Acquired defects in CFTR-dependent [beta]-adrenergic sweat secretion in chronic obstructive pulmonary disease

• Published in: Respiratory research 2014-02, Vol.15
• Main Authors: Courville, Clifford A, Tidwell, Sherry, Liu, Bo, Accurso, Frank J, Dransfield, Mark T, Rowe, Steven M
• Format: Article
• Language: English
• Subjects: Age; Analysis; Chronic obstructive pulmonary disease; Cigarettes; Clinical trials; Cystic fibrosis; Defects; Development and progression; Disease; Health aspects; Human subjects; Lung diseases; Mutation; Pathogenesis; Patient outcomes; Pediatrics; Risk factors; Smoking; Studies
• ISSN: 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-15-25

Rationale Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure [beta]-adrenergic sweat rate and specifically quantify CFTR function in the secretory coil of the sweat gland. Objectives To evaluate the presence and severity of systemic CFTR dysfunction in smoking-related lung disease using sweat evaporimetry to determine CFTR-dependent sweat rate. Methods We recruited a cohort of patients consisting of healthy never smokers (N = 18), healthy smokers (12), COPD smokers (25), and COPD former smokers (12) and measured [beta]-adrenergic sweat secretion rate with evaporative water loss, sweat chloride, and clinical data (spirometry and symptom questionnaires). Measurements and main results [beta]-adrenergic sweat rate was reduced in COPD smokers (41.9 [+ or -] 3.4, P < 0.05, [+ or -] SEM) and COPD former smokers (39.0 [+ or -] 5.4, P < 0.05) compared to healthy controls (53.6 [+ or -] 3.4). Similarly, sweat chloride was significantly greater in COPD smokers (32.8 [+ or -] 3.3, P < 0.01) and COPD former smokers (37.8 [+ or -] 6.0, P < 0.01) vs. healthy controls (19.1 [+ or -] 2.5). Univariate analysis revealed a significant association between [beta]-adrenergic sweat rate and female gender ([beta] = 0.26), age (-0.28), FEV.sub.1% (0.35), dyspnea (-0.3), and history of smoking (-0.27; each P < 0.05). Stepwise multivariate regression included gender (0.39) and COPD (-0.43) in the final model (R.sup.2 = 0.266, P < 0.0001). Conclusions [beta]-adrenergic sweat rate was significantly reduced in COPD patients, regardless of smoking status, reflecting acquired CFTR dysfunction and abnormal gland secretion in the skin that can persist despite smoking cessation. [beta]-adrenergic sweat rate and sweat chloride are associated with COPD severity and clinical symptoms, supporting the hypothesis that CFTR decrements have a causative role in COPD pathogenesis.