Attenuation of protection with repeated cromolyn dosing before exercise challenge in subjects with asthma

Though cromolyn sodium exhibits tachyphylaxis in laboratory models of allergy, this pattern has not been identified in clinical use or in human asthma provocation models. We looked for it using a treadmill exercise challenge scheme that had previously confirmed cromolyn's protective effect. Twelve exercise-sensitive asthmatic volunteers received in random order, 12 20-mg cromolyn inhalations, 12 placebo inhalations, and 11 placebo inhalations with a final 20-mg dose of cromolyn. Each regimen was given over a three-day period, with the final dose administered 30 minutes before exercise. Subjects' respiratory functions were measured before and repeatedly after exercise with body plethysmography and peak flow rates. Beginning six minutes after the end of exercise, parameters measured after single-dose cromolyn and placebo administration differed in all endpoints at most of the measurement intervals. Results with 12-dose cromolyn pretreatment were significantly different from those seen with placebo only at 40 minutes after exercise, whereas single- and multiple-dose cromolyn results differed at 20 and 30 minutes. Cromolyn accelerated recovery from exercise-induced falls in lung function; this effect was attenuated with multiple dosing. These results are consistent with development of tachyphylaxis.