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Introduction: Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) is linked to childhood asthma development. Despite a growing understanding of risk factors for developing post‐bronchiolitis asthma, protective factors remain unclear. In this study, we aimed to investigate whether exposure to residential greenness between birth and bronchiolitis hospitalization is associated with asthma and atopic asthma development by age 6 years. Methods: We analyzed a US severe bronchiolitis cohort from hospitalization to age 6 years, investigating how the normalized difference vegetation index (NDVI) and chlorophyll index green (CI green), measured in small (100 m) and large (500 m) radiuses around homes, relate to asthma and atopic asthma by age 6 years. We also explored whether maternal antibiotic use, daycare attendance, and respiratory virus type during hospitalization act as effect modifiers. Results: The study cohort included 861 infants, with 239 (28%) developing asthma by age 6 years—152 atopic, 17 nonatopic, and 70 unclassified. Early life residential exposure to high NDVI and CI green levels was associated with lower odds of asthma (ORAdj for NDVI within a 100 m radius, 0.18; 95% CI, 0.05–0.78; and ORAdj for CI green levels within a 100 m radius, 0.53; 95% CI, 0.31–0.90). Associations also were significant for the development of atopic asthma (ORAdj 0.16; 95% CI, 0.03–0.96; and ORAdj 0.46; 95% CI, 0.25–0.92; respectively). Results were similar for the 500 m radius exposures. No effect modification was noted. Conclusion: In a U.S. bronchiolitis cohort, exposure to residential greenness between birth and bronchiolitis hospitalization is linked to lower asthma and atopic asthma risk by age 6 years. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection mitigated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated antiapoptosis pathway as a target to battle severe RSV disease in infants. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The first evidence‐based Finnish guidelines for paediatric lower respiratory tract infections (LRTIs) were published in 2014 and completely updated in 2023. This paper, by the interdisciplinary working group that developed the 2023 guidelines, summarises the main recommendations.The 2023 guidelines were produced after a systematic review. Strong evidence was at least two separate, high‐quality studies, moderate evidence was at least one high‐quality study and weak evidence was at least one satisfactory study. The authors have now summarised the key points.There was strong evidence that antitussives and beta‐sympathomimetics were not effective for bronchitis‐related cough and that laryngitis should be treated with oral corticosteroids, with adrenaline inhalations added in severe cases. Also, that amoxicillin for 5 days provided sufficient treatment for paediatric community‐acquired pneumonia and that children with apparent viral pneumonia could be observed without antimicrobial therapy. There was moderate evidence that corticosteroids or inhaled agents were not effective for bronchiolitis and that administering salbutamol with a holding chamber could relieve symptoms of wheezing bronchitis. Also, pertussis should be considered for unvaccinated infants with coughs.The 2023 guidelines aim to improve acute evidence‐based treatment of LRTIs, through appropriate antibiotics, inhaled drugs, corticosteroids, radiology and laboratory testing. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This retrospective study aims to analyze the baseline characteristics and factors associated with poor outcomes in patients with necrotizing enterocolitis (NEC) complicating respiratory syncytial virus (RSV) infection. Using the Virtual Pediatric Systems data registry, patients under 2 years admitted to the pediatric intensive care unit (PICU) were screened. Patients with documented RSV infection and NEC, intestinal perforation, noninfectious gastroenteritis/colitis, or pneumatosis intestinalis occurring around the timing of RSV bronchiolitis diagnosis were included. Out of the screened patients, 41 were analyzed. Most patients (93%) were aged 30 days to 2 years, one-third had baseline anatomical cardiac defects, and 20% history of prematurity. Median PICU length of stay was 11.7 days. Seven patients died before hospital discharge. While not statistically significant, nonsurvivors tended to exhibit higher PRISM-3 scores, more acidemia, and lower systolic blood pressure. These findings emphasize the need for cautious assessment of gastrointestinal symptoms in critically ill patients with RSV infection. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a 6-month-old male with a rare inborn error of immunity that initially presented as acute respiratory failure. The patient's condition worsened despite treatment for bronchiolitis, leading to further investigations that revealed Pneumocystis jiroveci pneumonia (PJP) secondary to CD40L deficiency. CD40L deficiency is associated with various clinical manifestations and poor prognosis, but early management with IVIG and antibiotic prophylaxis can reduce life-threatening infections, with hematopoietic stem cell transplant (HSCT) being the only cure. The patient was discharged home after treatment and remains on prophylactic medications while awaiting HSCT. [Extracted from the article]

AbstractRespiratory syncytial virus (RSV) is a widespread viral infection that causes millions of high-risk illnesses annually. Medicinal herbs such as ginseng root, echinacea purpurea, and radix astragali have a positive effect on antiviral activity by preventing viral adhesion, syncytial development, inhibiting viral internalization, relieving respiratory inflammation, strengthening the immune system, and stimulating the release of interferons. The potential benefits of natural products in terms of lower costs, better patient outcomes, and fewer adverse effects are discussed. This review examines the current evidence on the prevention and control of RSV with natural ingredients and the challenges and opportunities in clinical practice. [ABSTRACT FROM AUTHOR]

Acute bronchiolitis affects around 30 % of infants each winter in France. Breastfeeding (BF) is described as being protective against acute lower respiratory infections in developing countries, but this effect is more difficult to demonstrate in industrialized countries. Moreover, the effect of using a pacifier in the occurrence of bronchiolitis is not clearly established. In this context, the aim of the study was to investigate the link between BF and the use of a pacifier in the occurrence of bronchiolitis in children under 1 year of age who presented to five pediatric emergency centers in Pays de la Loire, France. A questionnaire collecting data on diet, sociodemographic characteristics, and the reason for presentation was provided at the admission to pediatric emergency centers in five hospitals in Pays de Loire, France, between 2018 and 2020. Children with bronchiolitis were included in group 1, and children consulting for other reasons (except gastrointestinal infections or otitis) were included in group 2. Breastfeeding was classified as exclusive breastfeeding (EBF) and partial breastfeeding (PBF). Pacifier use was classified as frequent and during sleep or not used. The study included 671 children under 1 year of age, including 174 (25.8 %) who were admitted with bronchiolitis. In univariate analysis, a significantly smaller number of children in group 1 s were breastfed (EBF and PBF) at admission compared with children in group 2:21.8 % versus 32.8 %, respectively, (OR=0.57, 95 % CI: 0.38–0.86, p = 0.006); furthermore, children in group 1 used a pacifier more often than those in group 2: 84.5 % versus 75.8 % (OR=1.74, 95 % CI: 1.10–2.76, p = 0.017). In multivariate analysis, after adjusting for age, ongoing BF or EBF beyond 9 and 12 months of age remained a protective factor; however, the protective effect of BF disappeared with the introduction of a pacifier, and pacifier use was significantly associated with bronchiolitis. The protective effect of BF against bronchiolitis was demonstrated independently of pacifier use. However, due to the strong association between pacifier use and bronchiolitis, the effect of BF weakened. The advice to be given to parents for BF and pacifier use is discussed. [ABSTRACT FROM AUTHOR]

Severe acute bronchiolitis (SAB) can be life-threatening for infants and may be responsible for the congestion of intensive care units (ICU) during epidemics. We aimed to study the clinical and paraclinical characteristics of patients with SAB requiring a transfer to the ICU in order to examine their outcomes and to identify the predictors of a stay of ≥7 days and/or death. This was a cross-sectional retrospective study including infants aged ≤12 months transferred to the ICU for their first episode of SAB between 1 January 2010 and 31 December 2019. We collected data on 380 patients with a median age of 1.75 months. They had a history of prematurity (20.53 %), low birth weight (18.68 %), parental atopy (12.89 %), and comorbidity (7.37 %, mainly congenital heart disease [5 %]). The leading cause of transfer was hypoxemia and increased oxygen requirements (49.73 %). The patients required mechanical ventilation (MV) in 63.42 % of the cases and noninvasive ventilation (NIV) in 67.63 %. NIV has supplanted MV over the years. Its use has increased from 40.4 % in 2010 to 96 % in 2019 compared with 83.84 % and 42 % for MV. A total of 14 (3.68 %) patients died. The independent predictors of a stay of ≥7 days and/or death were young age ≤2 months (p = 0.002), failure to thrive (p = 0.006), apnea (p = 0.045), dehydration (p = 0.018), the presence of biological inflammatory reaction (p = 0.002), isolation of respiratory syncytial virus (p < 0.001), and bacterial coinfection (p = 0.013).NIV was a protective factor (p < 0.001). A severity score ranging from 0 to 17 was established with an optimal cut-off value of 5 points. Specific caution is needed in patients with these severity predictors. The generalization ofNIV in general pediatrics departments would improve SAB management and reduce transfers to the ICU. [ABSTRACT FROM AUTHOR]

Respiratory diseases (RDs) constitute a common public health problem both in industrialized and developing countries. The comprehension of the pathophysiological mechanisms underlying these conditions and the development of new therapeutic strategies are critical for improving the quality of life of affected patients. β2-adrenergic receptor (β2AR) and transient receptor potential vanilloid 1 (TRPV1) are both involved in physiological responses in the airways. β2AR is implicated in bronchodilation, mucociliary clearance, and anti-inflammatory effects, while TRPV1 is involved in the mediation of pain and cough reflexes. In RDs, such as respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, the concentration and expression of these receptors can be altered, leading to significant consequences. In this review, we provided an update on the literature about the role of β2AR and TRPV1 in these conditions. We reported how the diminished or defective expression of β2AR during viral infections or prolonged therapy with β2-agonists can increase the severity of these pathologies and impact the prognosis. Conversely, the role of TRPV1 was pivotal in neuroinflammation, and its modulation could lead to innovative treatment strategies in specific patients. We indicate future perspectives and potential personalized treatments in RDs through a comprehensive analysis of the roles of these receptors in the physiological and pathological mechanisms of these pathologies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is triggered by many environmental factors. We sought to determine the relationship between birth weight, infectious diseases, and AD. This retrospective cohort study analyzed data from the CGR Database for the period 2004 through 2015 in Taiwan. All diseases were classified using the International Classification of Disease codes. Logistic regression adjusted for birth weights and comorbidities were analyzed by SAS (version 9.4). P <.05 were considered statistically significant. In children with AD, bronchiolitis was significantly associated with the development of AD, whether the patients were aged < 2 years (odds ratio [OR] = 1.497; P =.014) or ≥ 2 years (OR = 1.882; P =.022). There was also no difference in the association between AD and different birth weights. We conclude that AD is associated with a previous history of bronchiolitis in children, regardless of age (less than or greater than 2 years). [ABSTRACT FROM AUTHOR]

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conliuhm@ ducted in China, we enrolled participants 1 to 24 months of age who were hospiond talized with RSV infection. Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir Cat a dose of 10 to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms). The intention-to-treat population included all the participants with RSV-confirmed infection who received at least one dose of ziresovir or placebo; the safety population included all the participants who received at least one dose of ziresovir or placebo. RESULTS: The intention-to-treat population included 244 participants, and the safety population included 302. The reduction from baseline in the Wang bronchiolitis clinical score at day 3 was significantly greater with ziresovir than with placebo (-3.4 points [95% confidence interval {CI}, -3.7 to -3.11 vs. -2.7 points [95% CI, -3.1 to -2.21; difference, -0.8 points [95% CI, -1.3 to -0.3]; P=0.002). The reduction in the RSV viral load at day 5 was greater in the ziresovir group than in the placebo group (-2.5 vs. -1.9 log1o copies per milliliter; difference, -0.6 logio copies per milliliter [95% CI, -1.1 to -0.2]). Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months of age or younger. The incidence of adverse events related to the drug or placebo was 16°/o with ziresovir and 13% with placebo. The most common adverse events that were assessed by the investigator as being related to the drug or placebo were diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1°/o). Resistance-associated mutations were identified in 15 participants (9°6) in the ziresovir group. CONCLUSIONS: Ziresovir treatment reduced signs and symptoms of bronchiolitis in infants and young children hospitalized with RSV infection. No safety concerns were identified. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. Despite notable progress in the diagnosis and management of pediatric RSV infection, the current biomarkers for early-stage detection remain insufficient to meet clinical needs. Therefore, the development of more effective biomarkers for early-stage pediatric respiratory syncytial virus infection (EPR) is imperative. Methods: The datasets used in this study were derived from the Gene Expression Omnibus (GEO) database. We used GSE188427 dataset as the training set to screen for biomarkers. Biomarkers of EPR were screened by Weighted Gene Co-expression Network Analysis (WGCNA), three machine-learning algorithms (LASSO regression, Random Forest, XGBoost), and other comprehensive bioinformatics analysis techniques. To evaluate the diagnostic value of these biomarkers, multiple external and internal datasets were employed as validation sets. Next, an examination was performed to investigate the relationship between the screened biomarkers and the infiltration of immune cells. Furthermore, an investigation was carried out to identify potential small molecule compounds that interact with selected diagnostic markers. Finally, we confirmed that the expression levels of the selected biomarkers exhibited a significant increase following RSV infection, and they were further identified as having antiviral properties. Results: The study found that lymphocyte antigen 6E (LY6E) and Transcobalamin-2 (TCN2) are two biomarkers with diagnostic significance in EPR. Analysis of immune cell infiltration showed that they were associated with activation of multiple immune cells. Furthermore, our analysis demonstrated that small molecules, 3ʹ-azido-3ʹ-deoxythymine, methotrexate, and theophylline, have the potential to bind to TCN2 and exhibit antiviral properties. These compounds may serve as promising therapeutic agents for the management of pediatric RSV infections. Additionally, our data revealed an upregulation of LY6E and TCN2 expression in PBMCs from patients with RSV infection. ROC analysis indicated that LY6E and TCN2 possessed diagnostic value for RSV infection. Finally, we confirmed that LY6E and TCN2 expression increased after RSV infection and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based on TCN2, our findings revealed the antiviral properties of a potentially efficacious compound, vitamin B12. Conclusion: LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection. LY6E and TCN2 inhibit RSV infection, indicating that LY6E and TCN2 are potential therapeutic target for RSV infection. [ABSTRACT FROM AUTHOR]

Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Zcombined detection−tIgE = 2.442, Zcombined detection−FeNO = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis. [ABSTRACT FROM AUTHOR]

Objectives: Bronchiolitis is a leading cause of infant hospitalisation in the first year of life, and it preferentially affects infants born to mothers with asthma. Here, we evaluate cord blood granulocytes in infants born to mothers with asthma participating in the Breathing for Life Trial (BLT), to investigate early life determinants of bronchiolitis hospitalisation within the first year of life. Methods: Cord blood from 89 participants was collected into EDTA tubes and processed within 6 h of birth. Cells were stained in whole cord blood for eosinophils (CD45+, CD193+, CD16−), and neutrophils (CD45+, CD193−, CD16+). Medical records were reviewed for bronchiolitis hospitalisation in the first 12 months of life. Statistical analyses were conducted using Stata IC16.1. Results: Logistic regression adjusted for caesarean section, gestational age, maternal smoking during pregnancy, foetal heart deceleration during labour, and season of birth revealed an association between cord blood eosinophil levels and bronchiolitis hospitalisation in the first 12 months of life with an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.943 (aOR = 1.35, P = 0.011). Neutrophils were associated with the risk of bronchiolitis hospitalisation in a univariable logistic regression (OR = 0.93, P = 0.029); however, there was no statistical significance in the adjusted model. Conclusions: Higher eosinophil numbers in cord blood were associated with bronchiolitis hospitalisation in the first 12 months in a cohort of infants born to asthmatic mothers. This suggests that susceptibility to bronchiolitis in later life is influenced by the immune cell profile prior to viral infection. [ABSTRACT FROM AUTHOR]

Objectives: To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. Methods: Retrospective cohort study of Medicaid-enrolled children 0–3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. Results: During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. Conclusions: Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies. [ABSTRACT FROM AUTHOR]

While concerns about high-flow nasal cannula oxygen (HFNC) overuse and associated increased use of hospital resources are rapidly spreading, a two-tiered approach in its use is recommended by recent bronchiolitis guidelines. However, data on its effects in practice have not been reported. We aimed to analyze the trends in use of HFNC, hospitalizations, length of stay (LOS), and intensive care unit (ICU) admissions for bronchiolitis in a tertiary care center using a two-tiered HFNC approach since its introduction in practice. We retrospectively included data of children < 12 months of age who presented to the Paediatric Emergency Department (PED) and were hospitalized for bronchiolitis at our institution in the epidemic season between October 1st and April 30th during the years 2012–2023 and compared the clinical data across the years. Of the 687 hospitalized children included, 79.9% required oxygen supplementation. Use of HFNC significantly increased since its implementation (from 25% in 2012–2013 to over 60% since 2019–2020, p < 0.0001) and was most frequently administered as rescue treatment (in 57.5% of patients). There was no increased trend in ICU admissions (between 1.5% and 10.0% of hospitalizations across seasons, p = 0.40), while LOS, after increasing between 2013 and 2016 (medians between 4.0 and 5.4 days), remained stable thereafter (medians between 3.8 and 4.3 days). Conclusions: The use of HFNC according to a two-tiered approach does not appear to be associated with an increase in ICU utilization or LOS. What is Known: • Bronchiolitis is one of the most common reasons for hospitalization in infants. • Use high-flow nasal canulae oxygen (HFNC) has rapidly spread outside the intensive care unit (ICU) to treat infants with bronchiolitis, although increasing evidence has dampened the initial enthusiasm about their effectiveness. • Concerns nowadays are rising about HFNC overuse and associated increased use of hospital resources, including escalation of care to ICU. What is New: • A more selective use of HFNC according to a "two-tiered approach", intended as a second-line rescue treatment in non-severely ill children who fail standard oxygen therapy, is not associated with increased ICU and length of hospital stay. [ABSTRACT FROM AUTHOR]

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2–6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. Conclusion: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. What Is Known: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. What Is New: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing. [ABSTRACT FROM AUTHOR]

Aim: Respiratory syncytial virus (RSV) represents a significant cause of morbidity for children worldwide, especially for newborns. As RSV vaccines are not routinely used for children yet, non‐pharmaceutical interventions (NPIs) represent the main strategy for prevention. The objective of this study was to investigate the correlation between school holidays and RSV transmission. Methods: Data were collected from the weekly reports on RSV incidence for the 2021/2022 and 2022/2023 seasons in Sweden. The 7‐day cumulative incidence of RSV was compared before and after the designated school holidays (Fall, Christmas, and Winter holidays). Results: Our findings reveal an immediate (−1.7%, p < 0.001, 95% CI [−3.1%, −0.4%]) and gradual (−1.4%/week, p < 0.001, 95%CI [−1.8, −1.0]) reduction in RSV incidence following the Fall holiday in 2021, especially among children under 1 year of age, both immediately (−107.6%, p < 0.05, 95% CI [−203.7, −11.5]) and gradually afterwards (−58.5%/week, p < 0.001, 95% CI [−72.7, −44.3]). Mixed results were obtained for the Fall in 2022/2023 and for the Winter and holidays in both the studied years. Conclusions: While the Fall holiday in 2021/2022 was associated with a decrease in RSV incidence in Sweden, our results do not support a universal effect of school holidays on reducing RSV transmission. [ABSTRACT FROM AUTHOR]

Bronchiolitis is one of the main reasons for the hospitalization of young children. Based on updated recommendations, only supportive therapy is recommended for treatment. In Poland, many children that are hospitalized with bronchiolitis undergo a treatment that is not supported by current research. The study aimed to assess clinicians’ adherence to the guidelines. This was a multicenter retrospective study of hospitalized infants with bronchiolitis; a cohort study design was utilized. Data were collected in four Pediatric Departments in Poland. All infants aged less than 24 months that had been hospitalized for their first and subsequent episodes of acute bronchiolitis from January 1, 2021, to December 31, 2022, were included. The exclusion criterion was an age over 24 months. A total of 629 infants with a median age of 8.5 months were included in this study. The medical interventions and treatments varied between the four hospitals. Laboratory blood tests were run for almost all children (99.5%), and the percentage of children for which a chest X-ray was performed ranged from 1.3% to 44%. The other measures were the use of intravenous hydration (51.3%-93.3%), use of hypertonic saline nebulization (1.3%-43.6%), use of normal saline nebulization (10%-95.1%), use of oxygen (7.3%-42%), use of beta-mimetics (19.1%-89.4%), use of nebulized steroids (8%-76.9%), use of systemic steroids (0.9%-42%), use of nebulized adrenaline (0%-8.1%), and use of antibiotics (12%-21.8%). Conclusions: In total, 70% of infants who were hospitalized in four hospitals in Poland underwent examinations and treatment methods that are not supported by current guidelines and evidence-based research. This study shows that non-recommended medications are overused in bronchiolitis treatment, and there is a need to take action to implement the guidelines into healthcare providers’ work. What is Known: • Bronchiolitis is a lower respiratory tract viral infection and is one of the main reasons for hospitalization among young children. • Only supportive therapy is recommended in the guidelines. • Bronchodilators, nebulized adrenaline, nebulized or systemic steroids, and antibiotics are not recommended. What is New: • Non-recommended medications are overused in bronchiolitis treatment in Poland. • Up to 70% of hospitalized children in the studied centers underwent treatment that is not supported by guidelines. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to assess the predictors of need for paediatric intensive care unit (PICU) admission for inter‐hospital transfer patients to a tertiary paediatric hospital ED on high flow (HF) or continuous positive airway pressure (CPAP) ventilation. Methods: Single‐centre retrospective study of patients transferred to the state's tertiary paediatric hospital. Demographic information and disease management information was obtained. Results: Between October 2021 and September 2022, 53 patients were transferred to the tertiary hospital on HF or CPAP. Of these, 23 required admission to PICU. Those admitted to PICU had a higher median fraction of inspired oxygen than those not admitted (0.4 vs 0.3, respectively, P = 0.013). Patients transported by road (vs flight) were more likely (20/23 patients, RR = 3.15, P = 0.016) to be admitted to PICU (56% vs 18%). Those who had received CPAP prior to or during transfer were more likely to require PICU admission (P = 0.012). Conclusion: We have demonstrated that children who require CPAP to manage their respiratory disease are more likely to require PICU care on transfer to the tertiary paediatric hospital. In addition, those patients being transferred from secondary metropolitan hospitals after a trial of HF are also likely to require PICU care. This suggests that these patients should be directly admitted to PICU, allowing for improved patient experience and flow as well as reducing unnecessary ED resource utilisation. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6 months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0–6 months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11 m-old with respect to 12-35 m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11 m-old and 12-35 m-old with respect to the > 35 m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11 m-old RR (95% CI) of RSV infection incidence for > 35 m-old was 1.7 (1.5–2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6–9.9), 8.8 (6.9–11.3), and 7.1 (5.7–8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11 m-old group compared to the 12-35 m-old, the pre-pandemic (2014/2015–2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2–9.6) and 6.0 (5.7–6.2), respectively, significantly higher than the RR of 3.6 (3.4–3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11 m-old compared to > 35 m-old has been reduced by 75.6% (73.4–77.5) in last season, and the risk for all-causes bronchiolitis for 12-35 m-old by 61.9% (60.9–62.9) from the pre-pandemic period and by 39.8% (39.3–40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6 months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using. primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11 m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%. [ABSTRACT FROM AUTHOR]

Bronchiolitis is the leading cause of infant hospitalization. However, the molecular networks driving bronchiolitis pathobiology remain unknown. Integrative molecular networks, including the transcriptome and metabolome, can identify functional and regulatory pathways contributing to disease severity. Here, we integrated nasopharyngeal transcriptome and metabolome data of 397 infants hospitalized with bronchiolitis in a 17-center prospective cohort study. Using an explainable deep network model, we identified an omics-cluster comprising 401 transcripts and 38 metabolites that distinguishes bronchiolitis severity (test-set AUC, 0.828). This omics-cluster derived a molecular network, where innate immunity-related metabolites (e.g., ceramides) centralized and were characterized by toll-like receptor (TLR) and NF-κB signaling pathways (both FDR < 0.001). The network analyses identified eight modules and 50 existing drug candidates for repurposing, including prostaglandin I2 analogs (e.g., iloprost), which promote anti-inflammatory effects through TLR signaling. Our approach facilitates not only the identification of molecular networks underlying infant bronchiolitis but the development of pioneering treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection and hospitalizations among infants, young children, and the elderly. This systematic literature review aimed to summarize the epidemiological and economic burden estimates of RSV infection at any age in Germany. Methods: We conducted a systematic literature search to identify full-text articles published from 2003 to 2023 and reporting data on the epidemiological or economic burden of RSV in Germany. Based on pre-specified eligibility criteria, data on incidence, rates of hospital and intensive care unit (ICU) admission, clinical manifestation, underlying conditions, seasonality, health care resource use and costs were extracted. Results: After screening 315 full-text articles, we included 42 articles in the review. The characteristics of the included studies were heterogenous regarding study population, setting, age groups and RSV-related outcome measures. The most frequently reported epidemiological outcome measures were RSV detection rate (n = 33), followed by clinical manifestation (n = 19), seasonality (n = 18), and underlying conditions of RSV infection (n = 13). RSV detection rates were reported across heterogenous study populations, ranging from 5.2 to 55.4% in pediatric inpatient cases and from 2.9 to 14% in adult inpatient cases. All articles that reported RSV detection rates across several age groups demonstrated the highest burden in infants and young children. Few articles reported RSV-related outcome measures distinctively for the outpatient setting. Health care resource use, such as hospital length of stay, ICU admission rate and treatment of patients with RSV infection were described in 23 articles, of which only one study quantified associated costs from 1999 to 2003 for children ≤ 3 years. In-hospital ICU admission rates varied between 3.6 and 45%, depending on population characteristics as age and underlying conditions. Conclusions: This systematic review revealed that RSV imposes substantial disease burden in infants, young children, and the elderly in Germany, whereby infants are particularly affected. To date, there has been limited exploration of the impact of RSV infection on healthy children or the elderly in Germany. Given their notably high reported burden in studies, the medical and economic RSV burden in these groups should move more into focus. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the effect of iron deficiency anemia (IDA) on the severity of symptoms in infants hospitalized for acute bronchiolitis. Methods: This is a case–control study, which was carried out on 80 infants from November 2022 to April 2023. The study involved 60 infants ranging in age from 2 months to 2 years, who were admitted to the Pediatric Pulmonology Unit and met the diagnostic criteria for acute bronchiolitis. Furthermore, a control group of 20 apparently healthy infants was incorporated into the study. Results: This study showed that patients with moderate and severe bronchiolitis exhibited notably reduced levels of hemoglobin, HCT, MCV, MCH, and MCHC. Concerning the iron status, a substantial decrease in serum iron and increase in TIBC in the severe group (P = 0.012, 0.001, respectively). No substantial correlation was detected between the severity of acute bronchiolitis and serum ferritin levels. Hemoglobin and serum iron were found to be independent predictors of the severity of acute bronchiolitis. Conclusions: Infants suffering from IDA exhibit increased vulnerability to acute bronchiolitis. The low levels of hemoglobin and serum iron may function as prognostic indicators for the severity of the condition in infants with acute bronchiolitis. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) primarily infects the respiratory epithelium, but growing evidence suggests that it may also be responsible for neurologic sequelae. In 3-dimensional microphysiologic peripheral nerve cultures, RSV infected neurons, macrophages, and dendritic cells along 2 distinct trajectories depending on the initial viral load. Low-level infection was transient, primarily involved macrophages, and induced moderate chemokine release with transient neural hypersensitivity. Infection with higher viral loads was persistent, infected neuronal cells in addition to monocytes, and induced robust chemokine release followed by progressive neurotoxicity. In spinal cord cultures, RSV infected microglia and dendritic cells but not neurons, producing a moderate chemokine expression pattern. The persistence of infection was variable but could be identified in dendritic cells as long as 30 days postinoculation. This study suggests that RSV can disrupt neuronal function directly through infection of peripheral neurons and indirectly through infection of resident monocytes and that inflammatory chemokines likely mediate both mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of glucocorticoid administration on anti-infective efficacy and prognosis of children diagnosed with bronchiolitis caused by Mycoplasma pneumoniae (MP). Methods: 100 children from January 2021 to June 2023 diagnosed with MP-induced bronchiolitis at the Department of Pediatrics, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China were randomized into study (n = 45) and control groups (n = 55). The study group received conventional medication (azithromycin at 10 mg/kg on the first day followed by 5 mg/kg/day for 5 days) in addition to glucocorticoids, while control group received the same conventional medication without glucocorticoids. The study group was treated with prednisone (2 mg/kg/day), once a day for 5 days. Inflammatory markers (C-reactive protein (CRP) and procalcitonin (PCT) levels) before and after treatment, duration of medication, disease course, clinical efficacy, and prognosis were compared. Results: There was no significant difference in baseline characteristics between both groups (p > 0.05). The study group showed significantly reduced CRP and PCT levels, shorter medication and disease duration, and a higher efficacy compared to control group (p < 0.05). Conclusions: Administration of glucocorticoids in addition to conventional medication in MP-induced bronchiolitis reduces levels of inflammatory markers, improves clinical symptoms, and enhances efficacy. Future studies using prospective, randomized controlled trials, larger sample sizes that cut across multicenter sites, standardized treatment protocols, and long-term follow-up will be required to more accurately confirm the safety and efficacy of glucocorticoids in the management of MP-induced bronchiolitis. [ABSTRACT FROM AUTHOR]

Le virus respiratoire syncytial (VRS) est le principal agent de la bronchiolite du nourrisson. Depuis sa découverte dans les années 1960, de nombreuses équipes ont cherché à développer des traitements préventifs de l'infection VRS. Jusqu'à récemment, les essais de vaccination sont toutefois restés infructueux. La prévention des infections sévères reposait sur un anticorps monoclonal réservé aux nourrissons à haut risque du fait d'un ratio coût/efficacité médiocre. La majorité des vaccins ou des anticorps monoclonaux ciblent la protéine de surface F du VRS. En 2013, des chercheurs ont obtenu la structure de la F dans la conformation qu'elle adopte à la surface des virions. En ciblant cette conformation particulière de F, différentes équipes ont développé des vaccins et des anticorps monoclonaux efficaces. Ainsi en 2022, un anticorps monoclonal à longue demi-vie, le nirsevimab, a été approuvé pour la prévention des infections sévères chez le nourrisson. En 2023, 2 vaccins ont été approuvés pour la prévention des infections sévères chez le sujet âgé et chez le nouveau-né pour l'un des 2. Ainsi 2 stratégies d'immunisation passive sont désormais disponibles pour la prévention des infections sévères du nourrisson par le VRS : injection unique d'un anticorps monoclonal avant la première exposition au VRS ou vaccination maternelle en fin de grossesse permettant un transfert transplacentaire des anticorps. Des questions demeurent quant à la stratégie qui sera appliquée dans les différents pays, la place d'une prévention des infections chez l'enfant après un an ou l'évolution du VRS face à cette nouvelle pression de sélection. Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young children. It is the leading cause of severe lower respiratory tract infections in children worldwide. Since its discovery in the 1960s, many teams have tried to develop preventive treatments for RSV infection. Until recent years, however, vaccine trials have been unsuccessful. Prevention of severe infection has relied on a monoclonal antibody, which has been reserved for high-risk infants because of its poor cost-effectiveness. The RSV surface F protein is the target of most vaccine or monoclonal antibodies. In 2013, researchers obtained the structure of F in its conformation on the viral surface. By targeting this particular conformation of F, several teams have developed effective vaccines and monoclonal antibodies to prevent severe RSV infections. In 2022, a monoclonal antibody with a long half-life, nirsevimab, was approved for the prevention of severe infections in infants. In 2023, 2 vaccines will be licensed for the prevention of severe infection in the elderly, one of them in neonates. This means that 2 passive immunisation strategies are now available to prevent severe RSV infection in infants: a single injection of a monoclonal antibody before the first exposure to RSV, or maternal vaccination at the end of pregnancy, allowing transplacental transfer of antibodies. Questions remain about the strategy to be adopted in different countries, the place of prevention of infection in children after one year of age, or the evolution of RSV in the face of this new selection pressure. [ABSTRACT FROM AUTHOR]

A 62-year-old woman came to our hospital with worsening cough and dyspnea over the preceding week, during which time she had been treated with azithromycin and prednisone for suspected pneumonia. She had no fever, chills, or sweats, but her cough had become productive of clear to blood-tinged phlegm during the interval. Medical history was significant for insulin-dependent diabetes mellitus and OSA. She had quit smoking 44 years earlier and had no history of lung disease. She was a bank teller residing in southeastern Minnesota and described no relevant inhalational or environmental exposures, drug use, aspiration, or travels preceding her illness. [ABSTRACT FROM AUTHOR]

