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

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 ß-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 ß-adrenergic sweat secretion rate with evaporative water loss, sweat chloride, and clinical data (spirometry and symptom questionnaires). MEASUREMENTS AND MAIN RESULTS: ß-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 ß-adrenergic sweat rate and female gender (ß = 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: ß-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. ß-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.

Cigarette smoke induces systemic defects in cystic fibrosis transmembrane conductance regulator function.

RATIONALE: Several extrapulmonary disorders have been linked to cigarette smoking. Smoking is reported to cause cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the airway, and is also associated with pancreatitis, male infertility, and cachexia, features characteristic of cystic fibrosis and suggestive of an etiological role for CFTR. OBJECTIVES: To study the effect of cigarette smoke on extrapulmonary CFTR function. METHODS: Demographics, spirometry, exercise tolerance, symptom questionnaires, CFTR genetics, and sweat chloride analysis were obtained in smokers with and without chronic obstructive pulmonary disease (COPD). CFTR activity was measured by nasal potential difference in mice and by Ussing chamber electrophysiology in vitro. Serum acrolein levels were estimated with mass spectroscopy. MEASUREMENTS AND MAIN RESULTS: Healthy smokers (29.45 ± 13.90 mEq), smokers with COPD (31.89 ± 13.9 mEq), and former smokers with COPD (25.07 ± 10.92 mEq) had elevated sweat chloride levels compared with normal control subjects (14.5 ± 7.77 mEq), indicating reduced CFTR activity in a nonrespiratory organ. Intestinal current measurements also demonstrated a 65% decrease in CFTR function in smokers compared with never smokers. CFTR activity was decreased by 68% in normal human bronchial epithelial cells exposed to plasma from smokers, suggesting that one or more circulating agents could confer CFTR dysfunction. Cigarette smoke-exposed mice had decreased CFTR activity in intestinal epithelium (84.3 and 45%, after 5 and 17 wk, respectively). Acrolein, a component of cigarette smoke, was higher in smokers, blocked CFTR by inhibiting channel gating, and was attenuated by antioxidant N-acetylcysteine, a known scavenger of acrolein. CONCLUSIONS: Smoking causes systemic CFTR dysfunction. Acrolein present in cigarette smoke mediates CFTR defects in extrapulmonary tissues in smokers.

Empower U: effectiveness of an adolescent outreach and prevention program with sixth-grade boys and girls: a pilot study.

Sixth graders are at a prime age to modify behaviors and beliefs regarding exercise, nutrition, body image, and smoking. Empower U was created to change knowledge, beliefs, and behaviors regarding these topics. This pilot study utilized pre/post assessments of 58 sixth graders from a private middle school in the midsouth. Results showed a significant increase in self-esteem as well as in exercise and nutrition knowledge and beliefs at posttest and a significant increase in body image as well as in self-reported exercise and nutrition behaviors at the 1-month follow-up. Empower U provides nurses with an effective educational program that may be useful in positively impacting health behaviors.

Lung volume reduction for advanced emphysema: surgical and bronchoscopic approaches.

Chronic obstructive pulmonary disease is the third leading cause of death in the United States, affecting more than 24 million people. Inhaled bronchodilators are the mainstay of therapy; they improve symptoms and quality of life and reduce exacerbations. These and smoking cessation and long-term oxygen therapy for hypoxemic patients are the only medical treatments definitively demonstrated to reduce mortality. Surgical approaches include lung transplantation and lung volume reduction and the latter has been shown to improve exercise tolerance, quality of life, and survival in highly selected patients with advanced emphysema. Lung volume reduction surgery results in clinical benefits. The procedure is associated with a short-term risk of mortality and a more significant risk of cardiac and pulmonary perioperative complications. Interest has been growing in the use of noninvasive, bronchoscopic methods to address the pathological hyperinflation that drives the dyspnea and exercise intolerance that is characteristic of emphysema. In this review, the mechanism by which lung volume reduction improves pulmonary function is outlined, along with the risks and benefits of the traditional surgical approach. In addition, the emerging bronchoscopic techniques for lung volume reduction are introduced and recent clinical trials examining their efficacy are summarized.

Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD.

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.