title: Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness.
abstract: BACKGROUND
  New drug evaluations in patients with mild asthma are sometimes complicated by enrollment of patients whose disease is too mild to show improvement with therapy. A peak expiratory flow (PEF) variability criterion may help to more clearly define a mild asthmatic population.
  
  
  OBJECTIVE
  To evaluate the effectiveness of zafirlukast (20 mg twice daily) and cromolyn sodium (1600 microg four times daily) compared with placebo as first-line therapy for mild asthma using a retrospective analysis, which stratified patients by PEF variability (<10% or > or =10%).
  
  
  METHODS
  Symptomatic patients (daytime asthma symptoms score > or =8) were randomized to 13 weeks of treatment in a double-blind, double-dummy, placebo-controlled, parallel-group, multicenter trial.
  
  
  METHODS
  Patients (n = 287) were nonsmokers (age > or =12 years) with reversible airway disease, a forced expiratory volume in one second (FEV1) of > or = 55% of predicted, and previous treatment with beta2-agonist or theophylline only. Assessments included changes from baseline to endpoint in daytime and nocturnal asthma symptoms, beta2-agonist use, PEF, and FEV1. Response to treatment was assessed by predetermined diary card and FEV1 criteria. Safety was determined from adverse events and laboratory test results.
  
  
  RESULTS
  No significant treatment effects were seen across efficacy measures for patients with PEF variability < 10%. For patients with PEF variability > or = 10%, both active treatments significantly (P < .05) decreased the daytime asthma symptoms score, nighttime awakenings, and beta2-agonist use, and increased morning PEF and FEV1 compared with placebo. Response to diary card criteria was 70% and 75% for zafirlukast and cromolyn, respectively; response to FEV1 criteria was 47% for both treatments. All treatments were tolerated well by patients.
  
  
  CONCLUSIONS
  Zafirlukast and cromolyn are effective first-line therapies for mild asthma, with both therapies producing greater benefits in patients whose PEF variability was > or = 10%. In prospective trials to evaluate therapies in patients with mild asthma, it may be worthwhile to include PEF variability with a 10% cutoff either as an inclusion criteria or as a tool for subset analysis.
authors.affiliation: Asthma and Allergy Associates, PC, Colorado Springs, Colorado 80907, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Nathan
authors.forename: M C
authors.initials: MC
authors.lastname: Minkwitz
authors.forename: C M
authors.initials: CM
authors.lastname: Bonuccelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002940:Circadian Rhythm; D004205:Cromolyn Sodium / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007211:Indoles; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D048448:Phenylcarbamates; D010919:Placebos; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D018927:Anti-Asthmatic Agents; D007211:Indoles; D048448:Phenylcarbamates; D010919:Placebos; D013449:Sulfonamides; D014105:Tosyl Compounds; D004205:Cromolyn Sodium; C062735:zafirlukast