Why particle size should affect clinical response to inhaled therapy

Studies with beta (2)-adrenergic agonists have shown that particle size and total dose are important determinants of optimum bronchodilation. Drug dep osition in the airways is probably the most important factor for bronchodil ation, since beta (2)-adrenoceptors and muscarinic M-3 receptors are presen t mainly in the peripheral and central airways, respectively. Furthermore, clinical efficacy can be maintained while minimizing systemic exposure by s electing an appropriate particle size. Changes in lung function provide a m eans of monitoring the relationship between delivery of the bronchodilator and its efficacy, whereas there is no such immediate means of assessing ant iinflammatory preventative therapy such as inhaled corticosteroids. Asthma is primarily an inflammatory disease but there are no simple tests to detec t the accumulation of inflammatory cells and mediators. Data are presented to demonstrate the reduction of certain inflammatory markers in bronchial b iopsy tissue taken from asthmatic patients after corticosteroid therapy. Me asurement of inflammatory markers in both bronchial biopsy tissue and bronc hoalveolar lavage samples may provide a way of monitoring the site of actio n and efficacy of inhaled corticosteroids in the future. Furthermore, it is envisaged that the effect of corticosteroid particle size on efficacy and systemic bioavailability may be investigated by exploiting these methods.