Dataset Information

The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma.

ABSTRACT:

Background

Infants hospitalized for bronchiolitis have a high rate of early childhood asthma. It is not known whether bronchiolitis severity correlates with the risk of early childhood asthma or with asthma-specific morbidity.

Objectives

We sought to determine whether a dose-response relationship exists between severity of infant bronchiolitis and both the odds of early childhood asthma and asthma-specific morbidity.

Methods

We conducted a population-based retrospective birth cohort study of term healthy infants born from 1995-2000 and enrolled in a statewide Medicaid program. We defined bronchiolitis severity by categorizing infants into mutually exclusive groups based on the most advanced level of health care for bronchiolitis. Health care visits, asthma-specific medications, and demographics were identified entirely from Medicaid and linked vital records files. Asthma was ascertained at between 4 and 5.5 years of age, and 1-year asthma morbidity (hospitalization, emergency department visit, or oral corticosteroid course) was determined between 4.5 and 5.5 years among children with prevalent asthma.

Results

Among 90,341 children, 18% had an infant bronchiolitis visit, and these infants contributed to 31% of early childhood asthma diagnoses. Relative to children with no infant bronchiolitis visit, the adjusted odds ratios for asthma were 1.86 (95% CI, 1.74-1.99), 2.41 (95% CI, 2.21-2.62), and 2.82 (95% CI, 2.61-3.03) in the outpatient, emergency department, and hospitalization groups, respectively. Children hospitalized with bronchiolitis during infancy had increased early childhood asthma morbidity compared with that seen in children with no bronchiolitis visit.

Conclusion

To our knowledge, this is the first study to demonstrate the dose-response relationship between the severity of infant bronchiolitis and the increased odds of both early childhood asthma and asthma-specific morbidity.

SUBMITTER: Carroll KN

PROVIDER: S-EPMC2703291 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma.

Carroll Kecia N KN Wu Pingsheng P Gebretsadik Tebeb T Griffin Marie R MR Dupont William D WD Mitchel Edward F EF Hartert Tina V TV

The Journal of allergy and clinical immunology 20090410 5

<h4>Background</h4>Infants hospitalized for bronchiolitis have a high rate of early childhood asthma. It is not known whether bronchiolitis severity correlates with the risk of early childhood asthma or with asthma-specific morbidity.<h4>Objectives</h4>We sought to determine whether a dose-response relationship exists between severity of infant bronchiolitis and both the odds of early childhood asthma and asthma-specific morbidity.<h4>Methods</h4>We conducted a population-based retrospective bir ...[more]

PMID: 19361850

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Project description:BackgroundGenome-wide association studies of asthma have identified associations with variants in type-2 related genes. Also, specific interactions between genetic variants and viral bronchiolitis in the development of asthma has been suggested.ObjectiveTo conduct a gene-based analysis of genetic variants in type 2 cytokine related genes as risk factors for allergic asthma at school age, and further, to study their interaction with specific viral infections in early childhood.MethodsA prospectively investigated cohort of children with previous bronchiolitis and controls came for follow-up at school age. The research visit, blinded to viral exposure, included detailed lung function tests, laboratory investigation, and questionnaires. Allergic asthma was defined as typical symptoms plus objective variable airway obstruction, in addition to laboratory verified atopy (elevated eosinophil count or sensitization to an allergen). Targeted and complete sequencing was performed for nine type 2 cytokine candidate genes: IL4, 5, 13, 25, 33 and 37, IL17RB, CRLF2 and TSLP.ResultsAt follow-up, there were 109 children with genetic data, 91 with a history of bronchiolitis (46% respiratory syncytial virus, 24% human rhinovirus, 15% human metapneumovirus and 14% mixed viral etiology) and 18 without. The median age was 9.4 years (range 6-13) and 41 (38%) had laboratory verified atopy. Twenty-one children (19%) met the definition of allergic asthma. After adjusting for age, sex and five viral categories, IL33 achieved nominal significance (p = 0.017) for a positive association with allergic asthma development. In the gene-virus interaction analysis, the variant set in IL17RB demonstrated a nominally significant positive interaction with human metapneumovirus infection (p=0.05).ConclusionThe results highlight the multifactorial nature of allergic asthma risk, with both viral infection and inherited genetic variants contributing to increasing risk. Results for IL33 and IL17RB were nominally significant and are potential candidate targets for designing therapeutics and early screening, but these results must be replicated in an independent study.

Project description:BackgroundInfants with bronchiolitis are at high risk for developing childhood asthma. While genome-wide association studies suggest common genetic susceptibilities between these conditions, the mechanisms underlying the link remain unclear.ObjectiveThrough integrated genetics-metabolomics analysis in this high-risk population, we sought to identify genetically driven metabolites associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility.MethodsIn a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we profiled the nasopharyngeal metabolome and genotyped the whole genome at hospitalization. We identified asthma-related metabolites from 283 measured compounds and conducted metabolite quantitative trait loci (mtQTL) analyses. We further examined the mtQTL associations by testing shared genetic loci for metabolites and asthma using colocalization analysis and the concordance between the loci and known asthma-susceptibility genes.ResultsIn 744 infants hospitalized with bronchiolitis, 28 metabolites (e.g., docosapentaenoate [DPA], 1,2-dioleoyl-sn-glycero-3-phosphoglycerol, sphingomyelin) were associated with asthma risk. A total of 349 loci were associated with these metabolites-161 for non-Hispanic white, 120 for non-Hispanic black, and 68 for Hispanics. Of these, there was evidence for 30 shared loci between 16 metabolites and asthma risk (colocalization posterior probability ≥0.5). The significant SNPs within loci were aligned with known asthma-susceptibility genes (e.g., ADORA1, MUC16).ConclusionThe integrated genetics-metabolomics analysis identified genetically driven metabolites during infancy that are associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility. Identifying these metabolites and genetic loci should advance research into the functional mechanisms of the infant bronchiolitis-childhood asthma link.

Project description:BackgroundBronchiolitis is the leading cause of hospitalization in U.S. infants and a major risk factor for childhood asthma. Growing evidence supports clinical heterogeneity within bronchiolitis. We aimed to identify endotypes of infant bronchiolitis by integrating clinical, virus, and serum proteome data, and examine their relationships with asthma development.MethodsThis is a multicenter prospective cohort study of infants hospitalized for physician-diagnosis of bronchiolitis. We identified bronchiolitis endotypes by applying unsupervised machine learning (clustering) approaches to integrated clinical, virus (respiratory syncytial virus [RSV], rhinovirus [RV]), and serum proteome data measured at hospitalization. We then examined their longitudinal association with the risk for developing asthma by age 6 years.ResultsIn 140 infants hospitalized with bronchiolitis, we identified three endotypes: (1) clinicalatopic virusRV proteomeNFκB-dysregulated , (2) clinicalnon-atopic virusRSV/RV proteomeTNF-dysregulated , and (3) clinicalclassic virusRSV proteomeNFκB/TNF-regulated endotypes. Endotype 1 infants were characterized by high proportion of IgE sensitization and RV infection. These endotype 1 infants also had dysregulated NFκB pathways (FDR < 0.001) and significantly higher risks for developing asthma (53% vs. 22%; adjOR 4.04; 95% CI, 1.49-11.0; p = 0.006), compared with endotype 3 (clinically resembling "classic" bronchiolitis). Likewise, endotype 2 infants were characterized by low proportion of IgE sensitization and high proportion of RSV or RV infection. These endotype 2 infants had dysregulated tumor necrosis factor (TNF)-mediated signaling pathway (FDR <0.001) and significantly higher risks for developing asthma (44% vs. 22%; adjOR 2.71; 95% CI, 1.03-7.11, p = 0.04).ConclusionIn this multicenter cohort, integrated clustering of clinical, virus, and proteome data identified biologically distinct endotypes of bronchiolitis that have differential risks of asthma development.

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.

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Dataset Information

The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma.

Background

Objectives

Methods

Results

Conclusion

Publications

The severity-dependent relationship of infant bronchiolitis on the risk and morbidity of early childhood asthma.

Similar Datasets

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