Viewpoint: untoward effects of beta-adrenoceptor agonists in asthma

Beta-adrenoceptor agonists are potent and selective relaxants of airway smooth muscle. They produce symptomatic bronchodilatory effects and are the most widely used therapy in asthma. In patients with asthma, they usually effect a reduction of airway resistance, but there have been several reports of episodes of increased airway obstruction, arterial hypoxaemia and even death associated with such therapy. "Anomalous or paradoxical bronchospasm" are appropriate terminologies to describe this unexpected phenomenon. Five mechanisms have been proposed to account for anomalous responses to these substances: 1) reactive myogenic tone; 2) metabolic products with spasmogenic activity; 3) adrenoceptor tachyphylaxis; 4) increased inflammatory burden; and 5) induction of airway hyperreactivity. Following a review of the relative merits of each proposal, it is concluded that increased inflammatory burden and induction of airway hyperreactivity, alone or in combination, provide the most plausible explanation for paradoxical bronchospasm.