Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers. The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.

中文翻译：

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吸烟会引起小气道蛋白质组的性别特异性变化

香烟烟雾会触发肺部的许多细胞和信号反应，由此产生的炎症在与烟雾相关的肺部疾病（如 COPD）中起着核心作用。我们探讨了吸烟对通过收集呼出颗粒获得的样本中小气道蛋白质组的影响，目的是识别因吸烟而失调的特定蛋白质。使用 PExA 方法从 38 名当前吸烟者、47 名前吸烟者和 22 名健康对照者中获得呼出的颗粒物。从个体受试者中收集 120 ng 样本，并使用 SOMAscan 蛋白质组学平台进行分析。进行了基于一般线性模型的统计。在 107 个总样本中至少有一半检测到 203 种蛋白质。主动吸烟对呼吸道衬液 (RTLF) 的蛋白质组成有显着影响，与从不吸烟者相比，当前吸烟者的 81 种蛋白质发生了改变（p < 0.05，q < 0.124）。最清楚地区分当前吸烟者和从不吸烟者的蛋白质是 sRAGE、FSTL3、SPOCK2 和蛋白质 S，所有这些蛋白质在当前吸烟者中的含量都较低。性别分层分析揭示了性别差异，女性比男性主动吸烟导致的蛋白质组学变化更明显。女性主动吸烟改变其丰度的蛋白质在更大程度上与补体系统有关。前吸烟者的小气道蛋白谱似乎与从不吸烟者中观察到的更相似。研究表明，吸烟对小气道中的蛋白质表达有很大影响，而且吸烟对男性和女性的影响不同，