DETERMINANTS OF THE BRONCHIAL RESPONSE TO HIGH-MOLECULAR-WEIGHT OCCUPATIONAL AGENTS IN A DRY AEROSOL FORM

In occupational challenge tests with isocyanate vapours, bronchial res ponsiveness is determined by the total dose rather than the concentrat ion or duration of exposure. Whether the same applies for high molecul ar weight (HMW) agents in powder form is unknown. The aim of this stud y was to determine whether the total dose of HMW agents in powder form is responsible for the immediate reaction documented in specific chal lenge tests. Included in the study were nine subjects (seven males and two females) with a diagnosis of occupational asthma proved by specif ic challenge tests carried out on a preliminary visit. Two challenge t ests (using a closed-circuit exposure chamber) were performed at an in terval of 2 weeks; the concentrations administered in a random order o n these two visits were half and double the one that had caused a 20% fall in forced expiratory volume in one second (FEV1) on a preliminary visit, The duration of exposure was adjusted until a significant fall in FEV1 (target of 20%) occurred, The two concentrations obtained wer e significantly different, by 2.07+/-0.36-fold (SD), The observed dura tions of exposure leading to a 20% fall in FEV1 on the two visits also differed significantly by 0.46+/-0.32-fold. Consequently, the cumulat ive efficient doses were not significantly different between the two v isits: 12+/-5.4 and 9+/-5 mg.mL(-1).min(-1), respectively. The corresp onding cumulative dose ratio was 0.96+/-0.61, The expected duration of exposure (10.8+/-24 min) was not significantly different from the obs erved duration (5.4+/-9 min), The mean and 95% confidence interval for the difference in concentration between the two visits was 1.83-fold (1.48-2.21). In conclusion, the total dose rather than the concentrati on or duration of exposure per se determines bronchial responsiveness to high molecular weight agents in powder form.