Viral load measurement of Respiratory syncytial virus (RSV) in acute bronchiolitis depends on specimen collection, viral load quantification, and transport media. The aim of this study was to investigate viral load in three-way-comparative analyses; nasal swab versus nasal wash, quantitative real-time polymerase chain reaction (RT-PCR) versus cell tissue culture, and various transport media. A prospective cohort study of infants aged < 12 months, admitted to the Soroka Medical Center, due to acute bronchiolitis, was conducted. Two nasal swabs and two nasal wash samples (in UTM and VCM) were collected from each infant upon admission and after 48 h. Samples were immediately stored at −80 °C and tested at Viroclinics DDL (Rotterdam, Netherlands). Quantitative RT-PCR and quantitative virus culture were performed using tissue culture infective dose (TCID50). Spearman's correlation coefficient test assessed the correlation between the different methods, viral load, and clinical severity score. One hundred samples were collected from 13 infants (mean age 5.7 ± 3.8 months, 46% males). Twelve patients were RSV-A positive, and one was RSV-B positive. A high correlation was found between transport media- UTM and VCM (0.92, P < 0.001) and between nasal swabs and nasal wash samples (0.62, P = 0.02). RSV signals were higher in nasal wash than in swabs. PCR signals were lower in the second collection compared to the first. No correlation was found between viral load and clinical severity. Conclusion: RSV viral load is comparable across nasal wash, nasal swabs, and various transport media. However, it did not correlate with clinical severity, probably due to the limited sample size. Broader analyses are warranted. What is Known: • Viral load measurement in Respiratory Syncytial Virus (RSV) bronchiolitis depends on specimen collection, viral load quantification, and transport media. • The COVID-19 pandemic underscored the paramount significance of proper specimen collection, notably through nasal swabs. What is New: • RSV viral load was investigated in three-way-comparative analyses. • RSV viral load correlated well across PCR and tissue culture, nasal wash and swabs, and various transport media. RSV viral load did not correlate with clinical severity. [ABSTRACT FROM AUTHOR]

This article discusses the use of nebulized hypertonic saline solution for the treatment of acute bronchiolitis in infants. Acute bronchiolitis is a common lower respiratory tract infection in children under 2 years old, often caused by the Respiratory Syncytial Virus (RSV). The article presents the findings of a Cochrane review, which suggests that nebulized hypertonic saline solution may slightly reduce the risk of hospitalization and decrease the length of hospital stay for infants with bronchiolitis. However, the evidence is of low to very low certainty, and more research is needed to determine the effectiveness and safety of this treatment. [Extracted from the article]

A study published in the Clinical & Experimental Allergy journal found that low levels of vitamin D in early childhood were associated with aeroallergen-specific IgE in children with a history of severe bronchiolitis. However, there was no association between vitamin D levels and total, food-specific, or outdoor-aeroallergen-specific IgE. The study suggests that vitamin D plays a role in immune modulation and may be involved in allergic diseases. The study had limitations, such as a small sample size and not accounting for geographic factors and individual allergen exposure. Further research is needed to fully understand the relationship between vitamin D and allergic sensitization. [Extracted from the article]

Background: High flow nasal cannula (HFNC) has been increasingly adopted in the past 2 decades as a mode of respiratory support for children hospitalized with bronchiolitis. The growing use of HFNC despite a paucity of high-quality data regarding the therapy's efficacy has led to concerns about overutilization. We developed an electronic health record (EHR) embedded, quality improvement (QI) oriented clinical trial to determine whether standardized management of HFNC weaning guided by clinical decision support (CDS) results in a reduction in the duration of HFNC compared to usual care for children with bronchiolitis. Methods: The design and summary of the statistical analysis plan for the REspiratory SupporT for Efficient and cost-Effective Care (REST EEC; "rest easy") trial are presented. The investigators hypothesize that CDS-coupled, standardized HFNC weaning will reduce the duration of HFNC, the trial's primary endpoint, for children with bronchiolitis compared to usual care. Data supporting trial design and eventual analyses are collected from the EHR and other real world data sources using existing informatics infrastructure and QI data sources. The trial workflow, including randomization and deployment of the intervention, is embedded within the EHR of a large children's hospital using existing vendor features. Trial simulations indicate that by assuming a true hazard ratio effect size of 1.27, equivalent to a 6-h reduction in the median duration of HFNC, and enrolling a maximum of 350 children, there will be a > 0.75 probability of declaring superiority (interim analysis posterior probability of intervention effect > 0.99 or final analysis posterior probability of intervention effect > 0.9) and a > 0.85 probability of declaring superiority or the CDS intervention showing promise (final analysis posterior probability of intervention effect > 0.8). Iterative plan-do-study-act cycles are used to monitor the trial and provide targeted education to the workforce. Discussion: Through incorporation of the trial into usual care workflows, relying on QI tools and resources to support trial conduct, and relying on Bayesian inference to determine whether the intervention is superior to usual care, REST EEC is a learning health system intervention that blends health system operations with active evidence generation to optimize the use of HFNC and associated patient outcomes. Trial registration: ClinicalTrials.gov NCT05909566. Registered on June 18, 2023. [ABSTRACT FROM AUTHOR]

Background Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. Methods We conducted a prospective observational study (BronchStart), enrolling children 0–23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. Results The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0–11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637–29 486) infants are admitted with RSV infection. Conclusions RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants. [ABSTRACT FROM AUTHOR]

BACKGROUND Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear. METHODS We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed. RESULTS The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]). CONCLUSIONS In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. [ABSTRACT FROM AUTHOR]

Acute respiratory infections (ARIs) remain a leading cause of global mortality and morbidity. Nearly 70% of children between the ages of one and four years and 90% of infants with respiratory illness are hospitalized. The causative agents of nearly 80% of ARIs are viruses. In Bulgaria, according to a study by the National Center of Infectious and Parasitic Diseases, in 82% and 70% of the cases of children with bronchiolitis and pneumonia, respectively, viral causative agents have been proven. This manuscript presents advanced methods for microbiological testing from respiratory specimens, with an accent on multiplex PCR and mass-spectrometry. These methods are a practical diagnostic approach, as they allow quick etiological diagnosis of ARIs in childhood (especially those caused by viruses and difficult-to-cultivate bacteria), detection of co-infections, rapid appointment of appropriate treatment and timely infection control. [ABSTRACT FROM AUTHOR]

