Sigenori Nakajima

Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients.

Background Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.

The effect of theophylline on blood and sputum eosinophils and ecp in patients with bronchial asthma

It was recently reported that theophylline has an anti-inflammatory and bronchodilating effect on bronchial asthma. Accordingly, to examine the anti-inflammatory effect of theophylline on asthma, especially its effect on eosinophil activation, a sustained-release theophylline preparation (Theolong) was administered (daily dose: 400 mg) to 18 patients with mild to moderate bronchial asthma. This was done in order to study the preparations effects on lung function, blood and sputum eosinophils and ECP four weeks pre- and post-administration. Lung function was determined by spirometry and sputum by induced sputum. Blood and sputum ECP levels were determined using an ECP RIA kit. In lung function, there were no differences in vital capacity (VC) or in forced expiratory volume 1 s (FEV 1.0) pre- and post-administration. There were also no differences in the number of blood and sputum eosinophils, but serum and sputum ECP levels decreased. Theophylline is thus expected to exert an inhibitory effect on eosinophil activation and it is suggested as an effective therapeutic drug for bronchial asthma.

The Effect of TYB-2285 on Dual Phase Bronchoconstriction and Airway Hypersensitivity in Guinea-pigs Actively Sensitized with Ovalbumin

Abstract— The effect of a new anti‐asthmatic drug, TYB‐2285 (3,5‐bis(acetoxyacetylamino)‐4‐chloro‐benzonitrile), was investigated in ovalbumin‐sensitized guinea‐pigs. When guinea‐pigs were pretreated with TYB‐2285 (300 mg kg−l, p.o., single dose or consecutively for 7 days), the immediate asthmatic response was inhibited as demonstrated by diminished cyanosis, but not the bronchoconstriction. TYB‐2285, given singly or consecutively, inhibited the appearance of late asthmatic response and the infiltration of inflammatory cells, such as eosinophils, into the airway. Additionally, airway hyper‐responsiveness was also reversed by the single administration of TYB‐2285. Luminol‐dependent chemiluminescence of airway‐infiltrated cells stimulated with A23187 was inhibited by TYB‐2285 in a dose‐dependent manner. The present study suggests that TYB‐2285 inhibits late asthmatic response and airway hyper‐responsiveness by inhibiting the accumulation of eosinophils and other inflammatory cells into the airway, and also by inhibiting the production of oxygen radicals from airway‐infiltrated cells.

Histopathology of the airway epithelium in an experimental dual-phase model of bronchial asthma

Lesions of trachea cuticles are a pathological histological characteristic of bronchial asthma. Furthermore, collected tracheal cuticles desquamated from the respiratory tract are found in patients’ sputum when asthma attacks occur or after the induction of allergen inhalation. From these facts, it is assumed that desquamation of trachea cuticle cells is a pathological symptom of bronchial asthma. However, there has not been any chronological report of desquamation of trachea cuticles through the process of bronchial asthma attacks.

Influence of Theophylline on Activated Lymphocytes and Eosinophils in Peripheral Blood and Sputum

The influence of a once-a-day sustained-release theophylline (Uniphyl®) on lymphocytes and eosinophils in the peripheral blood and sputum of patients with bronchial asthma was investigated. The peripheral blood lymphocytes included CD4, CD8, CD25 and HLA-DR. The sputum lymphocytes and eosinophils included CD4, CD8, CD25 and HLA-DR, and EG2, respectively. The results revealed that theophylline administration did not affect the numbers of activated CD4 and CD8 T lymphocytes in peripheral blood. No significant change in the lymphocyte count was observed in sputum, but the eosinophil count in the sputum decreased significantly after theophylline administration. EG2-positive eosinophils also decreased in number. CD4+HLA-DR+ and CD4+CD25+ T lymphocytes were significantly decreased, whereas CD8+ T lymphocytes in the sputum were not significantly reduced in number. Respiratory function test showed that forced expiratory volume in 1 s was significantly increased after theophylline administration. The results suggest that a new once-a-day sustained-release theophylline formulation would be useful in the treatment of chronic respiratory tract inflammation.

Effect of AA-2414 on Early and Late Bronchial Responses in Actively Sensitized Guinea-Pigs

The effect of a new thromboxane A2 receptor antagonist, AA-2414, (±)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid, on dual broncho-constriction and airway hyper-reactivity in actively sensitized guinea-pigs was investigated. Immediate and late bronchial responses were seen 1–10 min and 4–7 h, respectively, after inhalation of antigen. In guinea-pigs pretreated with AA-2414, 5 mg/kg orally, the immediate bronchial response was inhibited. An administration of AA-2414 inhibited the late bronchial response. The numbers of eosinophils, neutrophils and macrophages, but not of lymphocytes, in bronchoalveolar lavage fluid were increased at 4 h after antigen inhalation. AA-2414 did not affect the numbers of total cells, eosinophils, neutrophils or macrophages. Sensitized guinea-pigs showed a significant airway hyper-reactivity to inhaled histamine, which was not influenced by an administration of AA-2414. Luminol-dependent chemiluminescence of airway-infiltrated cells from sensitized guinea-pigs stimulated with A23187 was slightly inhibited by AA-2414. These results show that AA-2414 inhibits the late asthmatic response and the production of oxygen radicals from airway-infiltrated cells

Inhibitory effect of TMK-688 on late asthmatic responses as well as T-cell and eosinophilic infiltration in guinea pigs with asthmatic reactions.

The effects of an oral anti-allergic agent, TMK-688, which inhibits 5-lipoxygenase, at doses of 3.2 and 10 mg/kg were studied in guinea pigs with dual-phase asthmatic response. We previously observed that pretreatment with TMK-688 inhibited the late asthmatic response (LAR) induced by ovalbumin inhalation exposure. The present study focused on the effect of TMK-688 on infiltration by T-cells and eosinophils. TMK-688 inhibited both T-cell and eosinophilic infiltration. These findings suggest that TMK-688 is effective in inhibiting infiltration of T-cells and eosinophilic chemotaxis, and thereby suppresses LAR.

Inhibitory Effect of an Anti‐allergic Agent, TMK‐688, on Interleukin‐2 and Interleukin‐4 Release by Mite Antigen‐stimulated Monocytes From Peripheral Blood of Asthmatic Patients

The effect of an anti-allergic agent, TMK-688, which inhibits 5-lipoxygenase, on cytokine release by antigen-stimulated monocytes from peripheral blood of atopic asthmatic patients positive for mite antigen was studied. Monocytes were stimulated by mite antigen and then incubated for 72 h. The levels of interleukin-2 and interleukin-4 in the supernatant treated with TMK-688 (1 times 10−7 M) were significantly lower (P < 0.05 and P < 0.01, respectively) than levels in the untreated control. The findings suggest that TMK-688 is effective in treating bronchial asthma, as it not only inhibits 5-lipoxygenase but also has effects on T lymphocytes and inhibits various types of cytokine release.