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Cytokine response after severe respiratory syncytial virus bronchiolitis in early life.

ABSTRACT: Immune response after viral infection usually involves T(H)1-mediated response; however, severe respiratory syncytial virus (RSV) infection appears to be associated with the development of asthma, a T(H)2-predominant phenotype.To understand the early and subsequent immunologic response to a serious RSV infection in children over time.A total of 206 previously healthy infants hospitalized with severe RSV bronchiolitis were enrolled in a prospective cohort called the RSV Bronchiolitis in Early Life study. Peripheral blood T cells were obtained immediately after RSV infection and at 2, 4, and 6 years of age, stimulated with phorbol 12-myristate 13-acetate and ionomycin, and analyzed for IL-2, IL-4, IL-13, and IFN-gamma by flow cytometry and real-time PCR.Of the children, 48% (n = 97) developed asthma (physician-diagnosed), and 48% (n = 97) had eczema by age 6 years; 32% (n = 48 of 150) developed allergic sensitization by 3 years of age. Children with asthma had lower IL-13 expression at 6 years of age than those without (P = .001). IFN-gamma, IL-2, and IL-4 levels did not differ by asthma or eczema status during follow-up (all P > .05). Allergic sensitization was not associated with differences in cytokine levels during follow-up (all P > .05).Severe RSV infection early in life is associated with a high incidence of asthma and eczema. Contrary to expectations, subsequent immunologic development in those who developed asthma, eczema, or allergic sensitization was not associated with a T(H)2 phenotype in the peripheral blood.

SUBMITTER: Castro M

PROVIDER: S-EPMC2597800 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Cytokine response after severe respiratory syncytial virus bronchiolitis in early life.

Castro Mario M Schweiger Toni T Yin-DeClue Huiquing H Ramkumar Thiruvamoor P TP Christie Chandrika C Zheng Jie J Cohen Rebecca R Schechtman Kenneth B KB Strunk Robert R Bacharier Leonard B LB

The Journal of allergy and clinical immunology 20080828 4

<h4>Background</h4>Immune response after viral infection usually involves T(H)1-mediated response; however, severe respiratory syncytial virus (RSV) infection appears to be associated with the development of asthma, a T(H)2-predominant phenotype.<h4>Objective</h4>To understand the early and subsequent immunologic response to a serious RSV infection in children over time.<h4>Methods</h4>A total of 206 previously healthy infants hospitalized with severe RSV bronchiolitis were enrolled in a prospec ...[more]

PMID: 18760461

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Project description:BackgroundWe sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared.MethodsThis longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048). Asthma (primary definition) was based on parental identification of wheeze at 6 AND 12 months before 6 years of age; definitions based on physician diagnosis as well as parental identification of wheeze at 6 OR 12 months (to consider seasonal effect) were also assessed. Post-hoc analyses evaluated agreement among asthma diagnosis criteria.ResultsPrevalence of asthma (primary definition by parental identification), asthma (physician diagnosis), atopic disorders, and chronic asthma therapy use (parental identification) was 6.1%, 22.4%, 36.2%, and 14.5%, respectively. Predictors for asthma (primary definition) included male gender, a relative with asthma, and RAST positive for dog dander; for physician diagnosis of asthma, high severity score for RSV bronchiolitis, high respiratory rate, and asthma diagnosis before enrollment. Predictors of atopic disorders included allergic rhinitis before enrollment, a relative with asthma, and the plasma biomarkers IL-5, IL-16, and IL-18. Predictors of chronic asthma therapy use included asthma diagnosis before enrollment and geographic region (Europe and Africa). Only 42% of patients with asthma (primary definition) also met the asthma definition by physician diagnosis and chronic asthma therapy use.ConclusionAmong children with early RSV bronchiolitis, hereditary factors (i.e., having a relative with asthma) and RSV bronchiolitis severity were predictors of asthma and atopic disorders at 6 years of age. Of interest, there was poor agreement among the asthma definitions evaluated. Pediatr Pulmonol. 2016;51:1382-1392. © 2016 Wiley Periodicals, Inc.

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.).

Project description:BackgroundRespiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis. Precise and updated information about demographic characteristics, clinical manifestations, and risk factors for severe disease are needed for optimal implementation of upcoming new therapeutic and preventive interventions.ObjectivesThe main goals of this study were to define the epidemiology of acute bronchiolitis in hospitalized young children during 5 calendar years in Spain; evaluate the differences in clinical manifestations between children hospitalized with RSV infection and those hospitalized with non-RSV infection; and identify demographic characteristics, clinical parameters, and risk factors associated with disease severity.MethodsWe performed a retrospective review of the medical records of children younger than 2 years who were hospitalized with bronchiolitis between January 2015 and December 2019. We constructed multivariable models to identify independent predictors of disease severity defined as length of hospital stay (LOS), pediatric intensive care unit (PICU) admission, and need for a high-flow-nasal canula (HFNC).ResultsFrom January 2015 to December 2019, 1437 children were hospitalized with bronchiolitis and met the inclusion criteria. The proportion of children hospitalized with bronchiolitis caused by RSV increased significantly during the study period, from 60% to 65% (P = .03). The children with RSV bronchiolitis were younger than those with non-RSV bronchiolitis (median age = 3 months [interquartile range = 1.5-6.5 months] vs 4 months [interquartile range = 2-7.5 months], respectively (P < .01). The children younger than 6 months with RSV bronchiolitis had enhanced disease severity compared with those with non-RSV bronchiolitis, as defined by an LOS of more than 4 days, severity scores, need for an HFNC, intravenous fluids, enteral feeding, and PICU admissions (P < .01). Age younger than 6 months and RSV-positive etiology were independently associated with greater odds of PICU admission, need for an HFNC, and longer LOS.ConclusionThis study identified differences in disease severity between young children with RSV bronchiolitis and those with non-RSV bronchiolitis. These differences are particularly significant in children younger than 6 months, who comprise a group of infants with suboptimal innate immunity to RSV and may benefit from new preventive strategies.

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Cytokine response after severe respiratory syncytial virus bronchiolitis in early life.

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Cytokine response after severe respiratory syncytial virus bronchiolitis in early life.

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