The role of fine suspended particles of atmospheric air in the formation of eosinophilic inflammation in T2 endotype of asthma

O. Skorokhodkina, M. Khakimova, G. A. Timerbulatova, O. A. Bareycheva, Larisa Y. Saleeva, Rezeda G. Sharipova, Anastasia V. Ablyayeva, Lilia M. Fatkhutdinova
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Abstract

BACKGROUND: It is now well established that allergens induce eosinophilic inflammation in T2 endotype of asthma. However, much less is known about the role of non-specific factors (suspended particles in the atmospheric air-PM). AIMS: To define eosinophilic inflammation on the basis of several biomarkers in T2 endotype of asthma exposed to PM. MATERIALS AND METHODS: We studied 61 patients with T2 endotype of asthma (ages 18-65). Group 1 included 34 patients with allergic asthma and group 2 included 27 patients with non-allergic asthma. Moreover, 30 healthy matched controls without asthma and other allergic diseases were enrolled the study. We performed clinical examination and allergy testing. Additionally, serum levels of IL-33, IL-25, IL-4, IL-5, IL-13, DPP4 (multiplex assay) and periostin (ELISA) were evaluated. The analyses of annual concentration average (Avr) and maximal annual concentration (MaxAvr) average of PM2.5 and PM10 in Kazan were carried out using the database of the Center for Hygiene and Epidemiology in the Republic of Tatarstan for 2014-2020. Statistical analyseswere performedusing the R statistical software (version 4.0.5). The study was funded by RFBR (project number 19-05-50094). RESULTS: We detected increased blood eosinophil count and IL-5 levels in asthma patients. High levels of total IgE (p=0.0001), that correlated with IL-4 levels were observed only in patients with allergic asthma (rS=0.38; р=0.045). Moreover, elevated IL-25 levels were found in patients with allergic asthma (p=0.009). No significant differences in IL-13 levels in patient with asthma were found. Regression analysis revealed that the PM2.5Avr increase by 1 mcg/m3 results in the growth of IL-33 and IL-25 levels, but the PM10Avr increase raises the IL-25 levels only in patients with non-allergic asthma. No significant increase in IL-25 and IL-33 levels under the exposure to PM2.5Avr and PM 10Avr was detected in patients with allergic asthma. CONCLUSIONS: The results of this study indicate the pivotal role of fine suspended particles in the development and maintenance of eosinophilic inflammation in patients with non-allergic asthma.
大气细悬浮颗粒在哮喘T2内型嗜酸性粒细胞炎症形成中的作用
背景:现在已经确定过敏原在T2型哮喘中诱导嗜酸性粒细胞炎症。然而,人们对非特异性因素(大气中悬浮颗粒pm)的作用知之甚少。目的:根据暴露于PM的哮喘T2内型的几种生物标志物来定义嗜酸性粒细胞炎症。材料与方法:我们研究了61例T2型哮喘患者(年龄18-65岁)。1组过敏性哮喘34例,2组非过敏性哮喘27例。此外,30名没有哮喘和其他过敏性疾病的健康对照者参加了这项研究。我们进行了临床检查和过敏试验。同时检测血清IL-33、IL-25、IL-4、IL-5、IL-13、DPP4(多重检测)和骨膜蛋白(ELISA)水平。利用鞑靼斯坦共和国卫生与流行病学中心2014-2020年数据库对喀山市PM2.5和PM10的年平均浓度(Avr)和最大年平均浓度(MaxAvr)进行分析。采用R统计软件(4.0.5版)进行统计分析。本研究由RFBR资助(项目编号19-05-50094)。结果:我们检测到哮喘患者血液中嗜酸性粒细胞计数和IL-5水平升高。高水平的总IgE (p=0.0001)与IL-4水平相关,仅在过敏性哮喘患者中观察到(rS=0.38;р= 0.045)。此外,变应性哮喘患者IL-25水平升高(p=0.009)。哮喘患者IL-13水平无明显差异。回归分析显示,PM2.5Avr升高1 mcg/m3会导致IL-33和IL-25水平升高,而PM10Avr升高仅会使非过敏性哮喘患者IL-25水平升高。变应性哮喘患者暴露于PM2.5Avr和pm10avr下IL-25和IL-33水平未见明显升高。结论:本研究结果表明,细悬浮颗粒在非过敏性哮喘患者嗜酸性粒细胞炎症的发生和维持中起关键作用。
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