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The American Academy of Pediatrics recommends a permissive hypoxaemic target for an oxygen saturation of 90% for children with bronchiolitis, which is consistent with the WHO recommendations for targets in children with lower respiratory tract infections. No evidence exists to support this threshold. We aimed to assess whether the 90% or higher target for management of oxygen supplementation was equivalent to a normoxic 94% or higher target for infants admitted to hospital with viral bronchiolitis. We did a parallel-group, randomised, controlled, equivalence trial of infants aged 6 weeks to 12 months of age with physician-diagnosed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis of Infancy Discharge Study [BIDS]). A central computer randomly allocated (1:1) infants, in varying length blocks of four and six and without stratification, to be clipped to standard oximeters (patients treated with oxygen if pulse oxygen saturation [SpO2] <94%) or modified oximeters (displayed a measured value of 90% as 94%, therefore oxygen not given until SpO2 <90%). All parents, clinical staff, and outcome assessors were masked to allocation. The primary outcome was time to resolution of cough (prespecified equivalence limits of plus or minus 2 days) in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN28405428. Between Oct 3, and March 30, 2012, and Oct 1, and March 29, 2013, we randomly assigned 308 infants to standard oximeters and 307 infants to modified oximeters. Cough resolved by 15·0 days (median) in both groups (95% CI for difference −1 to 2) and so oxygen thresholds were equivalent. We recorded 35 serious adverse events in 32 infants in the standard care group and 25 serious adverse events in 24 infants in the modified care group. In the standard care group, eight infants transferred to a high-dependency unit, 23 were readmitted, and one had a prolonged hospital stay. In the modified care group, 12 infants were transferred to a high-dependency unit and 12 were readmitted to hospital. Recorded adverse events did not differ significantly. Management of infants with bronchiolitis to an oxygen saturation target of 90% or higher is as safe and clinically effective as one of 94% or higher. Future research should assess the benefits and risks of different oxygen saturation targets in acute respiratory infection in older children, particularly in developing nations where resources are scarce. National Institute for Health Research, Health Technology Assessment programme.

Chest physiotherapy (CP) using passive expiratory manoeuvres is widely used in Western Europe for the treatment of bronchiolitis, despite lacking evidence for its efficacy. We undertook an open randomised trial to evaluate the effectiveness of CP in infants hospitalised for bronchiolitis by comparing the time to clinical stability, the daily improvement of a severity score and the occurrence of complications between patients with and without CP. Children <1 year admitted for bronchiolitis in a tertiary hospital during two consecutive respiratory syncytial virus seasons were randomised to group 1 with CP (prolonged slow expiratory technique, slow accelerated expiratory flow, rarely induced cough) or group 2 without CP. All children received standard care (rhinopharyngeal suctioning, minimal handling, oxygen for saturation ≥92%, fractionated meals). Ninety-nine eligible children (mean age, 3.9 months), 50 in group 1 and 49 in group 2, with similar baseline variables and clinical severity at admission. Time to clinical stability, assessed as primary outcome, was similar for both groups (2.9 ± 2.1 vs. 3.2 ± 2.8 days, P  = 0.45). The rate of improvement of a clinical and respiratory score, defined as secondary outcome, only showed a slightly faster improvement of the respiratory score in the intervention group when including stethoacoustic properties ( P  = 0.044). Complications were rare but occurred more frequently, although not significantly ( P  = 0.21), in the control arm. In conclusion, this study shows the absence of effectiveness of CP using passive expiratory techniques in infants hospitalised for bronchiolitis. It seems justified to recommend against the routine use of CP in these patients.

This review on bronchiolitis in young children considers the viruses involved, the current understanding of pathogenesis, host genetic factors and the environment, and the role of season, race, and sex on attack rates and subsequent episodes of wheezing. Few diseases have a greater effect on the health of young children than viral lower respiratory tract illness. Approximately 800,000 children in the United States, or approximately 20% of the annual birth cohort, require outpatient medical attention during the first year of life because of illness caused by respiratory syncytial virus (RSV). 1 Between 2% and 3% of all children younger than 12 months of age are hospitalized with a diagnosis of bronchiolitis, which accounts for between 57,000 and 172,000 hospitalizations annually. 1 – 4 Estimated nationwide hospital charges for care related to bronchiolitis in children younger than 2 years of age exceeded . . .

