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The aim was to evaluate asthma and health-related quality of life (HRQoL) outcomes in adolescents, after hospital-treated bronchiolitis experienced in less than 6 months of age. A prospective cohort study started in 2001-2004 and followed up 166 children hospitalised for bronchiolitis in early infancy. At 16-20 years of age, 76 cases and 41 population-based controls without a history of bronchiolitis participated in the current study. Clinical asthma, presumptive symptoms and HRQoL data were collected with a structured questionnaire and the St. Georges Respiratory Questionnaire (SGRQ). Flow-volume spirometry was measured before and after bronchodilator administration. Asthma was present in 21.1% of cases in the post-bronchiolitis cohort compared to 9.8% in the control group (p = 0.21). Also, 35.5% of cases and 19.5% of controls reported dyspnea during the last 12 months (p = 0.04). In addition, total SGRQ scores were higher in the bronchiolitis group (4.26) than in the control group (1.67, p < 0.001) referring to a reduced health-related quality of life., Conclusion: Viral bronchiolitis in early infancy was associated with increased respiratory symptoms and lower health-related quality of life at age 16-20 years., What Is Known: • The prevalence of asthma at the school age and adolescence is increased after hospitalisation required bronchiolitis in infancy compared to those without hospitalisation due to bronchiolitis., What Is New: • Viral bronchiolitis requiring hospitalisation in early infancy was associated with increased respiratory symptoms, such as dyspnoea, and lower health-related quality of life at age 16-20 years in a prospectively followed post-bronchiolitis cohort., (© 2024. The Author(s).)

Background: Acute lower respiratory infections in children under 5 years present a real challenge for diagnosis and treatment and are the first cause of mortality for this group of age. The study aimed to describe the characteristics of infectious acute respiratory failure due to bronchiolitis, pulmonary infection or severe acute asthma related to a virus or bacteria in this population of children under 5 years old at admission to the paediatric intensive care unit (PICU), PICU management and outcomes in order to better identify the needs of these patients. Our secondary aim was to compare the characteristics and PICU management of this population (1) depending on their age (less or more than 6 months old) and (2) depending on the pulmonary imaging (absence or presence of an alveolar condensation on the chest X-ray or lung ultrasound)., Methods: We conducted a retrospective study in two PICUs in the Ile-de-France region. We included children under 5 years old hospitalised between 1 January 2017 and 31 December 2021 due to a respiratory infection complicated by acute respiratory failure., Results: We included 707 patients. The median age was 3 months. On arrival, patients were oxygen-dependent with a mean fraction of inspired oxygen (FiO2) of 34% and 63% required non-invasive ventilation (NIV). During hospitalisation, more than 70% required ventilatory support by NIV and 10% by tracheal intubation. 18% required volaemic expansion and 4% vasopressors. Nearly 90% of PCRs for respiratory viruses were positive, and respiratory syncytial virus (RSV) was found in almost two-thirds of cases. Streptococcus pneumoniae , Moraxella catarrhalis and Haemophilus influenzae were frequently found. Significantly, patients aged less than 6 months old needed more NIV, had less alveolar condensation, had slightly lower oxygen requirements, a less frank inflammatory syndrome and a more frequently positive PCR for respiratory viruses., Conclusions: We highlighted similarities between patients hospitalised for lower respiratory infection in PICU in France and those in Australia or Brazil. Optimal management relies mainly on NIV, oxygen therapy with FiO2 under 40% and available antibiotics. These results lead us to believe that the implementation of NIV training and equipment could help reduce mortality due to lower respiratory infections in children worldwide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The objective of this study was to compare HFNC therapy to noninvasive ventilation (NIV/BiPAP) in children with bronchiolitis who developed respiratory failure. We hypothesized that HFNC therapy would not be inferior to NIV., Methods: This was a noninferiority open-label randomized single-center clinical trial conducted at a tertiary Brazilian hospital. Children under 2 years of age with no chronic conditions admitted for bronchiolitis that progressed to mild to moderate respiratory distress (Wood-Downes-Férres score < 8) were randomized to either the HFNC group or NIV (BiPAP) group through sealed envelopes. Vital signs, FiO 2 , Wood-Downes-Férres score and HFNC/NIV parameters were recorded up to 96 h after therapy initiation. Children who developed respiratory failure despite receiving initial therapy were intubated. Crossover was not allowed. The primary outcome analyzed was invasive mechanical ventilation requirement. The secondary outcomes were sedation usage, invasive mechanical ventilation duration, the PICU LOS, the hospital LOS, and mortality rate., Results: A total of 126 patients were allocated to the NIV group (132 randomized and 6 excluded), and 126 were allocated to the HFNC group (136 randomized and 10 excluded). The median age was 2.5 (1-6) months in the NIV group and 3 (2-7) months in the HFNC group (p = 0,07). RSV was the most common virus isolated in both groups (72% vs. 71.4%, NIV and HFNC, respectively). Thirty-seven patients were intubated in the NIV group and 29 were intubated in the HFNC group (29% vs. 23%, p = 0.25). According to the Farrington-Manning test, with a noninferiority margin of 15%, the difference was 6.3% in favor of HFNC therapy (95% confidence interval: -4.5 to 17.1%, p < 0.0001). There was no significant difference in the PICU LOS or sedation duration. Sedation requirement, hospital LOS and invasive mechanical ventilation duration were lower in the HFNC group., Conclusion: HFNC therapy is noninferior to NIV in infants admitted with mild to moderate respiratory distress caused by bronchiolitis that progresses to respiratory failure., Trial Registration Numbers: U1111-1262-1740; RBR-104z966s. Registered 03/01/2023 (retrospectively registered). ReBEC: https://ensaiosclinicos.gov.br/rg/RBR-104z966s ., (© 2024. The Author(s).)

Background and Objectives: Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis., Methods: We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression., Results: We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07)., Conclusions: cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI., (Copyright © 2024 by the American Academy of Pediatrics.)

