title: Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD.
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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL. Electronic address: mdrans99@uab.edu.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wilhelm
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Brian
authors.initials: B
authors.lastname: Flanagan
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Clifford
authors.initials: C
authors.lastname: Courville
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Tidwell
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: S Vamsee
authors.initials: SV
authors.lastname: Raju
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Amit
authors.initials: A
authors.lastname: Gaggar
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Tang
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL; UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL; Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000407:Alabama; D001706:Biopsy; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004417:Dyspnea; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D011795:Surveys and Questionnaires; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
chemical_list: D014028:Tobacco Smoke Pollution; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
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