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Background: MicroRNAs (miRs) control gene expression and the development of the immune system and antiviral responses. MiR-155 is an evolutionarily-conserved molecule consistently induced during viral infections in different cell systems. Notably, there is still an unresolved paradox for the role of miR-155 during viral respiratory infections. Despite being essential for host antiviral TH1 immunity, miR-155 may also contribute to respiratory disease by enhancing allergic TH2 responses and NFkB-mediated inflammation. The central goal of this study was to define how airway miR-155 production is related to TH1, TH2, and pro-inflammatory cytokine responses during naturally occurring viral respiratory infections in young children. Methods: Normalized nasal airway levels of miR-155 and nasal protein levels of IFN-γ, TNF-α, IL-1β, IL-13, IL-4 were quantified in young children (≤2 years) hospitalized with viral respiratory infections and uninfected controls. These data were linked to individual characteristics and respiratory disease parameters. Results: A total of 151 subjects were included. Increased miR-155 levels were observed in nasal samples from patients with rhinovirus, RSV and all respiratory viruses analyzed. High miR-155 levels were strongly associated with high IFN-γ production, increased airway TH1 cytokine polarization (IFN-γ/IL-4 ratios) and increased pro-inflammatory responses. High airway miR-155 levels were linked to decreased respiratory disease severity in individuals with high airway TH1 antiviral responses. Conclusions: The airway secretion of miR-155 during viral respiratory infections in young children is associated with enhanced antiviral immunity (TH1 polarization). Further studies are needed to define additional physiological roles of miR-155 in the respiratory tract of human infants and young children during health and disease. [ABSTRACT FROM AUTHOR]

Sleep disorder breathing, particularly obstructive sleep apnea (OSA), has been identified as an independent risk factor for cardiovascular disease. Patients with cardiac disease and OSA have increased morbidity and mortality. Neuromuscular disorders are characterized by respiratory muscle weakness that frequently leads to sleep disorder breathing, and respiratory failure. Also, many neuromuscular conditions present with cardiac pathology. However, the relationship between respiratory morbidity and cardiovascular outcomes has been understudied in the neuromuscular population. This review aims to describe the relationship between respiratory pathology and cardiac disease in patients with neuromuscular disorders. We will review the available literature on the two most common types of cardiac disease, cardiomyopathy and arrhythmias, and their relationship with sleep disorder breathing. • Sleep disorder breathing has been identified as an independent risk factor for cardiovascular disease in the general population; however, the relationship between SBD and neuromuscular disease is not well studied. • The two most common types of cardiac disorders in the neuromuscular population are cardiomyopathy and heart rhythm problems, which can be disease and age-specific. • Ventilatory support improves symptoms and clinical outcomes of patients with neuromuscular disorders. However, the literature is not clear regarding improvement in cardiac function and heart rhythm in patients treated with positive pressure ventilation. • Sleep disorder breathing is associated with linked with worse cardiovascular outcomes. • Cardiomyopathy and arrhythmias are frequently seen in patients with neuromuscular disorders. • Respiratory support in neuromuscular patients could improve cardiac morbidity and overall survival. [ABSTRACT FROM AUTHOR]

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]

Background: Rhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities. Methods: We conducted a retrospective cross-sectional analysis of 145 children with PSG-diagnosed OSA. Outcomes included PSG parameters and obstructive apnea-hypopnea index (OAHI) during REM and non-REM. Linear multivariable models examined the joint effect of rhinitis and OSA parameters with control for potential confounders. Results: Rhinitis was present in 43% of children with OSA (n = 63) but overall OAHI severity was unaffected by the presence of rhinitis. In contrast, OAHI during REM sleep in children with moderate-severe OSA was significantly increased in subjects with rhinitis and OSA (44.1/hr; SE = 6.4) compared with those with OSA alone (28.2/hr; SE = 3.8). Conclusion: Rhinitis is highly prevalent in children with OSA. Although OSA is not more severe in children with rhinitis, they do have a distinct OSA phenotype characterized by more REM-related OSA. Further research is needed to delineate the link between REM-sleep and the physiology of the nose during health and disease. [ABSTRACT FROM AUTHOR]