism*
  • Smoking / pathology
  • Smoking / therapy

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator