Epidemiological shifts in bronchiolitis patterns and impact of the COVID-19: A two-season comparative study.

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection (LRTI) affecting infants and young children. Respiratory syncytial virus (RSV) has historically been the primary causative agent, but other viruses also contribute to the LRTI epidemiology. Recent changes in epidemiology and clinical patterns due to the coronavirus disease 2019 (COVID-19) pandemic have raised concerns. This study aims to analyze the impact of the pandemic on bronchiolitis epidemiology and severity. METHODS: Two consecutive bronchiolitis seasons (October 2021 to March 2022 and October 2022 to March 2023) were compared. Data on viral agents, hospitalization duration, clinical severity, and respiratory support requirements were collected from pediatric patients at San Marco Hospital, University of Catania. RESULTS: In the 2021-2022 season, RSV was the predominant virus (40%), followed by other viruses, with mild clinical outcomes. In the 2022-2023 season, RSV remained prevalent (58.7%), but other viruses, including rhinovirus (RV) and influenza, showed a significant increase (p < .05) in bronchiolitis cases and severity. Notably, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season, contrary to the previous year. CONCLUSION: The COVID-19 pandemic appears to have shifted the epidemiological landscape of bronchiolitis, with a peak incidence in November instead of January/February. Non-RSV viruses (RV, influenza A and B, as well as metapneumovirus) have gained prominence, possibly due to viral competition and reduced pandemic-related restrictions. Traditionally, RSV has been the primary pathogen responsible for most bronchiolitis cases. Nonetheless, the findings of this study indicate a shifting landscape in bronchiolitis etiology, with RSV gradually diminishing in its role. Contrary to the previous year, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season.

ROX (Respiratory rate-OXygenation) index to predict early response to high-flow nasal cannula therapy in infants with viral bronchiolitis.

INTRODUCTION: High-flow nasal cannula (HFNC) is commonly used as first step respiratory support in infants with moderate-to-severe acute viral bronchiolitis (AVB). This device, however, fails to effectively manage respiratory distress in about a third of patients, and data are limited on determinants of patient response. The respiratory rate-oxygenation (ROX) index is a relevant tool to predict the risk for HFNC failure in adult patients with lower respiratory tract infections. The primary objective of this study was to assess the relationship between ROX indexes collected before and 1 h after HFNC initiation, and HFNC failure occurring in the following 48 h in infants with AVB. METHOD: This is an ancillary study to the multicenter randomized controlled trial TRAMONTANE 2, that included 286 infants of less than 6 months with moderate-to-severe AVB. Collection of physiological variables at baseline (H0), and 1 h after HFNC (H1), included heart rate (HR), respiratory rate (RR), fraction of inspired oxygen (FiO2), respiratory distress score (modified Wood's Clinical Asthma Score [mWCAS]), and pain and discomfort scale (EDIN). ROX and ROX-HR were calculated as SpO 2 FiO 2 RR $\frac{\left(\frac{{\mathrm{SpO}}_{2}}{{\mathrm{FiO}}_{2}}\right)}{\mathrm{RR}}$ and 100 × ROX HR $100\times \frac{\mathrm{ROX}}{\mathrm{HR}}$ , respectively. Predefined HFNC failure criteria included increase in respiratory distress score or RR, increase in discomfort, and severe apnea episodes. The accuracies of ROX, ROX-HR indexes and clinical variable to predict HFNC failure were assessed using receiver operating curve analysis. We analyzed predictive factors of HFNC failure using multivariate logistic regressions. RESULT: HFNC failure occurred in 111 of 286 (39%) infants, and for 56 (50% of the failure) of them within the first 6 h. The area under the curve of ROX indexes at H0 and H1 were, respectively, 0.56 (95% confidence interval [CI] 0.48-0.63, p = 0.14), 0.56 (95% CI 0.49-0.64, p = 0.09). ROX-HR performances were better but remained poorly discriminant. HFNC failure was associated with higher mWCAS score at H1 (p < 0.01) and lower decrease in EDIN scale during the first hour of HFNC delivery (p = 0.02). In the multivariate analyses, age and mWCAS score were were found to be independent factors associated with HFNC failure at H0. At H1, weight and mWCAS were associated factors. CONCLUSION: In this study, neither ROX index, nor physiological variables usually collected in infants with AVB had early discriminatory capacity to predict HFNC failure.

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).

Measurement of the interbronchial angle in acute viral bronchiolitis.

