Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD.

Academic Article

Abstract

  • BACKGROUND: Cigarette smoke and smoking-induced inflammation decrease cystic fibrosis transmembrane conductance regulator (CFTR) activity and mucociliary transport in the nasal airway and cultured bronchial epithelial cells. This raises the possibility that lower airway CFTR dysfunction may contribute to the pathophysiology of COPD. We compared lower airway CFTR activity in current and former smokers with COPD, current smokers without COPD, and lifelong nonsmokers to examine the relationships between clinical characteristics and CFTR expression and function. METHODS: Demographic, spirometry, and symptom questionnaire data were collected. CFTR activity was determined by nasal potential difference (NPD) and lower airway potential difference (LAPD) assays. The primary measure of CFTR function was the total change in chloride transport (Δchloride-free isoproterenol). CFTR protein expression in endobronchial biopsy specimens was measured by Western blot. RESULTS: Compared with healthy nonsmokers (n = 11), current smokers (n = 17) showed a significant reduction in LAPD CFTR activity (Δchloride-free isoproterenol, -8.70 mV vs -15.9 mV; P = .003). Similar reductions were observed in smokers with and without COPD. Former smokers with COPD (n = 7) showed a nonsignificant reduction in chloride conductance (-12.7 mV). A similar pattern was observed for CFTR protein expression. Univariate analysis demonstrated correlations between LAPD CFTR activity and current smoking, the presence of chronic bronchitis, and dyspnea scores. CONCLUSIONS: Smokers with and without COPD have reduced lower airway CFTR activity compared with healthy nonsmokers, and this finding correlates with disease phenotype. Acquired CFTR dysfunction may contribute to COPD pathogenesis.
  • Published In

  • Chest  Journal
  • Keywords

  • Adult, Aged, Aged, 80 and over, Alabama, Biopsy, Blotting, Western, Bronchoalveolar Lavage Fluid, Bronchoscopy, Cystic Fibrosis Transmembrane Conductance Regulator, Dyspnea, Female, Humans, Male, Middle Aged, Mucociliary Clearance, Pulmonary Disease, Chronic Obstructive, Smoking, Spirometry, Surveys and Questionnaires, Tobacco Smoke Pollution
  • Digital Object Identifier (doi)

    Author List

  • Dransfield MT; Wilhelm AM; Flanagan B; Courville C; Tidwell SL; Raju SV; Gaggar A; Steele C; Tang LP; Liu B
  • Start Page

  • 498
  • End Page

  • 506
  • Volume

  • 144
  • Issue

  • 2