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上皮细胞因子与老年哮喘临床表型之间的关联

Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma.

作者信息

Ulambayar Bastsetseg, Lee So Hee, Yang Eun Mi, Ye Young Min, Park Hae Sim

机构信息

Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.

出版信息

Allergy Asthma Immunol Res. 2019 Jan;11(1):79-89. doi: 10.4168/aair.2019.11.1.79.

Abstract

PURPOSE

Asthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms.

METHODS

A total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay.

RESULTS

Significantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics ( < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics ( = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma ( < 0.05 for each).

CONCLUSIONS

These findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.

摘要

目的

老年哮喘具有不同的临床特征,包括更严重的表型和更高的合并症发生率。已知上皮细胞可在哮喘气道中引发先天性/适应性免疫反应。我们在一个成年哮喘患者的横断面队列中,比较了老年哮喘患者与非老年哮喘患者的临床特征和上皮来源的细胞因子水平,以进一步了解其发病机制。

方法

从一家三级医院招募了总共1452名成年哮喘患者,并将其分为两组:234名老年(初次诊断时年龄≥60岁)哮喘患者和1218名非老年(初次诊断时年龄<60岁)哮喘患者。比较两组之间与哮喘相关的临床参数。通过酶联免疫吸附测定法测量血清中上皮细胞来源的细胞因子水平,包括白细胞介素(IL)-31、IL-33、IL-8、嗜酸性粒细胞趋化因子-2、转化生长因子β1(TGF-β1)和骨膜蛋白。

结果

与非老年哮喘患者相比,老年哮喘患者中迟发性哮喘(发病年龄≥40岁)和重度哮喘的患病率显著更高,而特应性、血液/痰液嗜酸性粒细胞计数、总免疫球蛋白E和嗜酸性粒细胞阳离子蛋白水平更低(均P<0.05)。老年哮喘患者的第1秒用力呼气量(FEV1,预测值%)水平往往更低(P=0.07)。此外,老年哮喘患者血清IL-33和IL-31水平显著更低,而IL-8、嗜酸性粒细胞趋化因子-2、TGF-β1或骨膜蛋白的血清水平未发现差异。在老年哮喘患者中,重度哮喘患者的FEV1(预测值%)值更低,但与非重度哮喘患者相比,其血清嗜酸性粒细胞趋化因子-2和TGF-β1水平显著更高(均P<0.05)。

结论

这些发现表明,上皮细胞来源的细胞因子的年龄相关变化可能会影响老年哮喘的临床表型和严重程度:IL-33和IL-31水平降低可能导致Th2表型减少,而嗜酸性粒细胞趋化因子-2和TGF-β1水平升高可能导致病情严重。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d17/6267184/e6cc7ae89412/aair-11-79-g001.jpg

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