Acquired defects in CFTR-dependent β-adrenergic sweat secretion in chronic obstructive pulmonary disease

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作者：

CA Courville，S Tidwell，B Liu，FJ Accurso，MT Dransfield，SM Rowe

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摘要：

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 ??-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 ??-adrenergic sweat secretion rate with evaporative water loss, sweat chloride, and clinical data (spirometry and symptom questionnaires). Measurements and main results ??-adrenergic sweat rate was reduced in COPD smokers (41.9????????3.4, P???<???0.05, ?? SEM) and COPD former smokers (39.0????????5.4, P???<???0.05) compared to healthy controls (53.6????????3.4). Similarly, sweat chloride was significantly greater in COPD smokers (32.8????????3.3, P???<???0.01) and COPD former smokers (37.8????????6.0, P???<???0.01) vs. healthy controls (19.1????????2.5). Univariate analysis revealed a significant association between ??-adrenergic sweat rate and female gender (?????=???0.26), age (???0.28), FEV1% (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 (R2???=???0.266, P???<???0.0001). Conclusions ??-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. ??-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.

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关键词：

Medicine(General Internal Medicine

DOI：

10.1186/1465-9921-15-25

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年份：

2014