Background: Leukotrienes (LTs) are
important in asthma, and LT modifiers modulate antigen-induced asthma.
Overproduction of LT by suppression of cyclooxygenase activity is
involved in patients with aspirin-intolerant asthma (AIA).
Methods: House dust mite (HDM) inhalation provocation tests
were performed in HDM-sensitive asthmatic inpatients without AIA (HDM
group; n = 6), and aspirin oral provocation tests were performed in
AIA patients (ASA group; n = 7). Tests were repeated using the same
regimen after 7 days of treatment with pranlukast, an LT receptor
antagonist (LTRA). The effects of pranlukast on changes in sputum
LTC4-LTD4, eosinophil cationic protein (ECP),
eosinophil count, urinary LTE4/creatinine,
LTC4-LTD4, ECP, and peripheral blood eosinophil
count, during immediate asthmatic reaction (IAR) and late asthmatic
reaction (LAR) in the HDM group and during IAR in the ASA group for
each test, were compared in each group.
the HDM group, IAR and LAR were observed. Sputum
LTC4-LTD4 and urinary
LTE4/creatinine increased significantly both during IAR and
LAR. Sputum ECP increased during IAR and further increased during LAR.
Eosinophil count in the sputum did not increase during IAR but
significantly increased during LAR. Pranlukast suppressed the fall in
FEV1 both during IAR and LAR (73.8% and 51.9%,
respectively) and inhibited the increase in sputum eosinophil count
during LAR and sputum ECP during IAR and LAR. In the ASA group,
aspirin-induced IAR was associated with a fall in urinary
11-dhTXB2/creatinine, increased the levels of sputum
LTC4-LTD4 and ECP and urinary
LTE4/creatinine. Pranlukast suppressed IAR and inhibited
the increase of the level of sputum ECP, but failed to change
aspirin-induced LT production in the sputum and urine. The levels of
sputum LTC4-LTD4 and urinary
LTE4/creatinine in the stable phase in the ASA group were
significantly greater than those in the HDM group.
Conclusion: Our results indicated that HDM-provoked asthma
is associated with overproduction of LT with an antigen-antibody
reaction, while AIA is associated with overproduction of LT with a
shift to the 5-lipoxygenase series of the arachidonate cascade. LTRA
may be useful against both types of asthma through inhibition of LT
activity and eosinophilic inflammation of the