Anti-inflammatory Effect of Suplatast Tosilate on Mild Asthma

Abstract

Inhaled corticosteroids are generally recognized as effective in the suppression of eosinophil proliferation and migration into the bronchial mucosal of asthmatics.1Barnes PJ. Drug therapy: inhaled glucocorticoids for asthma.N Engl J Med. 1995; 332: 868-875Crossref PubMed Scopus (633) Google Scholar Suplatast tosilate (IPD; Taiho; Tokyo, Japan) is a novel capsular antiasthmatic drug that suppresses both IgE production and eosinophil infiltration through selective inhibition of interleukin (IL)-4 and IL-5 synthesis by helper T cells.2Yamaya H Basaki Y Togawa M et al.Down-regulation of Th2 cell-mediated murine peritoneal eosinophilia by antiallergic agents.Life Sci. 1995; 56: 1647-1654Crossref PubMed Scopus (98) Google Scholar The clinical and anti-inflammatory effects of IPD were assessed by symptom score, provocative concentration of histamine causing a 20% fall in FEV1, (PC20-histamine), induced sputum, and bronchial biopsy before and after 6 weeks of treatment with IPD capsules (300 mg/d tid or 400 mg/d bid) in patients with mild asthma. Eleven randomly selected patients aged 36 to 68 years (mean, 47.3 years) were treated with mild bronchodilators alone. The study protocol was approved by the Ethics Committee of Doai Memorial Hospital, and all subjects gave written informed consent. PC20-histamine was measured by the tidal breathing method after withdrawal of medications for at least 12 h. Sputum was collected by stepwise inhalation challenge with hypertonic saline (3 to 5%). Bronchial biopsy specimens were obtained from several bifurcations in eight patients by fiberoptic bronchoscopy. Bronchial mucosal tissues and induced sputum were stained with hematoxylin-eosin and with a monoclonal antibody against eosinophil cationic protein (anti-EG2; Pharmacia; Uppsala, Sweden) for immunohistochemical evaluation. Stained mucosal cells were counted according to the method of Moqbel et al,3Moqbel R Barkans J Kay AB et al.Application of monoclonal antibodies against major basic protein (BMK-13) and eosinophil cationic protein (EG1 and EG2) for quantifying eosinophils in bronchial biopsies from atopic asthma.Clin Exp Allergy. 1992; 22: 265-273Crossref PubMed Scopus (93) Google Scholar and such cells in the sputum were also counted and expressed as a percentage of 500 cells. As shown in Table 1, IPD caused a significant improvement in the PC20-histamine value, a significant reduction in the percentage of eosinophils in induced sputum, and a significant reduction in the number of eosinophils and EG2-positive cells in the bronchial mucosal tissues. Hematoxylin-eosin-stained bronchial mucosal tissues showed a clear reduction in mucosal eosinophil infiltration after IPD administration.Table 1Effects of IPD TherapyCharacteristicNo.Before IPD*Values±SE.After IPD*Values±SE.p ValuePC20-histamine, µg/mL10527919<0.05Sputum eosinophils, %1111.6 ± 2.16.0 ± 1.6<0.05Bronchial eosinophils, cells/mm2Yamaya H Basaki Y Togawa M et al.Down-regulation of Th2 cell-mediated murine peritoneal eosinophilia by antiallergic agents.Life Sci. 1995; 56: 1647-1654Crossref PubMed Scopus (98) Google Scholar8390.3 ± 98.890.0 ± 15.4<0.05Biopsy EG2, cells/mm2Yamaya H Basaki Y Togawa M et al.Down-regulation of Th2 cell-mediated murine peritoneal eosinophilia by antiallergic agents.Life Sci. 1995; 56: 1647-1654Crossref PubMed Scopus (98) Google Scholar8303.5 ± 83.362.0 ± 11.2<0.05* Values±SE. Open table in a new tab An ongoing airway mucosal inflammatory process has been demonstrated in patients with mild or asymptomatic asthma, characterized by eosinophilic and lymphocytic infiltrates, secondary epithelial injury, and subepithelial fibrosis.4Chung KF Durham SR. Asthma as an inflammatory disease: clinical perspectives.Br Med Bull. 1992; 48: 179-189PubMed Google Scholar The considerable eosinophil infiltration in the airway of patients with mild asthma observed in the recent study suggests the necessity of inhibiting eosinophil infiltration even in patients with mild asthma. In summary, asthmatic patients treated with IPD showed parallel changes in inhibition of eosinophil infiltration and improvement in bronchial hyperresponsiveness, suggesting that IPD may be as useful to treat mild bronchial asthma as inhaled corticosteroids.