Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in the Lower Airways in COPD
Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in the Lower Airways in COPD
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DOI：
10.1378/chest.13-0274
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发表时间：
2013-08-01
期刊：
影响因子：
9.6
通讯作者：
Rowe, Steven M.
中科院分区：
文献类型：
--
作者：
Dransfield, Mark T.;Wilhelm, Andrew M.;Rowe, Steven M.
背景资料：香烟烟雾和吸烟诱导的炎症降低了鼻气道和培养的支气管上皮细胞中囊性纤维化跨膜传导调节因子（CFTR）的活性和粘液纤毛转运。这增加了下气道CFTR功能障碍可能导致COPD的病理生理学的可能性。我们比较了下气道CFTR活性在当前和以前的吸烟者与COPD，当前吸烟者没有COPD，终身不吸烟者的临床特征和CFTR表达和functions.Methods：人口统计学，肺功能测定和症状问卷调查数据收集之间的关系。通过鼻电位差（NPD）和下气道电位差（LAPD）测定来确定CFTR活性。CFTR功能的主要测量是氯离子转运的总变化（Δ无氯异丙肾上腺素）。结果：与健康的非吸烟者（n = 11）相比，目前吸烟者（n = 17）的LAPD CFTR活性显著降低（Δ-无氯异丙肾上腺素，-8.70 mV vs -15.9 mV;P = 0.003）。在有和没有COPD的吸烟者中观察到类似的减少。既往吸烟的COPD患者（n = 7）显示氯离子电导无显著性降低（-12.7 mV）。观察到CFTR蛋白表达的类似模式。单因素分析表明，LAPD CFTR活性和目前的吸烟，慢性支气管炎的存在，呼吸困难scores.Conclusions：吸烟者和无COPD降低气道CFTR活性与健康的非吸烟者相比，这一发现与疾病表型相关。获得性CFTR功能障碍可能参与COPD的发病机制。
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 (Delta chloride-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 (Delta chloride-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.