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

Received 20 February 2008; received in revised form 22 July 2008; accepted 3 September 2008. published online 13 October 2008.

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.

Key words: Asthma, consistent bronchodilator response, outcomes

Abbreviations used: ATS, American Thoracic Society, BDR, Bronchodilator response, CAMP, Childhood Asthma Management Program, FVC, Forced vital capacity

a Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass

b Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Mass

c Divisions of Pediatric Clinical Pharmacology, Allergy, and Immunology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo

d Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo

e Department of Allergy, Kaiser Permanente Medical Center, San Diego, Calif

f Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass

Reprint requests: Sunita Sharma, MD, Channing Laboratory, 181 Longwood Ave, Boston, MA 02115.

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.

PII: S0091-6749(08)01562-5

doi:10.1016/j.jaci.2008.09.004

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