Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children.
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.
Covar
Ronina A
RA
Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo. Electronic address: covarr@njc.org.
Szefler
Stanley J
SJ
Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo.
Zeiger
Robert S
RS
Department of Pediatrics, University of California San Diego, and the Department of Allergy, Kaiser Permanente, San Diego, Calif.
Sorkness
Christine A
CA
Clinical Science Center, University of Wisconsin, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif.
Moss
Mark
M
Clinical Science Center, University of Wisconsin, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif.
Mauger
David T
DT
Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa.
Boehmer
Susan J
SJ
Department of Public Health Sciences, Pennsylvania State University, Hershey, Pa.
Strunk
Robert C
RC
Department of Pediatrics, Washington University, St Louis, Mo.
Martinez
Fernando D
FD
Arizona Respiratory Center, University of Arizona, Tucson, Ariz.
Taussig
Lynn M
LM
Department of Pediatrics, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, Colo.
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
D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D001993:Bronchodilator Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol