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.).

Impact of the COVID-19 Pandemic on Low-Value Testing and Treatment of Bronchiolitis.

BACKGROUND: Viral testing and treatments such as systemic steroids and inhaled corticosteroids are low-value care for routine bronchiolitis. We sought to determine the impact of the COVID-19 pandemic on low-value care in young children with bronchiolitis. METHODS: This was a retrospective, cross-sectional study using the Pediatric Health Information Systems database. We included children <2 years seen in a pediatric emergency department for bronchiolitis. We selected a priori 3 study periods: September 2018 to February 2020 (prepandemic), March 2020 to August 2022 (early pandemic), and September 2022 to January 2023 (late pandemic). Low-value care included respiratory syncytial virus testing, chest radiography, albuterol, or corticosteroids and was compared across the 3 time periods. RESULTS: At least 1 element of low-value care was provided in 45%, 47%, and 44% of encounters in the prepandemic, early pandemic, and late pandemic periods, respectively. There was little variation in the use of albuterol and chest radiography across time periods and a slight increase in systemic corticosteroid use from prepandemic to early and late pandemic groups. Viral testing increased from 36% prepandemic to 65% early pandemic and 67% late pandemic, which appeared to be driven by SARS-CoV-2 testing and combination viral testing. CONCLUSIONS: There was no clinically significant change in low-value care for bronchiolitis during the pandemic. Because of SARS-CoV-2 testing, however, overall frequency of viral testing increased dramatically over time. This marked increase in overall viral testing should be taken into consideration for future quality improvement efforts.

Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

Antibiotic Use in Korean Children Diagnosed With Acute Bronchiolitis: Analysis of the National Health Insurance Reimbursement Data.

BACKGROUND: Acute bronchiolitis, the most common lower respiratory tract infection in infants, is mostly caused by respiratory viruses. However, antibiotics are prescribed to about 25% of children with acute bronchiolitis. This inappropriate use of antibiotics for viral infections induces antibiotic resistance. This study aimed to determine the antibiotic prescription rate and the factors associated with antibiotic use in children with acute bronchiolitis in Korea, where antibiotic use and resistance rates are high. METHODS: Healthcare data of children aged < 24 months who were diagnosed with acute bronchiolitis between 2016 and 2019 were acquired from the National Health Insurance system reimbursement claims data. Antibiotic prescription rates and associated factors were evaluated. RESULTS: A total of 3,638,424 visits were analyzed. The antibiotic prescription rate was 51.8%, which decreased over time (P < 0.001). In the multivariate analysis, toddlers (vs. infants), non-capital areas (vs. capital areas), primary clinics and non-tertiary hospitals (vs. tertiary hospitals), inpatients (vs. outpatients), and non-pediatricians (vs. pediatricians) showed a significant association with antibiotic prescription (P < 0.001). Fourteen cities and provinces in the non-capital area exhibited a wide range of antibiotic prescription rates ranging from 41.2% to 65.4%, and five (35.7%) of them showed lower antibiotic prescription rates than that of the capital area. CONCLUSION: In Korea, the high antibiotic prescription rates for acute bronchiolitis varied by patient age, region, medical facility type, clinical setting, and physician specialty. These factors should be considered when establishing strategies to promote appropriate antibiotic use.

Management and outcomes of bronchiolitis in Italy and Latin America: a multi-center, prospective, observational study.

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.

Intravenous Magnesium Sulfate for Acute Bronchiolitis: Evaluation of the Effect on Clinical Course and Outcomes.

The aim of the present study was to assess the efficacy of intravenous (IV) magnesium sulfate (MgSO4) for children with bronchiolitis. A retrospective cohort study was performed at a pediatric emergency department. Aged between 1 and 24 months, children with moderate/severe bronchiolitis according to the Modified Respiratory Distress Assessment Instrument (mRDAI) score were included. Patients who received 40 mg/kg/dose of IV MgSO4 (group 1, n: 74) or not (group 2, n: 33) were compared. Respiratory rate and mRDAI score significantly decreased at the second hour of MgSO4 treatment and the decrease was observed for 4th, 8th, and 12th hours, compared with group 2. Patients in group 2 had a higher rate of requirement and an earlier start high-flow nasal cannula oxygen therapy and a longer hospital stay than group 1. Intravenous MgSO4 provided significant improvement on clinical severity, need for respiratory support, length of hospital stay, and outcomes.

Inhaled nitric oxide in acute bronchiolitis: A systematic review and meta-analysis.