BACKGROUND: Acute viral bronchiolitis (AVB) is the most common lower airway infection in children under 2 years. Attempts to determine disease severity based on clinical and radiological manifestations are a major challenge. Measurements of the anatomy of the trachea and main bronchi are not only limited to pure anthropometry, but are also useful for better care of critically ill patients. The purpose of the study is to verify the association between measurements of the interbronchial angle (ITB) and the severity of respiratory disease. METHODS: A cross-sectional study, which included all patients admitted to the Santo Antônio Children's Hospital, over a period of 1 year, with diagnosis of AVB by respiratory syncytial virus (RSV) was designed. ITB angle was measured and clinical characteristics were analyzed. Quantitative variables were compared and correlation analysis was performed using Pearson's correlation coefficient. A receiving operator characteristic (ROC) curve was performed. P-value <0.05 was statistically significant. RESULTS: A total of 425 patients with AVB due to RSV were included. Most of these patients were male and the median age was 130 days, 91.11% of them required oxygen therapy through a nasal catheter, 3.3% used noninvasive ventilation and 4% used mechanical ventilation. Those who required MV or NIV and intensive care unit support were considered severe. The mean ITB was lower for these patients than for those of lesser severity (p < 0.05). CONCLUSION: The present study demonstrates that there is an association between ITB and AVB severity. The smaller the ITB, the greater the disease severity.

Head-to-Head Comparison Between Respiratory Syncytial Virus and Human Metapneumovirus Bronchiolitis in the Setting of Increased Viral Testing.

We compared the epidemiology, severity and management of hospitalized respiratory syncytial virus (n = 305) and human metapneumovirus (n = 39) bronchiolitis in a setting with high respiratory virus testing (95% of admissions tested). Respiratory syncytial virus-positive infants were younger and tended to require more hydration support and longer hospital stays compared to human metapneumovirus-positive infants. Respiratory support requirements were similar between groups despite significant age differences.

Bronchiolitis guidelines: what about the Italian situation in a primary care setting?

Acute viral bronchiolitis is the most common cause of hospitalization in children under 12 months of age. The variable clinical presentation and the potential for sudden deterioration of the clinical conditions require a close monitoring by healthcare professionals.In Italy, first access care for children is provided by primary care physicians (PCPs) who often must face to a heterogeneous disease presentation that, in some cases, make the management of patient with bronchiolitis challenging. Consequently, Italian studies report poor adherence to national and international guidelines processed to guide the clinicians in decision making in acute viral bronchiolitis.This paper aims to identify the potential factors contributing to the lack of adherence to the suggested guidelines derived by clear and evidence-based recommendations among primary care physicians operating in an outpatient setting, with a specific focus on the context of Italy. Particularly, we focus on the prescription of medications such as ß2-agonists, systemic steroids, and antibiotics which are commonly prescribed by PCPs to address conditions that can mimic 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.

Multilevel analysis identifying the factors associated with RSV detection in infants admitted for viral bronchiolitis in the era of the COVID-19 pandemic.

OBJECTIVES: To identify factors independently associated with respiratory syncytial virus (RSV) detection in infants admitted for viral bronchiolitis during 3 consecutive years, before and during the COVID-19 pandemic, in Bogota, Colombia, a middle-income country with a subtropical highland climate. METHODS: An analytical cross-sectional study was conducted before and during the COVID-19 pandemic, including patients with a diagnosis of viral bronchiolitis admitted to all the hospitals of the city between January 2019 and November 2021. We evaluated a set of a priori-selected predictor variables that included individual, healthcare system, meteorological, air pollutant, and COVID-19 variables. Since the variables analyzed are hierarchical in nature, multilevel modeling was used to identify factors independently associated with detection of RSV as the causative agent of viral bronchiolitis. RESULTS: A total of 13,177 patients were included in the study. After controlling for potential confounders, it was found that age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.76-0.97), a third level of medical care institution (OR 3.05; 95% CI 1.61-5.76), temperature (OR 1.60; 95% CI 1.24-2.07), rainfall (OR 1.003, 95% CI 1.001, 1.005), NO2 (OR 0.97; 95% CI 0.95-0.99), CO (OR 0.99; 95% CI 0.99-0.99), and COVID-19 pandemic period (OR 0.84, 95% CI 0.71-0.99) were independently associated with RSV detection in our sample of patients. CONCLUSIONS: The identified factors associated with RSV detection provide additional scientific evidence that may be useful in the development of specific interventions aimed at ameliorating or preventing the impact of RSV in Bogota and probably other similar low- to middle-income countries in high-risk infants.

Bronchiolitis versus bronchopneumonia: navigating antibiotic use within the LRTI spectrum.

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

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.

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.

Respiratory effort during noninvasive positive pressure ventilation and continuous positive airway pressure in severe acute viral bronchiolitis.