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinical classic microbiome M. nonliquefaciens inflammation IFN-intermediate , B) clinical atopic microbiome S. pneumoniae / M. catarrhalis inflammation IFN-high , C) clinical severe microbiome mixed inflammation IFN-low , and D) clinical non-atopic microbiome M.catarrhalis inflammation IL-6 . Particularly, compared with endotype A infants, endotype B infants—who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response—had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08–21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development. Respiratory syncytial virus (RSV) bronchiolitis during infancy is a major risk factor for asthma development. Here, Raita et al. integrate clinical data with airway microbiome, transcriptome, and metabolome data and identity four endotypes with differential risks for developing asthma.

BackgroundAn increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma.MethodsFollow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge.ResultsIncreased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO.ConclusionsSevere early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.

Our main objective was to compare the lung function, the rate of allergic sensitization and the prevalence of asthma at 7–9 years in children hospitalized for bronchiolitis with viral coinfection versus single viral infection. Observational study in children with previous bronchiolitis and current age 7–9 years. Clinical data were collected. Fraction of exhaled nitric oxide (FeNO) determination, spirometry and skin prick test for common aeroallergens were performed. A total of 181 children hospitalized for bronchiolitis (40 coinfections and 141 single infections), with median age of 8.3 years (IQR:7.5–9.1) were included. Single-HRV-infections showed lower basal FEV1(%) than coinfections ( p  = 0.04) and lower z-score FEV 1 than single-RSV-infections ( p  = 0.04) or coinfections ( p  = 0.02). Also, single-HRV-infections had lower post-bronchodilator FEV1(%) and z-score FEV 1 values than coinfections ( p  = 0.03 and p  = 0.03). Single-HRV-bronchiolitis was an independent risk factor for FEV 1  < 80% ( p  = 0.007). FeNO value > 25 ppb was detected in 21(12.5%) cases, without differences between viral groups ( p  = 0.768). The prevalence of allergic sensitization was similar in coinfections (31.4%) versus single infections (38.7%), ( p  = 0.428). The highest frequency of allergic rhinitis was observed in single-HRV patients ( p  = 0.004). The respiratory morbidity at 7–9 years of coinfected patients was similar to the single-HRV ones. In contrast, the likelihood of current asthma was up to 5 times higher in RSV/HRV coinfections than in the single-RSV-infections ones ( p  = 0.012). The respiratory morbidity at 7–9 years of age after severe bronchiolitis is significantly higher in single-HRV or viral coinfection patients that in single-RSV ones. Single-HRV-bronchiolitis is independently associated with lower lung function at school-age.

Background Viral bronchiolitis is the most common cause of respiratory failure requiring invasive ventilation in young children. Bacterial co-infections may complicate and prolong paediatric intensive care unit (PICU) stay. Data on prevalence, type of pathogens and its association with disease severity are limited though. These data are especially important as bacterial co-infections may be treated using antibiotics and could reduce disease severity and duration of PICU stay. We investigated prevalence of bacterial co-infection and its association with disease severity and PICU stay. Methods Retrospective cohort study of the prevalence and type of bacterial co-infections in ventilated children performed in a 14-bed tertiary care PICU in The Netherlands. Children less than 2 years of age admitted between December 2006 and November 2014 with a diagnosis of bronchiolitis and requiring invasive mechanical ventilation were included. Tracheal aspirates (TA) and broncho-alveolar lavages (BAL) were cultured and scored based on the quantity of bacteria colony forming units (CFU) as: co-infection (TA > 10 ^5 /BAL > 10 ^4 CFU), low bacterial growth (TA < 10 ^5 /BAL < 10 ^4 CFU), or negative (no growth). Duration of mechanical ventilation and PICU stay were collected using medical records and compared against the presence of co-infection using univariate and multivariate analysis. Results Of 167 included children 63 (37.7%) had a bacterial co-infection and 67 (40.1%) low bacterial growth. Co-infections occurred within 48 h from intubation in 52 out 63 (82.5%) co-infections. H.influenza (40.0%), S.pneumoniae (27.1%), M.catarrhalis (22.4%), and S.aureus (7.1%) were the most common pathogens. PICU stay and mechanical ventilation lasted longer in children with co-infections than children with negative cultures (9.1 vs 7.7 days, p  = 0.04 and 8.1vs 6.5 days, p  = 0.02). Conclusions In this large study, bacterial co-infections occurred in more than a third of children requiring invasive ventilation for bronchiolitis and were associated with longer PICU stay and mechanical ventilation. These findings support a clinical trial of antibiotics to test whether antibiotics can reduce duration of PICU stay.

