一种新的非侵入性方法，可以从小气道中发现病理相关蛋白
2022/10/17
摘要
背景：个性化呼吸医学缺乏早期和精确的生物标志物。呼吸中含有一种由小液滴组成的气溶胶，是在小气道完全呼气时闭合和重新打开时，由上皮粘膜液形成的。这些颗粒可以通过PExA (R)方法(呼出空气中的颗粒)进行撞击收集，它们来自以前难以接近的临床高度关注的区域，这使它们成为反映小气道病理过程的生物标志物的潜在来源。我们的目的是研究PExA方法是否有助于发现反映小气道病理的生物标志物。
方法：10名健康对照者和20名哮喘受试者，其中10例肺清除指数(LCI >= 2.9 z-score)较高的小气道受累者，采用横断面设计，使用PExA仪器进行检查。使用SOMAscan蛋白质组学平台(SomaLogic Inc.)对样本进行分析。
结果：在多达80%的样本中检测到207种蛋白质。与健康对照组相比，哮喘和高LCI受试者中有9种蛋白质显示出不同的丰度。其中2个基因含量较低(ALDOA4,C4)，7个基因含量较高(FIGF, SERPINA1,CD93,CCL18,F10,IgM,IL1RAP)。sRAGE水平在戒烟组(n=14)低于不吸烟组(n=16)。基因本体论(GO)注释数据库分析显示，PEx蛋白组富集于细胞外泌体囊泡和先天免疫相关的细胞外蛋白中。
结论：应用的分析方法是可重复的，并允许从高LCI哮喘受试者的PEx样本中鉴别病理感兴趣的蛋白质。结果表明，基于PEx的蛋白质组学是一种新的和有前途的方法来研究小气道累及的呼吸道疾病。
A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways
Ostling J, Van Geest M, Olsson HK, et al
Abstract
BACKGROUND：There is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA (R) method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways. Our aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways.
METHODS：Ten healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI >= 2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc.).
RESULTS：Two hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n = 14) than in never smokers (n = 16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.
CONCLUSIONS：The applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement.
背景：个性化呼吸医学缺乏早期和精确的生物标志物。呼吸中含有一种由小液滴组成的气溶胶，是在小气道完全呼气时闭合和重新打开时，由上皮粘膜液形成的。这些颗粒可以通过PExA (R)方法(呼出空气中的颗粒)进行撞击收集，它们来自以前难以接近的临床高度关注的区域，这使它们成为反映小气道病理过程的生物标志物的潜在来源。我们的目的是研究PExA方法是否有助于发现反映小气道病理的生物标志物。
方法：10名健康对照者和20名哮喘受试者，其中10例肺清除指数(LCI >= 2.9 z-score)较高的小气道受累者，采用横断面设计，使用PExA仪器进行检查。使用SOMAscan蛋白质组学平台(SomaLogic Inc.)对样本进行分析。
结果：在多达80%的样本中检测到207种蛋白质。与健康对照组相比，哮喘和高LCI受试者中有9种蛋白质显示出不同的丰度。其中2个基因含量较低(ALDOA4,C4)，7个基因含量较高(FIGF, SERPINA1,CD93,CCL18,F10,IgM,IL1RAP)。sRAGE水平在戒烟组(n=14)低于不吸烟组(n=16)。基因本体论(GO)注释数据库分析显示，PEx蛋白组富集于细胞外泌体囊泡和先天免疫相关的细胞外蛋白中。
结论：应用的分析方法是可重复的，并允许从高LCI哮喘受试者的PEx样本中鉴别病理感兴趣的蛋白质。结果表明，基于PEx的蛋白质组学是一种新的和有前途的方法来研究小气道累及的呼吸道疾病。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Clinical Proteomics, 2022, 19(1). doi:ARTN2910.1186/s12014-022-09363-z）
（Clinical Proteomics, 2022, 19(1). doi:ARTN2910.1186/s12014-022-09363-z）
A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways
Ostling J, Van Geest M, Olsson HK, et al
Abstract
BACKGROUND：There is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA (R) method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways. Our aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways.
METHODS：Ten healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI >= 2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc.).
RESULTS：Two hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n = 14) than in never smokers (n = 16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.
CONCLUSIONS：The applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement.
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