The Journal of Allergy and Clinical Immunology
Volume 122, Issue 4 , Pages 741-747.e4, October 2008

Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children

  • Ronina A. Covar, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo
    • Corresponding Author InformationReprint requests: Ronina A. Covar, MD, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206.
    • ,
  • Stanley J. Szefler, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo
    • ,
  • Robert S. Zeiger, MD, PhD

      Affiliations

    • Department of Pediatrics, University of California San Diego, and the Department of Allergy, Kaiser Permanente, San Diego, Calif
    • ,
  • Christine A. Sorkness, PharmD

      Affiliations

    • Clinical Science Center, University of Wisconsin, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif
    • ,
  • Mark Moss, MD

      Affiliations

    • Clinical Science Center, University of Wisconsin, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif
    • ,
  • David T. Mauger, PhD

      Affiliations

    • Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa
    • ,
  • Susan J. Boehmer, PhD

      Affiliations

    • Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa
    • ,
  • Robert C. Strunk, MD

      Affiliations

    • Department of Pediatrics, Washington University, St Louis, Mo
    • ,
  • Fernando D. Martinez, MD

      Affiliations

    • Arizona Respiratory Center, University of Arizona, Tucson, Ariz
    • ,
  • Lynn M. Taussig, MD

      Affiliations

    • Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo
    • ,
  • Childhood Asthma Research and Education Network

Received 19 April 2008; received in revised form 22 August 2008; accepted 25 August 2008.

Background

Asthma exacerbations are a common cause of critical illness in children.

Objective

To determine factors associated with exacerbations in children with persistent asthma.

Methods

Regression modeling was used to identify historical, phenotypic, treatment, and time-dependent factors associated with the occurrence of exacerbations, defined by need for oral corticosteroids or emergency or hospital care in the 48-week Pediatric Asthma Controller Trial study. Children age 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive either fluticasone propionate 100 μg twice daily (FP monotherapy), combination fluticasone 100 μg AM and salmeterol twice daily, or montelukast 5 mg once daily.

Results

Of the 285 participants randomized, 48% had 231 exacerbations. Using a multivariate analysis, which included numerous demographic, pulmonary, and inflammatory parameters, only a history of an asthma exacerbation requiring a systemic corticosteroid in the past year (odds ratio [OR], 2.10; P < .001) was associated with a subsequent exacerbation during the trial. During the trial, treatment with montelukast versus FP monotherapy (OR, 2.00; P = .005), season (spring, fall, or winter vs summer; P ≤ .001), and average seasonal 5% reduction in AM peak expiratory flow (OR, 1.21; P = .01) were each associated with exacerbations. Changes in worsening of symptoms, β-agonist use, and low peak expiratory flow track together before an exacerbation, but have poor positive predictive value of exacerbation.

Conclusion

Children with mild-to-moderate persistent asthma with previous exacerbations are more likely to have a repeat exacerbation despite controller treatment. Inhaled corticosteroids are superior to montelukast at modifying the exacerbation risk. Available physiologic measures and biomarkers and diary card tracking are not reliable predictors of asthma exacerbations.

Key words: Airway inflammation, asthma, bronchial hyperresponsiveness, childhood asthma, exacerbations

Abbreviations used: AROCC, Area under the receiver operating characteristic curve, ED, Emergency department, eNO, Exhaled nitric oxide, OR, Odds ratio, PACT, Pediatric Asthma Controller Trial, PEF, Peak expiratory flow, ROC, Receiver operating characteristic

 

 Supported by grants 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313 from the National Heart, Lung, and Blood Institute; General Clinical Research Centers at Washington University School of Medicine (M01 RR00036); and National Jewish Medical and Research Center (M01 RR00051).

 Disclosure of potential conflict of interest: R. A. Covar has received honoraria from Aerocrine NIOX and has received research support as a coinvestigator from Abbott Laboratories. 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) Childhood Asthma Management Program, NHLBI Childhood Asthma Research and Education, the NIH/NHLBI Asthma Clin Res 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 Aerocrine, AstraZeneca, Dynavax, Genentech, Merck, Novartis, and GlaxoSmithKline and has received research support from Sanofi-Aventis, Teva-Pharmaceuticals, Merck, AstraZeneca, GlaxoSmithKline, and Genentech. C. A. Sorkness has served on the speakers' bureau for GlaxoSmithKline and has received research support from GlaxoSmithKline and Pharmaxis. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(08)01552-2

doi:10.1016/j.jaci.2008.08.021

The Journal of Allergy and Clinical Immunology
Volume 122, Issue 4 , Pages 741-747.e4, October 2008