Effect of Disodium Cromoglycate on Exacerbations of Asthma Produced by Hyperventilation

The prophylactic inhalation of disodium cromoglycate lessens the exacerbations which occur in some asthmatic patients after voluntary hyperventilation. Reasons are given for considering this to be a possible mechanism for certain types of emotional exacerbation of the disease and for disodium cromoglycate giving sypmtomatic relief of asthma disproportionate to the improvement in routine measurements of ventilatory capacity. It is suggested that one clinical indication for giving disodium cromoglycate is to observe whether a fall in FEV₁ occurs after two minutes hyperventilation.     

Disodium Cromoglycate in the Prevention of Induced Asthma

In 13 patients with allergic asthma disodium cromoglycate protected fully only two from an allergen-induced asthmatic attack.Inhalation of disodium cromoglycate did not improve lung function in five patients with long-standing chronic asthma.Previous clinical trials do not show convincing evidence that this drug improves bronchial asthma in a high percentage of cases, but it seems to help a small minority of patients.     

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.     

Effect of Disodium Cromoglycate on Exercise-induced Asthma

In eight patients with exercise-induced asthma, disodium cromoglycate was found to produce a definite inhibition of the post-exercise fall in forced expiratory volume in one second. This effect may be part of the cause for the subjective improvement experienced with this drug.     

A double-blind trial of disodium cromoglycate (Intal) in the treatment of bronchial asthma

The result of a double-blind crossover trial with disodium cromoglycate (Intal) in 22 patients, nine with extrinsic asthma and 13 with intrinsic asthma, is reported. While eight extrinsic asthmatics showed considerable symptomatic improvement, only five of the intrinsic group improved while on disodium cromoglycate. Twelve out of 13 patients with symptomatic improvement had associated decrease in airway obstruction as measured by the FEV₁.It is concluded that disodium cromoglycate is useful in the treatment of asthma, particularly of the extrinsic type.     

Effect of Alpha-receptor Blocking Drugs and Disodium Cromoglycate on Histamine Hypersensitivity in Bronchial Asthma

Twenty patients with extrinsic type bronchial asthma are shown to have a significant fall in vital capacity (V.C.) and forced expiratory volume in 1 second (F.E.V.₁) after an intravenous infusion of 50μg. of histamine dihydrochloride. In 10 of these subjects the fall in V.C. and F.E.V.₁ produced by intravenous histamine is inhibited by the alpha-receptor blocking drugs phentolamine and phenoxybenzamine injected before the histamine test. The inhalation of disodium cromoglycate in 10 subjects is also shown to inhibit the fall in V.C. and F.E.V.₁ produced by the intravenous infusion of histamine. It is suggested that bronchial smooth muscle in asthmatic subjects has alpha-adrenergic receptor sites, and that a possible mechanism for the action of disodium cromoglycate is that it stabilizes the cell membrane, thereby altering calcium ion transport.     

Trial of Disodium Cromoglycate in Bronchial Asthma

In a double-blind cross-over trial of disodium cromoglycate on 11 patients nine were symptomatically improved, and in all of these daily measurements of peak expiratory flow increased. The forced expiratory volume in the first second and specific airway conductance did not increase in all patients. In most cases the average values for residual volume and functional residual capacity fell; exercise capacity and ventilation did not change, but the pulse rate on exercise was lower. It is suggested that the changes produced by disodium cromoglycate are worth while.     

Long-term Trial of Disodium Cromoglycate and Isoprenaline in Children with Asthma

A year-long double-blind trial was carried out in 53 asthmatic children with severe perennial symptoms who were not receiving corticosteroids or corticotrophin. The treatment group were given disodium cromoglycate with isoprenaline (Intal Co.) while the placebo group were given lactose with isoprenaline four times daily. The groups were closely matched for clinical, physiological, and immunological features. Evaluation was based on the use of a diary and clinical and physiological investigations, including exercise tests.After one year 71% of the treatment group were still well controlled while 76% of the placebo group had dropped out because of inadequate control of symptoms. There was no rise in the rate of failure towards the end of the trial period and there were no seasonal variations in the failure rate. No important toxic effects were noted. It was impossible to predict the outcome of the trial in any given patient from his clinical, physiological, or immunological status at the beginning. However, the prevention of exercise-induced asthma by premedication with disodium cromoglycate in a laboratory exercise test did correlate well with the satisfactory clinical response to the drug.     

ACT与PEF在支气管哮喘缓解期管理中的应用

目的:观察在哮喘缓解期阶梯治疗中,哮喘控制测试(asthma control test,ACT)与最大呼气峰流速(PEF)作用的相关性,帮助支气管哮喘患者更加准确、简便的进行自我监测,提高患者的依从性。方法:选择我院哮喘专病门诊就诊的78例哮喘患者,吸入糖皮质激素(ICS)进行缓解期的阶梯治疗。要求每日早、晚监测PEF,并记录到哮喘日记上。每月哮喘专病门诊复诊一次,了解PEF值、PEF占个人预计值的百分比(PEFpred%),PEFpred%个人预计值80%为哮喘控制,PEFpred%个人预计值80%为哮喘未控制,同时进行ACT问卷,计算得分,20分为哮喘未控制;20~25分为哮喘控制。结果:ACT评分20~25分组与ACT评分20分组PEFpred%比较,差异有统计学意义(P0.01)。PEFpred%个人预计值80%组与PEFpred%个人预计值80%组ACT评分比较,差异有统计学意义(P0.01)。ACT评分与PEFpred%具有线性相关关系,P0.001。结论:在哮喘缓解期阶梯治疗中,ATC评分与PEF具有良好的相关性,对于没有条件或不能监测PEF的哮喘患者可以用ACT评分作为评估哮喘控制的指标,指导阶梯治疗。     

II. The late asthmatic responses

Immediate asthmatic responses have been regarded as the characteristic type of asthmatic response to follow exposure to inhaled allergens in patients with extrinsic asthma. They begin within minutes, clear within one to three hours and are inhibited by disodium cromoglycate but not by corticosteroids. They involve the reaction of antigen with antibodies usually of the IgE class. In recent years allergen inhalation tests have demonstrated the frequent occurrence of late asthmatic responses, either following immediate responses (dual responses) or occurring in isolation. The late asthmatic responses begin two to six hours after the allergen challenge, are prolonged and often severe, and are inhibited by both disodium cromoglycate and corticosteroids. The mechanisms involved in their provocation are not clearly understood but from the allergic viewpoint they may involve the participation of IgG ± IgM antibodies and/or IgE antibodies. Late asthmatic responses explain the frequent occurrence of allergen-induced prolonged asthma. Their features suggest that they are more important than immediate responses in the pathophysiology of asthma.     

Response to disodium cromoglycate in children with chronic asthma

Twenty-three children with chronic severe perennial asthma received randomly-allocated disodium cromoglycate or placebo four times a day for 12 weeks, and the alternative regimen for the subsequent 12 weeks. More than half the patients improved while on DSCG according to clinical assessment. There was a significant increase in the mean FEV_{0·75 second} during the drug period, largely owing to dramatic improvement in nine patients. No reduction in the mean decrease of FEV after exercise was demonstrated. Response, when it occurred, was evident within four weeks. The effect of the medication was consistent in individual patients throughout the 12-week period. No evidence of toxicity was discovered during the period of study.     

Standard exercise test to assess peripheral arterial disease.

The fall in ankle systolic pressure after exercise serves as an objective indicator of the severity of haemodynamically important peripheral arterial disease. Twenty-six patients were studied to establish the effects of different work loads on the pressure response and to develop a test to standardise these effects. The patients walked for one or two minutes at 4 km/h and one or two minutes at 6 km/h, and the fall in pressure was the same when measured immediately after exercise. The time taken for the pressure to return to the pre-exercise value varied. As the fall in pressure occurs after only one minute of exercise at 4 km/h on a 10% slope, this might be adopted as a standard test. It is acceptable to the patient, since claudication, angina, and shortness of breath rarely occur. It is sensitive enough to detect mild or asymptomatic disease and is useful in following up patients.     

Usefulness of testing histamine release from isolated human basophils in anti-allergic and anti-asthmatic drug assessment]

Histamine release from isolated human basophils test was used to evaluate an activity of: histamine receptors H1 and H2 blockers, agonists of beta-receptors, calcium channel blocking agents, hydrocortisone, and disodium cromoglycate (Intal). The study involved 84 patients hospitalized for the bronchial asthma. Basophils were isolated with Day's technique modified by Shov and Norn. Histamine was measured with Shov's spectrofluorimetric technique. It was found that histamine release from isolated human basophils may be used in both evaluation of the mechanism of action and efficiency of drugs used in allergic diseases therapy.     

Sudden Death in a Young Asthmatic

A 14-year-old boy with severe asthma was treated with prednisone and disodium cromoglycate with considerable subjective improvement, though there was persistent airways obstruction. After several weeks'' freedom from symptoms he died in a severe attack of nocturnal asthma. Necropsy findings suggested that hypersecretion had been occurring in die medium-sized airways for several days before death.     

Effect of ozagrel hydrochloride,a thromboxane synthetase inhibitor,on alcoholic beverage-induced bronchoconstriction in asthmatic patients

Acetaldehyde is thought to be a main factor of alcohol-induced asthma. The thromboxane (TX) synthetase inhibitor, ozagrel hydrochloride, inhibits acetaldehyde-induced bronchoconstriction in asthmatic patients. The present study evaluated the involvement of TXA(2) on alcoholic beverage-induced bronchoconstriction. Four patients with alcohol-induced asthma received ozagrel (400 mg for 4 days) or placebo using a single-blind, randomized, cross-over design. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese sake) and bronchoconstriction was assessed as the change in peak expiratory flow (PEF). The effect of ozagrel on the aerosolized challenge of acetaldehyde was investigated in the same subjects. Although aerosolized acetaldehyde-induced bronchoconstriction was significantly prevented by ozagrel, there were no differences in the time course of the decrease in PEF or the maximum fall in PEF after alcohol intake between placebo and ozagrel. We conclude that TXA(2) is not involved in alcoholic beverage-induced bronchoconstriction.     

Atropine,sodium cromoglycate,and thymoxamine in PGF2 alpha-induced bronchoconstriction in extrinsic asthma.

In six patients with extrinsic bronchial asthma the inhalation of prostaglandin (PG) F2 alpha in a small dosage produced significant bronchoconstriction, whereas PGE2 produced bronchodilatation. In these patients cholinergic blockade with atropine partially inhibited the PGF2 alpha-induced bronchoconstriction, but the alpha-receptor-blocking drug thymoxamine and sodium cromoglycate did not. These results suggest that the effect of PGF2 alpha is mediated through cholinergic receptors in the airways, and this effect is grossly exaggerated in asthma. The failure to inhibit PGF2 alpha-induced bronchoconstriction with sodium cromoglycate and the observation of an inhibitory effect of sodium cromoglycate in both allergic and exercise asthma suggest that locally formed PGF2 alpha may not be the main factor in the pathogenesis of bronchial asthma.     

Bronchial reactivity to histamine before and after sodium cromoglycate in bronchial asthma.

Out of 19 patients with extrinsic bronchial asthma challenged with 123 mug histamine acid phosphate by intravenous infusion only 13 responded with a fall in FEV1 of over 10% (mean 16%). Seventeen of these patients were given histamine 2 mg/ml by aerosol, and all responded with a mean decrease in FEV1 of 37.8%. When challenged with allergen extract by aerosol the mean decrease in FEV1 was 37.5%. After 40 mg sodium cromoglycate 15 of the 17 patients showed significant protection against allergen challenge with a mean decrease in FEV1 of only 23.6%. Inhalation of 40 mg sodium cromoglycate, however, failed to protect against histamine given by either the intravenous or aerosol route. Histamine given intravenously to asthmatic patients produces less of a bronchial response than when given by aerosol, even though the intravenous route produces many more systemic symptoms, such as flushing and throbbing headache. The protection of sodium cromoglycate against an allergen inhalation challenge is not due to histamine antagonsim.     

