title: Acquired defects in CFTR-dependent β-adrenergic sweat secretion in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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 β-adrenergic sweat rate and specifically quantify CFTR function in the secretory coil of the sweat gland.
  
  
  OBJECTIVE
  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 β-adrenergic sweat secretion rate with evaporative water loss, sweat chloride, and clinical data (spirometry and symptom questionnaires).
  
  
  RESULTS
  β-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 β-adrenergic sweat rate and female gender (β = 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
  β-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. β-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.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Courville
authors.forename: Sherry
authors.initials: S
authors.lastname: Tidwell
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: Mark T
authors.initials: MT
authors.lastname: Dransfield
authors.affiliation: Department of Medicine, MCLM 706, 1918 University Blvd, University of Alabama at Birmingham, Birmingham, AL, USA. smrowe@uab.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000378:metabolism*; D013542:Sweat / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator