Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation.
Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation.
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过敏性哮喘肺部的局部过敏原激发和支气管肺泡灌洗。
DOI：
10.1164/arrd.1987.135.2.433
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Hunninghake,GW
中科院分区：
文献类型：
--
作者：
Metzger,WJ;Zavala,D;Richerson,HB;Moseley,P;Iwamota,P;Monick,M;Sjoerdsma,K;Hunninghake,GW
导致过敏性支气管哮喘的细胞炎症和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和直接观察和支气管肺泡灌洗（BAL）的局部过敏原激发方法，以评估气道对过敏原的反应。在这些研究中，11名过敏性哮喘患者（所有患者先前均表现出对吸入变应原激发的晚期哮喘反应）和6名健康无症状受试者自愿在局部气道激发后通过楔入亚段气道的支气管镜进行支气管肺泡灌洗。这些研究表明哮喘气道对过敏原的反应是立即出现苍白，随后出现反应性充血、水肿和支气管狭窄。该部位和对照部位在立即反应后48或96 h再复律。中性粒细胞和嗜酸性粒细胞在激发后48 h显著增加，辅助性T淋巴细胞也显著增加。典型的，在96小时，中性粒细胞计数恢复到正常值，而嗜酸性粒细胞和辅助T细胞仍然升高。过氧化物酶染色细胞也升高，在48小时后，局部过敏原的挑战。电子显微镜检查发现脱粒肥大细胞和嗜酸性粒细胞，立即和稍后（48和96小时）后，局部过敏原的挑战。巨噬细胞高度活化，吞噬了来自嗜酸性粒细胞和肥大细胞的部分完整颗粒。在哮喘受试者中，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 < 0.001）。在首次局部激发和支气管肺泡灌洗后，FEV1较基线下降12.9%（p < 0.001），但在重复支气管肺泡灌洗期间没有变化。两名哮喘患者出现局部喘息，局部应用肾上腺素可轻松逆转。所有患者在激发后15 min内肺功能均恢复至基线水平，提示当变应原进入过敏性哮喘气道时，（1）立即出现局部反应，其特征为变白、充血和气道狭窄，（2）局部诱导显著程度的细胞炎症，这种炎症可持续长达4天。局部过敏原激发后支气管肺泡灌洗是一种安全有效的方法，用于检查过敏性哮喘气道过敏原激发的后果，从而研究慢性过敏性哮喘的机制。
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 < 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. The FEV1decreased 12.9% from baseline (p < 0.001) after the initial local challenge and bronchoalveolar lavage, but did not change during the repeat bronchoalveolar lavage. Two asthmatics developed localized wheezing, which was easily reversed with locally applied epinephrine. All patients reverted to baseline pulmonary function values within 15 min of challenge.These results suggest that when allergen is introduced into allergic asthmatic airways, there is (1) an immediate local response characterized by blanching, hyperemia, and airway narrowing, and (2) a significant degree of cellular inflammation induced locally, which can persist for as long as 4 days. Local allergen challenge followed by bronchoalveolar lavage is a safe and effective method for examining the consequences of allergen provocation of allergic asthmatic airways and, therefore, the mechanisms of chronic allergic asthma.