Rhinovirus-Induced Airway Cytokines and Respiratory Morbidity in Severely Premature Children

The purpose of this study was to evaluate the generation of Th2 and other pro-asthmatic cytokines (interleukin [IL]-4, IL-13, and IL-17 and thymic stromal lymphopoietin [TSLP]) in premature infants during rhinovirus (RV) infections. This study was a retrospective analysis of 264 subjects, aged 0 to 2 years with acute respiratory illness and polymerase chain reaction-confirmed RV infection or nondetectable virus (controls). Patients were stratified by gestational age (GA) including severe prematurity (37 weeks' GA) infants. Levels of Th2 and Th17 cytokines were obtained from nasal washings of subjects at the onset of an acute respiratory illness. Demographic variables were obtained via electronic medical record review and included gestational age, ethnicity, gender, perinatal history, including bronchopulmonary dysplasia (BPD), and number of hospitalizations and ICU admissions in the first 2 years of life. There were no significant demographical differences between RV-positive and control groups. Severely premature subjects with RV infection demonstrated significant elevations in IL-4, IL-13, and IL-17 compared with controls. In severely premature infants, BPD was an independent risk factor for higher IL-4 and IL-17 levels. Additionally, RV-infected premature children with high levels of IL-17 and IL-4 were 5 and 8 times more likely to have an ICU admission. High IL-4 levels and a family history of asthma were associated with an increased the risk for annual hospital admission during the first 2 years of life. This study shows that RV infections in premature children, especially those with BPD, are associated with enhanced secretion of Th2 and other pro-asthmatic cytokines, increasing the risk for hospital and ICU admission.