The reproducibility and effect on nonspecific airway responsiveness of inhaled prostaglandin D-2 and leukotriene D-4 in asthmatic subjects
Wood-Baker, R and Town, GI and Benning, B and Holgate, ST, The reproducibility and effect on nonspecific airway responsiveness of inhaled prostaglandin D-2 and leukotriene D-4 in asthmatic subjects, British Journal of Clinical Pharmacology, 39, (2) pp. 119-123. ISSN 0306-5251 (1995) [Refereed Article]
1. Mast cell mediators PGD2 and LTD4 may play important roles in asthma pathogenesis. There is little information on the repeatability of inhalation challenge with these agonists in the laboratory. 2. We assessed the repeatability of inhalation challenges using PGD2 and LTD4 in two groups of 10 asthmatic volunteers. Non-specific bronchial responsiveness was assessed by histamine inhalation challenges. 3. Using the Bland-Altman method, we found the coefficient of repeatability to be 1.2 doubling doses for LTD4 and 2.1 for PGD2 at a 1 week interval. 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 LTD4 challenge decreased significantly, mean PD20FEV1 increasing from 169 nmol on day 1 to 278 nmol on day 3 (P = 0.001), before returning to baseline levels. 5. A progressive decrease in non-specific bronchial responsiveness occurred following PGD2 challenge. Baseline PD20FEV1 was 195 nmol, increasing to 238 nmol by day 3 (NS) and 313 nmol by day 8 (P = 0.016). 6. PGD2 inhalation challenges performed a week apart are less reproducible than LTD4 challenges, possibly as a result of significant changes in histamine bronchial responsiveness. Our findings allow accurate power calculations to be made for studies to assess new pharmacological antagonists to these mediators.