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Infants requiring hospitalization due to a viral lower respiratory tract infection (LRTI) have a high risk of developing recurrent respiratory illnesses in early life and asthma beyond childhood. Notably, all validated clinical scales for viral LRTI have focused on predicting acute severity instead of recurrence. We present a novel clinical approach combining individual risk factors with bedside clinical parameters to predict recurrence after viral LRTI hospitalization in young children. A retrospective longitudinal cohort of young children (=3?years) designed to define clinical predictive factors of recurrent respiratory illnesses within 12 months after hospitalization due to PCR-confirmed viral LRTI. Data collection was through electronic medical record. We included 138 children hospitalized with viral LRTI. Using automatic stepwise logistic model selection, we found that the strongest predictors of recurrence in infants hospitalized for the first time were severe prematurity (=32 weeks’ gestational age, OR=5.19; 95%?CI 1.76 to 15.32; p=0.002) and a clinical score that weighted hypoxemia, subcostal retractions and wheezing (OR=3.33; 95%?CI 1.59 to 6.98; p<0.001). After the first hospitalization, the strongest predictors of subsequent episodes were wheezing (OR=5.62; 95%?CI 1.03 to 30.62; p=0.04) and family history of asthma (OR=5.39; 95%?CI 1.04 to 27.96; p=0.04). We found that integrating individual risk factors (eg, prematurity or family history of asthma) with bedside clinical assessment (eg, wheezing, subcostal retractions or hypoxemia) can predict the risk of recurrence after viral LRTI hospitalization in infants. This strategy may enable clinically oriented subsetting of infants with viral LRTI based on individual predictors for recurrent respiratory illnesses during early life.

Infants requiring hospitalization due to a viral lower respiratory tract infection (LRTI) have a high risk of developing recurrent respiratory illnesses in early life and asthma beyond childhood. Notably, all validated clinical scales for viral LRTI have focused on predicting acute severity instead of recurrence. We present a novel clinical approach combining individual risk factors with bedside clinical parameters to predict recurrence after viral LRTI hospitalization in young children. A retrospective longitudinal cohort of young children (≤3 years) designed to define clinical predictive factors of recurrent respiratory illnesses within 12 months after hospitalization due to PCR-confirmed viral LRTI. Data collection was through electronic medical record. We included 138 children hospitalized with viral LRTI. Using automatic stepwise logistic model selection, we found that the strongest predictors of recurrence in infants hospitalized for the first time were severe prematurity (≤32 weeks’ gestational age, OR=5.19; 95% CI 1.76 to 15.32; p=0.002) and a clinical score that weighted hypoxemia, subcostal retractions and wheezing (OR=3.33; 95% CI 1.59 to 6.98; p<0.001). After the first hospitalization, the strongest predictors of subsequent episodes were wheezing (OR=5.62; 95% CI 1.03 to 30.62; p=0.04) and family history of asthma (OR=5.39; 95% CI 1.04 to 27.96; p=0.04). We found that integrating individual risk factors (eg, prematurity or family history of asthma) with bedside clinical assessment (eg, wheezing, subcostal retractions or hypoxemia) can predict the risk of recurrence after viral LRTI hospitalization in infants. This strategy may enable clinically oriented subsetting of infants with viral LRTI based on individual predictors for recurrent respiratory illnesses during early life.

Viral respiratory infections are often grouped as a single respiratory syndrome named ‘viral bronchiolitis’, independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification.

Viral respiratory infections are often grouped as a single respiratory syndrome named ‘viral bronchiolitis’, independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification.