To clarify the predictive role of club cell 10-kDa protein (CC10) and cysteinyl leukotrienes (CysLTs) for subsequent wheezing after RSV infection. From October 1, 2022, to October 31, 2023, children diagnosed with RSV-induced bronchiolitis hospitalized in the pediatric ward were included. Nasopharyngeal aspirates (NPAs) were obtained on the day of admission. NPAs from hospitalized children without respiratory infections served as the control group. We analyzed the correlation between CC10 and CysLTs levels in NPAs and disease severity. Follow-up assessments were conducted to observe the subsequent wheezing. There were 169 hospitalized infants diagnosed with RSV-bronchiolitis, and 22 healthy controls matched for age were selected. The levels of CC10 in the NPAs were significantly lower in the RSV group (219.4 ± 83.1 pg/mL) than those in the control group (284.1 ± 68.1 pg/mL; p < 0.001). Levels of CysLTs were significantly greater in the RSV group (346.3 ± 98.1 pg/mL) than in the control group (288.3 ± 82.5 pg/mL; p < 0.05). Pearson correlation analysis showed that CC10 protein level was negatively correlated with severity (r = 0.34, p < 0.001). Conversely, the level of CysLTs was positively correlated with severity (r = 0.09, p < 0.001). 142 cases were completed with follow-up within a year after discharge. 47 cases (33.1%) had experienced subsequent wheezing, and 95 cases (66.9%) did not have subsequent wheezing. The multivariate logistic regression analysis indicates a higher likelihood of subsequent wheezing in children with CysLTs levels over 335.3 pg/mL (OR = 5.496), allergy history (OR = 3.466), and longer ventilation duration (OR = 1.364). While CC10 and CysLTs levels correlated with the severity of RSV-bronchiolitis, only CysLTs, along with allergy history and duration of ventilation, showed a suggestive link to subsequent wheezing, but further validation is needed.

Abstract Rationale Bronchiolitis during infancy is associated with an increased risk of childhood asthma. Whether winter viral infections cause asthma or are a manifestation of a predisposition to asthma development is unknown. Objectives To study the relationship of winter virus infection during infancy and the development of childhood asthma. Methods We studied over 95,000 infants born between 1995 and 2000 and followed through 2005 who were enrolled in the Tennessee Medicaid program from birth through early childhood to determine whether infant birth in relationship to the winter virus peak alters the risk of developing early childhood asthma. Measurements and Main Results Among 95,310 children studied during five winter virus seasons from birth through early childhood, the risk of developing asthma tracked with the timing of infant birth in relationship to the winter virus peak. Infant birth approximately 4 months before the winter virus peak carried the highest risk, with a 29% increase in odds of developing asthma compared with birth 12 months before the peak (adjusted odds ratio, 1.29; 95% confidence interval, 1.19–1.40). Infant age at the winter virus peak was comparable to or greater than other known risk factors for asthma. Conclusions Timing of birth in relationship to winter virus season confers a differential and definable risk of developing early childhood asthma, establishing winter virus seasonality as a causal factor in asthma development. Delay of exposure or prevention of winter viral infection during early infancy could prevent asthma.