Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness

Ann Allergy Asthma Immunol. 1999 May;82(5):497-503. doi: 10.1016/S1081-1206(10)62728-7.

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%).

Study design: 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.

Patients and 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy*
  • Child
  • Circadian Rhythm
  • Cromolyn Sodium / adverse effects
  • Cromolyn Sodium / therapeutic use
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Indoles
  • Male
  • Middle Aged
  • Peak Expiratory Flow Rate / drug effects
  • Phenylcarbamates
  • Placebos
  • Sulfonamides
  • Tosyl Compounds / adverse effects
  • Tosyl Compounds / therapeutic use

Substances

  • Anti-Asthmatic Agents
  • Indoles
  • Phenylcarbamates
  • Placebos
  • Sulfonamides
  • Tosyl Compounds
  • Cromolyn Sodium
  • zafirlukast