Importance: A recent study showed an association between high hospital-level noninvasive positive pressure ventilation (NIPPV) use and in-hospital cardiac arrest (IHCA) in children with bronchiolitis., Objectives: We aimed to determine if patient-level exposure to NIPPV in children with bronchiolitis was associated with IHCA., Design, Setting and Participants: Retrospective cohort study at a single-center quaternary PICU in North America including children with International Classification of Diseases primary or secondary diagnoses of bronchiolitis in the Virtual Pediatric Systems database., Main Outcomes and Measures: The primary exposure was NIPPV and the primary outcome was IHCA., Measurements and Main Results: Of 4698 eligible ICU admissions with bronchiolitis diagnoses, IHCA occurred in 1.2% (57/4698). At IHCA onset, invasive mechanical ventilation (IMV) was the most frequent level of respiratory support (65%, 37/57), with 12% (7/57) receiving NIPPV. Patients with IHCA had higher Pediatric Risk of Mortality-III scores (3 [0-8] vs. 0 [0-2]; p < 0.001), more frequently had a complex chronic condition (94.7% vs. 46.2%; p < 0.001), and had higher mortality (21.1% vs. 1.0%; p < 0.001) compared with patients without IHCA. Return of spontaneous circulation (ROSC) was achieved in 93% (53/57) of IHCAs; 79% (45/57) survived to hospital discharge. All seven children without chronic medical conditions and with active bronchiolitis symptoms at the time of IHCA achieved ROSC, and 86% (6/7) survived to discharge. In multivariable analysis restricted to patients receiving NIPPV or IMV, NIPPV exposure was associated with lower odds of IHCA (adjusted odds ratio [aOR], 0.07; 95% CI, 0.03-0.18) compared with IMV. In secondary analysis evaluating categorical respiratory support in all patients, compared with IMV, NIPPV was associated with lower odds of IHCA (aOR, 0.35; 95% CI, 0.14-0.87), whereas no difference was found for minimal respiratory support (none/nasal cannula/humidified high-flow nasal cannula [aOR, 0.56; 95% CI, 0.23-1.36])., Conclusions and Relevance: Cardiac arrest in children with bronchiolitis is uncommon, occurring in 1.2% of bronchiolitis ICU admissions. NIPPV use in children with bronchiolitis was associated with lower odds of IHCA., Competing Interests: Dr. Shepard’s participation in this project was supported by the Pediatric Hospital Epidemiology and Outcomes Research Training program, the National Institutes of Health, and the National Institute of Child Health and Human Development-funded postdoctoral fellowship (T32 HD060550). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: To describe rates and associated risk factors for functional decline 6 months after critical bronchiolitis in a large, multicenter dataset., Design: Nonprespecified secondary analysis of existing 6-month follow-up data of patients in the Randomized Evaluation of Sedation Titration for Respiratory Failure trial ( RESTORE , NCT00814099)., Setting: Patients recruited to RESTORE in any of 31 PICUs in the United States, 2009-2013., Patients: Mechanically ventilated PICU patients under 2 years at admission with a primary diagnosis of bronchiolitis., Interventions: There were no interventions in this secondary analysis; in the RESTORE trial, PICUs were randomized to protocolized sedation versus usual care., Measurements and Main Results: "Functional decline," defined as worsened Pediatric Overall Performance Category and/or Pediatric Cerebral Performance Category (PCPC) scores at 6 months post-PICU discharge as compared with preillness baseline. Quality of life was assessed using Infant Toddler Quality of Life Questionnaire (ITQOL; children < 2 yr old at follow-up) or Pediatric Quality of Life Inventory (PedsQL) at 6 months post-PICU discharge. In a cohort of 232 bronchiolitis patients, 28 (12%) had functional decline 6 months postdischarge, which was associated with unfavorable quality of life in several ITQOL and PedsQL domains. Among 209 patients with normal baseline functional status, 19 (9%) had functional decline. In a multivariable model including all subjects, decline was associated with greater odds of worse baseline PCPC score and longer PICU length of stay (LOS). In patients with normal baseline status, decline was also associated with greater odds of longer PICU LOS., Conclusions: In a random sampling of RESTORE subjects, 12% of bronchiolitis patients had functional decline at 6 months. Given the high volume of mechanically ventilated patients with bronchiolitis, this observation suggests many young children may be at risk of new morbidities after PICU admission, including functional and/or cognitive morbidity and reduced quality of life., Competing Interests: Dr. Watson’s institution received funding from the National Institutes of Health (NIH); he received support for article research from the NIH. Dr. Shein received funding from Ceribell and Hill Ward Henderson. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Rhinovirus (RV) positive bronchiolitis episodes in infancy confer a higher risk to develop asthma in later childhood with associated lung function impairments. We aimed to investigate the association between the type of virus causing a bronchiolitis hospitalization episode and lung ventilation inhomogeneities at preschool age., Methods: Infants hospitalized with a clinical diagnosis of moderate (ward admission) or severe (pediatric intensive care ward admission) bronchiolitis were prospectively followed-up at preschool age to assess nitrogen (N 2 ) multiple breath washout (MBW). Lung clearance index (LCI), functional residual capacity (FRC), and concentration normalized phase III slope analysis (Sn III ) indices were reported from ≥2 technically acceptable trials. Differences between groups were calculated using logistic and linear regression and adjusted for confounders (sex, age at bronchiolitis admission, height at visit, maternal asthma, and doctor-diagnosed asthma, including interaction terms between the latter three). An interaction term was included in a regression model to test for an interaction between RV bronchiolitis severity and MBW parameters at preschool age., Results: One hundred and thirty-nine subjects attended preschool follow-up, of which 84 out of 103 (82%) performing MBW had technically acceptable data. Children with a history of RV positive bronchiolitis (n = 39) had increased LCI (adjusted β-coefficient [aβ] = 0.33, 95% confidence interval [CI] 0.02-0.65, p = 0.040) and conductive airways ventilation inhomogeneity [S cond ] (aβ = 0.016, CI 0.004-0.028, p = 0.011) when compared with those with a RV negative bronchiolitis history (n = 45). In addition, we found a statistical interaction between RV bronchiolitis and bronchiolitis severity strengthening the association with LCI (aβ = 0.93, CI 0.20-1.58, p = 0.006)., Conclusion: Children with a history of hospital admission for RV positive bronchiolitis in infancy might be at a higher risk of lung ventilation inhomogeneities at preschool age, arising from the peripheral conducting airways., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background and Objectives: Bronchiolitis and asthma have similar acute clinical presentations in young children yet have opposing treatment recommendations. We aimed to assess the role of age and other factors in the diagnosis of bronchiolitis and asthma in children <24 months of age., Methods: We conducted a retrospective cross-sectional analysis of the Pediatric Health Information System database. We included children aged <2 years diagnosed with bronchiolitis, asthma, wheeze, or bronchospasm in emergency department or hospital encounters from 2017 to 2021. We described variation by age and between institutions. We used mixed-effects models to assess factors associated with a non-bronchiolitis diagnosis in children 12 to 23 months of age., Results: We included 554 158 encounters from 42 hospitals. Bronchiolitis made up 98% of encounters for children <3 months of age, whereas asthma diagnoses increased with age and were included in 44% of encounters at 23 months of age. Diagnosis patterns varied widely between hospitals. In children 12 to 23 months of age, the odds of a non-bronchiolitis diagnosis increased with month of age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.12-1.13), male sex (OR 1.37, 95% CI 1.35-1.40), non-Hispanic Black race (OR 1.54, 95% CI 1.50-1.58), number of previous encounters (OR 2.73, 95% CI 2.61-2.86, for 3 or more encounters), and previous albuterol use (OR 2.24, 95% CI 2.16-2.32)., Conclusions: Non-bronchiolitis diagnoses and the use of inhaled bronchodilators and systemic steroids for acute wheezing respiratory illness increase with month of age in children aged 0 to 23 months. Better definitions of clinical phenotypes of bronchiolitis and asthma would allow for more appropriate treatment in acute care settings, particularly in children 12 to 23 months of age., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: We aimed to analyze whether the expression of inflammatory and antiviral genes in respiratory syncytial virus (RSV)-infected infants' peripheral blood is associated with bronchiolitis progression., Methods: We conducted a prospective study on 117 infants between 2015 and 2023. The expression levels of nine genes were quantified by quantitative polymerase chain reaction. Infants were classified according to their clinical evolution during hospital admission: (i) non-progression (n = 74), when the RSV bronchiolitis severity remained stable or improved; (ii) unfavorable progression (n = 43), when the RSV bronchiolitis severity increased. The association analysis was performed by logistic regression, adjusted by age, gender, prematurity, and RSV bronchiolitis severity in the emergency room., Results: Infants were 57.3% male, and the median age of the study population was 61 days. Thirty-five infants (30.7%) were admitted to the intensive care unit after hospital admission. Univariate logistic models showed that tumor necrosis factor (TNFα) and chemokine (C-C motif) ligand (CCL5) gene expression at baseline were inversely associated with unfavorable progression, which was confirmed by multivariate analyses: TNFα (adjusted odds ratio = 0.8 [95% confidence interval = 0.64-0.99], P-value = 0.038) and CCL5 (adjusted odds ratio = 0.76 [95% confidence interval = 0.62-0.93], P-value = 0.007)., Conclusions: An inadequate immune response to RSV, characterized by reduced gene expression levels of CCL5 and TNFα in peripheral blood, was associated with an unfavorable progression of RSV bronchiolitis., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Acute bronchiolitis causes many hospitalizations in children younger than 2 years. Early enteral nutrition is associated with improved outcomes in these patients. However, often nutrition is withheld when patients require noninvasive respiratory support because of the risk of aspiration worsening respiratory failure, possibly requiring intubation. We hypothesize that achieving goal energy intake is associated with a lower intubation rate in hospitalized children with bronchiolitis who require noninvasive ventilation., Methods: This retrospective cohort study examined the association between goal enteral nutrition (60% of dietary reference energy intake) and intubation rates. We grouped patients by severity of illness and compared intubation rates in those who met goal energy to those who did not. We use stratified analysis methods (for both level of respiratory support and feeding route) to evaluate progression to intubation., Results: Of the 272 patients, 215 met goal feeds. These groups had similar demographics, but the goal-feeds group started on higher respiratory support in the pediatric intensive care unit. We found that 4.65% of the patients who met goal feeds required intubation compared with 24.6% of patients who did not meet goal feeds (P < 0.0001), even after controlling for respiratory status at admission and time of feed initiation and feeding route., Conclusion: We observed when adjusting for severity, feeding route, and respiratory support, achieving goal energy intake remained associated with a lower rate of intubation, without higher rates of aspiration. Confounding factors include practice variation and difference in severity of illness that objective scoring may have missed., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Introduction: Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood., Methods: Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study. Follow-up information on respiratory infections (bronchiolitis, pneumonia, otitis media and cold or flu), wheeze and cough symptoms, healthcare utilisation and medication prescription was collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data., Results: Follow-up was obtained on 1344 children. Daycare was associated with increased odds of pneumonia (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.04-5.49), bronchiolitis (OR = 1.40, 1.02-1.90), otitis media (OR = 1.68, 1.32-2.14) and emergency department attendance for wheeze (RR = 1.81, 1.17-2.80). Breastfeeding beyond 6 months was associated with a reduced odds of bronchiolitis (OR = 0.55, 0.39-0.77) and otitis media (OR = 0.75, 0.59-0.99). Siblings at home was associated with an increased odds of bronchiolitis (OR = 1.65, 1.18-2.32) and risk of reliever inhaler prescription (RR = 1.37, 1.02-1.85). Visible damp was associated with an increased odds of wheeze (OR = 1.85, 1.11-3.19), and risk of reliever inhaler (RR = 1.73, 1.04-2.89) and inhaled corticosteroid prescription (RR = 2.61, 1.03-6.59). ETS exposure was associated with an increased odds of primary care attendance for cough or wheeze (OR = 1.52, 1.11-2.08). Dense traffic around the child's home was associated with an increased odds of bronchiolitis (OR = 1.32, 1.08-2.29)., Conclusion: Environmental factors likely influence the wide variation in infection frequency and symptoms observed in early childhood. Larger population studies are necessary to further inform and guide public health policy to decrease the burden of respiratory infections and wheeze in young children., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Purpose: For successful prevention and intervention, it is important to unravel the complex constellation of factors that affect neurocognitive functioning after pediatric intensive care unit (PICU) admission. This study aims (1) to elucidate the potential relevance of patient and PICU-related characteristics for long-term adverse neurocognitive outcome after PICU admission for bronchiolitis, and (2) to perform a preliminary exploration of the potential of machine learning as compared to linear regression to improve neurocognitive outcome prediction in a relatively small sample of children after PICU admission., Methods: This cross-sectional observational study investigated 65 children aged 6-12 years with previous PICU admission for bronchiolitis (age ≤ 1 year). They were compared to demographically comparable healthy peers (n = 76) on neurocognitive functioning. Patient and PICU-related characteristics used for the prediction models were as follows: demographic characteristics, perinatal and disease parameters, laboratory results, and intervention characteristics, including hourly validated mechanical ventilation parameters. Neurocognitive outcome was measured by intelligence and computerized neurocognitive testing. Prediction models were developed for each of the neurocognitive outcomes using Regression Trees, k-Nearest Neighbors, and conventional linear regression analysis., Results: The patient group had lower intelligence than the control group (p < .001, d = -0.59) and poorer performance in neurocognitive functions, i.e., speed and attention (p = .03, d = -0.41) and verbal memory (p < .001, d = -0.60). Lower intelligence was predicted by lower birth weight and lower socioeconomic status (R 2  = 25.9%). Poorer performance on the speed and attention domain was predicted by younger age at follow-up (R 2  = 53.5%). Poorer verbal memory was predicted by lower birth weight, younger age at follow-up, and greater exposure to acidotic events (R 2  = 50.6%). The machine learning models did not reveal added value in terms of model performance as compared to linear regression., Conclusion: The findings of this study suggest that in children with previous PICU admission for bronchiolitis, (1) lower birth weight, younger age at follow-up, and lower socioeconomic status are associated with poorer neurocognitive outcome; and (2) greater exposure to acidotic events during PICU admission is associated with poorer verbal memory outcome. The findings of this study provide no evidence for the added value of machine learning models as compared to linear regression analysis in the prediction of long-term neurocognitive outcome in a relatively small sample of children., What Is Known: • Adverse neurocognitive outcomes are described in PICU survivors, which are known to interfere with development in other major domains of functioning, such as mental health, academic achievement, and socioeconomic success, highlighting neurocognition as an important outcome after PICU admission. • Machine learning is a rapidly growing field of artificial intelligence that is increasingly applied in health care settings, with great potential to capture the complexity of outcome prediction., What Is New: • This study shows that lower birth weight, lower socioeconomic status, and greater exposure to acidotic events during PICU admission for bronchiolitis are associated with poorer long-term neurocognitive outcome after PICU admission. Results provide no evidence for the added value of machine learning models in a relatively small sample of children. • As bronchiolitis seldom manifests neurologically, the relation between acidotic events and neurocognitive outcome may reflect either potentially harmful effects of acidosis itself or related processes such as hypercapnia or hypoxic and/or ischemic events during PICU admission. This study further highlights the importance of structured follow-up to monitor long-term outcome of children after PICU admission., (© 2023. The Author(s).)