OBJECTIVES: To assess if noninvasive positive pressure ventilation (NIPPV) is associated with a greater reduction in respiratory effort as compared to continuous positive airway pressure (CPAP) during severe acute bronchiolitis, with both supports set either clinically or physiologically. METHODS: Twenty infants (median [IQR] age 1.2 [0.9; 3.2] months) treated <24 h with noninvasive respiratory support (CPAP Clin, set at 7 cmH2 O, or NIPPV Clin) for bronchiolitis were included in a prospective single-center crossover study. Esogastric pressures were measured first with the baseline support, then with the other support. For each support, recordings were performed with the clinical setting and a physiological setting (CPAP Phys and NIPPV Phys), aiming at normalising respiratory effort. Patients were then treated with the optimal support. The primary outcome was the greatest reduction in esophageal pressure-time product (PTPES /min). Other outcomes included improvement of the other components of the respiratory effort. RESULTS: NIPPV Clin and Phys were associated with a lower PTPES /min (164 [105; 202] and 106 [78; 161] cmH2 O s/min, respectively) than CPAP Clin (178 [145; 236] cmH2 O s/min; p = 0.01 and 2 × 10-4 , respectively). NIPPV Clin and Phys were also associated with a significant reduction of all other markers of respiratory effort as compared to CPAP Clin. PTPES /min with NIPPV (Clin or Phys) was not different from PTPES /min with CPAP Phys. There was no significant difference between physiological and clinical settings. CONCLUSION: NIPPV is associated with a significant reduction in respiratory effort as compared to CPAP set at +7 cmH2 O in infants with severe acute bronchiolitis. CPAP Phys performs as well as NIPPV Clin.

Temporal-spatial analysis of hospitalizations for bronchiolitis in Brazil: prediction of epidemic regions and periods for immunization against the Respiratory Syncytial Virus.

OBJECTIVE: Due to the high cost and short term of passive immunization against the respiratory syncytial virus, the main virus causing acute viral bronchiolitis, predicting epidemic regions and epidemic months is extremely important. The objective of this study is to identify both the month when the seasonal peak begins and Brazilian regions and states with the highest incidence of monthly hospitalizations due acute viral bronchiolitis. METHODS: Based on data obtained from DATASUS, monthly hospitalization rates due acute viral bronchiolitis were calculated for every 10,000 live births to children under 12 months of age in all Brazilian states and the Federal District between 2000 and 2019. Seasonal autoregressive integrated moving average models were estimated to forecast monthly hospitalization rates in 2020. RESULTS: A higher incidence of hospitalizations was found for male children, especially under six months of age. As for Brazilian regions, between 2000 and 2019, the South region registered the highest incidence of hospitalizations, followed by the Southeast, Midwest, North and Northeast regions, in this order. Considering the seasonal peak, the period between March and July 2020 comprised the highest expected hospitalization rates. CONCLUSIONS: Palivizumab is suggested to be started between February/March and June/July for most Brazilian states, with the exception of Rio Grande do Sul, which, in addition to presenting the highest rates of hospitalizations for acute viral bronchiolitis per 10,000 live births, has the longest seasonal peak between May and September.

Oxygen saturation thresholds for bronchiolitis at high altitudes: a cost-effectiveness analysis.

BACKGROUND: There is evidence suggesting that exaggerated reliance on pulse oximetry (SpO2) and the use of arbitrary/inadequate thresholds of SpO2 might drive unnecessary hospitalizations for viral bronchiolitis, especially among high-altitude residents. The aim of the present study was to compare the cost-effectiveness of two oxygen SpO2 thresholds for deciding whether infants with viral bronchiolitis living at high altitudes need hospital admission or can be discharged home. METHODS: A cost-effectiveness study was performed to compare the cost and clinical outcomes of two oxygen SpO2 thresholds, adjusted or not, to an altitude above the sea level of Bogota, Colombia (2640 m), for deciding whether infants with viral bronchiolitis need hospitalization or can be discharged home. The principal outcome was avoidance of hospital admission. RESULTS: Compared to the use of an SpO2 threshold of 90%, using an SpO2 threshold of 85% in infants with viral bronchiolitis was associated with lower overall costs (US$130.4 vs. US$194.0 average cost per patient) and a higher probability of hospitalization avoided (0.7500 vs. 0.5900), thus leading to dominance. CONCLUSIONS: The use of an SpO2 threshold below 90% for deciding on hospitalization in infants with viral bronchiolitis living at high altitudes appears to be logical, secure, and cost-effective.

Increased RSV-A Bronchiolitis Severity in RSV-Infected Children Admitted to a Reference Center in Catalonia (Spain) Between 2014 and 2018.

Between 2014 and 2018, we evaluated the severity of 687 cases of bronchiolitis caused by respiratory syncytial virus (RSV) in Catalonia, Spain. Compared to RSV-B, RSV-A cases required intensive care (adjusted relative risk (aRR) = 1.44, p < 0.01) and respiratory support (aRR = 1.07, p < 0.01) more often; hospital stay was one day longer (p < 0.01). Subgroup identification may aid clinical evaluation and seasonal healthcare planning.