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

Abstract

BackgroundPatients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown.Study settingA 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.ResultsOf 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.ConclusionsAsthma 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.

Why are people with asthma more susceptible to influenza?

“…The evidence provided by JHA et al [15] supports the view that the effect of viruses such as influenza on asthma exacerbations is not the result of either exaggerated type 1 or 2 immune responses in asthma, consistent with Salter's view that it is the "exalted sensibility that the inflammation gives rise to" that results in susceptibility to viruses such as influenza. To prevent acute exacerbations in asthma we need to restore or bring balance back to the innate immune responses present in the airways of asthmatics.…”

“…The influenza pandemic of 2009 provided a unique opportunity, unlike seasonal influenza the "novel" virus did not target those at the extremes of age and its impact had the greatest effect on other, less appreciated, at risk populations; those with asthma, obesity and pregnancy [5]. The paper by JHA et al [15] describes the effect of influenza H1N1pdm09 on 133 adults admitted during this time to UK hospitals. Asthma was the most prevalent pre-existent condition, in 30%, with most being female.…”

Insights Into Type I and III Interferons in Asthma and Exacerbations

“…It has also been assumed for quite some time that asthmatics fare worse than the general population during influenza infection. Asthmatics were hospitalized earlier than non-asthmatics (99) during the 2009 H1N1 influenza pandemic but, surprisingly, were less likely to die (100). In a larger retrospective study of the pandemic outcomes, corticosteroid use and earlier hospital admission explained the lower death rate of asthmatics compared with healthy controls (101).…”

Seasonal and pandemic influenza: 100 years of progress, still much to learn

“…Notably, those with asthma did not demonstrate a heightened type 2 immune signature and (although peripheral blood eosinophils and atopic status were not recorded) there was no difference in serum total IgE, periostin, blood eosinophil gene expression, or nasal IL-13, IL-4 or IL-5. 22 Thus, those with asthma were more likely to present because of their airway symptoms as opposed to the seriousness of the systemic influenza infection. For those without asthma, a greater systemic immune response is associated with worse outcomes.…”