Individuals with asthma experienced significant morbidity during the 2009 H1N1 outbreak (2
). Although this has been shown in multiple retrospective studies, we had the unique opportunity to prospectively examine infectivity rates in an H1N1-naive population and demonstrated that children with asthma had an increased susceptibility for H1N1 infection. Although increased infectivity among children with asthma is an unexpected finding, it may explain why children with asthma fared worse during the H1N1 pandemic; not only were they experiencing increased symptoms (compared with other viral illness) once infected, they were being infected at a greater rate than their nonasthmatic counterparts. Given the increased susceptibility to H1N1 infection and greater hospitalization rates for those with asthma, these findings raise new questions about the mechanism for enhanced susceptibility to infection with influenza (and not other respiratory viruses) in asthma. In addition, we found that H1N1 accounted for 23% of episodes of loss of asthma control during the peak fall viral season, suggesting that administration of the H1N1 vaccine may have prevented a significant number of asthma exacerbations.
Compared with other viruses, H1N1 caused significantly more severe illness, and there was also a nonsignificant trend between H1N1 infection and increased loss of asthma control. Numerically, most episodes of loss of asthma control were associated with HRV infection, which was much more common than H1N1 infection. However, the proportion of infections leading to loss of asthma control was almost twice as high with H1N1 compared with HRV.
Studies suggest that HRV infection may protect an individual from H1N1 infectivity (17
). Overall, we observed that HRV infections peaked earlier than H1N1 infections, and HRV infections were diminishing as H1N1 infections were on the rise. However, in contrast to these previous studies, the time trend analysis was not consistent with a protective effect with HRV, but rather found those who were infected with HRV were just as likely to become infected with H1N1 the following week.
Only influenza infections were increased in asthma, suggesting that the mechanism may be related to specific infective properties of the influenza virus or associated receptors on airway epithelial cells. Previous studies have shown that influenza uses sialic acid on epithelial cells to cleave hemagglutinin and infect the cells (19
). Perhaps individuals with asthma have increased protease activation leading to increased susceptibility to infection. Alternatively, several studies have provided evidence that asthma is associated with impaired innate antiviral responses (20
). In our study, peripheral blood mononuclear cell innate responses to HRV or RSV between children with and without asthma were similar, suggesting that increased H1N1 infectivity in individuals with asthma is not the result of a defect in innate immunity. It is possible that bronchial epithelial cells have impaired responses to influenza, and additional studies are needed to test this hypothesis.
This study has a number of unique advantages, and some limitations that should be considered in interpreting these data. The prospective study design allowed us to monitor children for rates of both viral infection and associated cold and asthma symptoms, and a wide range of viruses was tested using sensitive polymerase chain reaction–based diagnostics during the peak of the H1N1 pandemic in Wisconsin (9
). Furthermore, this was a unique opportunity to observe how the H1N1 pandemic affected a naive population of children. In most years, many patients have partial protection from seasonal influenza because of prior vaccines or infections with related strains. In contrast, children and young adults were especially susceptible to 2009 H1N1 given their lack of prior exposure and the unusually early onset of the influenza season before the H1N1 vaccine was available. In the main RhinoGen study, we monitored subject asthma symptoms and treatment for 1 year, allowing us to confirm the entry diagnosis of asthma. Although our main analysis was run on asthma diagnosis at study completion, the analysis of H1N1 infection rates was similar when using asthma diagnosis at study entry. In fact, only four subjects had a change in asthma diagnosis; three moved to the asthma group and one moved to the nonasthmatic group. One limitation of our study is that children were enrolled after the onset of H1N1 infections in Wisconsin the previous April, although screening in our community indicated that the number of cases was low until the fall season (9
). Also, we used a simple scoring system to encourage daily score reporting, and as a result more than 90% of the children turned in satisfactory symptom diaries. The scoring system has proven to be informative in previous studies (8
), but has not been validated. Other common cold instruments are available (e.g., Jackson score, WURSS-21), but none have been formally validated in children.
In summary, our findings indicate that children with asthma were more likely to contract infections with 2009 H1N1, but not other respiratory viruses. These findings support recommendations for influenza vaccination in children with asthma and, in addition, suggest that additional studies are warranted to identify mechanisms for this effect. Understanding why children with asthma are uniquely more susceptible to influenza infection could lead to new strategies for prevention and treatment.