Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine
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 9
,11
-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
9
,11
-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.
© 1998 by Thorax
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