Patterns of systemic and local inflammation in patients with asthma hospitalised with influenza

MOSAIC Investigators

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Abstract

Background: Patients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown. Study setting: A prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression. Results: Of 133 admissions, 40 (30%) had previous asthma; these were more often female (70% versus 38.7%, OR 3.69, 95% CI 1.67-8.18; p=0.0012), required less mechanical ventilation (15% versus 37.6%, Chi-squared 6.78; p=0.0338) and had shorter hospital stays (mean 8.3 versus 15.3 days, p=0.0333) than those without. In patients without asthma, severe outcomes were more frequent in those given corticosteroids (OR 2.63, 95% CI 1.02-6.96; p=0.0466) or presenting >4 days after disease onset (OR 5.49, 95% CI 2.28-14.03; p=0.0002). Influenza vaccination in at-risk groups (including asthma) were lower than intended by national policy and the early use of antiviral medications were less than optimal. Mucosal immune responses were equivalent between groups. Those with asthma had higher serum interferon (IFN)-α, but lower serum tumour necrosis factor, interleukin (IL)-5, IL-6, CXCL8, CXCL9, IL-10, IL-17 and CCL2 levels (all p<0.05); both groups had similar serum IL-13, total IgE, periostin and blood eosinophil gene expression levels. Asthma diagnosis was unrelated to viral load, IFN-α, IFN-γ, IL-5 or IL-13 levels. Conclusions: Asthma is common in those hospitalised with influenza, but may not represent classical type 2-driven disease. Those admitted with influenza tend to be female with mild serum inflammatory responses, increased serum IFN-α levels and good clinical outcomes.

Original languageEnglish
Article number1900949
JournalEuropean Respiratory Journal
Volume54
Issue number4
DOIs
Publication statusPublished - 1 Oct 2019

Bibliographical note

Funding Information:
Conflict of interest: A. Jha holds a clinical lectureship at the University of Cambridge that is supported jointly by the University of Cambridge Experimental Medicine Training Initiative (EMI) programme in partnership with GlaxoSmithKline (EMI-GSK) and Cambridge University Hospitals NHS Foundation Trust. The funding received by A. Jha from the EMI-GSK programme is not relevant to the content of this manuscript. J. Dunning has nothing to disclose. T. Tunstall has nothing to disclose. R.S. Thwaites has nothing to disclose. L.T. Hoang has nothing to disclose. O.M. Kon has nothing to disclose. M.C. Zambon has nothing to disclose T.T. Hansel and Imperial Innovations are involved in setting up a medical device company called Mucosal Diagnostics (MD), which is an Imperial College spin-off company. P.J. Openshaw reports personal fees for consultancy from Janssen, grants from MRC, EU, NIHR Biomedical Research Centre, MRC/GSK, Wellcome Trust, NIHR and MRC Global Challenge Research Fund, personal fees for online presentations from European Respiratory Society, non-financial support from AbbVie, outside the submitted work; and is past president and trustee of British Society for Immunology, vice-chair and member of NERVTAG (New and Emerging Respiratory Virus Threats Advisory Group; Department of Health).

Funding Information:
Support statement: MOSAIC (Mechanisms of Severe Influenza Consortium) was supported by the MRC (UK) and Wellcome Trust (090382/Z/09/Z). The study was also supported by the National Institute of Healthcare Research (NIHR) Biomedical Research Centres (BRCs) in London and Liverpool and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England (PHE). P.J. Openshaw was supported by EU FP7 PREPARE project 602525. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, Public Health England or the EU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding information for this article has been deposited with the Crossref Funder Registry.

Publisher Copyright:
Copyright © ERS 2019

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