OBJECTIVE: Until date there is lack of effective therapies in acute bronchiolitis in infants. The aim was to analyze inhaled nitric oxide efficacy in acute bronchiolitis. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: Pediatric specialized healthcare. PATIENTS: All infants (age less than 2 years) having acute bronchiolitis, which requires emergency room visit or hospitalization. INTERVENTION: Inhaled nitric oxide. MAIN OUTCOME MEASURES: Need for intensive care unit admission. Secondary outcomes were length of hospital stay and adverse events. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) calculated by random-effects DerSimonian and Laird inverse variance method. Peto Odds ratios were used for rare outcomes. Evidence certainty assessed according to GRADE. RESULTS: 186 studies were screened and three included for analysis. Two had low risk of bias and one had some concerns. Three studies (166 infants) analyzed length of hospital stay and the duration was -11.3 h (CI: -26.8 to +4.2 h) shorter in the nitric oxide group. Evidence certainty was ranked as low. Overall adverse event rates were similar (3 studies, 166 infants, RR: 0.94, CI: 0.70-1.26), but treatment related harms were more common in nitric oxide group (2 studies, 98 infants, OR: 3.86, CI: 1.04-14.40). Evidence certainty in both was rated as low. CONCLUSIONS: Low certainty evidence suggests that inhaled nitric oxide does not reduce length of hospital stay but may have higher rate of treatment associated harms. Future studies with larger sample sizes are needed to better estimate both the efficacy and adverse events.

Changes in Bronchiolitis Characteristics During the COVID-19 Pandemic: A Description of Pediatric Emergency Department Visits in a Community Hospital, 2019-2021.

A retrospective, cross-sectional study of children with bronchiolitis aged 1 to 24 months during an ED visit between 2019 and 2021 was performed. Chi-square or Kruskal-Wallis was used to compare groups. The gamma coefficient was used to measure the association of variables through time. Bronchiolitis cases decreased by 75% from 2019 to 2020 and rose back to prepandemic levels by 2021. Radiographs (gamma -0.443), steroids (gamma -0.298), and bronchodilators (gamma -0.414) decreased during the study period (P < .001). Laboratory studies (gamma 0.032), viral testing (gamma 0.097), antibiotic use (gamma -0.069), and respiratory support (gamma 0.166) were unchanged. The decrease in steroids and bronchodilators was related to a clinical pathway that discouraged their use. Respiratory support remained unchanged. The COVID-19 pandemic (2019-2021) seems to have had little effect on the severity or resource utilization associated with bronchiolitis but may have unraveled a potential bronchiolitis phenotype that may have been more prominent during the pandemic.

Nebulised 3% hypertonic saline versus 0.9% saline for treating patients hospitalised with acute bronchiolitis: protocol for a randomised, double-blind, multicentre trial.

INTRODUCTION: Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis. METHODS AND ANALYSIS: This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation. ETHICS AND DISSEMINATION: The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06069336).

Nirsevimab for the prevention of respiratory syncytial virus disease in children. Statement of the Spanish Society of Paediatric Infectious Disease (SEIP).

INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease. METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions. RESULTS: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis. CONCLUSIONS: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.

Management Practices for Standard-Risk and High-Risk Patients With Bronchiolitis.

OBJECTIVE: Management guidelines for bronchiolitis advocate for supportive care and exclude those with high-risk conditions. We aim to describe and compare the management of standard-risk and high-risk patients with bronchiolitis. METHODS: This retrospective study examined patients <2 years of age admitted to the general pediatric ward with an International Classification of Diseases, 10th Revision discharge diagnosis code of bronchiolitis or viral syndrome with evidence of lower respiratory tract involvement. Patients were defined as either standard- or high-risk on the basis of previously published criteria. The frequencies of diagnostic and therapeutic interventions were compared. RESULTS: We included 265 patients in this study (122 standard-risk [46.0%], 143 high-risk [54.0%]). Increased bronchodilator use was observed in the standard-risk group (any albuterol dosing, standard-risk 65.6%, high-risk 44.1%, P = .003). Increased steroid use was observed in the standard-risk group (any steroid dosing, standard-risk 19.7%, high-risk 14.7%, P = .018). Multiple logistic regression revealed >3 doses of albuterol, hypertonic saline, and chest physiotherapy use to be associated with rapid response team activation (odds ratio [OR] >3 doses albuterol: 8.36 [95% confidence interval (CI): 1.99-35.10], P = .048; OR >3 doses hypertonic saline: 13.94 [95% CI: 4.32-44.92], P = .001); OR percussion and postural drainage: 5.06 [95% CI: 1.88-13.63], P = .017). CONCLUSIONS: A varied approach to the management of bronchiolitis in both standard-risk and high-risk children occurred institutionally. Bronchodilators and steroids continue to be used frequently despite practice recommendations and regardless of risk status. More research is needed on management strategies in patients at high-risk for severe disease.

Impact of an Intervention to Reduce Bronchodilator Use in Bronchiolitis - A Time Series Analysis.

BACKGROUND AND OBJECTIVES: International guidelines recommend against the use of bronchodilators in bronchiolitis. Despite attempts to address low value care practices in pediatrics, the literature is still evolving regarding which interventions are most effective in low value care reduction. We aim to assess the impact of a multifaceted intervention on rates of bronchodilator prescription in bronchiolitis. METHODS: With electronic medical record (EMR) data over a 76- month period, we evaluated changes in bronchodilator prescription among infants aged 1 to 12 months diagnosed with bronchiolitis, using interrupted time series analysis, controlling for preintervention prescribing trends. The setting was the emergency department of a large teaching pediatric hospital. The intervention included education, clinician audit-feedback, and an EMR alert, implemented February 2019. The main outcome measure was rate of bronchodilator prescription per month. RESULTS: There were 9576 infants, aged 1 to 12 months, diagnosed in the emergency department with bronchiolitis over the study period. Bronchodilator ordering reduced from 6.9% to 3.2% after the intervention. Once underlying trends were accounted for, the multifaceted intervention was associated with a reduction in the rate of prescribing (inter-rater reliability 0.98, 95% confidence interval 0.96 to 0.99, P = .037). CONCLUSIONS: We found that the multifaceted intervention, including an EMR alert, may be an effective method of reducing low value care prescribing in bronchiolitis, accelerating the reduction of unnecessary care and supporting sustainable change.

Respiratory Syncytial Virus Bronchiolitis: Rapid Evidence Review.

Bronchiolitis is the most common lower respiratory tract infection in young children. Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis. RSV is spread through respiratory droplets, and the number of cases varies with season. For most patients, standard precautions (e.g., hand hygiene, surface cleaning, avoiding contact with sick individuals) are recommended. However, prophylaxis with palivizumab may be considered for infants at high risk. Initial symptoms occur after an incubation period of four to six days and include rhinorrhea, congestion, sneezing, and fever. Signs of lower respiratory tract involvement may follow and include cough, tachypnea, retractions, difficulty feeding, and accessory muscle use. Diagnosis is typically clinical; routine use of radiography or viral testing is not recommended. Treatment of RSV bronchiolitis is mainly supportive. Oxygen saturation should be maintained above 90%. Hydration and nutrition should be maintained by nasogastric or intravenous routes, if needed. Therapies such as bronchodilators, epinephrine, nebulized hypertonic saline, corticosteroids, antibiotics, and chest physiotherapy are not recommended. Although most episodes of RSV bronchiolitis are self-limited, some children have an increased risk of asthma later in life.

Variation in Inhaled Medication Use for Infants With Congenital Heart Disease and Bronchiolitis.

BACKGROUND AND OBJECTIVES: Current viral bronchiolitis guidelines exclude infants with congenital heart disease (CHD). Variations in the use of common therapeutics in this population and their associations with clinical outcomes are unknown. Our objective was to evaluate variations in (1) the use of ß-2-agonists and hypertonic saline across hospitals among infants with CHD hospitalized with bronchiolitis, and (2) hospital-level associations between medication use and outcomes. METHODS: We performed a multicenter retrospective cohort study using administrative data from 52 hospitals in the Pediatric Health Information System. We included infants ≤12 months old hospitalized from January 1, 2015 to June 30, 2019 for bronchiolitis with a secondary diagnosis of CHD. Primary exposures were the hospital-level proportion of days that patients received ß-2-agonists or hypertonic saline. Linear regression models assessed the association between the primary exposure and length of stay, 7-day readmission, mechanical ventilation use, and ICU utilization, adjusting for patient covariates and accounting for clustering by center. RESULTS: We identified 6846 index hospitalizations for bronchiolitis in infants with CHD. Overall, 43% received a ß-2-agonist, and 23% received hypertonic saline. The proportion of days with the use of ß-2-agonists (3.6% to 57.4%) and hypertonic saline (0.0% to 65.8%) varied widely across hospitals in our adjusted model. For both exposures, adjusted models revealed no association between days of use and patient outcomes. CONCLUSIONS: For children with CHD hospitalized with bronchiolitis, hospital-level use of ß-2-agonists and hypertonic saline varied widely, and their use was not associated with clinical outcomes.