Pharmacological modulation of bronchial hyperreactivity.

The airways of asthmatics are hyperreactive, not only to allergens but to a wide range of non-specific physical and chemical stimuli. Four mechanisms which have been proposed to be causes of hyperreactivity are (i) a decrease in baseline airway calibre (ii) an increase in the responsiveness of the bronchial smooth muscle (iii) an imbalance in the autonomic neurophysiological regulation of airway calibre and (iv) epithelial changes which lead to an increase in the accessibility of allergens and non-specific stimuli to the mast cells, sensory nerve endings or bronchial smooth muscle beneath the airway mucosa. We have studied the effects of some of the proposed mediators of asthma on lung mechanics and irritant receptor activity in dogs with a respiratory tract infection and in dogs following exposure to SO2 gas at a concentration (400 ppl) sufficient to damage the airway epithelium (Jackson and Richards, 1980). In dogs naturally infected with Bordetella bronchiseptica there was an increased airway reactivity to histamine which was almost completely abolished by vagotomy. The hyperreactivity to histamine was shown to be due to an increased responsiveness of lung irritant receptors. In dogs exposed to SO2 gas changes in RL induced by 5-hydroxytryptamine or electrical stimulation of the vagus nerves were significantly increased when compared to the responses in normal dogs. Altounyan (1970) has shown that continuous exposure to allergens in patients with seasonal allergic asthma also leads to an increase in non-specific bronchial reactivity. Pharmacological modulation of airway reactivity can be divided into the acute and long term effects of drugs. Acute effects of drugs have been studied by several groups of workers using the airway responses to inhalation of various non-specific stimuli (e.g. distilled water, cold air, SO2 gas). Beta-stimulants and sodium cromoglycate are usually effective inhibitors and anticholinergic drugs are effective when a reflex component contributes to the bronchoconstriction. Few controlled studies of the effect of long-term treatment with drugs on bronchial hyperreactivity have been carried out although as early as 1970 Altounyan showed that long-term treatment with sodium cromoglycate could inhibit the development of non-specific hyperreactivity during the pollen season in pollen-sensitive asthmatics. A number of further studies have confirmed these early observations.(ABSTRACT TRUNCATED AT 400 WORDS)