期刊
EBIOMEDICINE
卷 19, 期 -, 页码 128-138出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.03.033
关键词
Rhinovirus; Asthma; Mucosal immunology; Absorption of mucosal lining fluid; Interferons; Type II inflammation
资金
- European Research Council (ERC FP7) [233015]
- Asthma UK [CH11SJ]
- MRC Centre [G1000758]
- National Institute of Healthcare Research Biomedical Research Centre (NIHR BRC) [P26095]
- NIHR BRCs at Imperial College London and King's College London [260895]
- Novartis Institute for Biomedical Research (Horsham, UK)
- Hunt Developments (UK) Ltd, Midhurst, UK
- MRC [MC_UP_0801/1, MC_UU_00002/10] Funding Source: UKRI
- Asthma UK [MRC-Asthma UK Centre, CH11SJ, MRC-AsthmaUKCentre] Funding Source: researchfish
- Medical Research Council [G1000758, MC_UP_0801/1, MC_UU_00002/10] Funding Source: researchfish
Background: Rhinovirus infection is a major cause of asthma exacerbations. Objectives: We studied nasal and bronchial mucosal inflammatory responses during experimental rhinovirus-induced asthma exacerbations. Methods: We used nasosorption on days 0, 2-5 and 7 and bronchosorption at baseline and day 4 to sample mucosal lining fluid to investigate airway mucosal responses to rhinovirus infection in patients with allergic asthma (n = 28) and healthy non-atopic controls (n = 11), by using a synthetic absorptive matrix and measuring levels of 34 cytokines and chemokines using a sensitive multiplex assay. Results: Following rhinovirus infection asthmatics developed more upper and lower respiratory symptoms and lower peak expiratory flows compared to controls (all P < 0.05). Asthmatics also developed higher nasal lining fluid levels of an anti-viral pathway (including IFN-lambda, IFN-lambda/IL-29, CXCL11/ITAC, CXCL10/IP10 and IL-15) and a type 2 inflammatory pathway (IL-4, IL-5, IL-13, CCL17/TARC, CCL11/eotaxin, CCL26/eotaxin-3) (area under curve day 0-7, all P < 0.05). Nasal IL-5 and IL-13 were higher in asthmatics at day 0 (P < 0.01) and levels increased by days 3 and 4 (P < 0.01). A hierarchical correlation matrix of 24 nasal lining fluid cytokine and chemokine levels over 7 days demonstrated expression of distinct interferon-related and type 2 pathways in asthmatics. In asthmatics IFN-gamma, CXCL10/IP10, CXCL11/ITAC, IL-15 and IL-5 increased in bronchial lining fluid following viral infection (all P < 0.05). Conclusions: Precision sampling of mucosal lining fluid identifies robust interferon and type 2 responses in the upper and lower airways of asthmatics during an asthma exacerbation. Nasosorption and bronchosorption have potential to define asthma endotypes in stable disease and at exacerbation. (C) 2017 The Authors. Published by Elsevier B.V.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据