Introduction
Asthma exacerbation is a major cause of disease morbidity that increases health care costs, and in some patients, progressive loss of lung function1. Exposure to aeroallergens and environmental factors, such as smoking, PM2.5, or diesel exhaust particles, triggers asthma exacerbation2,3. Respiratory viral infection is also associated with the pathophysiology of asthma exacerbation, particularly in childhood4. The most prominent pathogens involved in asthma exacerbation include human rhinovirus, respiratory syncytial virus, enterovirus, influenza virus, and human metapneumovirus5,6.
Many severe and fatal cases of the 2009 HIN1 pandemic [A(H1N1)pdm09] infection have been reported, both in patients with underlying diseases as well as in healthy children and young adults7-9. Asthma is among the most common underlying conditions in patients hospitalized with A(H1N1)pdm09 infection and asthmatic children show greater susceptibility to A(H1N1)pdm09 viral infection10, suggesting that severe asthma exacerbation is an important comorbidity of influenza infection in patients with asthma7-9.
We previously reported that A(H1N1)pdm09 infection, but not seasonal H1N1 infection, induces severe pulmonary inflammation with elevated cytokine levels in a mouse model of asthma11,12. Moreover, asthmatic model mice with A(H1N1)pdm09 infection are prone to an earlier onset of severe pulmonary inflammation compared to those with seasonal H1N1 infection13, suggesting that a hyper-cytokine condition is involved in severe pneumonia and atelectasis. Another report showed that A(H1N1)pdm09 induces AHR in a non-asthmatic mouse model14. However, no reports have evaluated the effect of A(H1N1)pdm09 on airway constriction in patients with asthma and, to date, the mechanisms of severe asthma exacerbation due to A(H1N1)pdm09 infection remain unclear.
In this study, we investigated airway hyperresponsiveness (AHR) induced by A(H1N1)pdm09 infection in comparison to that caused by seasonal H1N1 influenza. We show that changes in AHR are greater in asthmatic mice with A(H1N1)pdm09 infection than in those with seasonal H1N1 influenza. Enhanced AHR becomes normalized by 10 days post-infection in the mouse model, a trend that supports post infection observations of AHR in paediatric patients with A(H1N1)pdm09 infection. These findings indicate that enhanced AHR contributes to the severe asthma exacerbation phenotype triggered by A(H1N1)pdm09 infection.