Sodium cromoglycate in chronic asthma.

A long-term double-blind trial of sodium cromoglycate (SCG) with and without isoprenaline, with a placebo control, was undertaken in Edinburgh to a similar design as a previously reported trial in London. The results from the two centres were compared and combined. In Edinburgh 41 patients were studied for 36 weeks and 40 for 52 weeks and in the combined series 121 were studied for 36 weeks and 114 for 52 weeks. In the second year 14 patients were followed-up in Edinburgh and 27 in London. The two SCG regimens were superior overall to placebo both in the Edinburgh and London patients. SCG was effective in similar proportions of patients with extrinsic and intrinsic asthma. In the second year the effectiveness of SCG was further tested by randomly allocating half the patients to a placebo. Some patients derived a continuing benefit from SCG, but its continued use did not appear to be necessary for others, whose progress on placebo was satisfactory.     

Calcium antagonists in exercise-induced asthma.

Ten patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled verapamil (estimated dose 3 mg) and sodium cromoglycate (estimated dose 12 mg). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after running on a treadmill for eight minutes. There was no significant change in baseline FEV1 values after each agent. In the exercise periods, however, FEV1 fell by 45.4% (SEM 4.0) after saline inhalation, 18.4% (5.1) after sodium cromoglycate, and 16.7% (4.3) after verapamil. The inhibitory effects of sodium cromoglycate and verapamil were comparable and significantly different from saline (p less than 0.02 and p less than 0.01 respectively). Nevertheless, considerable intrasubject variability was observed. The findings suggest that mediator release, which is calcium dependent, may play an important part in exercise-induced asthma, and calcium antagonists may inhibit post-exercise bronchoconstriction by their blocking effect on calcium channels.     

Aspirin and exercise-induced asthma.

In four subjects with exercise-induced asthma, aspirin and placebo were administered prior to exercise in a double blind study. Pulmonary function tests did not reveal any difference between the response after aspirin or placebo. We conclude that in these four subjects aspirin did not prevent the bronchoconstrictor response. This might suggest that prostaglandins have no significant role in exercise-induced asthma.     

Disodium cromoglycate attenuates hypoxia induced enlargement of end-expiratory lung volume in rats

Mechanism responsible for the enlargement of end-expiratory lung volume (EELV) induced by chronic hypoxia remains unclear. The fact that the increase in EELV persists after return to normoxia suggests involvement of morphological changes. Because hypoxia has been also shown to activate lung mast cells, we speculated that they could play in the mechanism increasing EELV similar role as in vessel remodeling in hypoxic pulmonary hypertension (HPH). We, therefore, tested an effect of mast cells degranulation blocker disodium cromoglycate (DSCG) on hypoxia induced EELV enlargement. Ventilatory parameters, EELV and right to left heart weight ratio (RV/LV+S) were measured in male Wistar rats. The experimental group (H+DSCG) was exposed to 3 weeks of normobaric hypoxia and treated with DSCG during the first four days of hypoxia, control group was exposed to hypoxia only (H), two others were kept in normoxia as non-treated (N) and treated (N+DSCG) groups. DSCG treatment significantly attenuated the EELV enlargement (H+DSCG = 6.1+/-0.8; H = 9.2+/-0.9; ml +/-SE) together with the increase in minute ventilation (H + DSCG = 190+/-8; H = 273 +/- 10; ml/min +/- SE) and RV/LV + S (H + DSCG = 0.39 +/- 0.03; H = 0.50 +/- 0.06).     

Aspirin and exercise-induced asthma

In four subjects with exercise-induced asthma, aspirin and placebo were administered prior to exercise in a double blind study. Pulmonary function tests did not reveal any difference between the response after aspirin or placebo. We conclude that in these four subjects aspirin did not prevent the bronchoconstrictor response. This might suggest that prostaglandins have no significant role in exercise-induced asthma.     

Urinary leukotriene E4 excretion in exercise-induced asthma.

Recent evidence suggests that the cysteinyl-leukotrienes (LTC4, LTD4, and LTE4) may be important in the pathogenesis of exercise-induced asthma. To evaluate the role of these mediators further, nine asthmatic subjects with exercise-induced bronchoconstriction were studied on two occasions. On visit 1, subjects performed 6 min of treadmill exercise; the mean maximal percent fall in FEV1 was 38.0 +/- 5.3%. On visit 2, maximal bronchoconstriction observed after exercise was matched with aerosolized methacholine. Urine was collected in two 90-min fractions (0-90 and 90-180 min) after challenges and analyzed by high-performance liquid chromatography-radioimmunoassay for LTE4. There were no significant differences in urinary LTE4 excretion between exercise and methacholine challenges for the periods 0-90 min (16.9 +/- 5.4 vs. 20.4 +/- 4.2 ng/mmol urinary creatinine), 90-180 min (24.9 +/- 8.2 vs. 20.1 +/- 5.5), or 0-180 min (21.5 +/- 6.5 vs. 18.8 +/- 4.1). Thus in contrast to allergen-induced bronchoconstriction, there is little evidence for enhanced cysteinyl-leukotriene generation in exercise-induced bronchoconstriction as assessed by urinary LTE4. If local release and subsequent participation of functionally active cysteinyl-leukotrienes in the pathways that ultimately lead to bronchoconstriction after exercise challenge do occur, these are of insufficient magnitude to perturb urinary LTE4 excretion.