Disodium cromoglycate has been shown in several studies to be partially effective in the prevention of exercise-induced asthma; however, the reports on the effectiveness of atropine are conflicting. While Sly et al showed that premedication with atropine failed to prevent exercise-included asthma in the majority of his patients, Simonsson and co-workers found that there was protection in six out of nine patients. Sch 1000 is a derivative of atropine (methyl bromide of N-isopropyl nortropine) and has been found in several clinical trials to possess broncho-dilator activity equivalent to β-adrenergic drugs, but with usually minimal or no atropine-like side effects.
The present investigation was done to evaluate the efficacy of Sch 1000 in the prevention of exercise-induced asthma and to compare Sch 1000 with disodium cromoglycate.
Nine patients with asthma (by the criteria of the American Thoracic Society) were studied. The characteristics of these patients are shown in Table 1. The age range was 18 to 52 years. All patients gave a history of asthma induced by exercise. Seven of them were in remission at the time of the study and required no medication, while two (patients 6 and 8) were maintained on therapy with prednisone (10 mg daily). With the exception of patient 8, the initial forced expiratory volume in one second (FEV,) of these patients was above 80 percent of the predicted value. Four patients (patients 1 to 4) were atopic subjects and had immediate positive cutaneous reaction to more than one common allergen; the remaining five were nonatopic subjects. All patients were nonsmokers.
The FEV1 and forced vital capacity (FVC) were measured, using a 13.5-L spirometer (Collins). Spirometric measurements were made before and at five-minute intervals for 30 minutes after exercise. The average of three readings was taken each time.
Exercise tests were performed on a treadmill for all patients. The speed, slope, and time required to induce an attack of asthma are shown in Table 1. In three patients (patients 2, 4, and 9), the treadmill exercise failed to induce an attack of asthma, and they were asked to jog around one or two city blocks. The duration of jogging required to induce an attack of asthma in these patients is also shown in Table 1.
Subsequent studies were done at an interval of three to seven days, when an identical exercise test was performed by the same patient at about the same time of day. Placebo (lactose powder), disodium cromoglycate (20 mg), and Sch 1000 (80^) were given in a random single-blind manner to the patients 15 minutes before exercise. Placebo and disodium cromoglycate were administered through a Spinhaler and Sch 1000 through a Freon-propelled inhaler delivering 40^g per puff. All patients were asked not to take any medication (with the exception of prednisone) for at least six hours before each study.
Table 1—Characteristics of Patients and Type of Exercise Test for Induction of Asthma
|Patient, Sex, Age (yr)1, M, 31||Height, cm 166||Allergy Skin TestePositive||Initial FEVi, Percent of Predicte90||d Type of ExerciseTreadmill, 3 mph, 22 percent grade, 3.5 min|
|2, F, 19||165||Positive||94||Jogging, 5 min|
|3, M, 24||175||Positive||103||Treadmill, 3 mph, 20 percent grade, 6 min|
|4, F, 18||162||Positive||80||Jogging, 2 min|
|5, M, 50||175||Negative||80||Treadmill, 3 mph, 16 percent grade, 3.5 min|
|6, F, 43||160||Negative||88||Treadmill, 3 mph, 12 percent grade, 5.5 min|
|7, F, 42||168||Negative||99||Treadmill, 2.5 mph, 12 percent grade, 5 min|
|8, M, 52||188||Negative||70||Treadmill, 2.5 mph, 8 percent grade, 2.5 min|
|9, M, 19||175||Negative||108||Jogging, 4 min|