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

Ronina A. Covar, Stanley J. Szefler, Robert S. Zeiger, Christine A. Sorkness, Mark Moss, David T. Mauger, Susan J. Boehmer, Robert C. Strunk, Fernando Martinez, Lynn M. Taussig

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Abstract

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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
Volume122
Issue number4
DOIs
Publication statusPublished - Oct 2008

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Keywords

  • Airway inflammation
  • asthma
  • bronchial hyperresponsiveness
  • childhood asthma
  • exacerbations

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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