Title | Rhinovirus-induced airway cytokines and respiratory morbidity in severely premature children. | ||
Author | Perez, Geovanny F; Pancham, Krishna; Huseni, Shehlanoor; Jain, Amisha; Rodriguez-Martinez, Carlos E; Preciado, Diego; Rose, Mary C; Nino, Gustavo | ||
Journal | Pediatr Allergy Immunol | Publication Year/Month | 2015-Mar |
PMID | 25640734 | PMCID | PMC5542573 |
Affiliation | 1.Division of Pulmonary and Sleep Medicine, Children's National Medical Center, Washington, DC, USA; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Department of Integrative Systems Biology, George Washington University, Washington, DC, USA; Center for Genetic Research Medicine, Children's National Medical Center, Washington, DC, USA. |
BACKGROUND: Rhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro-asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (<32 wks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and whether RV-induced Th2-Th17 responses are linked to more respiratory morbidity in premature children during the first 2 yrs of life. METHODS: We measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0-2 yrs with PCR-confirmed RV infection or non-detectable virus. Protein levels of IL-4, IL-13, TSLP, and IL-17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review. RESULTS: The study comprised 214 children born full term (n = 108), preterm (n = 44) or severely premature (n = 62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL-4 and IL-13) and Th17 (IL-17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV-induced airway IL-4 had recurrent respiratory hospitalizations (median 3.65 hosp/yr; IQR 2.8-4.8) and were more likely to have at least one pediatric intensive care unit admission during the first 2 yrs of life (OR 8.72; 95% CI 1.3-58.7; p = 0.02). CONCLUSIONS: Severely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first 2 yrs of life.