Bronchodilator therapy with nebuhaler: how important is the delay between firing the dose and inhaling?

Metered dose inhalers are sometimes used in conjunction with Nebuhaler^R, a 750 ml holding chamber, but the permissible delay time between actuating the aerosol into Nebuhaler and commencing inhalation is unknown. We have compared in 10 asthmatic patients the bronchodilator responses following inhalations of terbutaline sulphate from Nebuhaler after delays of 1, 5 and 30 seconds and following placebo inhalation. Terbutaline sulphate was administered as 2 puffs, each of 250 μg, separated by approximately 15 minutes. After each delay time, terbutaline produced increases in forced expiratory volume in one second (FEV₁), peak expiratory flow rate (PEFR) and maximum expiratory flow following exhalation of 75% of the forced vital capacity ($\text{c}\text{V\_.}{}_{\mathrm{max25}}$) significantly greater than those after placebo (P<0.01). Changes in PEFR did not vary significantly among the three delay times, but the increases in FEV₁ and in $\text{c}\text{V\_.}{}_{\mathrm{max25}}$ were significantly reduced with 30 seconds' delay. It is concluded that the delay between actuation into Nebuhaler and commencing inhalation can be extended from 1 second to 5 seconds without significant loss of drug efficacy, and that further extension to 30 seconds causes only a small loss of bronchodilatation: hence the delay time is unlikely to be of major importance in clinical practice.