Background: The imaging findings of Mycoplasma pneumoniae pneumonia (MPP) vary; however, few studies have focused on the relationship of imaging classification with clinical manifestations and outcomes., Objective: To prospectively investigate whether chest imaging classification in Mycoplasma pneumoniae pneumonia (MPP) is associated with its clinical features and outcomes., Methods: A total of 1,401 hospitalized children with MPP were enrolled from January 2019 to December 2021. Imaging findings were categorized as bronchopneumonia and consolidation/atelectasis according to X-ray, and bronchopneumonia, consolidation/atelectasis, bronchiolitis, and mosaic pattern according to computed tomography (CT). Clinical characteristics and outcomes of patients with different imaging classifications were prospectively analyzed based on electronic medical records., Results: Bronchopneumonia was the most common finding (59.6%), while consolidation/atelectasis was the most severe group. Clinical manifestations and laboratory indicators for the consolidation/atelectasis group included serious abnormalities. Further, outcomes of the patients were worse, including having longer total durations of fever and hospitalization, greater hospitalization expenses, and a higher likelihood of developing refractory MPP, necrotizing pneumonia, and bronchiolitis obliterans (BO) in this group. The incidence of bronchiolitis, a disease characterized by a high prevalence of fever, moist rales, and an atopic constitution, tended to increase after the coronavirus disease pandemic and predisposed patients to BO. A mosaic pattern occurred in allergic and young individuals, with wheezing as the main manifestation, with patients having relatively mild symptoms and good outcomes., Conclusion: Different imaging classifications have different clinical features and clinical outcomes; thus, formulating an imaging-based classification system is of great clinical value., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Respiratory syncytial virus (RSV) is a highly contagious respiratory virus that can cause mild to severe illness in children. It is the leading cause of lower respiratory tract infections (LRTI) in children under the age of one year, and it can also affect older children and adults, especially those with underlying medical conditions. In the post-COVID period, there seems to be an increase in the incidence, possibly due to 'immunity debt'. Symptoms of RSV infection in children may include fever, runny nose, and cough. In severe cases, it can lead to bronchiolitis (inflammation of the small airways in the lungs) or pneumonia (infection of the lungs). Most children with RSV infection recover within a week or two, but some may require hospitalization, especially those who are premature or have underlying medical conditions. As there is no specific treatment for RSV infection, supportive care is the mainstay of management. In severe cases, oxygen therapy or mechanical ventilation may be necessary. High flow nasal cannula seems to be beneficial. There have been promising advances in development of RSV vaccines; few trials in adults and pregnant women have reported encouraging results. The US FDA has approved two RSV vaccines for use in older adults (GSK's Arexvy and Pfizer's ABRYSVO)., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background and Objectives: High-flow nasal cannula (HFNC) therapy for hospitalized children with bronchiolitis is associated with a longer length of stay (LOS) when used outside of the ICU. We sought to explore the association between HFNC and LOS to identify if demographic and clinical factors may modify the effect of HFNC usage on LOS., Methods: In this multicenter retrospective cohort study, we used a combination of hospital records and the Pediatric Health Information System. We included encounters from September 1, 2018 to March 31, 2020 for patients <2 years old diagnosed with bronchiolitis. Multivariable Poisson regression was performed for the association of LOS with measured covariates, including fixed main effects and interaction terms between HFNC and other factors., Results: Of 8060 included patients, 2179 (27.0%) received HFNC during admission. Age group, weight, complex chronic condition, initial tachypnea, initial desaturation, and ICU services were significantly associated with LOS. The effect of HFNC on LOS differed among hospitals (P < .001), with the estimated increase in LOS ranging from 32% to 139%. The effect of HFNC on LOS was modified by age group, initial desaturation, and ICU services, with 1- to 6-month-old infants, patients without initial desaturation, and patients without ICU services having the highest association between HFNC and LOS, respectively., Conclusions: We identified multiple potential effect modifiers for the relationship between HFNC and LOS. The authors of future prospective studies should investigate the effect of HFNC usage on LOS in non-ICU patients without documented desaturation., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: Electrolyte disorders occurs frequently in children with bronchiolitis. The aim of the present study was to describe the frequency of hypophosphatemia and to evaluate its association with length of mechanical ventilation in infants admitted to a pediatric intensive care unit (PICU) with bronchiolitis., Methods: This retrospective cohort study included infants aged between 7 days and 3 months admitted to a PICU between September 2018 and March 2020 and diagnosed with severe acute bronchiolitis requiring respiratory support. Infants with a chronic condition that could potentially be a confounding factor were excluded. The primary outcome was the frequency of hypophosphatemia (<1.55 mmol/L); the secondary outcomes were the frequency of hypophosphatemia during the PICU stay, and the association with length of mechanical ventilation (LOMV)., Results: Among the 319 infants admitted 178 had at least one phosphatemia value and were included in the study. The frequency of hypophosphatemia was 41% at PICU admission (61/148) and 46% during the PICU stay (80/172). The median [IQR] LOMV was significantly longer in children with hypophosphatemia at admission (109 [65-195] h vs. 67 [43-128] h, p = 0.007), and in multivariable linear regression lower phosphatemia at admission was associated with longer LOMV (p < 0.001) after controlling for severity (PELOD2 score) and weight., Conclusion: Hypophosphatemia was frequent in infants with severe bronchiolitis admitted to a PICU and was associated with a longer LOMV., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objective: To investigate the long-term impact of pediatric intensive care unit (PICU) admission on daily life functioning while exploring the potential mediating role of neurocognitive outcome., Study Design: This cross-sectional observational study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation ("patient group," n = 65) to demographically comparable healthy peers ("control group," n = 76). The patient group was selected because bronchiolitis is not expected to affect neurocognitive functioning in itself. Assessed daily life outcome domains were behavioral and emotional functioning, academic performance, and health-related quality of life (QoL). The role of neurocognitive outcomes in the relationship between PICU admission and daily life functioning was assessed by mediation analysis., Results: The patient group did not differ from the control group regarding behavioral and emotional functioning but performed poorer on academic performance and school-related QoL (Ps ≤ .04, d = -0.48 to -0.26). Within the patient group, lower full-scale IQ (FSIQ) was associated with poorer academic performance and school-related QoL (Ps ≤ .02). Poorer verbal memory was associated with poorer spelling performance (P = .002). FSIQ mediated the observed effects of PICU admission on reading comprehension and arithmetic performance., Conclusions: Children admitted to the PICU are at risk for long-term adverse daily life outcomes in terms of academic performance and school-related QoL. Findings suggest that lower intelligence may contribute to academic difficulties after PICU admission. Findings underline the importance of monitoring daily life and neurocognitive functioning after PICU admission., Competing Interests: Declaration of Competing Interest This study was supported by grants of the Janivo, C.J. Vaillant and Louise Vehmeijer charity foundations. This study was supported by the Emma Children's Hospital, Amsterdam UMC. The funder/sponsor did not participate in the work. The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Bilirubin is a potent antioxidant and anti-inflammatory molecule that has been shown to ameliorate airway inflammation. We aimed to study whether serum bilirubin is protective and can predict the development of subsequent recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis., Methods: The medical records of 188 infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were retrospectively reviewed. Our main outcome of interest was the development of subsequent recurrent wheezing by the age of 3 years. Each infant's serum bilirubin concentration was extracted from their blood biochemical results., Results: Seventy-one (37.8%) infants developed recurrent wheezing by the age of 3 and 117 (62.2%) did not. The serum total bilirubin, unconjugated bilirubin, and conjugated bilirubin levels at hospital admission were lower in infants who developed recurrent wheezing as compared to those who did not (p ＜ 0.001). The area under the receiver-operating characteristic curve of serum total bilirubin, unconjugated bilirubin, and conjugated bilirubin for the prediction of subsequent recurrent wheezing were 0.71 (95% confidence interval [CI], 0.64-0.78), 0.70 (95% CI, 0.63-0.78), and 0.67 (95% CI, 0.59-0.75), respectively. Higher admission serum total bilirubin levels were independently associated with a lower risk of development of subsequent recurrent wheezing (adjusted OR 0.17, p ＜ 0.001)., Conclusion: During the first episode of severe RSV bronchiolitis in infants <6 months of age, moderately higher levels of serum bilirubin are associated with a reduced risk of developing subsequent recurrent wheezing by 3 years of age., (© 2023 Wiley Periodicals LLC.)

