Development and validation of a nomogram for predicting severe respiratory syncytial virus-associated bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and is related to the severity of the disease. This study aimed to develop and validate a nomogram for predicting severe bronchiolitis in infants and young children with RSV infection. METHODS: A total of 325 children with RSV-associated bronchiolitis were enrolled, including 125 severe cases and 200 mild cases. A prediction model was built on 227 cases and validated on 98 cases, which were divided by random sampling in R software. Relevant clinical, laboratory and imaging data were collected. Multivariate logistic regression models were used to determine optimal predictors and to construct nomograms. The performance of the nomogram was evaluated by the area under the characteristic curve (AUC), calibration ability and decision curve analysis (DCA). RESULTS: There were 137 (60.4%) mild and 90 (39.6%) severe RSV-associated bronchiolitis cases in the training group (n = 227) and 63 (64.3%) mild and 35 (35.7%) severe cases in the validation group (n = 98). Multivariate logistic regression analysis identified 5 variables as significant predictive factors to construct the nomogram for predicting severe RSV-associated bronchiolitis, including preterm birth (OR = 3.80; 95% CI, 1.39-10.39; P = 0.009), weight at admission (OR = 0.76; 95% CI, 0.63-0.91; P = 0.003), breathing rate (OR = 1.11; 95% CI, 1.05-1.18; P = 0.001), lymphocyte percentage (OR = 0.97; 95% CI, 0.95-0.99; P = 0.001) and outpatient use of glucocorticoids (OR = 2.27; 95% CI, 1.05-4.9; P = 0.038). The AUC value of the nomogram was 0.784 (95% CI, 0.722-0.846) in the training set and 0.832 (95% CI, 0.741-0.923) in the validation set, which showed a good fit. The calibration plot and Hosmer‒Lemeshow test indicated that the predicted probability had good consistency with the actual probability both in the training group (P = 0.817) and validation group (P = 0.290). The DCA curve shows that the nomogram has good clinical value. CONCLUSION: A nomogram for predicting severe RSV-associated bronchiolitis in the early clinical stage was established and validated, which can help physicians identify severe RSV-associated bronchiolitis and then choose reasonable treatment.

Metabolome subtyping of severe bronchiolitis in infancy and risk of childhood asthma.

BACKGROUND: Infants with bronchiolitis are at increased risk for developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition. OBJECTIVES: We sought to identify biologically distinct subgroups based on the metabolome signatures (metabotypes) in infants with severe bronchiolitis and to examine the longitudinal relationships of metabotypes with asthma development. METHODS: In a multicenter prospective cohort study of infants (age, <12 months) hospitalized for bronchiolitis, the nasopharyngeal airway metabolome was profiled at hospitalization. Using a clustering approach, this study identified mutually exclusive metabotypes. This study also examined their longitudinal association with the risk of developing asthma by 5 years of age. RESULTS: Of 918 infants hospitalized for bronchiolitis (median age, 3 months), this study identified 5 distinct metabotypes-characterized by their nasopharyngeal metabolome profile: A, glycerophosphocholine-high; B, amino acid-high, polyunsaturated fatty acid-low; C, amino acid-high, glycerophospholipid-low; D, glycerophospholipid-high; and E, mixed. Compared with infants with metabotype A (who clinically resembled "classic" bronchiolitis), infants with metabotype B had a significantly higher risk for developing asthma (23% vs 41%; adjusted odds ratio, 2.22; 95% CI, 1.07-4.69). The pathway analysis showed that metabotype B had enriched amino acid (eg, methionine, histidine, glutathione) and α-linolenic/linoleic acid metabolism pathways (false discovery rate, <5 × 10-14 for all). Finally, the transcriptome analysis revealed that infants with metabotype B had upregulated IFN-α and IL-6/JAK/STAT3 pathways and downregulated fatty acid metabolism pathways (false discovery rate, <0.05 for both). CONCLUSIONS: In this multicenter prospective cohort study of infants with severe bronchiolitis, the clustering analysis of metabolome data identified biologically distinct metabotypes, including a metabotype characterized by high inflammatory amino acids and low polyunsaturated fatty acids that is at significantly increased risk for developing asthma.

Systematic review and meta-analysis of efficacy and safety of continuous positive airways pressure versus high flow oxygen cannula in acute bronchiolitis.

INTRODUCTION: There are a trend towards increasing use of High-Flow Nasal Cannula (HFNC), outside of paediatric intensive care unit. Give this trend is necessary to update the actual evidence and to assess available published literature to determinate the efficacy of HFNC over Continuous Positive Air Pressure (CPAP) as treatment for children with severe bronchiolitis. METHODS: We searched MEDLINE, EMBASE, LILACS, and COCHRANE Central, and gray literature in clinical trials databases ( www. CLINICALTRIALS: gov ), from inception to June 2022. The inclusion criteria for the literature were randomized clinical trials (RCTs) that included children < 2 years old, with acute moderate or severe bronchiolitis. All study selection and data extractions are performed independently by two reviewers. RESULTS: The initial searches including 106 records. Only five randomized controlled trial that met the inclusion criteria were included in meta-analysis. The risk of invasive mechanical ventilation was not significantly different in CPAP group and HFNC group [OR: 1.18, 95% CI (0.74, 1.89), I² = 0%] (very low quality). The risk of treatment failure was less significantly in CPAP group than HFNC group [OR: 0.51, 95% CI (0.36, 0.75), I² = 0%] (very low quality). CONCLUSION: In conclusion, there was no significant difference between HFNC and CPAP in terms of risk of invasive mechanical ventilation. CPAP reduces de risk of therapeutic failure with a highest risk of non severe adverse events. More trials are needed to confirm theses results.

