Effects of pranlukast on chemical mediators in induced sputum on provocation tests in atopic and aspirin-intolerant asthmatic patients.
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 LTC(4)-LTD(4), eosinophil cationic protein (ECP), eosinophil count, urinary LTE(4)/creatinine, 11-dehydrothromboxane B(2) (11-dhTXB(2))/creatinine, serum LTC(4)-LTD(4), 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.


RESULTS
In the HDM group, IAR and LAR were observed. Sputum LTC(4)-LTD(4) and urinary LTE(4)/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 FEV(1) 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-dhTXB(2)/creatinine, increased the levels of sputum LTC(4)-LTD(4) and ECP and urinary LTE(4)/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 LTC(4)-LTD(4) and urinary LTE(4)/creatinine in the stable phase in the ASA group were significantly greater than those in the HDM group.


CONCLUSIONS
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 airways.
Obase
Yasushi
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. yasushi.obase@hus.fi
Shimoda
Terufumi
T
Tomari
Shin-ya
SY
Mitsuta
Kazuko
K
Kawano
Tetsuya
T
Matsuse
Hiroto
H
Kohno
Shigeru
S
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001798:Blood Proteins / Q000032:analysis; D001985:Bronchial Provocation Tests; D002867:Chromones / Q000008:administration & dosage* / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count; D017998:Leukotriene D4 / Q000032:analysis*; D017999:Leukotriene E4 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000032:analysis
D018927:Anti-Asthmatic Agents; D001798:Blood Proteins; D002867:Chromones; D047091:Eosinophil Granule Proteins; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D017998:Leukotriene D4; D017999:Leukotriene E4; D012260:Ribonucleases; D001241:Aspirin; C047681:pranlukast