The results of the present study show that longterm (three months) treatment of subjects with perennial asthma with sodium cromoglycate reduces nonspecific bronchial hyperresponsiveness to inhaled histamine. The drug was found to be an effective prophylactic agent producing significant amelioration of symptoms without any remarkable adverse effect. Consistent with this symptomatic improvement, a reduction in airway obstruction also was seen. The effect of sodium cromoglycate on bronchial responsiveness to inhaled histamine or methacholine has been the subject of investigation in several studies. In some studies, the drug was given only once prior to the test. In two reports using intravenous histamine challenge, contradicting results were obtained.
In other single-dose studies, using the more conventional inhaled route, minor or no protection against induced bronchospasm was observed. Clinical efficacy of sodium cromo-glycate may not be apparent for a few weeks. Therefore, studies evaluating the effect of treatment over a longer period may be more meaningful. Altounyan, Dickson and Dickson and Cole observed a protective effect of sodium cromoglycate after long-term use of the drug during the pollen season in patients allergic to pollen. However, in other studies of one week, two weeks, four weeks and six weeks duration, conducted out of and during the pollen season, no such protection was observed. A major reason for this may have been the short duration of treatment, by which time the full effect of sodium cromoglycate may not have been produced. Stafford et al reported an increased tolerance to histamine after a three-month treatment during the pollen season. other
As bronchial hyperresponsiveness reflects the ease with which asthma may be triggered off, a reduction in this characteristic would be a desirable goal in the treatment of asthma. Sodium cromoglycate appears to be capable of achieving this reduction, at least partially. It must be emphasized that statistically significant reduction in bronchial hyperresponsiveness observed in this study may not be clinically significant because even after treatment the PD^SGaw remained well within the range for asthma. Whether continuous treatment for several years ultimately reduces bronchial responsiveness to normal levels remains to be seen.
The basic cause of bronchial hyperresponsiveness remains elusive. The earlier concepts of autonomic (parasympathetic-sympathetic) imbalance have been replaced by the importance of airway inflammation in the genesis and perpetuation of bronchial hyperresponsiveness.*
The inflammation is a consequence of actions of mediators released from various cells, among which mast cells may be of the greatest importance. While mediator release has been established in allergen-induced asthma, it probably occurs in all types of asthma since the increased mast cell releasability and airway inflammation are universal features of this disease. By a mast-cell stabilizing action, sodium cromoglycate would reduce mediator release and hence may be considered to be an antiinflammatory drug. Therefore, a reduced bronchial hyperresponsiveness observed in the present as well as earlier studies could be the result of a reduced airway inflammation. Numeroso et al suggested a similar mechanism to explain the protective effect of sodium cromoglycate on bronchospasm induced by ultrasonically nebulized distilled water in patients with nonatopic chronic bronchitis. The inhibitory effect of sodium cromoglycate on histamine-induced reflex bronchoconstriction, shown in the anesthetized dog, also may be a contributing factor in humans.