原標題：嚴重哮喘患者的外周氣道2型炎癥、中性粒細胞增多癥和微生物失調(diào)
背景：IL-13被認為是哮喘臨床診斷指標中的典型T2型細胞因子。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樣品重復進行16S rRNA分析。
結果：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，中性粒細胞百分比顯著增高，但嗜酸性粒細胞比例沒有差異。這一發(fā)現(xiàn)在第二個隊列中得到了重復，這進一步將BAL IL-13和中性粒細胞增多癥與外周氣道中潛在致病菌聯(lián)系起來。
結論：我們的研究結果表明，IL-13的類固醇無效與重癥哮喘患者的BAL中性粒細胞增多癥和細菌失調(diào)有關。我們的研究結果強調(diào)了重癥哮喘的生物學復雜性，以及更好地了解這種疾病外周氣道中的先天性和適應性免疫反應的重要性。


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、預防的共享平臺。