Nirsevimab and Hospitalization for RSV Bronchiolitis.

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. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.).

Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

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.

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze.

BACKGROUND: Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. OBJECTIVE: To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). METHODS: A total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. RESULTS: Upper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). CONCLUSION: Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. TRIAL REGISTRATION: This study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

IFN-λ Diminishes the Severity of Viral Bronchiolitis in Neonatal Mice by Limiting NADPH Oxidase-Induced PAD4-Independent NETosis.

Infants with attenuated type III IFN (IFN-λ) responses are at increased risk of severe lower respiratory tract infection (sLRI). The IL-28Rα-chain and IL-10Rß-chain form a heterodimeric receptor complex, necessary for IFN-λ signaling. Therefore, to better understand the immunopathogenic mechanisms through which an IFN-λlo microenvironment predisposes to a sLRI, we inoculated neonatal wild-type and IL-28R-deficient (IL-28R -/-) mice with pneumonia virus of mice, a rodent-specific pneumovirus. Infected IL-28R -/- neonates displayed an early, pronounced, and persistent neutrophilia that was associated with enhanced reactive oxygen species (ROS) production, NETosis, and mucus hypersecretion. Targeted deletion of the IL-28R in neutrophils was sufficient to increase neutrophil activation, ROS production, NET formation, and mucus production in the airways. Inhibition of protein-arginine deiminase type 4 (PAD4), a regulator of NETosis, had no effect on myeloperoxidase expression, citrullinated histones, and the magnitude of the inflammatory response in the lungs of infected IL-28R -/- mice. In contrast, inhibition of ROS production decreased NET formation, cellular inflammation, and mucus hypersecretion. These data suggest that IFN-λ signaling in neutrophils dampens ROS-induced NETosis, limiting the magnitude of the inflammatory response and mucus production. Therapeutics that promote IFN-λ signaling may confer protection against sLRI.

Viral load in hospitalized infants with respiratory syncytial virus bronchiolitis: a three-way comparative analysis.

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.

Does weight influence the course of RSV bronchiolitis in hospitalized infants?

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.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

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.

Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections.

OBJECTIVES: To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration. DESIGN: Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration. SETTING: PICUs in 12 high and low/middle-income countries. PATIENTS: Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% ( n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684-1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value. CONCLUSIONS: Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.

Parent and staff experiences of a feasibility trial evaluating neurally adjusted ventilatory assist in infants with acute viral bronchiolitis: A qualitative study.

BACKGROUND: There is limited literature regarding family and staff experiences of participating in clinical trials. A qualitative study was embedded in the NAVABronch feasibility trial evaluating the effectiveness of a novel mode of ventilation, neurally adjusted ventilatory assist (NAVA), in infants with acute viral bronchiolitis. AIM: The aim of this qualitative study was to explore the experiences of parents and health care practitioners (HCPs) involved in the NAVABronch Trial. STUDY DESIGN: Semi-structured interviews were conducted with two parents and two focus groups were held with six HCPs. RESULTS: Four themes were identified from the focus groups: (1) Creating staff engagement, (2) Education to deliver NAVA, (3) Normalizing NAVA in clinical practice (4) Creating meaningful study outcomes and (5) support of parents during the trial, this theme was generated from the parent interviews. The findings indicated the need for education regarding NAVA for HCPs which would lead to increased confidence, better guidance around the use of NAVA and the need for NAVA to be normalized and embedded into the unit culture. Parents identified the need for further support around preparation for what may happen as a result of the interventions, particularly the weaning of sedation. CONCLUSION: Our study indicates that staff and parents had no concerns regarding the trial methods and procedures. RELEVANCE TO CLINICAL PRACTICE: Conducting clinical trials in Paediatric Intensive Care Units (PICUs) is challenging and complex. There is limited literature regarding family and staff experiences of participating in clinical trials. Understanding their experiences is crucial in ensuring trial success.

Bronchiolitis.

Viral bronchiolitis is the most common cause of admission to hospital for infants in high-income countries. Respiratory syncytial virus accounts for 60-80% of bronchiolitis presentations. Bronchiolitis is diagnosed clinically without the need for viral testing. Management recommendations, based predominantly on high-quality evidence, advise clinicians to support hydration and oxygenation only. Evidence suggests no benefit with use of glucocorticoids or bronchodilators, with further evidence required to support use of hypertonic saline in bronchiolitis. Evidence is scarce in the intensive care unit. Evidence suggests use of high-flow therapy in bronchiolitis is limited to rescue therapy after failure of standard subnasal oxygen only in infants who are hypoxic and does not decrease rates of intensive care unit admission or intubation. Despite systematic reviews and international clinical practice guidelines promoting supportive rather than interventional therapy, universal de-implementation of interventional care in bronchiolitis has not occurred and remains a major challenge.

Bronchiolitis therapies and misadventures.

Viral bronchiolitis, which is most commonly caused by an infection with the respiratory syncytial virus (RSV), can lead to respiratory difficulties in young children which may require hospitalization. Despite years of research and medical trials, the mainstay of bronchiolitis treatment remains supportive only. This review provides an overview of the history of different treatments for bronchiolitis, including those that failed, as well as new therapies that are under study. Future studies for the treatment of bronchiolitis should consider different age-groups, important subgroups (i.e., those with a prior history of wheezing, those with a family history of asthma and those with non-RSV viral etiologies) whose response to treatment may differ from that of the composite group.

Acute kidney injury in infants hospitalized for viral bronchiolitis.

We investigated prevalence of and factors associated with acute kidney injury (AKI) in a group of patients hospitalized with viral bronchiolitis. We retrospectively enrolled 139 children (mean age = 3.2 ± 2.1 months; males = 58.9%) hospitalized for viral bronchiolitis in a non-pediatric intensive care unit (PICU) setting. The Kidney Disease/Improving Global Outcomes creatinine criterion was used to diagnose AKI. We estimated basal serum creatinine by back-calculating it by Hoste (age) equation assuming that basal eGFR were the median age-based eGFR normative values. Univariate and multivariate logistic regression models were used to explore associations with AKI. Out of 139 patients, AKI was found in 15 (10.8%). AKI was found in 13 out of 74 (17.6%) patients with and in 2 out of 65 (3.1%) without respiratory syncytial virus (RSV) infection (p = 0.006). No patient required renal replacement therapies, while 1 out of 15 (6.7%) developed AKI stage 3, 1 (6.7%) developed AKI stage 2, and 13 (86.6%) developed AKI stage 1. Among the 15 patients with AKI, 13 (86.6%) reached the maximum AKI stage at admission, 1 (6.7%) at 48 h, and 1 (6.7%) at 96 h. At multivariate analysis, birth weight < 10th percentile (odds ratio, OR = 34.1; 95% confidence interval, CI = 3.6-329.4; p = 0.002), preterm birth (OR = 20.3; 95% CI = 3.1-129.5; p = 0.002), RSV infection (OR = 27.0; 95% CI = 2.6-279.9; p = 0.006), and hematocrit levels > 2 standard deviation score (SDS) (OR = 22.4; 95% CI = 2.8-183.6; p = 0.001) were significantly associated with AKI. CONCLUSION: About 11% of patients hospitalized with viral bronchiolitis in a non-PICU setting develop an AKI (frequently mild in degree). Preterm birth, birth weight < 10th percentile, hematocrit levels > 2SDS, and RSV infection are significantly associated with AKI in the setting of viral bronchiolitis. WHAT IS KNOWN: • Viral bronchiolitis affects children in the first months of life and in 7.5% of cases it can be complicated by acute kidney injury (AKI). • No studies investigated associations with AKI in infants hospitalized for viral bronchiolitis. WHAT IS NEW: • About 11% of patients hospitalized with viral bronchiolitis can develop an AKI (frequently mild in degree). • Preterm birth, birth weight <10th percentile, hematocrit levels > 2 standard deviation score, and respiratory syncytial virus infection are associated with AKI development in infants with viral bronchiolitis.

Variation in Early Pediatric Intensive Care Management Strategies and Duration of Invasive Mechanical Ventilation for Acute Viral Bronchiolitis in the United Kingdom: A Retrospective Multicenter Cohort Study.

OBJECTIVES: Management of mechanically ventilated patients with bronchiolitis is not standardized and duration of mechanical ventilation has been shown to vary widely between centers. The aim of this study was to examine practice in a large number of U.K. PICUs with a view to identify if early management choices relating to fluid prescription, sedative agent use, and endotracheal tube (ETT) placement were associated with differences in duration of invasive mechanical ventilation (IMV). DESIGN: Retrospective multicenter cohort study. Primary outcome was duration of IMV. A hierarchical gamma generalized linear model was used to test for associations between practice variables (sedative and neuromuscular blocking agents, route of endotracheal intubation at 24 hr and fluid balance at 48 hr) and duration of IMV after adjustment for known confounders. SETTING: Thirteen U.K. PICUs. Duration of 2 months between November and December 2019. PATIENTS: Three hundred fifty infants receiving IMV for bronchiolitis. Excluded were patients receiving long-term ventilation, extracorporeal life support, or who died before separation from IMV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for confounders, several variables were associated with an increase in the geometric mean duration of IMV (expressed as a percentage) including: nasal ETT use, 16% (95% CI, 1-32%); neuromuscular blockade use, 39% (95% CI, 21-61%); and fluid balance at 48 hr, 13% per 100 mL/kg positive fluid balance (95% CI, -1% to 28%). The association of sedative use varied with class of agent. The use of an alpha-2 agonist alone was associated with a reduction in duration of IMV by 19% in relation to no sedative agent (95% CI, -31 to -5%), whereas benzodiazepine uses alone or with alpha-2 agonist in combination were similar to using neither agent. CONCLUSIONS: Early management strategies for bronchiolitis were associated with the duration of IMV across U.K. centers after adjustment for confounders. Future work should prospectively assess the impact of fluid restriction, route of endotracheal intubation, and alpha-2 agonist use on duration of IMV in infants with bronchiolitis, with the aim of reducing seasonal bed pressure.

Lung ultrasound systematic review shows its prognostic and diagnostic role in acute viral bronchiolitis.

AIM: Lung ultrasound (LUS) has not been included in the current guidelines for the diagnosis of bronchiolitis so far, even though data concerning its effectiveness have been published. METHODS: A systematic literature review was carried out to determine the role of LUS scores in the diagnosis and prognosis of patients aged 0-2 years with bronchiolitis, using MEDLINE, Scopus and ScienceDirect databases from their inception to December 2021. RESULTS: A total of 18 studies matching our eligibility criteria were analysed for the purposes of this review and 1249 patients with bronchiolitis were included. The sonographic and radiological findings were comparable and chest radiography was found to have a higher sensitivity in ruling out severe complications such as concomitant pneumonia. The LUS scores were correlated to the clinical course of bronchiolitis and it was able to predict the need of admission in paediatric intensive care unit, the duration of hospitalisation and the need for respiratory support. CONCLUSION: This review suggests that LUS could have both a diagnostic and a prognostic role in bronchiolitis during first evaluation in the emergency department and hospitalisation. Physicians could adjust management according to sonographic findings as a useful adjunct to the clinical ones.

Severe bronchiolitis profiling as the first step towards prevention of asthma.

Bronchiolitis is the most common respiratory infection leading to hospitalization and constitutes a significant healthcare burden. The two main viral agents causing bronchiolitis, respiratory syncytial virus (RSV) and rhinovirus (RV), have distinct cytopathic, immune response, and clinical characteristics. Different approaches have been suggested for subtyping bronchiolitis based on viral etiology, atopic status, transcriptome profiles in blood, airway metabolome, lipidomic data, and airway microbiota. The highest risk of asthma at school age has been in a subgroup of bronchiolitis characterized by older age, high prevalence of RV infection, previous breathing problems, and/or eczema. Regarding solely viral etiology, RV-bronchiolitis in infancy has been linked to a nearly three times higher risk of developing asthma than RSV-bronchiolitis. Although treatment with betamimetics and systemic corticosteroids has been found ineffective in bronchiolitis overall, it can be beneficial for infants with severe RV bronchiolitis. Thus, there is a need to develop a more individualized therapeutic approach for bronchiolitis and follow-up strategies for infants at higher risk of asthma in the future perspective.

Antimicrobial Stewardship in Bronchiolitis: A Retrospective Cohort Study of Three PICUs in Canada.

OBJECTIVES: To determine the association between the implementation of an antimicrobial stewardship program at a local PICU and to determine the association between the presence of an antimicrobial stewardship programs and antimicrobial use across three Canadian PICUs, among critically ill children with bronchiolitis. DESIGN: A multicenter retrospective cohort study. SETTING: Three Canadian PICUs over two winter seasons. INTERVENTIONS: An antimicrobial stewardship program was implemented at PICU 1 at the end of season 1. PATIENTS: Patients less than or equal to 2 years old admitted with bronchiolitis. MEASUREMENTS AND MAIN RESULTS: We used regression models with an interaction term between site (PICU 1 and PICU 2) and season (1 and 2) as the primary analysis to determine the association between implementation of an antimicrobial stewardship program at PICU 1 and 1) the proportion of antimicrobials discontinued 72 hours after hospital admission (logistic regression), 2) antimicrobial treatment duration (negative binomial regression), and 3) antimicrobial prescriptions within 48 hours of hospital admission (logistic regression). As a secondary analysis, we determined the association between having an antimicrobial stewardship program present and the aforementioned outcomes across the three PICUs. A total of 372 patients were included. During seasons 1 and 2, median age was 2.2 months (interquartile range, 1.2-6.2 mo) and 2.1 months (interquartile range, 1.3-6.8 mo), respectively. Among patients with viral bronchiolitis, implementation of an antimicrobial stewardship program at PICU 1 was associated with increased odds of discontinuing antimicrobials (odds ratio, 25.63; 95% CI, 2.86-326.29), but not with antimicrobial duration (odds ratio, 0.56; 95% CI, 0.31-1.02) or antimicrobial prescriptions (odds ratio, 0.33; 95% CI, 0.10-1.04). The presence of an antimicrobial stewardship program was similarly associated with antimicrobial discontinuation among patients with viral bronchiolitis (odds ratio, 20.79; 95% CI, 2.46-244.92), but not with antimicrobial duration (odds ratio, 0.57; 95% CI, 0.32-1.03) or antimicrobial prescriptions (odds ratio, 0.37; 95% CI, 0.12-1.11). CONCLUSIONS: Antimicrobial stewardship programs were associated with increased likelihood of discontinuing antimicrobial treatments in the PICU patients with viral bronchiolitis. However, larger studies are needed to further determine the role of an antimicrobial stewardship programs in reducing unnecessary antimicrobial use in this patient population.

Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis.

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.

Deficiency in ST2 signaling ameliorates RSV-associated pulmonary hypertension.

Pulmonary hypertension (PH) observed during respiratory syncytial virus (RSV) bronchiolitis is associated with morbidity and mortality, especially in children with congenital heart disease. Yet, the pathophysiological mechanisms of RSV-associated PH remain unclear. Therefore, this study aimed to investigate the pathophysiological mechanism of RSV-associated PH. We used a translational mouse model of RSV-associated PH, in which wild-type (WT) and suppression of tumorigenicity 2 (ST2) knockout neonatal mice were infected with RSV at 5 days old and reinfected 4 wk later. The development of PH in WT mice following RSV reinfection was evidenced by elevated right ventricle systolic pressure, shortened pulmonary artery acceleration time (PAT), and decreased PAT/ejection time (ET) ratio. It coincided with the augmentation of periostin and IL-13 expression and increased arginase bioactivity by both arginase 1 and 2 as well as induction of nitric oxide synthase (NOS) uncoupling. Absence of ST2 signaling prevented RSV-reinfected mice from developing PH by suppressing NOS uncoupling. In summary, ST2 signaling was involved in the development of RSV-associated PH. ST2 signaling inhibition may be a novel therapeutic target for RSV-associated PH.NEW & NOTEWORTHY We report that the pathogenic role of ST2-mediated type 2 immunity and mechanisms contribute to RSV-associated pulmonary hypertension. Inhibiting ST2 signaling may be a novel therapeutic target for this condition.

Assessment of Peak Inspiratory Flow in Young Infants with Acute Viral Bronchiolitis: Physiological Basis for Initial Flow Setting in Patients Supported with High-Flow Nasal Cannula.

OBJECTIVE: To assess the inspiratory demand in young infants with acute viral bronchiolitis to provide a physiological basis for initial flow setting for patients supported with high flow nasal cannula. STUDY DESIGN: Prospective study in 44 infants up to 6 months old with acute viral bronchiolitis, admitted to a pediatric intensive care unit from November 2017 to March 2019. Airflow measurements were performed using spirometry. The primary endpoint was the inspiratory demand as measured by peak tidal inspiratory flow (PTIF). The secondary endpoints were the relationships determined between PTIF, patient weight, and disease severity. RESULTS: Median (Q25-Q75) age and weight of the patients were 37 (20-67) days and 4.3 (3.5-5.0) kg, respectively. Mean PTIF was 7.45 (95% CI 6.51-8.39, min-max: 2.40-16.00) L/minute. PTIF indexed to weight was 1.68 (95% CI 1.51-1.85, min-max: 0.67-3.00) L/kg/minute. PTIF was <2.5 L/kg/minute in 89% (95% CI 75-96) of infants. PTIF was correlated with weight (ρ= 0 .55, P < .001) but not with markers of disease severity, including modified Woods clinical asthma score, Silverman-Andersen score, respiratory rate, fraction of inspired oxygen, and PCO2. CONCLUSIONS: High flow nasal cannula therapy is used commonly to support infants with acute viral bronchiolitis. The efficiency of the device is optimal if the flow setting matches the patient's inspiratory demand. According to our results, a flow rate of <2.5 L/kg/minute would be appropriate in most situations.