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Thorax 1998;53:1041-1046 ( December )

Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine

Siobhan O'Sullivan,a Sven-Erik Dahlen,a Kjell Larsson,b Britt-Marie Larsson,b Per Malmberg,b Maria Kumlin,a Lena Palmbergb

a Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, b National Institute for Working Life, Solna, Sweden

Correspondence to: Dr L Palmberg, Department of Occupational Health, National Institute for Working Life, Solna, Sweden.

Received 27 January 1998; Returned to authors 30 March 1998; Revised version received 24 June 1998; Accepted for publication 13 July 1998

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 9alpha ,11beta -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 9alpha ,11beta -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.

Keywords: swine dust; leukotrienes; prostaglandin D2


© 1998 by Thorax



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