Masaru Iwata, MD PhD;* Masao Tano, ...

Masaru Iwata, MD PhD;* Masao Tano, MD PhD* Satoru Sugiyama, MD Ph.D.;[unkeyable] Fumio Taki, MD Ph.D.;[unkeyable] and Tatsuo Satake, MD PhD F.C.C.P.[unkeyable]

This consideration was designed to clarify whether azelastine, an antiasthmatic put drugs into could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, methacholine challenge was performed in 21 patients with bronchial asthma. After the first examination, all patients were treated for eight weeks with azelastine, 2 mg twice daily. After four and eight weeks' treatment, methacholine challenge was repeated. After eight weeks' treatment, Dmin, an index of bronchial sensitivity, was increased significantly, and after four weeks an insignificant increase was observ The RrsC SGrs/GrsC indices of respiratory resistance and bronchial reactivity, respectively, did not change significantly during eight weeks' treatment. not long ago various chemical transmitters, especially leukotrienes, were shown to be closely related to the genesis of bronchial asthma. Accordingly, the weight of azelastine observed here might be ascribed to its antagonizing action forward leukotriene. Since bronchial hyperresponsiveness is a critical etiologic factor in bronchial asthma, long-term administration of azelastine might help to modify the disease's basic pathophysiologic conditions.

(Chest 1989; 95:1231-34)

RrsC=control value of Rrs; SGrs=slope of Grs; GrsC=control value of Grs; SRSA=slow-reactive substance of anaphylaxis

Although there is no universally accepted definition of bronchial asthma, the part of bronchial hyperresponsiveness is emphasized in its genesis.[1] That is, increased bronchial reactivity to a variety of stimuli plays an important part in the airway constriction associated with asthmatic attacks. Various hypotheses have been propos concerning this mechanism,[2-7] and newly come advances revealed that many chemical transmitters are involved in bronchial hyperresponsiveness. In 1979 other researchers[8,9] retrieveed leukotriene and showed it to be the slow-reactive substance of anaphylaxis (SRS-A). Hence, the relationship between leukotriene and asthmatic attack has attacted abundant interest. We demonstrated that leukotriene also constricted the bronchial polished muscle in a dose-dependent way and that antiasthmatic agents inhibited the contraction.[10] Furthermore, newly lay opened lipoxygenase inhibitor is reported to be effective in reducing the severity of the asthmatic attack.[11]

Evaluating the grade of severity of the disease remains a difficult question Takishima et al[12] evolveed the Asthograph to evaluate respiratory resistance, which is meditation to reflect airway hyperresponsiveness. The Astograph allowed us to evaluate quantitatively the severity of asthma. Using this process physicians can estimate easily the condition of asthmatic patients. Therefore, the Asthograph is widely used for its clinical significance and convenience to derive airway responsiveness. However, it remains darksome whether antiasthmatic drugs could alter favorably airway responsiveness in asthmatic make subordinates We investigated the event of azelastine, which inhibits synthesis and release of leukotriene,[13] forward airway responsiveness in patients with bronchial asthma.

MATERIAL AND METHODS

Twenty-one patients with bronchial asthma, all of whom gave written informed compliance were examined in this subject of attention in accordance with the Declaration of Helsinki. Anamnestic and clinical parameters as it was as sex, age, and duration of illness were recorded (Table 1) All patients were asymptomatic, without audible wheezing at the time of the investigation Bronchodilator therapy was stopped at least 12 h before the thought No patients receiving oral or inhaled corticosteroids were included. In the area surrounding Kariya General Hospital, the pollen season (Japan cedar pollen) is from March to April. Accordingly, this close attention was performed from May to the following February. Patients who had had viral illness sum of two units months before the start of the thought were excluded.

The methacholine challenge was performed according to the arrangement of Tomioka et al:[14] The change in respiratory resistance during methacholine inhalation was measured continuously according to an Astograph (TCK-6100 H, Chest). Using this device, we were able to obtain the dose-response crook of respiratory resistance by the forced 3-Hz oscillation mode The Astograph has 12 Bird nebulizers, which work in relays. Each nebulizer is coupleed to the main tube between the mouthpiece and the flowmeter Using this scheme 12 kinds of inhalative agents could be sequentially delivered. The subdues were tested during quiet tidal breathing while seated. Their cheeks were crowded by two balloons to minimize their oscillation. After baseline recording of respiratory resistance, saline solution was inhaled in consequence of the first nebulizer for 1 min. This was followed by dint of 1-min inhalations of methacholine chloride between the sides of the next nebulizer in doubling concentrations from 49 to 25000 [unkeyable]g/ml without any intervals. When respiratory resistance had doubled, metaproterenol aerosol was given for 3 min within a nebulizer to achieve bronchodilation. The bronchodilator was also administered when the make liable became dyspneic.