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To elucidate the cause of intractable asthma, guinea pigs were actively sensitized by intraperitoneal injection of ascaris suum as an antigen. We repeated the inhalation of aerosolized ascaris antigen eight times in the animal models which consisted of a non-treated group, a metopirone-treated group and a steroid-treated group. We investigated the course of asthmatic response by evaluating the ratio of expirations to inspirations after the inhalation challenge. The frequency of late asthmatic response (LAR) was increased by repeated inhalation of the antigen. There was no significant differnce in the frequency between non-treated group and steroid-treated group, but the metopirone-treated group showed strong LAR compared with the other two groups. The intensity of LAR was gradually increased and that of immediate asthmatic response (LAR) was decreased in the metopirone-treated group. Finally, we established a chronic asthma model in which LAR was strong and the asthma attack was prolonged over twenty-four hours. These results suggest that the model will be useful in clarifying the causes of intractable asthma in humans.

In investigating the etiological mechanisms of intractable asthma, ascaris suum was used as a sensitizing antigen in experimental animal models of re-inhalation in the late asthmatic response (LAR). Our results suggest that marked expiratory prolongation was caused by re-inhalation of the antigen in LAR. Moreover, the number of neutrophils and eosinophils increased in BALF after re-inhalation of the antigen more in LAR than in IAR (P