1 Department of Medicine.
Am J Respir Crit Care Med. 2013 Dec 1;188(11):1321-30. doi: 10.1164/rccm.201304-0733OC.
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.
To study the effect of cigarette smoke on extrapulmonary CFTR function.
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.
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.
Smoking causes systemic CFTR dysfunction. Acrolein present in cigarette smoke mediates CFTR defects in extrapulmonary tissues in smokers.
已有多种肺外疾病与吸烟相关。有报道称，吸烟可导致气道中囊性纤维化跨膜电导调节因子（CFTR）功能障碍，并且与胰腺炎、男性不育和恶病质相关，这些都是囊性纤维化的特征，提示 CFTR 可能在其中发挥作用。
研究香烟烟雾对肺外 CFTR 功能的影响。
对吸烟且不伴有慢性阻塞性肺疾病（COPD）的患者和吸烟伴有 COPD 的患者进行人口统计学分析、肺量测定、运动耐量、症状问卷、CFTR 遗传学和汗液氯化物分析。采用鼻电位差法在小鼠中测量 CFTR 活性，采用 Ussing 室电生理学方法在体外测量 CFTR 活性。采用质谱法估计血清丙烯醛水平。
健康吸烟者（29.45 ± 13.90 mEq）、吸烟伴有 COPD 患者（31.89 ± 13.9 mEq）和吸烟伴有 COPD 的前吸烟者（25.07 ± 10.92 mEq）的汗液氯化物水平均高于正常对照组（14.5 ± 7.77 mEq），表明非呼吸器官的 CFTR 活性降低。肠道电流测量也表明，与从不吸烟者相比，吸烟者的 CFTR 功能降低了 65%。暴露于吸烟者血浆中的正常人类支气管上皮细胞的 CFTR 功能降低了 68%，提示一种或多种循环因子可能导致 CFTR 功能障碍。暴露于香烟烟雾的小鼠的肠道上皮 CFTR 活性分别降低了 84.3%和 45%（分别在 5 周和 17 周后）。丙烯醛是香烟烟雾的一种成分，在吸烟者中的含量较高，通过抑制通道门控来阻断 CFTR，并被抗氧化剂 N-乙酰半胱氨酸减弱，N-乙酰半胱氨酸是丙烯醛的已知清除剂。
吸烟导致全身 CFTR 功能障碍。香烟烟雾中的丙烯醛介导吸烟者肺外组织中的 CFTR 缺陷。
