Metzger W J, Zavala D, Richerson H B, Moseley P, Iwamota P, Monick M, Sjoerdsma K, Hunninghake G W
Am Rev Respir Dis. 1987 Feb;135(2):433-40. doi: 10.1164/arrd.1987.135.2.433.
The local mechanisms that result in the cellular inflammation and bronchial airway hyperreactivity that characterize allergic bronchial asthma are poorly defined. In order to study these processes, we developed a method for local allergen challenge using a fiberoptic bronchoscope and direct observation and bronchoalveolar lavage (BAL) to assess the airway responses to allergen. In these studies, 11 allergic asthmatics (all of whom had previously demonstrated a late-phase asthmatic response to aeroallergen challenge) and 6 healthy, asymptomatic subjects volunteered to undergo bronchoalveolar lavage after local airway challenge via a bronchoscope wedged into subsegmental airways. These studies revealed that asthmatic airways respond to allergen with an immediate pallor followed by reactive hyperemia, edema, and bronchial narrowing. This site and a control site were relavaged at 48 or 96 h after the immediate response. Neutrophils and eosinophils increased significantly at 48 h after challenge, as did helper T-lymphocytes. Characteristically, at 96 h, neutrophil counts returned to normal values, whereas eosinophiles and helper T-cells remained elevated. Peroxidase-staining cells were also elevated at 48 h after local allergen challenge. Electron microscopy revealed degranulation of mast cells and eosinophils, both immediately and later (48 and 96 h) after local allergen challenge. Macrophages were highly activated and had phagocytized, partially intact granules from both eosinophils and mast cells. There was a significant correlation (p less than 0.001) between the concentration of allergen required to produce a visible airway response and a positive end-point skin titration in the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
导致过敏性支气管哮喘特征性细胞炎症和支气管气道高反应性的局部机制尚不清楚。为了研究这些过程,我们开发了一种使用纤维支气管镜进行局部变应原激发的方法,并通过直接观察和支气管肺泡灌洗(BAL)来评估气道对变应原的反应。在这些研究中,11名过敏性哮喘患者(所有患者先前均已证明对气传变应原激发有迟发性哮喘反应)和6名健康无症状受试者自愿在通过楔入亚段气道的支气管镜进行局部气道激发后接受支气管肺泡灌洗。这些研究表明,哮喘气道对变应原的反应先是立即苍白,随后是反应性充血、水肿和支气管狭窄。在即刻反应后48或96小时对该部位和对照部位再次进行灌洗。激发后48小时,中性粒细胞和嗜酸性粒细胞显著增加,辅助性T淋巴细胞也是如此。典型的是,在96小时时,中性粒细胞计数恢复到正常水平,而嗜酸性粒细胞和辅助性T细胞仍保持升高。局部变应原激发后48小时,过氧化物酶染色细胞也升高。电子显微镜显示,局部变应原激发后即刻以及之后(48和96小时)肥大细胞和嗜酸性粒细胞均出现脱颗粒。巨噬细胞被高度激活,并吞噬了嗜酸性粒细胞和肥大细胞的部分完整颗粒。在哮喘患者中,产生可见气道反应所需的变应原浓度与阳性终点皮肤滴定之间存在显著相关性(p小于0.001)。(摘要截短于250字)