Pulmonary hypertension (PH) often complicates chronic lung disease. However, there are few reports of PH associated with diffuse panbronchiolitis, and there is no effective treatment. We herein report a 64-year-old woman diagnosed with PH due to diffuse panbronchiolitis. She received erythromycin, carbocysteine, and home oxygen therapy (1 L O 2 /min). After 4 months of therapy, the respiratory function (diffusing capacity of the lungs for carbon monoxide: 23.3% to 76.1%) and PH (mean pulmonary arterial pressure: 50 to 28 mmHg; pulmonary vascular resistance: 680 to 518 dynes・sec・cm -5 ; pre- vs post-therapy, respectively) had improved markedly.

Background: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year., Methods: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models., Results: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma., Conclusion: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aimed to determine whether there was an association between certain factors in patients with bronchiolitis and recurrent wheezing in childhood., Method: In 2021 we tracked children hospitalized for bronchiolitis at Chengdu Women's and Children's Central Hospital in 2017. The patients were classified into recurrent wheezing group (RWG) and non-recurrent wheezing group (NRWG). Possible risk factors including maternal age, school-age siblings, allergic history, atopic dermatitis, allergic rhinitis, atopic family history, severity of the condition, duration of hospitalization, nasopharyngeal secretions culture, blood eosinophil counts, FeNO and skin prick test were compared between the two groups. Continuous variables were analyzed by independent sample t-test for normal distribution and Mann-Whitney U-test for non-normal distribution. Categorical variables were tested using chi-square tests. Multifactor analysis was conducted by stepwise logistics regression analysis., Results: In total 167 participants were included, of which 26 and 141 were in RWG and NRWG respectively. In RWG children represented higher maternal age (P = 0.02) and greater probability of allergic history, atopic dermatitis, allergic rhinitis, atopic family history (odds ratio [OR] = 4.0,3.7, 7.8, 10.9 respectively, P < 0.01). However, school-age siblings, severity of the condition, duration of hospitalization, blood eosinophil counts, fractional exhaled nitric oxide and skin prick test results seemed unrelated to recurrent wheezing. In the subgroup analysis of nasopharyngeal secretion culture, there were more Moraxella catarrhalis-positive in RWG(P = 0.043). Atopic dermatitis, allergic rhinitis and atopic family history were identified as independent risk factors for recurrent wheezing., Conclusion: Some children with bronchiolitis will develop recurrent wheezing, and the risk factors are allergic history, Moraxella catarrhalis infection or colonization, atopic dermatitis, allergic rhinitis and atopic family history; the latter three are independent risk factors., (© 2023. The Author(s).)

Objectives: Tonic diaphragmatic activity (tonic Edi, i.e., sustained diaphragm activation throughout expiration) reflects diaphragmatic effort to defend end-expiratory lung volumes. Detection of such elevated tonic Edi may be useful in identifying patients who need increased positive end-expiratory pressure. We aimed to: 1) identify age-specific definitions for elevated tonic Edi in ventilated PICU patients and 2) describe the prevalence and factors associated with sustained episodes of high tonic Edi., Design: Retrospective study using a high-resolution database., Setting: Single-center tertiary PICU., Patients: Four hundred thirty-one children admitted between 2015 and 2020 with continuous Edi monitoring., Interventions: None., Measurements and Main Results: We characterized our definition of tonic Edi using data from the recovery phase of respiratory illness (i.e., final 3 hr of Edi monitoring, excluding patients with significant persistent disease or with diaphragm pathology). High tonic Edi was defined as population data exceeding the 97.5th percentile, which for infants younger than 1 year was greater than 3.2 μV and for older children as greater than 1.9 μV. These thresholds were then used to identify patients with episodes of sustained elevated tonic Edi in the first 48 hours of ventilation (acute phase). Overall, 62 of 200 (31%) of intubated patients and 138 of 222 (62%) of patients on noninvasive ventilation (NIV) had at least one episode of high tonic Edi. These episodes were independently associated with the diagnosis of bronchiolitis (intubated patients: adjusted odds [aOR], 2.79 [95% CI, 1.12-7.11]); NIV patients: aOR, 2.71 [1.24-6.0]). There was also an association with tachypnea and, in NIV patients, more severe hypoxemia., Conclusions: Our proposed definition of elevated tonic Edi quantifies abnormal diaphragmatic activity during expiration. Such a definition may help clinicians to identify those patients using abnormal effort to defend end-expiratory lung volume. In our experience, high tonic Edi episodes are frequent, especially during NIV and in patients with bronchiolitis., Competing Interests: Drs. Plante’s, Sauthier’s, and Emeriaud’s research programs are supported by scholarship awards from the Fonds de Recherche du Québec – Santé (FRQS). Drs. Sauthier and Emeriaud received funding from FRQS. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Introduction: The COVID-19 pandemic has changed the circulation of some viruses associated with acute bronchiolitis. We analyzed the epidemiology of bronchiolitis admissions during the COVID-19 pandemic compared with 8 previous epidemic seasons., Methods: An observational and ambispective study was performed, including infants admitted with bronchiolitis in a tertiary hospital during 2 periods: COVID-19 pandemic (15th March 2020 to 3rd August 2021) and pre-pandemic (1st September 2012 to 14th March 2020). Demographic, clinical data and etiologies were collected., Results: Five hundred ten patients were hospitalized with bronchiolitis: 486 in the pre pandemic period with an average of 61 admissions per season vs 24 during the pandemic, observing a 60.7% reduction in bronchiolitis admissions. During the pandemic, bronchiolitis outbreak was delayed until spring-summer 2021. Respiratory syncytial virus was the most frequent etiological agent in both periods., Conclusion: We observed a change in the seasonality of bronchiolitis during the pandemic COVID-19, possibly influenced by control measures against SARS-CoV-2., (Copyright © 2021 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Improving lung health in children requires understanding the risk factors for decreased lung function. Our objective was to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and lung function in children. We analyzed data from a prospective cohort of infants hospitalized with bronchiolitis (severe bronchiolitis), a group at high risk for developing childhood asthma. Children were followed longitudinally, and 25(OH)D and spirometry testing were conducted at ages 3 and 6, respectively. We used a multivariable linear regression adjusted for race/ethnicity, annual household income, premature birth, and secondhand smoke exposure to examine the association between serum 25(OH)D level and primary outcomes (percent predicted [pp] of forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC)) and secondary outcome (FEV1pp/FVCpp). Serum 25(OH)D level and age 6 spirometry were available for 363 children. In adjusted analyses comparing the highest quintile (Q5) of serum 25(OH)D (median 37 ng/mL) to the lowest quintile (Q1; median 18 ng/mL), FEV1pp was 6% lower ( p = 0.03) in Q1. Likewise, FVCpp was 7% lower ( p = 0.03) in Q1. There was no difference in FEV1pp/FVCpp across the serum 25(OH)D quintiles. Compared to children with higher vitamin D status at age 3, those with lower status had decreased FEV1pp and FVCpp at 6 years.