Preemptive high-flow nasal cannula treatment in severe bronchiolitis: Results from a high-volume, resource-limited pediatric emergency department.

BACKGROUND: The aims of this study were to evaluate the outcomes of patients with severe bronchiolitis who received preemptive high-flow nasal cannula (HFNC) treatment according to the authors' protocol, and to identify potential baseline characteristics that might predict patients who will not benefit from HFNC. METHODS: This was a retrospective chart review of patients with severe bronchiolitis, who received preemptive HFNC treatment according to the authors' protocol and who were admitted to the pediatric emergency department between January 1, 2015, and December 31, 2016. RESULTS: Eighty-four patients in total were enrolled over the 2 year period. Twenty-three patients (27.3%) failed HFNC. Of these, four responded to non-invasive mechanical ventilation and 19 required subsequent invasive ventilation. According to logistic regression analysis, existence of a chronic condition, significant tachycardia, existence of dehydration, and a venous pH <7.30 at admission were found to be predictors of HFNC failure. There were no cases of pneumothorax or any other reported adverse effects related to HFNC therapy. CONCLUSIONS: Preemptive HFNC treatment, complying with a preestablished protocol, might be a safe way to support patients with severe bronchiolitis in high-volume, resource-limited pediatric emergency departments. The existence of a chronic condition, significant tachycardia, dehydration, and a venous pH <7.30 at admission could be risk factors for preemptive HFNC treatment failure in severe bronchiolitis.

TLR4 Gene Polymorphisms Interaction With Ascaris Infection in Severe RSV Bronchiolitis.

Introduction: The identification of gene-environment interactions allows the recognition of groups with higher risk of morbidity. This study evaluated the interaction between the presence of TLR4 gene polymorphisms and Ascaris infection with severe bronchiolitis in a tropical Colombian region. Methods: We included all infants younger than 24 months hospitalized due to bronchiolitis in Hospital centers in the county of Rionegro, Colombia. To identify interaction between severe bronchiolitis and presence of TLR4 polymorphisms and Ascaris infection, we used log-binomial regression. Results: Four hundred and seventeen infants were hospitalized due to bronchiolitis, of which 115 (27%) had severe bronchiolitis. In infants with respiratory syncytial virus (RSV) acute infection and positive anti-Ascaris IgE, TLR4 Asp299Gly was associated to low risk of severe bronchiolitis (OR 0.09, CI 95% 0.01-0.48). Conversely, in infants RSV negative with negative anti-Ascaris IgE, TLR4 Asp299Gly was associated with an increased risk of severe bronchiolitis (OR 14.5, CI 95% 2.2-96). Conclusion: In our population there is an interaction between the presence of severe bronchiolitis, TLR4 Asp299Gly and Ile399Thr polymorphisms, anti-Ascaris IgE levels and RSV. This association should be evaluated in other populations to elucidate its role in the pathogenesis of severe bronchiolitis.

Optimal level of positive end-expiratory pressure during nasal continuous airway pressure for severe bronchiolitis: a prospective study.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) has been increasingly applied in the pediatric setting. However, there is no uniform standard for setting and titrating positive end-expiratory pressure (PEEP) level, which is paramount to the effectiveness of the treatment. This study aimed to investigate the optimal parameters for nCPAP in the treatment of severe bronchiolitis based on clinical efficacy and pulmonary function parameters. METHODS: A before-after prospective study was conducted with a total of 152 study subjects. These 152 hospitalized patients with severe bronchiolitis were treated and observed from December 2018 to February 2019. Comparisons were made between subjects for clinical symptoms, oxygenation improvement, correction of CO2 retention, degree of airway obstruction and respiratory mechanics improvement between three different positive end-expiratory pressure levels (PEEP). RESULTS: nCPAP could effectively improve the clinical manifestations, blood gas analysis, pulmonary function and respiratory muscle energy consumption. The m-WCAS score, PaCO2, TPTEF/TE, VPEF/VE, respiratory system compliance (Crs) and resistance (Rrs) were significantly different at different PEEP levels (P<0.05). Although there were no hemodynamic changes at peep parameter levels in the three groups. Group 2 (PEEP: 6 cmH2O) had optimal clinical effects, and improvement in airway obstruction and respiratory mechanics compared with the group 1 (PEEP: 4 cmH2O) and the group 3 (PEEP: 7 cmH2O). CONCLUSIONS: PEEP of 6 cmH2O via nCPAP is considered as the optimal level in the treatment of infants with severe bronchiolitis.

The physiological effects of human immunoglobulin on severe bronchiolitis patients before and after treatment.

The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1-3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p < 0.05). As such, the CD8, IgA, IgG, IgM and IFN-γ levels were also significantly lower in the children with severe bronchiolitis than in the children in the healthy control group (p < 0.05). Furthermore, the CD4, IgE, IL-4, and IL-4/IFN-γ levels and CD4/CD8 ratio were dramatically higher than in the healthy control group (p < 0.05). Serum levels of the aforementioned indicators either increased or decreased after IVIG treatment. The amount of time required for coughing, wheezing, and pulmonary rales to seize, and the duration of illness for the children with the severe bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis.