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Patterns of systemic and local inflammation in patients with asthma hospitalised with influenza
Rabu, 14 Ags 2019 08:00:00

Akhilesh JhaJake DunningTanushree TunstallRyan S. ThwaitesLong T. HoangOnn Min KonMaria C. ZambonTrevor T. HanselPeter J. Openshaw

European Respiratory Journal 2019; DOI: 10.1183/13993003.00949-2019

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 to 8.18, p=0.0012), required less mechanical ventilation (15% versus 37.6%, χ2 6.78, p=0.0338) and had shorter hospital stays (mean 8.3 versus 15.3 d, 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 IFN-α but lower serum TNF, 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.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Jha holds a Clinical Lectureship at the University of Cambridge which 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 AJ from the EMI-GSK programme is not relevant to the content of this manuscript.

Conflict of interest: Dr. Dunning has nothing to disclose.

Conflict of interest: Dr. Tunstall has nothing to disclose.

Conflict of interest: Dr. Thwaites has nothing to disclose.

Conflict of interest: Dr. Hoang has nothing to disclose.

Conflict of interest: Professor Kon has nothing to disclose.

Conflict of interest: Professor Zambon has nothing to disclose

Conflict of interest: Professor Hansel and Imperial Innovations are involved in setting up a medical device company called Mucosal Diagnostics (MD) that is an Imperial College spin-off company.

Conflict of interest: Professor Openshaw reports personal fees from Consultancy, grants from MRC, grants from EU Grant, grants from NIHR Biomedical Research Centre, grants from MRC/GSK, grants from Wellcome Trust, grants from NIHR (HPRU), grants from NIHR Senior Investigator, personal fees from European Respiratory Society, grants from MRC Global Challenge Research Fund, non-financial support from AbbVie, outside the submitted work; and Past President and Trustee of British Society for Immunology; Vice-Chair and Member, NERVTAG (New and Emerging Respiratory Virus Threats Advisory Group; Department of Health) No costs involved.