原標(biāo)題：嚴(yán)重哮喘患者的外周氣道2型炎癥、中性粒細(xì)胞增多癥和微生物失調(diào)
背景：IL-13被認(rèn)為是哮喘臨床診斷指標(biāo)中的典型T2型細(xì)胞因子。重癥哮喘患者可通過吸入高劑量的類固醇來調(diào)節(jié)中央氣道支氣管上皮的IL-13應(yīng)答基因。然而，在外周氣道內(nèi)情況并非如此。我們試圖通過分析支氣管肺泡來進(jìn)一步了解重癥哮喘患者外周氣道中的 IL-13。
方法：支氣管肺泡灌洗液（BAL）樣本來自203名哮喘患者和健康志愿者，其中78名為重癥哮喘。使用多細(xì)胞因子免疫測定平臺測量炎癥介質(zhì)。使用末端限制性片段長度多態(tài)性方法對另外59名志愿者的BAL樣品重復(fù)進(jìn)行16S rRNA分析。
結(jié)果：盡管接受了大劑量吸入性糖皮質(zhì)激素治療，重癥哮喘患者BAL中 IL-13增高，具有高濃度BAL IL-13的重癥哮喘患者與具有正常BAL IL-13濃度的患者相比，其肺功能更差，中性粒細(xì)胞百分比顯著增高，但嗜酸性粒細(xì)胞比例沒有差異。這一發(fā)現(xiàn)在第二個隊列中得到了重復(fù)，這進(jìn)一步將BAL IL-13和中性粒細(xì)胞增多癥與外周氣道中潛在致病菌聯(lián)系起來。
結(jié)論：我們的研究結(jié)果表明，IL-13的類固醇無效與重癥哮喘患者的BAL中性粒細(xì)胞增多癥和細(xì)菌失調(diào)有關(guān)。我們的研究結(jié)果強(qiáng)調(diào)了重癥哮喘的生物學(xué)復(fù)雜性，以及更好地了解這種疾病外周氣道中的先天性和適應(yīng)性免疫反應(yīng)的重要性。


延伸閱讀
Allergy                                                  
Peripheral airways type 2 inflammation, neutrophilia and microbial dysbiosis in severe asthma
DOI: 10.1111/all.14732
Abstract:
Background: IL-13 is an archetypal T2 cytokine central to the clinical disease expression of asthma. The IL-13 response genes, which are upregulated in central airway bronchial epithelial of asthma patients, can be normalized by high-dose inhaled steroid therapy in severe asthma. However, this is not the case within the peripheral airways. We have sought to further understand IL-13 in the peripheral airways in severe asthma through bronchoalveolar analysis.
Methods: Bronchoalveolar lavage samples were collected from 203 asthmatic and healthy volunteers, including 78 with severe asthma. Inflammatory mediators were measured using a multiple cytokine immunoassay platform. This analysis was replicated in a further 59 volunteers, in whom 16S rRNA analysis of BAL samples was undertaken by terminal restriction fragment length polymorphism.
Results: Severe asthma patients with high BAL IL-13, despite treatment with high-dose inhaled corticosteroids, had more severe lung function and significantly higher BAL neutrophil percentages, but not BAL eosinophils than those with normal BAL-13 concentrations. This finding was replicated in the second cohort, which further associated BAL IL-13 and neutrophilia with a greater abundance of potentially pathogenic bacteria in the peripheral airways.
Conclusion: Our findings demonstrate a steroid unresponsive source of IL-13 that is associated with BAL neutrophilia and bacterial dysbiosis in severe asthma. Our findings highlight the biological complexity of severe asthma and the importance of a greater understanding of the innate and adaptive immune responses in the peripheral airways in this disease.
First Author:
Adnan Azim
Correspondence:
Peter Howarth, Clinical & Experimental Sciences Academic Unit, University of Southampton, Southampton, UK.
All Authors:
Adnan Azim, Ben Green, Laurie Lau, Hitasha Rupani, Nivenka Jayasekera, Kenneth Bruce, Peter Howarth
2021-08-02 Article
　　創(chuàng)建過敏性疾病的科研、科普知識交流平臺，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺。