Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D-2, and bronchial responsiveness to methacholine

Background-Acute exposure of healthy subjects to swine house dust causes in creased bronchial responsiveness to methacholine but no acute bronchoconstr iction. The role of cysteinyl leukotrienes and mast cells in increased bron chial responsiveness is unclear. Methods-Ten non-asthmatic subjects were exposed to swine dust for three hou rs while weighing pigs in a piggery. Urine was collected prior to and for u p to 12 hours after entering the piggery and at the same times five days be fore and the day after exposure. As indices of whole body leukotriene produ ction and mast cell activation, urinary levels of leukotriene E-4 (LTE4) an d 9 alpha,11 beta-PGF(2), the earliest appearing urinary metabolite of pros taglandin D-2 (PGD(2)), were measured. Bronchial responsiveness to methacho line was determined five days before and the day after the exposure. Results-Methacholine PD20FEV1 decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p<0.01). A ssociated with the increase in bronchial responsiveness there was a signifi cant mean difference between post- and prechallenge levels of LTE4 (differe nce 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p<0.01) and 9 alpha,11 b eta-PGF(2) (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p<0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fol d increase in the total cell number and a 12-fold increase in IL-8 levels i n the nasal lavage fluid. The levels of LTB4 and LTE4 in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. Conclusions-The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased b ronchial responsiveness following inhalation of organic swine dust.