Background: The debated link between severe respiratory syncytial virus (RSV) infection in early life and asthma has yet to be investigated within a social inequity lens. We estimated the magnitude of socioeconomic disparity in childhood asthma which would remain if no child were admitted to hospital for bronchiolitis, commonly due to RSV, during infancy., Methods: The cohort, constructed from national administrative health datasets, comprised 83853 children born in Scotland between 1 January 2007 and 31 June 2008. Scottish Index for Multiple Deprivation (SIMD) was used to capture socioeconomic position. Emergency admissions for bronchiolitis before age 1 year were identified from hospital records. Yearly indicators of asthma/wheeze from ages 2 to 9 years were created using dispensing data and hospital admission records., Results: Using latent class growth analysis, we identified four trajectories of asthma/wheeze: early-transient (2.2% of the cohort), early-persistent (2.0%), intermediate-onset (1.8%) and no asthma/wheeze (94.0%). The estimated marginal risks of chronic asthma (combining early-persistent and intermediate-onset groups) varied by SIMD, with risk differences for the medium and high deprivation groups, relative to the low deprivation group, of 7.0% (95% confidence interval: 3.7-10.3) and 13.0% (9.6-16.4), respectively. Using counterfactual disparity measures, we estimated that the elimination of bronchiolitis requiring hospital admission could reduce these risk differences by 21.2% (4.9-37.5) and 17.9% (10.4-25.4), respectively., Conclusions: The majority of disparity in chronic asthma prevalence by deprivation level remains unexplained. Our paper offers a guide to using causal inference methods to study other plausible pathways to inequities in asthma using complex, linked administrative data., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Aim: To study if blood eosinophils during bronchiolitis were associated with atopy, asthma and lung function in young adults and if these associations differed between respiratory syncytial virus (RSV) bronchiolitis and non-RSV bronchiolitis., Methods: This historical cohort enrolled 225 subjects. Blood eosinophils were measured during bronchiolitis in infancy, and the subjects were invited to a follow-up at 17-20 years of age including questionnaires for asthma and examinations of lung function and atopy., Results: The level of eosinophils was positively associated with subsequent atopy in the unadjusted analysis, but not in the adjusted analysis, and not with asthma. There was a negative association between the level of eosinophils and forced vital capacity (FVC) (-0.11; -0.19, -0.02) and forced expiratory volume in first second (FEV 1 ) (-0.12; -0.21, -0.03) (regression coefficient; 95% confidence interval). The non-RSV group had higher levels of eosinophils during bronchiolitis, but there was no interaction between the level of eosinophils and RSV status for any outcome., Conclusions: The level of eosinophils during bronchiolitis was negatively associated with lung function in young adult age, but we found no associations with atopy or asthma. These associations were not different after RSV bronchiolitis compared to non-RSV bronchiolitis., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The coronavirus disease 2019 (COVID-19) pandemic has changed the epidemiology of respiratory syncytial virus (RSV) infection which accounts for most bronchiolitis and viral pneumonias in infants. This systematic review and meta-analysis aimed to quantitatively assess the effect of the COVID-19 pandemic on RSV-associated bronchiolitis among hospitalized infants. The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesize the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). We identified and screened 189 articles and systematically reviewed 50 full texts. Eight qualified studies from Europe and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021 were pooled by random-effects meta-analysis. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 bronchiolitis cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73, 22.43%, 95% prediction interval 0.032, 34.16). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20% (95% CI 12.01, 27.59%, 95% prediction interval 0.046, 42.35). There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic., Competing Interests: None

Background: Children hospitalized for bronchiolitis have increased risk of asthma and low lung function persisting into adulthood, but the underlying mechanisms are poorly understood. Body mass index (BMI) and adipokines are associated with respiratory morbidity. We aimed to investigate if associations between BMI and adipokines and the outcomes asthma, atopy, and lung function differed between young adults previously hospitalized for bronchiolitis and control subjects., Methods: This sub study of a historical cohort enrolled 185 young adults previously hospitalized for bronchiolitis and 146 matched control subjects. Exposures (BMI and the adipokines: adiponectin, leptin, resistin, and ghrelin) and outcomes (asthma, atopy, and lung function) were measured cross-sectionally at 17-20 years of age. Associations were tested in regression models, and differences between the post-bronchiolitis- and control group were tested by including interaction terms., Results: BMI was associated with asthma and lung function, but we did not find that the associations differed between the post-bronchiolitis- and control group. We also found some associations between adipokines and outcomes, but only associations between adiponectin and forced vital capacity (FVC) and between resistin and current asthma differed between the groups (p-value interaction term 0.027 and 0.040 respectively). Adiponectin tended to be positively associated with FVC in the post-bronchiolitis group, with an opposite tendency in the control group. Resistin was positively associated with current asthma only in the control group., Conclusion: The increased prevalence of asthma and impaired lung function observed in young adults previously hospitalized for bronchiolitis do not seem to be related to growth and fat metabolism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Bronchiolitis is a common airway infection in young children. Hemodynamically significant congenital heart disease (CHD) predicts a more complicated course. However, the role of airway anomalies remains unknown., Methods: We retrospectively reviewed the records of patients under 2 years old, diagnosed with CHD, and admitted between January 2011 and December 2013, before the palivizumab era. Records of bronchiolitis admissions were also extracted. Patients were grouped according to CHD condition and airway anomalies., Results: A total of 230 patients with CHD were enrolled. A total of 180 (78%) and 71 (31%) patients had hemodynamically significant CHD and airway anomalies, respectively. A total of 52 (22.6%) patients were admitted for bronchiolitis 78 times. Among them, 33 (63.5%) had hemodynamically significant CHD, and 28 (53.8%) had airway anomalies. In patients with bronchiolitis admissions, the mean ventilator use, intensive care unit stay, and hospital stay were 1.08, 4.08, and 15.19 days, respectively. When compared, the mean hospital stay for bronchiolitis patients with airway anomalies was significantly longer than that of those without airway anomalies (19.8 vs. 9.9 days, p = 0.008). When further divided the patients by the presence hemodynamic significance, patients with hemodynamically significant CHD and airway anomaly had longer hospital stay than those who had neither. (21.7 vs. 8.3 days, p = 0.004) Airway anomaly was a significant risk factor for longer hospital stay in linear regression model (p = 0.007)., Conclusions: Airway anomalies are common in children with CHD and are associated with longer hospital stays on bronchiolitis admission. An active survey for airway anomalies and adequate prophylaxis for bronchiolitis infection might be important in the care of children with CHD associated with airway anomalies., (© 2023 Wiley Periodicals LLC.)

Bronchiolitis, a common reason for infant hospitalisation in South Africa (SA), is caused by viral pathogens. Bronchiolitis is typically an illness of mild to moderate severity that occurs in well-nourished children. Hospitalised SA infants frequently have severe disease and/or coexisting medical conditions, and these cases of bronchiolitis may have bacterial co-infection that requires antibiotic therapy. However, the existence of widespread antimicrobial resistance in SA warrants the judicious use of antibiotics. This commentary describes: (i) common clinical pitfalls leading to an incorrect diagnosis of bronchopneumonia; and (ii) considerations for antibiotic therapy in hospitalised infants with bronchiolitis. If antibiotics are prescribed, the indication for their use should be clearly stated, and antibiotic therapy must be stopped promptly if investigations indicate that bacterial co-infection is unlikely. Until more robust data emerge, we recommend a pragmatic management strategy to inform antibiotic use in hospitalised SA infants with bronchiolitis in whom bacterial co-infection is suspected.

