Document Detail


Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD.
MedLine Citation:
PMID:  23538783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Mark T Dransfield; Andrew M Wilhelm; Brian Flanagan; Clifford Courville; Sherry L Tidwell; S Vamsee Raju; Amit Gaggar; Chad Steele; Li Ping Tang; Bo Liu; Steven M Rowe
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chest     Volume:  144     ISSN:  1931-3543     ISO Abbreviation:  Chest     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-08-06     Completed Date:  2014-01-09     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  498-506     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Alabama
Biopsy
Blotting, Western
Bronchoalveolar Lavage Fluid / chemistry
Bronchoscopy
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
Dyspnea
Female
Humans
Male
Middle Aged
Mucociliary Clearance
Pulmonary Disease, Chronic Obstructive / metabolism*
Questionnaires
Smoking / adverse effects
Spirometry
Tobacco Smoke Pollution / adverse effects
Grant Support
ID/Acronym/Agency:
5UL1 RR025777/RR/NCRR NIH HHS; P30 DK072482/DK/NIDDK NIH HHS; P30 DK072482/DK/NIDDK NIH HHS; R01 HL07783/HL/NHLBI NIH HHS; R01 HL102371/HL/NHLBI NIH HHS; R01 HL105487/HL/NHLBI NIH HHS; R01 HL105487/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Tobacco Smoke Pollution; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator
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