Studies on the regulation of eosinophils in bronchial asthma Part 2. Migratory responses of eosinophils from asthmatics

Eosinophil infiltration in lung tissue is one of the characteristic features of bronchial asthma. Such cell infiltration seems to be induced by the eosinophil chemotactic factor (ECF). PAF and IL-5 are potent chemoattractants and activators for eosinophils. To evaluate the reactivity of eosinophils in asthmatics under various conditions, the migratory function of eosinophils to PAF and IL-5 was investigated by the modified Boyden chamber method. Eosinophils of asthmatics were highly purified using a flow cytometric method previously reported. The migratory response of the eosinophils of asthmatics was greater than that of healthy suljects. Eosinophils from atopic asthmatics showed a higher response to PAF than those from non-atopic asthmatics. Eosinophils in the attack stage showed a higher response than those in the non-attack stage. Hypodense eosinophils showed an increased migratory response. The migratory response was correlated to the serum concentration of ECP and blood eosinophil count. These findings suggest that the reactivity of eosinophils is heterogenous and relates to the degree of eosinophilia, and that IL-5 as well as PAF plays an important role in the pathogenesis of bronchial asthma

Studies on the regulation of eosinophils in bronchial asthma Part 1. Characterization of eosinophil chemotactic factor (ECF) derived from peripheral blood mononuclear cells stimulated with Candida antigen

Eosinophilic infiltration in bronchial tissue is characteristic in the pathogenesis of bronchial asthma. The eosinophil chemotactic factor (ECF) derived from mononuclear cells has been reported to have some effect on the cell infiltration, and interleukin-5 (IL-5), a lymphokine derived from T lymphocytes, to be a factor related to growth, chemotaxis and activation for eosinophils. Lymphocytes accumulated in the bronchoalveolar lavage fluids of non-atopic and severe asthmatics have been shown to be highly responsive to Candida antigen, and high ECF production was observed in non-atopic and severe asthmatics by measurement of ECF activity in the supernatant of peripheral blood mononuclear cells cultured with Candida antigen. In this report, the molecular weight by gel filtration and inhibition test using anti-murine IL-5 antibody were studied to characterize the lymphocyte-derived ECF. Gel filtration analysis of the ECF indicated a molecular weight of 20,000 to 65,000 Da with a peak of activity around 40,000 to 50,000 Da. The ECF activity was reduced by incubation with anti-murine IL-5 antibody, which suggests that the supernatant contains IL-5. ECF from mononuclear cells, containing IL-5, may play an important role in the pathogenesis of eosinophil infiltration in non-atopic and severe asthmatics

Studies on the regulation of eosinophils in bronchial asthma Part 1. Characterization of eosinophil chemotactic factor (ECF) derived from peripheral blood mononuclear cells stimulated with Candida antigen

Eosinophilic infiltration in bronchial tissue is characteristic in the pathogenesis of bronchial asthma. The eosinophil chemotactic factor (ECF) derived from mononuclear cells has been reported to have some effect on the cell infiltration, and interleukin-5 (IL-5), a lymphokine derived from T lymphocytes, to be a factor related to growth, chemotaxis and activation for eosinophils. Lymphocytes accumulated in the bronchoalveolar lavage fluids of non-atopic and severe asthmatics have been shown to be highly responsive to Candida antigen, and high ECF production was observed in non-atopic and severe asthmatics by measurement of ECF activity in the supernatant of peripheral blood mononuclear cells cultured with Candida antigen. In this report, the molecular weight by gel filtration and inhibition test using anti-murine IL-5 antibody were studied to characterize the lymphocyte-derived ECF. Gel filtration analysis of the ECF indicated a molecular weight of 20,000 to 65,000 Da with a peak of activity around 40,000 to 50,000 Da. The ECF activity was reduced by incubation with anti-murine IL-5 antibody, which suggests that the supernatant contains IL-5. ECF from mononuclear cells, containing IL-5, may play an important role in the pathogenesis of eosinophil infiltration in non-atopic and severe asthmatics

Cross-reactivity of chironomid midge antigens in patients with bronchial asthma

In order to better understand the characteristics of bronchial asthma caused by chironomid midges, cross-reactivity of midges was examined in 163 asthmatics through observation of skin reactions and specific IgE and histamine release. Positive skin reactions were observed in 17 of 73 asthmatics (23.3%) for Chironomus plumosus, 89 of 276 (32.2%) of those for Tokunagayusurika akamusi, and 33 of 128 (25.8%) of those for Chironomus yoshimatsui. Two cases of 32 (6.3%) asthmatics for Chironomus plumosus, 16 of 144 (11.1%) of those for Tokunagayusurika akamusi, and 7 of 77 (9.1%) of those for Chironomus yoshimatsui showed a significant amount of histamine release (more than 15%). Cross-reactivity was present for Chironomus plumosus, Tokunagayusurika akamusi, Chironomus yoshimatsui, by both skin tests and basophil histamine release. It is suggested that both the male and female of Chironomus plumosus have common antigenecity, and cross-reactivity was observed between them

Addition of Leukotriene Receptor Antagonists to Inhaled Corticosteroids Improved QOL of Patients with Bronchial Asthma Surveyed in Suburban Tokyo, Japan

Background: Bronchial asthma is a chronic inflammatory disease that has a severe impact on health worldwide. Methods: A survey of 10,771 patients with bronchial asthma in the Tama region, Tokyo was conducted for 5 years to examine treatment and quality of life (QOL). Subjects were patients aged ≥16 years and their physicians who replied to a questionnaire sent in November from 2002 to 2006. Symptoms of bronchial asthma, visits to an emergency room, use of drugs, and severity of asthma were investigated. Results: Asthmatic symptoms improved over the 5 years, with a reduction in the number of emergency room visits. Since inhaled corticosteroids (ICS) were used by >80% of patients in 2002, we suspected that increased use of concomitant leukotriene receptor antagonists (LTRA) and long-acting β2 agonists (LABA) might have contributed to these findings. The effects of these drugs were compared between ICS + LTRA (n = 45) and ICS + LABA (n = 54) groups of patients. There was no significant difference in the ICS dose between these groups. In the ICS + LABA group, 18.5% and 22.2% of patients visited an emergency room before and after initiation of combination therapy, respectively, with no statistically significant difference. In contrast, the rate of emergency room visits in the ICS + LTRA group decreased from 24.4% to 6.6% after addition of LTRA. Conclusions: These results suggest that the frequency of visits to an emergency room was decreased by complementing the anti-inflammatory effect of ICS with further treatment of inflammation, particularly with LTRA

Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

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