RATIONALE Epidemiologic studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) is among the most harmful urban pollutants and is closely linked to respiratory disease. OBJECTIVES Based on the knowledge that the small airway epithelium (SAE) plays a central role in the pathogenesis of smoking-related lung disease, we hypothesized that elevated PM2.5 levels are associated with dysregulation of SAE gene expression, which may contribute to the development of respiratory disease. METHODS From 2009 to 2012, healthy nonsmoker (n = 29) and smoker (n = 129) residents of New York City underwent bronchoscopy with SAE brushing (2.6 ± 1.3 samples/subject; total of 405 samples). SAE gene expression was assessed by Affymetrix HG-U133 Plus 2.0 microarray. New York City PM2.5 levels (Environmental Protection Agency data) were averaged for the 30 days before bronchoscopy. A linear mixed model was used to assess PM2.5-related gene dysregulation accounting for multiple clinical and methodologic variables. MEASUREMENTS AND MAIN RESULTS Thirty-day mean PM2.5 levels varied from 6.2 to 18 μg/m3. In nonsmokers, there was no dysregulation of SAE gene expression associated with ambient PM2.5 levels. In marked contrast, n = 219 genes were significantly dysregulated in association with PM2.5 levels in the SAE of smokers. Many of these genes relate to cell growth and transcription regulation. Interestingly, 11% of genes were mitochondria associated. CONCLUSIONS PM2.5 exposure contributes to significant dysregulation of the SAE transcriptome of smokers, linking pollution and airway epithelial biology in the risk of development of respiratory disease in susceptible individuals.

中文翻译：

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人类小气道上皮转录组的环境污染相关重编程。


基本原理 流行病学研究表明，暴露于颗粒物环境污染会对肺部健康产生不利影响，吸烟会加剧这种影响。空气动力学直径小于或等于2.5微米的颗粒物（PM2.5）是危害最大的城市污染物之一，与呼吸道疾病密切相关。目的 基于小气道上皮 (SAE) 在吸烟相关肺部疾病发病机制中发挥核心作用的知识，我们假设 PM2.5 水平升高与 SAE 基因表达失调相关，这可能有助于该疾病的发展呼吸道疾病。方法 从 2009 年到 2012 年，纽约市健康的非吸烟者 (n = 29) 和吸烟者 (n = 129) 居民接受了 SAE 刷检的支气管镜检查（2.6 ± 1.3 个样本/受试者；总共 405 个样本）。通过 Affymetrix HG-U133 Plus 2.0 微阵列评估 SAE 基因表达。纽约市 PM2.5 水平（环境保护局数据）是支气管镜检查前 30 天的平均值。使用线性混合模型来评估 PM2.5 相关基因失调，考虑多个临床和方法学变量。测量结果和主要结果 30 天平均 PM2.5 水平在 6.2 至 18 μg/m3 之间变化。在非吸烟者中，SAE 基因表达不存在与环境 PM2.5 水平相关的失调。与此形成鲜明对比的是，在吸烟者的 SAE 中，n = 219 个基因与 PM2.5 水平相关显着失调。其中许多基因与细胞生长和转录调控有关。有趣的是，11% 的基因与线粒体相关。结论 PM2.5 暴露会导致吸烟者 SAE 转录组的显着失调，将污染和气道上皮生物学与易感个体患呼吸道疾病的风险联系起来。