The results of previous studies comparing bronchodilatation from beta agonists administered by
metered-dose inhaler (MDI) and
nebulizer solution have been conflicting. We therefore evaluated a range of
albuterol doses administered by these two methods, using
histamine bronchoprovocation as a bioassay for the amount of
drug reaching the beta 2 receptors in the lung. Twelve stable asthmatic volunteers received, in a double-blind, randomized, crossover design on different days, placebo or one, two, four, or six puffs from an MDI attached to an InspirEase device (90 micrograms per puff) or 0.625, 1.25, 2.5, or 5.0 mg of
solution delivered in 2 ml of buffered saline through a Hudson Updraft II
nebulizer. The
histamine concentration required to decrease FEV1 by 20 percent (PC20) was measured 1 h before and 30 min after administration of each treatment and expressed as the increase in PC20 from baseline. The dose-response curves for change in PC20 indicated that the higher doses of the
nebulizer solution delivered more
drug to beta 2 receptors in the lung than the lower doses from the MDI. For example, the geometric mean increase in PC20 was 1.1 +/- 1.6 (SD) after placebo, 7.5 +/- 2.7 after two puffs from the MDI, and 20.0 +/- 2.1 after 2.5 mg of
nebulizer solution (p less than 0.05). Using this bioassay method and administration technique, we estimated that ten puffs from the MDI (0.9 mg) would deliver approximately the same amount of
albuterol to lung receptors as 2.5 mg of the
nebulizer solution. Taking into account previously published reports and the results of the present study, we conclude that differences in dose, administration technique,
nebulizer system efficiency, and severity of
airway obstruction can alter the amount of
drug reaching the beta 2 receptors in the lungs and, thus, the clinical response.