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Clinical Investigations: ASTHMA |

Effects of Pranlukast on Chemical Mediators in Induced Sputum on Provocation Tests in Atopic and Aspirin-Intolerant Asthmatic Patients*

Yasushi Obase, MD; Terufumi Shimoda, MD; Shin-ya Tomari, MD; Kazuko Mitsuta, MD; Tetsuya Kawano, MD; Hiroto Matsuse, MD; Shigeru Kohno, MD, FCCP
Author and Funding Information

*From The Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.

Correspondence to: Yasushi Obase, MD, Skin and Allergy Hospital, Helsinki University Central Hospital, PO Box 160, HUS, Helsinki, Finland; e-mail: yasushi.obase@hus.fi



Chest. 2002;121(1):143-150. doi:10.1378/chest.121.1.143
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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, 11-dehydrothromboxane B2 (11-dhTXB2)/creatinine, serum 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.

Results: In 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 airways.

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