Use of whole-body plethysmography to compare bronchodilator inhaler efficacy

Whole-body plethysmography is not included in guidelines from regulatory authorities for the development of treatments or delivery devices for lung disease, despite its potential advantages compared to spirometry, Two separate studies were undertaken to assess the use of specific airway conductance (sG(aw)) as a pharmacodynamic endpoint for the comparison of two bronchodilator delivery systems (a novel dry powder inhaler and a standard metered dose inhaler). The first pilot study involved delivery of a single dose of salbutamol (200 mu g) to 13 healthy volunteers and determination of sG(aw) up to 120 min after treatment. The second study involved delivery of cumulative doses of salbutamol (100, 200 and 400 mu g) to 19 healthy volunteers with demonstrated reversibility of sG(aw) to the bronchodilator and measurement of sG(aw) up to 240 min after treatment. In both studies, increases in sG(aw) after treatment were significant compared to placebo and larger than the recorded increases in FEV1. Increases in sG(aw) were similar for both delivery devices and support the therapeutic equivalence of the two products. Power calculations indicated that the second study had appropriate statistical power to discriminate between treatments. It is concluded that the assessment of sG(aw) in healthy volunteers may be a useful and sensitive pharmacodynamic endpoint for use in the development of bronchodilators and their delivery devices.