Beta2-adrenergic agents in asthma
This project postulated a clinically significant anti-inflammatory action of beta2-agonists, in particular of salmeterol, a beta2-agonist with clinically proven bronchodilator properties. This hypothesis was investigated by two distinct approaches. Firstly, phagocyte function was taken as a marker of inflammation and was investigated using a novel microtitre plate chemiluminescence assay. Phagocyte response to salbutamol and terbutaline in vitro was assessed to ensure that the microtitre plate assay was sensitive enough to detect suppression. Salmeterol was then investigated to see if its properties differed from more conventional beta2-agonists. The relationship between peripheral blood polymorphonuclear leukocyte and monocyte function and pulmonary function was explored in asthmatic subjects on different treatment regimes. Included in this investigation was a double blind, crossover study of the effects of inhaled salmeterol on peripheral phagocyte function in subjects with mild asthma. The hypothesis was also treated by investigating the effect of chronic dosing with salmeterol on exercise induced bronchoconstriction. Assessment of the protection offered was by comparing the fall in FEV1 following standard treadmill exercise challenge in a placebo controlled, double blind, crossover study. Neither approach yielded evidence to support the hypothesis of a clinically significant anti-inflammatory effect of beta2-agonists. Although suppression of phagocyte function by salbutamol, terbutaline and salmeterol was demonstrated in vitro, no evidence of modulation of phagocyte function was seen during clinical studies. Interestingly, there was evidence from the in vitro study that the action of salmeterol on phagocytes may not be totally beta-receptor mediated.