1 Department of Genetic Medicine and.
2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medical College, New York, New York.
Am J Respir Crit Care Med. 2018 Dec 1;198(11):1413-1422. doi: 10.1164/rccm.201712-2526OC.
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 (PM) is among the most harmful urban pollutants and is closely linked to respiratory disease.
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 PM levels are associated with dysregulation of SAE gene expression, which may contribute to the development of respiratory disease.
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 PM levels (Environmental Protection Agency data) were averaged for the 30 days before bronchoscopy. A linear mixed model was used to assess PM-related gene dysregulation accounting for multiple clinical and methodologic variables.
Thirty-day mean PM levels varied from 6.2 to 18 μg/m. In nonsmokers, there was no dysregulation of SAE gene expression associated with ambient PM levels. In marked contrast, n = 219 genes were significantly dysregulated in association with PM levels in the SAE of smokers. Many of these genes relate to cell growth and transcription regulation. Interestingly, 11% of genes were mitochondria associated.
PM 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.
流行病学研究表明，暴露于大气颗粒物污染会对肺部健康造成不良影响，而吸烟会使其恶化。空气动力学直径（PM）小于或等于 2.5 微米的颗粒物是城市中最有害的污染物之一，与呼吸道疾病密切相关。
基于小气道上皮（SAE）在与吸烟相关的肺部疾病发病机制中发挥核心作用的知识，我们假设升高的 PM 水平与 SAE 基因表达的失调有关，这可能导致呼吸道疾病的发生。
2009 年至 2012 年，纽约市的健康非吸烟者（n=29）和吸烟者（n=129）接受了支气管镜检查和 SAE 刷检（每个受试者 2.6±1.3 个样本；总共 405 个样本）。通过 Affymetrix HG-U133 Plus 2.0 微阵列评估 SAE 基因表达。在支气管镜检查前的 30 天内，计算了纽约市 PM 水平（环境保护局数据）的平均值。采用线性混合模型评估与 PM 相关的基因失调，该模型考虑了多种临床和方法变量。
30 天平均 PM 水平范围为 6.2 至 18μg/m。在非吸烟者中，环境 PM 水平与 SAE 基因表达失调无关。相比之下，吸烟者的 SAE 中与 PM 水平相关的基因失调明显，有 n=219 个基因。其中许多基因与细胞生长和转录调控有关。有趣的是，11%的基因与线粒体有关。
PM 暴露会导致吸烟者的 SAE 转录组发生显著失调，将污染与气道上皮生物学联系起来，使易感个体发生呼吸道疾病的风险增加。
