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Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program.

ABSTRACT: Among asthmatic subjects, bronchodilator response (BDR) to inhaled beta(2)-adrenergic agonists is variable, and the significance of a consistent response over time is unknown.We assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma.In the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV(1) of 12% or greater (and 200 mL) after inhaled beta(2)-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR.We identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV(1) values (odds ratio, 0.71; P < .0001), higher log10 IgE levels (odds ratio, 1.97; P = .002), and lack of treatment with inhaled corticosteroids (odds ratio, 0.31; P = .009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (P = .007), required more prednisone bursts (P = .0007), had increased nocturnal awakenings caused by asthma (P < .0001), and missed more days of school (P = .03) than nonresponders during the 4-year follow-up.We have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.

SUBMITTER: Sharma S

PROVIDER: S-EPMC2947830 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program.

Sharma Sunita S Litonjua Augusto A AA Tantisira Kelan G KG Fuhlbrigge Anne L AL Szefler Stanley J SJ Strunk Robert C RC Zeiger Robert S RS Murphy Amy J AJ Weiss Scott T ST

The Journal of allergy and clinical immunology 20081010 5

<h4>Background</h4>Among asthmatic subjects, bronchodilator response (BDR) to inhaled beta(2)-adrenergic agonists is variable, and the significance of a consistent response over time is unknown.<h4>Objective</h4>We assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-to-moderate persistent asthma.<h4>Methods</h4>In the 1041 participants in the Childhood Asthma Management Program, subjects with a c ...[more]

PMID: 18848350

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Project description:RationaleBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.ObjectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.MethodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into high and low bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N= 277) vs low (N= 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.ResultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR=2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.ConclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.Trial registrationLOCCS cohort [ClinicalTrials.gov number: NCT00156819], GACRS cohort [ClinicalTrials.gov number: NCT00021840].

Dataset Information

Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program.

Publications

Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program.

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