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

作者：Courville Clifford A; Tidwell Sherry; Liu Bo; Accurso Frank J; Dransfield Mark T; Rowe Steven M^*

来源：Respiratory Research, 2014, 15(1): 25.

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 +/- 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 beta-adrenergic sweat rate and female gender (beta = 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 (R-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.

• 出版日期2014-2-25