Introduction: Antibiotic use may shorten mechanical ventilation duration and length of stay for patients with bronchiolitis that require intubation. The goals of this study were to describe antibiotic use in previously healthy children with bronchiolitis admitted to the intensive care unit (ICU) for noninvasive respiratory support and to describe associations of early antibiotic use with clinical outcomes., Methods: The Pediatric Health Information Systems database was queried for children <2 years of age without significant comorbidities admitted to the ICU for bronchiolitis. Children requiring mechanical ventilation on the first ICU day were excluded. Two groups were analyzed: those patients receiving antibiotics on the first day of their ICU stay (early antibiotics), and those receiving no antibiotics on their first ICU day (no antibiotics). Primary outcome was the length of ICU stay., Results: A total of 11,029 admissions met criteria, 2522 (22.9%) in the early antibiotic group, and 8507 (77.1%) in the no antibiotic group. The use of early antibiotics varied by center from 10% to 54%. In multivariate analysis, the early antibiotic group had similar ICU length of stay compared to the no antibiotic group (relative risk, RR [95% confidence interval, CI] 1.01 [0.98-1.05]). For patients on noninvasive ventilation, the first ICU day early antibiotics did not impact ICU length of stay (RR [95% CI] 0.97 [0.92-1.02]) or need for intubation (RR [95% CI] 1.11 [0.77-1.58])., Conclusion: Early antibiotic use was common with significant variation between centers. Early antibiotic use was not associated with improved clinical outcomes in children admitted to the ICU for noninvasive respiratory support for bronchiolitis., (© 2022 Wiley Periodicals LLC.)

Objective: Oral feeding by children with bronchiolitis on high-flow nasal cannula (HFNC) is questioned, resulting in high practice variability. Our objective was to determine the incidence of aspiration pneumonia and adverse feeding events in otherwise healthy children with bronchiolitis on HFNC who fed orally from admission., Methods: We conducted a single-center, retrospective chart review, in a tertiary children's hospital, of 876 children who were <24 months old, admitted for bronchiolitis, and treated with HFNC in the pediatric ward from March 2017 to May 2020. Primary outcomes included the incidence of aspiration pneumonia and adverse feeding events. Secondary outcomes included escalation of care, frequency and duration of nil per os status, length of stay, and 7-day readmission., Results: Most patients (77.2%) met inclusion criteria and were fed orally within 2 hours of admission. The average maximum HFNC flow rate was 8 L/min (1 L/kg/min); the average maximum respiratory rate was 62 ± 10. Adverse feeding events occurred in 11 patients (1.6%), of which 3 had a concern for possible microaspiration. None were diagnosed with or treated for aspiration pneumonia. Few patients (8.1%) were made nil per os while on HFNC but returned to oral feeding by discharge., Conclusion: Among those with bronchiolitis on HFNC who received oral nutrition on admission, there were few incidences of adverse feeding events and no diagnoses of aspiration pneumonia, suggesting that oral feeding while on HFNC can be well-tolerated in similar populations. However, this study was limited by its single-center retrospective design, and future prospective studies are needed., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age., Methods: Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6-7-year-old children, was also employed., Results: A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5-6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051-7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20-9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284-0.918, p:0.025)., Conclusions: Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions., (© 2023. The Author(s).)

Objectives: Overweight negatively affects pediatric respiratory function. In this study, we evaluate if overweight is associated with more severe bronchiolitis in hospitalized infants., Methods: This retrospective cohort study analyzed infants aged 30 to 365 days hospitalized for bronchiolitis from September 2019 to April 2020. Exclusion criteria included known risk factors for severe bronchiolitis, asthma treatment, or bacterial pneumonia. Weight-for-length z-score was categorized per the World Health Organization's growth assessments as overweight (z-score >2), underweight (z-score <-2), and standard weight (between -2 and ≤2). Primary outcomes included respiratory support, ICU stay, and local bronchiolitis score. Secondary outcomes included supplemental interventions., Results: After exclusion criteria, 385 of 644 infants were categorized as overweight (n = 24), standard (n = 335), or underweight (n = 26). There were differences in need for respiratory support (overweight, 100%; standard weight, 81.8%; underweight, 76.9%; P = .03), highest support of high-flow nasal cannula (overweight, 75%; standard weight, 48%; underweight, 42%; P = .03), admission to ICU (overweight, 54.2%; standard weight, 21.5%; underweight, 34.7%; P < .001), and median bronchiolitis score (overweight, 8 [interquartile range 5-10]; standard weight, 4 [3-7]; underweight, 4 [3-7]; P = .01). Findings remained significant after age adjustments. Additionally, overweight experienced higher frequency of certain treatments., Conclusions: This study suggests overweight is associated with more severe bronchiolitis in hospitalized infants supported by increased respiratory support level, bronchiolitis scores, and interventions. Higher need for ICU admission may be related to high-flow nasal cannula limitations on the acute care floor., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: Extrapulmonary manifestations of bronchiolitis have been previously studied, with some identifying right ventricle (RV) diastolic/systolic dysfunction. We hypothesized that severe cases of bronchiolitis would have cardiac dysfunction resulting an increase in N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) values and worse outcomes. Therefore, the objective was to evaluate the existence of cardiac dysfunction and to determine its association with severe bronchiolitis., Methods: This prospective cohort study included children hospitalized for bronchiolitis under 1-year old between January 2019 and March 2020. At admission, an echocardiography was performed and plasma levels of NT-proBNP were measured. To analyze outcomes, the cohort was divided into two groups based on the need for positive pressure respiratory support (PPRS), and both were compared to healthy infants., Statistics: bivariant analysis, significant differences p < 0.05., Results: One hundred eighty-one patients were included; median age was 2 months. Seventy-three patients required PPRS. Compared to controls, patients requiring PPRS showed worse RV systolic function, with lower tricuspid annular-plane systolic excursion (p = 0.002) and parameters of worse right and left diastolic function (trans-tricuspid E and A wave [p = 0.004 and p = 0.04, respectively] and tricuspid tissue doppler imaging [TDI] e' [p = 0.003], trans-mitral E and mitral TDI a' [p = 0.02 and p = 0.005, respectively]). An NT-ProBNP greater than 3582 pg/dl predicts the need for longer necessity of PPRS in patients younger than 2 months., Conclusions: In addition to the expected RV systolic dysfunction, patients with severe bronchiolitis have parameters of global diastolic worse function possibly secondary to intrinsic myocardial involvement. NT-ProBNP values at admission had strong discriminatory power to predict worse outcomes., (© 2022 Wiley Periodicals LLC.)

