Hikaru Kitani

Allergen- and Anti-IgE-Induced Histamine Release from Whole Blood

The release of histamine by allergen and anti-IgE from whole blood was observed in 34 asthmatic subjects with a positive skin test to house dust. The time course of histamine release showed that the release by allergen and anti-IgE peaked after 15 min incubation. There was no significant difference in the time course of the release from whole blood between allergen and anti-IgE. Anti-IgE-induced histamine release correlated to a certain extent with the serum IgE level. Histamine release by house dust, on the other hand, correlated with the radioallergosorbent test score. A striking difference was present in the dose-response slope between allergen and anti-IgE. The maximum percent release correlated with the dose-response slope by allergen, but not by anti-IgE. The amount of histamine release induced by anti-IgE paralleled the amount of the release by house dust in the cases sensitive to the allergen; less sensitive basophils to anti-IgE were less sensitive to house dust.

Changes in the Proportions of Bronchoalveolar Lymphocytes, Neutrophils and Basophilic Cells and the Release of Histamine and Leukotrienes from Bronchoalveolar Cells in Patients with Steroid-Dependent Intractable Asthma

The proportion of inflammatory cells in bronchoalveolar lavage (BAL) fluid and the release of chemical mediators from BAL and peripheral blood cells were examined in 40 patients with steroid-dependent intractable asthma (SDIA) to clarify the effects of a long-term glucocorticoid regimen on these cells. The proportion of BAL lymphocytes was significantly reduced (p < 0.01) and the proportion of BAL neutrophils was significantly increased (p < 0.01) in SDIA patients compared with non-SDIA patients. The proportion of basophilic cells (mast cells and basophils) in BAL fluid was significantly lower in SDIA patients compared to non-SDIA patients (p < 0.02). The values of six ventilatory parameters were significantly lower in SDIA patients with a high proportion of BAL neutrophils (more than 10%) compared with the values in non-SDIA patients. The release of histamine and leukotriene C4 (LTC4) from the BAL cells of patients with atopic asthma was significantly reduced in SDIA patients compared with non-SDIA patients (p < 0.05). These results show that the changes in the proportion of BAL cells are observed in patients with SDIA, and these changes are related to suppressed ventilatory function and a reduction in the release of histamine and LTC4 from BAL cells.

Mucus Hypersecretion and Eosinophils in Bronchoalveolar Lavage Fluid in Adult Patients with Bronchial Asthma

Mucus hypersecretion was clinically analyzed in 46 adult patients with bronchial asthma, including 22 with steroid-dependent intractable asthma (SDIA). A large amount of expectoration, over 50 ml/day, was observed in 16 of these patients (34.8%), of whom 12 (75.0%) had SDIA and 13 (81.3%) were women. The mean amount of expectoration increased with increasing patient age, although no significant difference was found among the six age groups. A large amount of expectoration (over 50 ml/day) was clearly correlated with an increased proportion of eosinophils in bronchoalveolar lavage (BAL) fluid. The proportion of BAL eosinophils was significantly higher in patients with expectoration between 50 and 99 ml/day (p < 0.05) and over 100 ml/day (p < 0.01) than in patients whose expectoration volume was between 30 and 49 ml/day. These results show that in bronchial asthma patients, mucus hypersecretion is more often observed clinically in those with SDIA and in women, and that this hypersecretion is closely correlated with BAL eosinophilia, which is a feature of the pathophysiological changes that occur in the airways of these patients.

Decrease in reactivity of basophils by immunotherapy with housedust extract

Changes of basophil reactivity to housedust extract and anti‐IgE during immunotherapy was examined in thirteen patients with bronchial asthma sensitive to housedust. (i) A significant decrease in the morphological reactivity of basophils to housedust extract was observed 6 months after the beginning of immunotherapy with the antigen, and a significant decrease after 12 and 18 months’ therapy, accompanied with the decrease of histamine release from the cells. The percent reactive basophils to the antigen decreased from 59.2 ± 2.9% before the therapy to 40.0 ± 1.8% after 18 months’immunotherapy. (ii) A decrease in the morphological reactivity of basophils to anti‐IgE was also shown during immunotherapy. The basophil reactivity to anti‐IgE decreased significantly at the late stage (18 months) of immunotherapy. (iii) A significant reduction of specific IgE antibody to housedust was observed 12 and 18 months after the beginning of immunotherapy. It was suggested from these results that immunotherapy causes some changes on the surface of basophils and decreased reactivity of the cells, and that a decrease of reactive basophils to anti‐IgE in the process of immunotherapy might be due to a decrease in number of IgE receptors essentially or functionally.

Effects of Long-Term Glucocorticoid Therapy on Bronchoalveolar Cells in Adult Patients with Bronchial Asthma

The effects of long-term glucocorticoid therapy on airway inflammation were examined in 84 asthma patients. The proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid was significantly decreased in patients with steroid-dependent intractable asthma (SDIA) compared to results in non-SDIA patients, while BAL neutrophils were significantly increased in SDIA patients compared to results in non-SDIA patients. Regarding age, in patients under the age of 69 (except those between 30 and 39), BAL lymphocyte number was significantly decreased in SDIA compared with non-SDIA subjects, and in patients between 50 and 69, BAL neutrophils were significantly increased in SDIA compared with non-SDIA subjects. The number of BAL lymphocytes was significantly lower in patients with serum cortisol levels of less than 5.0 micrograms/dl than in those with levels of more than 5.1 micrograms/dl. BAL lymphocyte number was also significantly lower in patients who had received glucocorticoid therapy for more than 6 years than in those who had received such therapy for 2 years. These results show that long-term glucocorticoid therapy decreases the number of lymphocytes and increases neutrophil numbers in the airways.

Effects of Glucocorticoids on Humoral and Cellular Immunity and on Airway Inflammation in Patients with Steroid-Dependent Intractable Asthma

The effects of glucocorticoids on the proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid in relation to humoral and cellular immunity were studied in 56 patients with steroid-dependent intractable asthma. To analyze the mechanism responsible for reduced numbers of BAL lymphocytes, we divided the subjects into 4 groups according to their BAL lymphocyte proportions: 0-4.9%, 5.0-9.9%, 10.0-14.9%, and 15.0-20.0%. Serum IgG levels and the peripheral lymphocyte count were significantly reduced in patients with a low proportion of BAL lymphocytes (less than 9.9%) than in those with more than 10% BAL lymphocytes. Delayed cutaneous reactivity to purified protein derivative was suppressed in patients with a low proportion of BAL lymphocytes (less than 4.9%). The mean proportion of BAL neutrophils tended to increase as the proportion of BAL lymphocytes decreased. These results show that the reduction in BAL lymphocytes produced by glucocorticoids is associated with suppressed humoral and cellular immunity, and that under such conditions the proportion of BAL neutrophils increases.

An Increased Level of Specific IgG4 Antibodies Against Candida albicans in Patients with Bronchial Asthma

Specific IgG4 antibodies against Candida albicans in sera were measured in 76 asthmatics. The increased level of specific IgG4 was found in cases 10-40 years old sensitive to house dust mite and/or Candida albicans, in cases with steroid-dependent intractable asthma (SDIA) and in elderly cases. The frequency of SDIA was the highest in cases 41 to 60 years old with higher frequency of increased IgG4 antibodies. The results show that specific IgG4 increases in relation to IgE-mediated immune response, long-term steroid therapy, and aging. All of these conditions may induce depressed cell-mediated immunity.