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Background:Live attenuated influenza vaccine (LAIV) is recommended for annual influenza vaccination in children from age 2 years. However, some guidelines recommend against its use in children with asthma or recurrent wheeze due to concerns over its potential to induce wheezing. Objective: To assess the safety of LAIV in children with moderate-severe asthma, and in preschool children with recurrent wheeze. Methods: Prospective, multi-center, open label, phase IV intervention studyin 14 specialist UK clinics.LAIV was administered under medical supervision, with follow-up of asthma symptoms 72 hours and 4 weeks late, using validated questionnaires.Clinical Trials.gov registration NCT02866942, EU Clinical Trials registration 2016-002352-24. Results: 478 young people (median 9.3, range 2–18 years) with physician-diagnosed asthma or recurrent wheeze were recruited, including 208 (44%) prescribed high-dose inhaled corticosteroids and 122 (31%) with severe asthma.There was no significant change in asthma symptoms in the 4 weeks following administration (median change 0, P=.26, McNemar’s test), with no impact of level of baseline asthma control/symptoms in predicting either a worsening of asthma or exacerbation following LAIV using a regression model. 47 subjects (14.7%, 95%CI 11% to 19.1%) reported a severe asthma exacerbation in the four weeks following immunization, requiring short course of systemic corticosteroids; in four cases, this occurred within 72 hours of vaccine. No association with asthma severity, baseline lung function or asthma control was identified.Conclusions: LAIV appears to be well-tolerated in the vast majority of children with asthma or recurrent wheeze, includingthosewhose asthma is categorized as severe or poorly controlled

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with TH2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and TH2 mediators. With the renewed interest in anti-TH2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis.