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기관지 천식환자의 중증도에 따른 기관지 폐포 세척액과 기관지 점막 병리 소견에 관한 연구
조상헌,조영주,최동철,민경업,김유영,김건열,이건국,서정욱 대한천식알레르기학회 1991 천식 및 알레르기 Vol.11 No.4
This study was designed to evaluate the cellular component in bronchoalveolar lavage fluid (BALF) and histologic abnormalities in asthmatics according to the severity of asthma and their pathogenetic roles. Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 4 nonasthmatic controls. Total cell counts in BALF showed no difference between asthmatics and controls, but the proportions of epithelial cells and eosinophils were significantly increased in asthmatics and showed significant correlations with PC20 Meth. Light microscopic exarnination revealed loss of epithelium, inflammatory cell infiltrations and thickening of basement membrane which also showed significant correlation with PC20 Meth Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma, Ultrastrutural examination revealed that basement membrane thickening on light micoscopic examination is due to the increased subepithelial collagen deposition with normal thickness of basal lamina, These data suggested that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and nonspecific bronchial hyperresponsiveness And these data can be applied to the studies of drug which prevents irreversible pathologic changes of bronchial asthma,
Pharmacogenomic Approaches to Asthma Treatment
조상헌 대한천식알레르기학회 2010 Allergy, Asthma & Immunology Research Vol.2 No.3
Major classes of medication in asthma management include bronchodilating B2-agonists, anti-inflammatory inhaled corticosteroids, leukotriene modifiers and theophyllines. However, all asthmatics do not respond to the same extent to a given medication. Available data suggest that a substantial range of individual variability, as much as 70%, may be due to genetic characteristics of each patient. Pharmacogenomics offers the potential to optimize medications for individual asthmatics by using genetic information to improve efficacy or avoid adverse effects. The best-studied case of the potential contribution of pharmacogenomics to treatment response in asthma comes from studies on human B2 adrenergic receptors. In addition, genetic variation in B2-adrenergic receptor (Arg16Gly) may predict response to anticholinergics for the treatment of asthma. In case of inhaled corticosteroids, a recent investigation using a traditional SNP-based approach identified a gene for corticotropin releasing hormone receptor 1as a potential marker of response. Another major pathway that has been investigated is the pathway underlying response to cysteinyl leukotriene receptor antagonist. It is likely that in the near future, pharmacogenomic approaches based on individual genetic information will be introduced into an asthma treatment guideline and this guideline will allow us to identify those who have the best chance to respond to a specific medication.
아토피 환자에서 IgE항체 생성 조절기전 : 말초혈액 림프구의 IL - 4 , IFN - γ생성의 불균형
조상헌,송숙희,김윤근,지영구,최동철,윤호주,민경업,김유영 대한천식알레르기학회 1995 천식 및 알레르기 Vol.15 No.2
IgE antibodies play a major role in the development of stopic disease because they bind to high affinity receptors on mast cells and basophils and when cross linked by allergen cause cellular degranulation with the release of vasoactive amines. After discovery of IgE rnolecule by Ishizaka in 1966, there has been many studies about IgE synthesis and its regulation. Recent- ly, it has been demonstrated that IL-4 induce IgE synthesis in vitro from mononuclear cells isolated from peripheral blood, tonsils and spleens of healthy persons and IL 4 induced IgE synthesis is blocked by IFN . Spontaneous IgE synthesis in vitro from mononuclear cells of atopic patients is also higher than that from healthy persons. There is evidence that IL-4 and IFN y are produced by different subsets of helper T cell, TH1 and TH2 cell. IL-4 is produced by TH2, while IFN y is produced by TH1. The differences of IL-4 and IFN y secretion by allergen and mitogen between atopic patients and healthy persons are not clear until now. To investigate the differences of IL-4 and IFN-y secretion by allergen and mitogen between atopic patients and healthy subjects, concentrations of IL 4 and IFN y in the culture supernatants stimulated with and without mitogens and allergens were measured by ELISA rnethod. The results are as follows .1) IL 4 levels in culture supernatants of PBMNCs were increased by stimulation with PMA and calcium ionophore A 23187 and allergen in both group. In atopic patients sctivation of PBMNCs resulted in higher levels of IL 4 than those of healthy controls. 2) There was a significant correlation between IL-4 level in culture supernatant of PBMNCs stirnulated with PMA and calcium ionophore A 23187 and serum total IgE (r=0. 57, p<0.05). And there was a significant correlation bet,ween IL 4/IFN y ratio and serum total IgE(r=0.48, P<0.05). 3) In atopic patients, activation of PBMNCs resulted in lower levels of IFN y than those of healthy controls. There was no significant correlation between the levels of IFN y in cultures supernatant stimulated with PMA and calcium ionophore and serum total IgE(r=0.35, p>0. 05). These results suggest that high levels of IgE antibody in serum of atopic patients may be due to imbalance of IL-4 and IFN y secreting capacities of atopic patients.