Viral respiratory tract infections are frequently associated with exacerbations of wheezing in infants, children, and young adults. During infancy, respiratory syncytial virus (RSV) is the viral pathogen most often linked with wheezing. However, the majority of infants with wheezing caused by RSV (60-70 percent) will stop experiencing attacks during their pre-school years. By comparison, RV is more strongly associated with wheezing exacerbations in community-based studies of school-aged children and adults with asthma; however, information about the prevalence of RV among children who require hospitalization for asthma is limited. In addition, the age at which RV becomes an important trigger of severe wheezing, and the relationship between RV and the atopic status of children hospitalized for asthma is unknown. It is also not clear what factors will determine which patients will develop increased bronchial hyperreactivity and lower respiratory tract symptoms with an RV infection, and evidence as to whether RV infects the lower airway remains controversial. These questions are critical to understanding the capacity of RV to induce exacerbations of asthma. In this project, studies are planned to: 1) evaluate viral infections and the atopic characteristics of actively wheezing children treated in the hospital (Specific Aim 1) together with 2) a comparison of immune responses and airway inflammation stimulated by natural and experimental RV infections in children and young adults with asthma and in non-asthmatic controls (Specific Aims 2 and 3). The hospital study is designed to: a) determine the prevalence of RV relative to other viral pathogens in wheezing infants and children, and b) examine the relationship between RV-induced wheezing and the age and atopic status of the child.
Specific Aim 2 (a study of actively wheezing children in the emergency room) and Specific Aim 3 (a study of experimental RV infections in patients with mild asthma and high levels of total serum IgE) will investigate whether symptoms stimulated by RV are due to an altered immune response to this virus in the asthmatic host and/or due to an augmentation of pre-existing allergic inflammation in the airways. Bronchoscopies are planned in a subgroup of the experimentally infected patients to determine whether RV can infect the lower airways. The results are expected to provide a better understanding for the pathogenesis of asthma exacerbations in children and young adults when they are infected with RV.
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