THE REPRODUCIBILITY AND EFFECT ON NONSPECIFIC AIRWAY RESPONSIVENESS OF INHALED PROSTAGLANDIN D-2 AND LEUKOTRIENE D-4 IN ASTHMATIC SUBJECTS

1 Mast cell mediators PGD(2) and LTD(4) may play important roles in as thma pathogenesis. There is little information on the repeatability of inhalation challenge with these agonists in the laboratory. 2 We asse ssed the repeatability of inhalation challenges using PGD(2) and LTD(4 ) in two groups of 10 asthmatic volunteers. Non-specific bronchial res ponsiveness was assessed by histamine inhalation challenges. 3 Using t he Bland-Altman method, we found the coefficient of repeatability to b e 1.2 doubling doses for LTD(4) and 2.1 for PGD(2) at a 1 week interva l. Repeatability for histamine inhalation challenge over the same time period was similar at 1.4 and 2.1 doubling doses respectively. 4 Non- specific bronchial responsiveness following LTD challenge decreased si gnificantly, mean PD(20)FEV(1) increasing from 169 nmol on day 1 to 27 8 nmol on day 3 (P = 0.001), before returning to baseline levels. 5 A progressive decrease in non-specific bronchial responsiveness occurred following PGD(2) challenge. Baseline PD(20)FEV(1) was 195 nmol, incre asing to 238 nmol by day 3 (NS) and 313 nmol by day 8 (P = 0.016). 6 P GD(2) inhalation challenges performed a week apart are less reproducib le than LTD(4) challenges, possibly as a result of significant changes in histamine bronchial responsiveness. Our findings allow accurate po wer calculations to be made for studies to assess new pharmacological antagonists to these mediators.