Plasma vasopressin, renin activity, and aldosterone responses to maximal exercise in active college females

The effect of maximal treadmill exercise on plasma concentrations of vasopressin (AVP); renin activity (PRA); and aldosterone (ALDO) was studied in nine female college basketball players before and after a 5-month basketball season. Pre-season plasma AVP increased (p less than 0.05) from a pre-exercise concentration of 3.8 +/- 0.5 to 15.8 +/- 4.8 pg X ml-1 following exercise. Post-season, the pre-exercise plasma AVP level averaged 1.5 +/- 0.5 pg X ml-1 and increased to 16.7 +/- 5.9 pg X ml-1 after the exercise test. PRA increased (p less than 0.05) from a pre-exercise value of 1.6 +/- 0.6 to 6.8 +/- 1.7 ngAI X ml-1 X hr-1 5 min after the end of exercise during the pre-season test. In the post-season, the pre-exercise PRA was comparable (2.4 +/- 0.6 ngAI X ml- X hr-1), as was the elevation found after maximal exercise (8.3 +/- 1.9 ngAI X ml- X hr-1). Pre-season plasma ALDO increased (p less than 0.05) from 102.9 +/- 30.8 pg X ml-1 in the pre-exercise period to 453.8 +/- 54.8 pg X ml-1 after the exercise test. In the post-season the values were 108.9 +/- 19.4 and 365.9 +/- 64.4 pg X ml-1, respectively. Thus, maximal exercise in females produced significant increases in plasma AVP, renin activity, and ALDO that are comparable to those reported previously for male subjects. Moreover, this response is remarkably reproducible as demonstrated by the results of the two tests performed 5 months apart.     

Changes in blood gas tensions and functional residual capacity in chronic asthmatics treated with disodium cromoglycate

Twenty chronic asthmatic subjects were treated with disodium cromoglycate in open trial. Although in the group as a whole spirometric findings improved, some patients showed a significant increase in arterial oxygen tension or a significant fall in functional residual capacity without any appreciable changes in spirometry. These changes may partly explain the clinical efficacy of this drug.     

The effects of high-intensity intermittent exercise on the plasma concentrations of glutamine and organic acids

Glutamine is an essential substrate for the proper functioning of cells of the immune system. Falls in plasma glutamine concentration after exercise may have deleterious consequences for immune cell function and render the individual more susceptible to infection. The purpose of the present study was to examine changes in plasma glutamine concentration (measured using a validated enzymatic spectrophotometric method) following an acute bout of intermittent high-intensity exercise. Eight well-trained male games players took part in the study. Subjects reported to the laboratory following an overnight fast and performed a 1-h cycle exercise task consisting of 20 1-min periods at 100% maximal O₂ consumption (V˙O_2max) each separated by 2 min of recovery at 30% V˙O_2max. Venous blood samples were taken before exercise and at 5 min, 1 h, 2.5 h, 5 h and 24 h post-exercise. Glutamine was measured by enzymatic spectrophotometric determination of the ammonia concentration before and after treatment of the plasma with glutaminase (EC 3.5.1.2). Plasma glutamine concentration did not fall in the immediate post-exercise period [pre-exercise 681 (23) μM compared with 663 (46) μM at 5 min post-exercise, mean (SEM)], but fell to 572 (35) μM at 5 h post-exercise (P < 0.05 compared with pre-exercise). Plasma lactate concentration rose to 8.8 (1.0) mM at the end of exercise and fell to 1.8 (0.4) mM at 1 h post-exercise, but plasma concentrations of free fatty acids and β-hydroxybutyrate both rose substantially in the post-exercise period (to 240% and 400% of pre-exercise levels, respectively). The circulating leucocyte count increased significantly during exercise (P < 0.01), continued to increase in the hours following exercise and peaked at 2.5 h post-exercise (mainly due to a neutrophilia). The fall in the plasma glutamine concentration at 5 h post-exercise could be due to increased renal uptake of glutamine, which generally occurs in conditions of metabolic acidosis or due to a greater removal of glutamine from the plasma resulting from the elevated circulating leucocyte count. Accepted: 22 October 1997