The effect of increasing doses of β-agonists on airflow in patients with chronic airflow limitation

Abstract

Objective: To determine the increase in FEV 1 associated with increasing doses of inhaled terbutaline and salbutamol, the reproducibility of the increase in FEV 1, and the reproducibility of the associated optimal bronchodilator dose, in patients with chronic airflow limitation (CAL). Design: Double-blind, randomized, controlled trial examining spirometric response to cumulative doses of bronchodilators. Patients and Setting: Patients with clinical diagnosis of CAL, FEV 1 below 70% predicted, and FEV 1 to FVC ratio less than 0·7 after administration of bronchodilator recruited from secondary care respirology practices. Measures of outcome: The estimates of maximum and optimal bronchodilation, as well as the associated drug dosages, were established in each patient on three occasions (twice on terbutaline and once on salbutamol). The ‘optimal’ drug dose was defined as the lowest dose associated with an FEV 1 not exceeded by 50 ml on any other dose. Main results: Thirty-five patients completed the trial. FEV 1 improved from 0·93 to a maximum of 1·19 l with terbutaline (average of the two administrations) and from 0·95 l to 1·14 l with inhaled salbutamol (difference in increase in FEV 1 between terbutaline and salbutamol P=0·006). In less than 50% of cases administration of more than four puffs of bronchodilator resulted in FEV 1 increase by more than 50 ml. The average dose of salbutamol and terbutaline associated with optimal bronchodilation were 430 μg and 1160 μg respectively. Patients varied widely in the optimal dose. Estimates of optimal dose were not reproducible (intraclass correlation coefficient <0·5). Conclusion: Substantial incremental increase in FEV 1 in response to increasing doses of β-agonists beyond those commonly used in clinical practice is restricted to a minority of patients. Lack of reproducibility limits the clinical usefulness of establishing the optimal dose of β-agonist for a given patient.