Determinants of the bronchial response to high molecular weight occupational agents in a dry aerosol form

In occupational challenge tests with isocyanate vapours, bronchial responsiveness is determined by the total dose rather than the concentration or duration of exposure. Whether the same applies for high molecular weight (HMW) agents in powder form is unknown. The aim of this study was to determine whether the total dose of HMW agents in powder form is responsible for the immediate reaction documented in specific challenge tests. Included in the study were nine subjects (seven males and two females) with a diagnosis of occupational asthma proved by specific challenge tests carried out on a preliminary visit. Two challenge tests (using a closed-circuit exposure chamber) were performed at an interval of 2 weeks; the concentrations administered in a random order on 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 were significantly different, by 2.07+/-0.36-fold (SD). The observed durations of exposure leading to a 20% fall in FEV1 on the two visits also differed significantly by 0.46+/-0.32-fold. Consequently, the cumulative efficient doses were not significantly different between the two visits: 12+/-5.4 and 9+/-5 mg x mL(-1) x min(-1), respectively. The corresponding cumulative dose ratio was 0.96+/-0.61. The expected duration of exposure (10.8+/-24 min) was not significantly different from the observed 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 concentration or duration of exposure per se determines bronchial responsiveness to high molecular weight agents in powder form.