Aim: Uptake of nasal high‐flow therapy in infants with bronchiolitis has grown in the last decade with some evidence suggesting a reduction in escalation of care. The effect of the implementation of recent available evidence on clinical practice remains unclear. Methods: In a prospective observational study over 6 months in six metropolitan hospitals in Australia, we investigated the clinical practice of high‐flow in infants admitted with bronchiolitis and an oxygen requirement. To assess the choice by clinicians of the initial oxygen therapy (standard oxygen or high‐flow) the disease severity was measured by physiological parameters obtained prior to oxygen therapy commencement. Additional secondary outcomes were hospital length of stay and transfers to intensive care. Results: Two hundred thirty‐five infants with bronchiolitis were admitted for oxygen therapy over 6 months during the winter season. Infants who received high‐flow on admission to hospital displayed significantly higher respiratory rates, higher heart rates and higher early warning tool scores with more severe work of breathing than those commenced on standard oxygen therapy as a first line of oxygen therapy. A significantly longer hospital length of stay of 0.6 days occurred in infants commenced on high‐flow. A significantly greater proportion on high‐flow (23.3%) were admitted to intensive care compared to infants commenced on SOT (10.4%) despite the severity of disease in both groups being similar. Conclusions: Infants with bronchiolitis presenting with greater disease severity are more likely to receive high‐flow therapy. Escalation of care in an intensive care unit occurred more frequently on infants on high‐flow. Trial Registration: This trial is registered in the Australian New Zealand Clinical Trial Registry ACTRN12618001206213. [ABSTRACT FROM AUTHOR]

Severe bronchiolitis patients are often supported with non-invasive ventilation (NIV). In case of NIV failure, we recently started to use non-invasive neurally adjusted ventilatory assist ventilation (NIV-NAVA) with a total face mask interface (TFM) and report now our experience with this modality of respiratory support. Retrospective study was made from October 2022 to May 2023 at the Geneva University Hospital Paediatric Intensive Care Unit. Inclusion criteria were children, aged from 0 to 6 months, with severe bronchiolitis with initial NIV failure and switch to NIV-NAVA-TFM. From 49 children with respiratory syncytial virus (RSV)-induced bronchiolitis requiring any form of respiratory support, 10 (median age 61 days (IQR 44–73) failing CPAP or NIV underwent rescue treatment with NIV-NAVA using a TFM. Patients were switched to TFM-NIV-NAVA 8 h (IQR 3–22) after admission for 24.5 h (IQR 13–60). After initiation of TFM-NIV-NAVA, oxygenation improved significantly as early as 1 h after initiation, whereas transcutaneous CO2 values remained stable. None of the patients needed to be intubated and there was no episode of TFM discontinuation due to interface discomfort or other unwanted side effects. Sedation was used in all patients with high proportion of intravenous dexmedetomidine. Median ventilatory assistance duration was 2.5 days (IQR 2–4) and median PICU stay was 4.5 (IQR 3–6). Conclusion: In infants with severe RSV-induced bronchiolitis, respiratory support with TFM-NIV-NAVA seems to be feasible as a rescue therapy and might be considered in selected patients. What is Known: • Bronchiolitic patients with NIV support failure may require invasive mechanical ventilation. • Interface related complications, especially facial sores, can be a cause of NIV failure. What is New: • Total face mask with non-invasive neurally adjusted ventilatory assist (TFM-NIV-NAVA) seems feasible as a rescue therapy in deteriorating patients with CPAP or NIV failure. • TFM-NIV-NAVA can improve oxygenation rapidly in patients with aggravating hypoxemia and seems to be well tolerated. [ABSTRACT FROM AUTHOR]

Background: This study was performed to determine the relationship between chest X-ray findings and the severity of bronchiolitis using the modified Tal score scale (MTS). Methods: This retrospective study was conducted among 999 children aged 2-24 months admitted to a referral teaching hospital in Isfahan, Iran. The severity of bronchiolitis was determined by MTS criteria, with scores ranging from 0 to 12. We considered scores 0-5 mild, 6-9 moderate, and 10-12 severe bronchiolitis. The patient's CXRs were also extracted from the hospital's picture archiving and communication system (PACS) and reported by an expert Pediatric radiologist. The radiologic findings were compared with the MTS criteria. Results: The mean (SD) of the MTS score in the patients was 4.58 ± 1.92. Overall, 757 patients (75.78%) had normal radiographies. The frequency of normal radiography was 75.3% in the group of mild bronchiolitis and 77.3% in the group of moderate bronchiolitis. Reports of 9 patients with severe disease showed that 6 of them had normal CXRs (66.7%), 2 had hyperinflation, and 1 had atelectasis. There was no statistically significant relationship between radiographic results and the severity of bronchiolitis, according to MTS criteria (P = 0.23). The agreement between radiographic results and the severity of bronchiolitis was very weak (0.004) without statistical significance (P = 0.632). Conclusion: Considering that 99.3% of children with bronchiolitis do not have significant findings in chest X-rays, routine chest X-ray is not recommended in these patients. [ABSTRACT FROM AUTHOR]

Background: Acute undifferentiated fever (AUF) remains a significant reason for hospitalization among children, particularly in Southeast Asia. Common causative agents include dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever. This study aims to delineate the clinical and etiological profiles of AUF in children. Materials and Methods: A prospective observational study was conducted over one year in the Department of Pediatrics at a tertiary care hospital in Central India. The study enrolled children with fever lasting less than 21 days and without a specific focus of infection identified through history, physical examination, and routine investigations. Results: Among the 90 children included in the study, the most prevalent cause of undifferentiated fever was typhoid fever (31.1%), followed by malaria (21.1%), dengue fever (18.9%), and urinary tract infections (10%). Other notable causes included acute gastroenteritis (8.9%), pneumonia (5.6%), bronchiolitis (2.2%), hepatitis (1.1%), and pharyngotonsillitis (1.1%). Common clinical symptoms observed were pyrexia (100%), headache (65.6%), rash (47.8%), and abdominal pain (31.1%). Laboratory findings indicated mild anemia in the majority of cases, leukopenia in cases of dengue and malaria, and thrombocytopenia in dengue cases. Conclusion: Non-malarial infections are predominant causes of AUF in children within this region of Central India. Scrub typhus, dengue, and enteric fever were identified as significant contributors. The study underscores the necessity for improved diagnostic facilities to reduce the proportion of undiagnosed fevers, often assumed to be viral in nature. [ABSTRACT FROM AUTHOR]

The text provides a summary of various research studies and initiatives related to implementation science in healthcare settings. The studies cover a wide range of topics, including the implementation of interventions for different health issues, the use of implementation strategies, and the challenges and opportunities in implementing evidence-based practices. The findings highlight the importance of tailoring strategies to specific contexts, engaging stakeholders, and addressing barriers to successful implementation. The studies provide valuable insights for researchers, practitioners, and policymakers interested in improving the implementation of interventions in diverse healthcare settings. [Extracted from the article]

