Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine
- Siobhan O’Sullivana,
- Sven-Erik Dahlena,
- Kjell Larssonb,
- Britt-Marie Larssonb,
- Per Malmbergb,
- Maria Kumlina,
- Lena Palmbergb
- aExperimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, bNational Institute for Working Life, Solna, Sweden
- Dr L Palmberg, Department of Occupational Health, National Institute for Working Life, Solna, Sweden.
- Received 27 January 1998
- Revision requested 30 March 1998
- Revised 24 June 1998
- Accepted 13 July 1998
Abstract
BACKGROUND Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear.
METHODS Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E4(LTE4) and 9α,11β-PGF2, the earliest appearing urinary metabolite of prostaglandin D2(PGD2), were measured. Bronchial responsiveness to methacholine 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). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and pre-challenge levels of LTE4 (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p<0.01) and 9α,11β-PGF2 (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-fold increase in the total cell number and a 12-fold increase in IL-8 levels in 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 bronchial responsiveness following inhalation of organic swine dust.
