Identifying the burden of hospitalization due to Rhinovirus (RV) in children and mechanisms of pathogenesis using airway molecular profiling - PROJECT SUMMARY/ABSTRACT Rhinoviruses (RVs), underestimated in the past as simply the cause of the common cold, are increasingly appreciated as a major cause of severe, acute respiratory illnesses involving the lower respiratory tract (LRT) across all age groups. As the most frequent cause of the common cold for both children and adults, RVs set the stage for secondary bacterial infections (acute otitis media and sinusitis) responsible for serious medical, social and economic consequences. RVs are 2nd to respiratory syncytial virus (RSV) as a cause of bronchiolitis in infants and toddlers resulting in numerous Emergency Department visits and hospitalizations. They are also recognized as the most important triggers for asthma exacerbations in children and adults, as well as chronic obstructive lung disease in adults, leading to substantial morbidity and rare mortality. RVs have long been appreciated as a cause of LRT infection in immunocompromised children and adults. However, the role of RVs as an important cause of community acquired pneumonia (CAP) in either children or adults is still a matter of debate. This is in large part because of the high frequency of subclinical RV infections which complicate the interpretation when RVs are identified in persons with serious respiratory disease. The goal of this study is to determine the burden of RVs as a cause of acute, severe, respiratory illnesses leading to hospitalization. We will create a cohort of children in Madison, Wisconsin. They will be enrolled in the 2nd year of life and followed longitudinally (when well and sick) for 36 months to identify the circulating RVs and provide samples to confirm/establish a host nasal transcriptome differentiating clinical RV infections from subclinical RV infections and clinical infections caused by other respiratory viruses. Simultaneously, we will evaluate all episodes of severe, acute respiratory infection, including CAP, admitted to the American Family Children’s Hospital to determine etiology in general and the role of RVs in particular. We will be able to determine the precise proportion of cases of lower respiratory tract illness, including CAP, that are actually caused by RV, a current gap in our clinical knowledge. We hypothesize that the nasal transcriptome will provide a signature for RV in subjects with severe, acute LRT infection that will distinguish it from asymptomatic infection and that study of host transcriptomics in severe cases of RV infection will identify immune/inflammatory defects and other targets for management. This will have vitally important implications for antibiotic stewardship and development of management strategies including vaccines and other therapeutics. Given the commanding role of RV in respiratory infections (especially as a reduction of RSV is on the clinical horizon), there must be increased efforts at both prevention of and intervention for RV infections.