Vaccine hesitancy is a concept that has persisted from the time smallpox vaccine was first introduced to this day. When encountering vaccine-hesitant caregivers in clinical practice, it is important to approach vaccine hesitancy in accordance with evidence-based practices to effectively utilise the limited time available. Our case describes a 6-month and 20-day-old patient admitted to the paediatric ward with acute bronchiolitis and missed vaccinations. The patient's mother revealed that she did not get the infant vaccinated after 2 months of age because she was influenced by people around her. A structured interview was conducted with the mother following the CASE method. After the interview, the mother decided to get her baby vaccinated. The infant received Hepatitis B, diphtheria, tetanus, acellular pertussis, inactivated polio, Haemophilus influenzae type b, and conjugated pneumococcal vaccines on the day of discharge. Subsequent clinic visits confirmed adherence to the vaccination schedule. [ABSTRACT FROM AUTHOR]

Bronchiolitis due to respiratory syncytial virus (RSV) is the leading cause of hospitalization among American infants. The overall burden of RSV among infants has been historically under-estimated due to variable testing practices, particularly in the outpatient setting. Universal masking and social distancing implemented during the coronavirus disease 2019 (COVID-19) pandemic altered RSV seasonality, however potential consequences on RSV testing practices across different healthcare settings and sociodemographic groups have not been described. Variable testing practices could also affect accurate assessment of the effects of two recently approved RSV preventative agents targeting infants. Utilizing real-time clinical and viral surveillance, we examined RSV testing practices among infants with bronchiolitis within four United States healthcare systems across different healthcare settings and sociodemographic groups pre- and post-COVID-19. RSV testing among infants with bronchiolitis increased since 2015 within each healthcare system across all healthcare settings and sociodemographic groups, with a more dramatic increase since the COVID-19 pandemic. Outpatient testing remained disproportionately low compared to hospital-based testing, although there were no major differences in testing frequency among sociodemographic groups in either setting. Although RSV testing increased among infants with bronchiolitis, relatively low outpatient testing rates remain a key barrier to accurate RSV surveillance. • RSV testing rates among infants with bronchiolitis are increasing. • The percent of positive RSV tests is unchanged even with increased testing. • RSV testing rates were not affected by sociodemographic factors. • Outpatient testing remains a barrier to accurate RSV surveillance. [ABSTRACT FROM AUTHOR]

Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3–23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness. [ABSTRACT FROM AUTHOR]

We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons. This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form. Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy. Conclusions: We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world. What is Known: • Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world. What is New: • There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations. • Understanding these differences should be a priority to optime and standardize bronchiolitis care globally. [ABSTRACT FROM AUTHOR]

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13–3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17–1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease. Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study. [ABSTRACT FROM AUTHOR]

Vitamin D's role in immune system regulation and its contribution to host defenses against respiratory infections may have implications for bronchiolitis pathophysiology. This cross-sectional study aimed to determine the association between the clinical severity of bronchiolitis and serum vitamin D levels in infants. Infants aged 1 month to 12 months, diagnosed with bronchiolitis, and healthy controls attending routine immunization were enrolled. Baseline characteristics were recorded, including clinical details, bronchiolitis severity, and course during hospital stay. Bronchiolitis severity score (BSS) was used to score the severity. A 1–2 ml serum sample was obtained for vitamin D levels estimation. The median age of cases (n = 64; 65.6% male) was 5 [3, 8] months, and that of the control group (n = 30) was 3 [2, 9] months. No statistically significant differences were observed between the two groups in age, gender, weight, mode of delivery, family history of atopy/asthma, feeding pattern, smoke exposure, and daily vitamin D supplementation. The median vitamin D levels were not significantly different between the groups (p = 0.68). Among infants with bronchiolitis, 62.5% had vitamin D insufficiency (≤ 20 ng/ml). A significantly higher median BSS indicates that infants with vitamin D insufficiency exhibited more severe disease (p = 0.019). Although a negative correlation between BSS and vitamin D levels was noted, it did not reach statistical significance [rs = (−)0.17; p = 0.16]. Conclusion: Infants with Vitamin D insufficiency experienced more severe bronchiolitis with elevated BSS scores. It highlights the potential role of vitamin D deficiency in severe bronchiolitis. What is Known: • Vitamin D level is low in infants with bronchiolitis. What is New: • Infant with low vitamin D level experienced more severe bronchiolitis. [ABSTRACT FROM AUTHOR]

Background It is crucial to understand the trends in paediatric antibiotic prescribing and serious and nonserious infections to improve antibiotic prescribing practices for children in ambulatory care. Objectives Assessing trends in paediatric antibiotic prescribing and infection incidence in general practice from 2002 to 2022. Methods In this retrospective cohort study using INTEGO network data from 162 507 patients in Flanders (Belgium), we calculated antibiotic prescribing rates and proportions alongside incidence rates of serious and nonserious infections, stratified by age (0–1, 2–6, 7–12 years) and municipality. We performed autoregressive moving average time-series analyses and seasonality analyses. Results From 2002 to 2022, antibiotic prescribing rate decreased significantly: 584/1000 person-years (PY) (95% CI 571–597) to 484/1000PY (95% CI 478–491); so did antibiotic overall prescribing proportion: 46.3% (95% CI 45.1–47.6) to 23.3% (95% CI 22.9–23.7) (59.3% amoxicillin and 17.8% broad spectrum). Prescribing proportions dropped significantly for nonserious (45.6% to 20.9%) and increased for serious infections (64.1% to 69.8%). Proportions significantly dropped for acute suppurative otitis media (74.7% to 64.1%), upper respiratory tract infections (44.9% to 16.6%), bronchitis/bronchiolitis (73.6% to 44.1%) and acute tonsillopharyngitis (59.5% to 21.7%), while significantly increasing for pneumonia (65.2% to 80.2%). Nonserious and serious infection incidence rates increased from 785/1000PY and 34.2/1000PY to 1223/1000PY and 64.1/1000PY, respectively. Blood and CRP testing proportions increased significantly. Conclusions Antibiotic prescribing in general practice for children declined from 2002 to 2022. Further targeted antibiotic stewardship initiatives are needed to reduce the use of broad-spectrum antibiotics and antibiotic prescribing for conditions such as otitis media and bronchitis/bronchiolitis. [ABSTRACT FROM AUTHOR]

Background: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023–2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. Methods: In the epidemic season of 2023–2024, a test‐negative case–control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non‐immunized, and non‐eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. Results: Two hundred thirty‐four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p <.001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV‐associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9–90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7–96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. Conclusions: This study provides real‐world evidence of the effectiveness of nirsevimab in preventing RSV‐lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted. [ABSTRACT FROM AUTHOR]