title: Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children.
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 microg twice daily (FP monotherapy), combination fluticasone 100 microg 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 < or = .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, beta-agonist use, and low peak expiratory flow track together before an exacerbation, but have poor positive predictive value of exacerbation.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo. Electronic address: covarr@njc.org.
authors.forename: Ronina A
authors.initials: RA
authors.lastname: Covar
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.affiliation: Department of Pediatrics, University of California San Diego, and the Department of Allergy, Kaiser Permanente, San Diego, Calif.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Zeiger
authors.affiliation: Clinical Science Center, University of Wisconsin, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.affiliation: Clinical Science Center, University of Wisconsin, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif.
authors.forename: Mark
authors.initials: M
authors.lastname: Moss
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa.
authors.forename: David T
authors.initials: DT
authors.lastname: Mauger
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Boehmer
authors.affiliation: Department of Pediatrics, Washington University, St Louis, Mo.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Strunk
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, Ariz.
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Martinez
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Taussig
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000150:complications* / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008954:Models, Biological; D015999:Multivariate Analysis; D012044:Regression Analysis; D000068299:Salmeterol Xinafoate; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol