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Background: Human Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV., Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve (hypoxemia and tachypnea) in young children with HRV infections. Demographic and clinical variables were obtained from reviewing electronic medical records (EMR)., Results: This study included a total of 205 children; 71% of these children were born full-term (>37 weeks gestation), 10% preterm (32-37 weeks) and 19% severely premature (<32 weeks). Our results demonstrated that: 1) HRV infections in the first 3 years of life were associated with higher overall respiratory distress scores in severely premature children relative to children born preterm or full-term; 2) HRV-infected severely premature children ≤3 years old were more likely to have lower airway obstruction than HRV-infected children born preterm or full-term; and 3) other clinical signs of respiratory distress such as tachypnea and hypoxemia were not more common in severely premature than in preterm and full-term children during an HRV infection., Conclusions: Our results indicate that HRV infections in severely premature children are associated with lower airway obstruction rather than hypoxemia or tachypnea. The latter suggests that enhanced airway reactivity is the underlying mechanism for the increased susceptibility to HRV in severely premature children. Longitudinal studies are needed to understand why premature babies develop airway hyper-reactivity to HRV and the long-term effects of early HRV infection in this population., (Copyright © 2017. Published by Elsevier B.V.)

Background: Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood., Methods: Nasal airway secretions were obtained from children (≤3 yrs. old) during PCR-confirmed RV infections (n = 10) and age-matched controls (n = 10). Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC) differentiated at air-liquid interface (ALI). Bioinformatics tools were used to determine the unified (nasal and bronchial) signature airway secretory miRNAome and changes during RV infection in children., Results: Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV., Conclusions: Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway secretion of EVs containing miR-155, which is predicted in silico to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages., Competing Interests: The authors have declared that no competing interests exist.

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. [ABSTRACT FROM AUTHOR]