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Original Research: COPD |

Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in the Lower Airways in COPDCFTR Dysfunction in COPD

Mark T. Dransfield, MD; Andrew M. Wilhelm, MD; Brian Flanagan, MD; Clifford Courville, MD; Sherry L. Tidwell, RRT; S. Vamsee Raju, PhD; Amit Gaggar, MD, PhD; Chad Steele, PhD; Li Ping Tang, DVM; Bo Liu, MD; Steven M. Rowe, MD, MSPH
Author and Funding Information

From the Department of Medicine (Drs Dransfield, Wilhelm, Flanagan, Courville, Raju, Gaggar, Steele, Tang, Liu, and Rowe and Ms Tidwell), Department of Pediatrics (Dr Rowe), UAB Lung Health Center (Drs Dransfield, Wilhelm, Raju, Gaggar, Steele, and Rowe and Ms Tidwell), and Cystic Fibrosis Research Center (Drs Dransfield, Raju, Gaggar, Steele, Tang, Liu, and Rowe and Ms Tidwell), University of Alabama at Birmingham, Birmingham, AL.

Correspondence to: Mark T. Dransfield, MD, Department of Medicine, University of Alabama at Birmingham, 422 THT, 1900 University Blvd, Birmingham, AL 35294; e-mail: mdrans99@uab.edu


Funding/Support: This research is sponsored by the National Institutes of Health [R01 HL105487 to Dr Rowe, R01 HL07783, P30 DK072482, and 5UL1 RR025777] and the Cystic Fibrosis Foundation (CLANCY09Y0 to Dr Rowe and R464-CF). Dr Rowe is supported by American Lung Association Senior Research Fellowship (RT-219427-N).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(2):498-506. doi:10.1378/chest.13-0274
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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.

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