Perspectives in the Treatment of Reversible Airway Obstruction

The pharmacological therapy of asthmatic syndromes is based essentially on the programmed use of disodium cromoglycate, beta-2-stimulants, antimuscarinics, theophyllines and corticosteroids. However, the continual progress being made in pathogenesis and pharmacology suggests, to an ever-increasing extent, the application of new therapeutic approaches for these diseases, some of which are fairly interesting from a speculative point of view although they are as yet of limited practical value. Calcium antagonists and alpha-blockers have a mild anti-reactive effect but this is not sufficiently potent to justify use of these products in the treatment of asthma unless there are also cardiovascular disorders for which these drugs are particularly indicated. Despite the initial promising prospects, all attempts to obtain PGE analogues of therapeutic value as antiasthmatics have proved fruitless. Research into orally active chromone derivatives has proved equally unproductive. On the other hand, certain new inhalatory chromones are decidedly more promising. Specific antagonization of mediators (histamine, prostaglandin, leukotrienes) did not produce the effect hoped for in asthma, but this was foreseeable insofar as the major pathogenic mediators are too vast in number (and no doubt there are still many more to be discovered) to allow one to conceive it possible to achieve a satisfactory therapeutic effect by merely blocking some of them. Inflammation of the bronchial wall is currently considered to be one of the basic pathogenic factors provoking the recurrence of asthma: this is proved indirectly by the potent antiasthmatic effect of corticosteroids which are the most effective anti-inflammatory agents. As regards nonsteroidal anti-inflammatory drugs (NSAID), however, matters are more complicated. Some patients (approximately 10% of all adult asthmatics) suffer from violent asthmatic attacks after taking NSAIDs. For this reason the possibility of desensitization treatment was suggested whereby gradually increasing doses of aspirin (ASA) or another NSAID are given. However, the results proved negative insofar as only the rhinitic component showed any real improvement while the asthma remained more or less unchanged. In a low percentage of asthmatic patients (less than 1 %) NSAIDs lead to sudden and extensive bronchodilatation. However, if they are administered repeatedly, this effect tends to wear off quickly: thus, the possibility of using these for long-term treatment on a regular basis can be excluded.