Rationale The nasopharyngeal (NP) microbiota of newborns and infants plays a key role in modulating airway inflammation and respiratory symptoms during viral infections. Premature (PM) birth modifies the early NP environment and is a major risk factor for severe viral respiratory infections. However, it is currently unknown if the NP microbiota of PM infants is altered relative to full-term (FT) individuals.Objectives To characterize the NP microbiota differences in preterm and FT infants during rhinovirus (RV) infection.Methods We determined the NP microbiota of infants 6 months to =2 years of age born FT (n=6) or severely PM<32 weeks gestation (n=7). We compared microbiota composition in healthy NP samples and performed a longitudinal analysis during naturally occurring RV infections to contrast the microbiota dynamics in PM versus FT infants.Results We observed significant differences in the NP bacterial community of PM versus FT. NP from PM infants had higher within-group dissimilarity (heterogeneity) relative to FT infants. Bacterial composition of NP samples from PM infants showed increased Proteobacteriaand decreased in Firmicutes. There were also differences in the major taxonomic groups identified, including Streptococcus, Moraxella, and Haemophilus. Longitudinal data showed that these prematurity-related microbiota features persisted during RV infection.Conclusions PM is associated with NP microbiota changes beyond the neonatal stage. PM infants have an NP microbiota with high heterogeneity relative to FT infants. These prematurity-related microbiota features persisted during RV infection, suggesting that the NP microbiota of PM may play an important role in modulating airway inflammatory and immune responses in this vulnerable group.

RationaleThe nasopharyngeal (NP) microbiota of newborns and infants plays a key role in modulating airway inflammation and respiratory symptoms during viral infections. Premature (PM) birth modifies the early NP environment and is a major risk factor for severe viral respiratory infections. However, it is currently unknown if the NP microbiota of PM infants is altered relative to full-term (FT) individuals.ObjectivesTo characterize the NP microbiota differences in preterm and FT infants during rhinovirus (RV) infection.MethodsWe determined the NP microbiota of infants 6 months to ≤2 years of age born FT (n=6) or severely PM<32 weeks gestation (n=7). We compared microbiota composition in healthy NP samples and performed a longitudinal analysis during naturally occurring RV infections to contrast the microbiota dynamics in PM versus FT infants.ResultsWe observed significant differences in the NP bacterial community of PM versus FT. NP from PM infants had higher within-group dissimilarity (heterogeneity) relative to FT infants. Bacterial composition of NP samples from PM infants showed increased Proteobacteriaand decreased in Firmicutes. There were also differences in the major taxonomic groups identified, including Streptococcus, Moraxella, and Haemophilus. Longitudinal data showed that these prematurity-related microbiota features persisted during RV infection.ConclusionsPM is associated with NP microbiota changes beyond the neonatal stage. PM infants have an NP microbiota with high heterogeneity relative to FT infants. These prematurity-related microbiota features persisted during RV infection, suggesting that the NP microbiota of PM may play an important role in modulating airway inflammatory and immune responses in this vulnerable group.

Background:It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity.Methods:Nasal airway secretions were collected from 140 children =3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFN?, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay.Results:Full-term children with HMPV and RSV infection had increased levels of nasal airway IFN?, CCL5, and IL-10 along with an elevation in Th1 (IFN?)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (< 32?wk gestation) did not exhibit increased Th1/Th2 ratios or elevated nasal airway secretion of IFN?, CCL5, and IL-10 relative to uninfected controls.Conclusion:Our study is the first to demonstrate that premature infants have defective IFN?, CCL5/RANTES, and IL-10 airway responses during HMPV infection and provides novel insights about the potential reason why HMPV causes severe respiratory disease in children with history of prematurity.

Rhinovirus (RV) infections account for most asthma exacerbations among children and adults, yet the fundamental mechanism responsible for why asthmatics are more susceptible to RV than otherwise healthy individuals remains largely unknown. Nonetheless, the use of models to understand the mechanisms of RV-induced airway disease in asthma has dramatically expanded our knowledge about the cellular and molecular pathogenesis of the disease. For instance, ground-breaking studies have recently established that the susceptibility to RV in asthmatic subjects is associated with a dysfunctional airway epithelial inflammatory response generated after innate recognition of viral-related molecules, such as double-stranded RNA. This review summarizes the novel cardinal features of the asthmatic condition identified in the past few years through translational and experimental RV-based approaches. Specifically, we discuss the evidence demonstrating the presence of an abnormal innate antiviral immunity (airway epithelial secretion of types I and III interferons), exaggerated production of the master Th2 molecule thymic stromal lymphopoietin, and altered antimicrobial host defense in the airways of asthmatic individuals with acute RV infection.

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 A. 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 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.