Asthma and lower airway disease
Clinical predictors and outcomes of consistent bronchodilator response in the childhood asthma management program

https://doi.org/10.1016/j.jaci.2008.09.004Get rights and content

Background

Among asthmatic subjects, bronchodilator response (BDR) to inhaled β2-adrenergic agonists is variable, and the significance of a consistent response over time is unknown.

Objective

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.

Methods

In the 1041 participants in the Childhood Asthma Management Program, subjects with a change in FEV1 of 12% or greater (and 200 mL) after inhaled β2-agonist administration at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR.

Results

We identified 52 children with consistent BDRs over the 4-year trial. Multivariable logistic regression modeling demonstrated that lower baseline prebronchodilator FEV1 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.

Conclusions

We have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.

Section snippets

Study population

CAMP was a multicenter, randomized, double-blind, placebo-controlled trial established to investigate the long-term effects of commonly prescribed asthma treatment regimens. In total, 1041 children were randomized to receive inhaled budesonide, inhaled nedocromil, or placebo. Participants were subsequently followed for a mean of 4.3 years with lung function studies and questionnaires at regular intervals. Phenotypic characteristics including lung function parameters, IgE levels, peripheral

Results

Observational data from CAMP nicely illustrate the heterogeneous nature of the response to inhaled β2-adrenergic agonists in children with mild-to-moderate persistent asthma. The distribution of response to bronchodilators at randomization is shown in Fig 1. The distributions of BDRs at each of the yearly follow-up visits were similar to that shown. As expected, the vast majority of children in the CAMP demonstrated a variable response to inhaled β2-adrenergic agonists at each of their yearly

Discussion

Before this study, there had been little research into the clinical predictors of consistent response to inhaled β2-adrenergic agonists or the clinical outcomes associated with this asthma phenotype. With more than 1000 patients with repeated measures of BDRs and a notable variability in response to bronchodilators, CAMP is a good cohort in which to study the consistent BDR phenotype. Based on the current analysis, it is clear that certain clinical parameters are associated with consistency in

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      The cut point of a 10% predicted change in FVC was selected arbitrarily, lacking published guidelines for a minimally important change for this variable. However, a 10% change in FEV1 with bronchodilation in children has diagnostic specificity for asthma15 and an association with asthma instability16 in children. Because FEV1 changes proportionally with changes in FVC,5 our cut point for a change in FVC should be meaningful.

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    The Childhood Asthma Management Program is supported by contracts NO1-HR-16044, 16045, 16046, 16047, 16048, 16049, 16050, 16051, and 16052 with the National Heart, Lung, and Blood Institute and General Clinical Research Center grants M01RR00051, M01RR0099718-24, M01RR02719-14, and RR00036 from the National Center for Research Resources. Additional support for this study was provided by grants U01 HL075419, U01 HL65899, P01 HL083069, and T32 HL07427 from the National Heart, Lung, and Blood Institute, National Institutes of Health.

    Disclosure of potential conflict of interest: A. L. Fuhlbrigge has served on the speakers' bureau and respiratory specialist advisory panel for GlaxoSmithKline and Merck, has received funding from Novartis and Sepracor, and has received research grants from Boehringer Ingelheim, GlaxoSmithKline, and Merck. S. J. Szefler has served as a consultant for AstraZeneca, GlaxoSmithKline, Aventis, Genentech, and Merck and has received research grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI); the Childhood Asthma Management Program; NHLBI Childhood Asthma Research and Education; the NIH/NHLBI Asthma Clinical Research Network; the NIH/National Institute of Allergy and Infectious Diseases Inner-City Asthma Consortium; and Ross Pharmaceuticals. R. S. Zeiger has served as a consultant for AstraZeneca, Aerocrine, Merck, Schering-Plough, Genentech, Dynavac, and GlaxoSmithKline and has received research grant from Sanofi-Aventis, GlaxoSmithKline, Genentech and the NHLBI. S. T. Weiss has received research support from the NIH and Genentech. The rest of the authors have declared that they have no conflict of interest.

    The members of the research group are listed at the end of the article.

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