Dataset Information

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

ABSTRACT: Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPCR) in nasal wash samples from children with RSV-associated bronchiolitis. Correlations were sought with host cytokines/chemokines and biomarkers. Associations with disposition from the emergency department (hospitalized or sent home) and pulse oximetry O2 saturation levels were also sought. Additionally, RNase P copy number was measured and used to normalize nasal wash data. RSV gene copy numbers were found to significantly correlate with both cytokine/chemokine and biomarker levels; and RNase P-normalized viral gene copy numbers (NS1, NS2, N and G) were significantly higher in infants with less severe disease. Moreover, three of the normalized viral gene copy numbers (NS1, NS2, and N) correlated significantly with arterial O2 saturation levels. The data support a model where a higher viral load early in infection can promote a robust innate immune response that protects against progression into hypoxic RSV-induced lower respiratory tract illness.

SUBMITTER: Piedra FA

PROVIDER: S-EPMC5340370 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

Piedra Felipe-Andrés FA Mei Minghua M Avadhanula Vasanthi V Mehta Reena R Aideyan Letisha L Garofalo Roberto P RP Piedra Pedro A PA

PloS one 20170307 3

Respiratory syncytial virus (RSV) causes significant infant morbidity and mortality. For decades severe RSV-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. To shed light on host-virus interactions and the viral determinants of disease, copy numbers of five RSV genes (NS1, NS2, N, G, F) were measured by quantitative real-time polymerase chain reaction (qPC ...[more]

PMID: 28267794

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Project description:ObjectiveThe aim of this study was to examine differences between general and pediatric emergency departments (PEDs) in adherence to the American Academy of Pediatrics bronchiolitis management guidelines.MethodsWe conducted a nationally representative study of ED visits by infants younger than 24 months with bronchiolitis from 2002 to 2011 using the National Hospital Ambulatory Medical Care Survey. Diagnostic testing (complete blood counts, radiographs) and medication use (albuterol, corticosteroids, antibiotics and intravenous fluids) in general emergency departments (GEDs) were compared with those in PEDs before and after 2006 American Academy of Pediatrics guideline publication. Weighted percentages were compared, and logistic regression evaluated the association between ED type and resource use.ResultsOf more than 2.5 million ED visits for bronchiolitis from 2002 to 2011, 77.3% occurred in GEDs. General emergency departments were more likely to use radiography (62.7% vs 42.1%; adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.4-4.1), antibiotics (41.3% vs 18.8%; aOR, 2.8; 95% CI, 1.5-5.2), and corticosteroids (24.3% vs 12.5%; aOR, 2.1; 95% CI, 1.0-4.5) compared with PEDs. Compared with preguideline, after guideline publication PEDs had a greater decrease in radiography use (-19.7%; 95% CI, -39.3% to -0.03%) compared with GEDs (-12.2%; 95% CI, -22.3% to -2.1%), and PEDs showed a significant decline in corticosteroid use (-12.4%; 95% CI, -22.1% to -2.8%), whereas GEDs showed no significant decline (-4.6%; 95% CI, -13.5% to 4.3%).ConclusionsThe majority of ED visits for bronchiolitis in the United States occurred in GEDs, yet GEDs had increased use of radiography, corticosteroids, and antibiotics and did not show substantial declines with national guideline publication. Given that national guidelines discourage the use of such tests and treatments in the management of bronchiolitis, efforts are required to decrease ED use of these resources in infants with bronchiolitis, particularly in GEDs.

Project description:BackgroundEarly-life severe respiratory syncytial virus (RSV) bronchiolitis is a risk factor for childhood asthma. Because azithromycin may attenuate airway inflammation during RSV bronchiolitis, we evaluated whether it would reduce the occurrence of post-RSV recurrent wheeze.MethodsWe prospectively enrolled 200 otherwise healthy 1- to 18-month-old children hospitalized with RSV bronchiolitis in this single-center, double-blind, placebo-controlled study and randomly assigned them to receive oral azithromycin (10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days) or placebo. Randomization was stratified by recent open-label antibiotic use. The primary outcome was the occurrence of recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2 to 4 years.ResultsAs an indication of the biologic activity of azithromycin, nasal wash interleukin-8 levels, at day 14 after randomization, were lower among azithromycin-treated participants (P<0.01). Despite evidence of biologic activity, azithromycin did not reduce the risk of post-RSV recurrent wheeze (47% in the azithromycin group vs. 36% in the placebo group; adjusted hazard ratio, 1.45; 95% confidence interval [CI], 0.92 to 2.29; P=0.11). Azithromycin also did not modify the risk of recurrent wheeze among participants already receiving other antibiotic treatment at the time of enrollment (hazard ratio, 0.94; 95% CI, 0.43 to 2.07). There was a potential signal among antibiotic-naïve participants who received azithromycin to have an increased risk of recurrent wheeze (hazard ratio, 1.79; 95% CI, 1.03 to 3.1).ConclusionsAzithromycin therapy for 14 days during acute severe RSV bronchiolitis did not reduce recurrent wheeze occurrence over the following 2 to 4 years. Our data suggest no benefit of azithromycin administration with the goal of preventing recurrent wheeze in later life. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02911935.).

Dataset Information

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

Publications

The interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.

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