This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The viral RTI associated with wheezing protocol will allow us to investigate the role of common respiratory viruses, RSV, parainfluenza, rhinovirus, and adenovirus, have during an acute RTI (serious enough to warrant hospitalization), during convalescence (two months later), and finally in those that do or do not develop persistent wheezing (three years later). We have chosen these select respiratory viruses due to their potential link with the development of asthma, or as potential cause of transient wheezing, or due to their potential role of subverting the interferon- immune response. We will utilize blood and upper airway epithelial cells for activated Stat 1 in these children with viral RTI associated with wheezing by examining airway epithelial cells for activated Stat 1. Since activated Stat 1 is constitutively activated in asthmatic subjects and RSV infection (presumably interferon-gamma) can activate Stat 1, the persistence of high levels of activated Stat 1 in early life following a serious RTI associated with wheezing may be a marker for the development of asthma. This protocol will allow these molecular and cellular mechanisms of asthma to be investigated in a human model.
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