Pulmonary hypertension has been reported as a crucial factor in the pathophysiology of severe bronchiolitis. The aim of this study was to evaluate pulmonary artery pressure (PAP) in patients with bronchiolitis and to analyze their correlation with clinical outcomes. This prospective cohort study examined children admitted for bronchiolitis. PAP was assessed by right ventricle (RV) acceleration/ejection time ratio (AT/ET), isovolumic relaxation time, eccentricity index, and the presence of a pulmonary systolic notch. Pulmonary hypertension (PH) was considered if at least two altered parameters were present. Severity of clinical course was established by higher N-terminal (NT)-prohormone BNP (NT-proBNP) values, the need for positive pressure respiratory support (PPRS), and the duration of hospital admission. One hundred sixty-nine children were included in analysis. Sixty-eight patients (40%) required PPRS, and those patients had increased NT-proBNP values and worse tricuspid annular systolic excursion (TAPSE) compared to mild cases (p < 0.001and p < 0.001, respectively). Twenty-two (13%) cases had at least two altered parameters of PAP and met criteria for presumed PH, with no differences in NT-proBNP values, TAPSE, need for PPRS or hospital length of stay compared to normal PAP group (p = 0.98, p = 0.07, p = 0.94 and p = 0.64, respectively). We found no correlation between altered RV AT/ET and worse cardiac function, NT-proBNP values or hospital length of stay. In our cohort, the presence of echocardiographic findings of PH were not associated with worse clinical outcomes. Patients with severe bronchiolitis had higher values ​​of NT-proBNP but, interestingly, no clear association with PH., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Viral bronchiolitis is a common condition and a leading cause of hospitalization in young children., Objective: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV., Methods: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR "respiratory syncytial virus infection". The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article., Results: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young children. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagnosis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effective. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramuscularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood., Conclusion: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Wheezing, starting early in life, is a heterogeneous medical condition caused by airway obstruction due to different underlying mechanisms. Primary immunodeficiencies are also among the risk factors that cause wheezing and recurrent bronchiolitis. ADA deficiency is a primary immunodeficiency, also a rare metabolic disease associated with multisystemic clinical findings., Objective: This report will be helpful for adressing the importance of thinking primary immunodeficiency in case of wheezing and recurret bronchiolitis., Methods: The patient was diagnosed by using a targeted next generation sequencing PID panel. Lymphocyte subsets were measured by flow-cytometry., Results: Here we present an infant with ADA deficiency who admitted with wheezing and recurrent bronchiolitis as the first presentation. He was found to have wheezing, relative CD4+ T cell deficiency, and prolonged neutropenia., Conclusions: Primary immunodeficiencies including ADA deficiency should be considered in infants with wheezing, recurrent bronchiolitis, lymphopenia and neutropenia.

Background: Bronchiolitis is the leading cause of hospitalisation of US infants and an important risk factor for childhood asthma. Recent evidence suggests that bronchiolitis is clinically heterogeneous. We sought to derive bronchiolitis endotypes by integrating clinical, virus and lipidomics data and to examine their relationship with subsequent asthma risk., Methods: This is a multicentre prospective cohort study of infants (age <12 months) hospitalised for bronchiolitis. We identified endotypes by applying clustering approaches to clinical, virus and nasopharyngeal airway lipidomic data measured at hospitalisation. We then determined their longitudinal association with the risk for developing asthma by age 6 years by fitting a mixed-effects logistic regression model. To account for multiple comparisons of the lipidomics data, we computed the false discovery rate (FDR). To understand the underlying biological mechanism of the endotypes, we also applied pathway analyses to the lipidomics data., Results: Of 917 infants with bronchiolitis (median age, 3 months), we identified clinically and biologically meaningful lipidomic endotypes: (A) cinical classic lipid mixed (n=263), (B) clinical severe lipid sphingolipids-high (n=281), (C) clinical moderate lipid phospholipids-high (n=212) and (D) clinical atopic lipid sphingolipids-low (n=161). Endotype A infants were characterised by 'classic' clinical presentation of bronchiolitis. Profile D infants were characterised by a higher proportion of parental asthma, IgE sensitisation and rhinovirus infection and low sphingolipids (eg, sphingomyelins, ceramides). Compared with endotype A, profile D infants had a significantly higher risk of asthma (22% vs 50%; unadjusted OR, 3.60; 95% CI 2.31 to 5.62; p<0.001). Additionally, endotype D had a significantly lower abundance of polyunsaturated fatty acids (eg, docosahexaenoic acid; FDR=0.01). The pathway analysis revealed that sphingolipid metabolism pathway was differentially expressed in endotype D (FDR=0.048)., Conclusions: In this multicentre prospective cohort study of infants with bronchiolitis, integrated clustering of clinical, virus and lipidomic data identified clinically and biologically distinct endotypes that have a significantly differential risk for developing asthma.Delete., Competing Interests: Competing interests: JCCC has received research materials from Pharmavite (vitamin D and placebo capsules) and GSK and Merck (inhaled steroids) to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bronchiolitis is the leading cause of hospitalization in U.S. infants and a major risk factor for childhood asthma. Growing evidence supports clinical heterogeneity within bronchiolitis. We aimed to identify endotypes of infant bronchiolitis by integrating clinical, virus, and serum proteome data, and examine their relationships with asthma development., Methods: This is a multicenter prospective cohort study of infants hospitalized for physician-diagnosis of bronchiolitis. We identified bronchiolitis endotypes by applying unsupervised machine learning (clustering) approaches to integrated clinical, virus (respiratory syncytial virus [RSV], rhinovirus [RV]), and serum proteome data measured at hospitalization. We then examined their longitudinal association with the risk for developing asthma by age 6 years., Results: In 140 infants hospitalized with bronchiolitis, we identified three endotypes: (1) clinical atopic virus RV proteome NFκB-dysregulated , (2) clinical non-atopic virus RSV/RV proteome TNF-dysregulated , and (3) clinical classic virus RSV proteome NFκB/TNF-regulated endotypes. Endotype 1 infants were characterized by high proportion of IgE sensitization and RV infection. These endotype 1 infants also had dysregulated NFκB pathways (FDR < 0.001) and significantly higher risks for developing asthma (53% vs. 22%; adjOR 4.04; 95% CI, 1.49-11.0; p = 0.006), compared with endotype 3 (clinically resembling "classic" bronchiolitis). Likewise, endotype 2 infants were characterized by low proportion of IgE sensitization and high proportion of RSV or RV infection. These endotype 2 infants had dysregulated tumor necrosis factor (TNF)-mediated signaling pathway (FDR <0.001) and significantly higher risks for developing asthma (44% vs. 22%; adjOR 2.71; 95% CI, 1.03-7.11, p = 0.04)., Conclusion: In this multicenter cohort, integrated clustering of clinical, virus, and proteome data identified biologically distinct endotypes of bronchiolitis that have differential risks of asthma development., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Similarly to many respiratory viruses, respiratory syncytial virus (RSV) is surprising in its ability to reinfect children and adults who have already been immunized. It is not so much in the evolution of its genome that we must look for the cause, but more probably in the structure/function of its viral proteins, which are capable of interfering with the immune response and memory. After an incubation of three to eight days, RSV infection most often results in nasopharyngitis with little or no fever. RSV infection of the respiratory epithelium is characterized by marked mucus production, desquamation of infected respiratory cells and persistent impairment of mucociliary transport. The extension of the infection to the lower respiratory tract therefore contributes to the formation of mucous plugs obstructing the lumen of the bronchioles. This is the cause of the clinical most commonly associated with RSV infection: bronchiolitis in newborns and infants which is a frequent reason for hospitalization due to secondary respiratory and digestive complications. The recent data from the literature, however, indicate that by far the most frequent complication is a community infection: acute otitis media. RSV infections are therefore a very common reason for the prescription of antibiotics., Competing Interests: J.-S. Casalegno déclare faire partie du comité scientifique d’une étude non rémunérée menée par Pfizer sur le VRS.