Mitsunobu, Fumihiro

Bronchial asthma was classified by the pathophysiology and by the mechanism of onset of the disease. Forty asthmatics who had serum IgE levels lower than 200 IU/ml were evaluated by two classification methods. 1. In asthma classified by a score based on clinical findings and examinations, the characteristics of the findings and examination results were compared among three asthma types, i.e., Ia. simple broncho-constriction type, Ib. bronchoconstriction+hypersecretion type, and II. bronchiolar obstruction type. Type Ib patients, in addition to manifesting hypersecretion, had a significantly higher proportion of eosinophils in the bronchoalveolar lavage (BAL) fluid compared to other asthma types. Significantly decreased values for ventilatory parameters and an increased proportion of BAL neutrophils were found in type II compared with other asthma types. 2. In a new classification by mechanism of onset, asthma was classified into three types according to the degree of participation of IgE-mediated reactions associated with specific IgE antibodies and serum levels of total IgE: asthma induced by definite IgE-mediated reaction (atopic asthma), possible IgE-mediated reactions (asthma), and asthma induced by non-IgE-mediated reaction (asthma syndrome).

Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001) and adults (r = 0.629, p less than 0.01). However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.

Immunoallergological studies were carried out to clarify the differences between 24 patients with drug-induced asthma (DIA) and 240 with non-drug-induced asthma (non-DIA). The mean values of age, skin reaction to Candida albicans (C. albicans), serum IgE levels, specific IgE antibodies to house dust (HD) and C. albicans, bronchial sensitivity and leukotriene B4 (LTB4) synthesis from peripheral venous blood in patients with DIA were not significantly different from those in patients with non-DIA. In contrast, the frequency of positive skin reaction to HD and histamine release from peripheral basophils by anti-IgE were significantly lower in DIA than in non-DIA. These results agree with the reports that DIA was often observed in non-atopic asthma. But, the mean value of serum IgE was very high in DIA as well as in non-DIA. This result suggests that IgE mediated reaction in DIA is important. Furthermore, the proportion of neutrophils in bronchoalveolar lavage fluid (BALF) was significantly lower in DIA than in non-DIA. Our findings suggest that a decrease of intrapulmonary neutrophils might play an important role in the pathophysiology of DIA.

The effects of long-term glucocorticoid therapy on chemical mediator and cellular reaction in the airways were examined in 69 patients with bronchial asthma. The histamine release induced by Ca ionophore A23187 from cells in the bronchoalveolar lavage (BAL) fluid of atopic asthmatics was significantly lower in the subgroup with steroid-dependent intractable asthma (SDIA) than in non-SDIA patients (p < 0.05). In contrast, histamine release in nonatopic SDIA patients did not differ from nonatopic non-SDIA patients. The release of leukotriene C4 (LTC4) was significantly lower in atopic patients with SDIA (p < 0.02). However, there was no significant difference in LTC4 release between nonatopic patients with SDIA and without SDIA. The proportion of BAL lymphocytes was significantly lower in atopic patients with SDIA than in those without it (p < 0.05), although there was no significant difference between the nonatopic patients with and without SDIA. These results show that glucocorticoids affect humoral and cellular events in the airways of atopic asthmatics more than in those of nonatopic asthmatics.

Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C. albicans). The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old. The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01). The C. albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05). The delayed skin reaction to PPD and C. albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml. Delayed skin reaction to PPD and C. albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C. albicans-induced reaction.