Wenzel S E
National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, Denver, USA.
J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S17-21; discussion S33-40.
Increases in numbers and the activation state of inflammatory cells are typical findings even in patients with mild asthma. Periods of worsening inflammation are characterized by further changes, such as an increased number of eosinophils in patients with nocturnal asthma, an increased number of lymphocytes and basophils after allergen provocation, and an increased number of neutrophils after exposure to toluene diisocyanate. Correlations of bronchoalveolar lavage (BAL) findings with physiologic changes in patients with asthma are helpful but must be analyzed in the context of the difficulties in absolute quantification of cells and mediators in lavage. Correlations have been reported between BAL mast cells, eosinophils, and eosinophilic cationic protein and methacholine PC20 and FEV1. Correlations of other cell types or mediators with physiologic changes are either controversial (as with lymphocytes and their activation) or nonexistent (as with most mediators that have been measured). Ex vivo mediator production may be a useful measure. The ability to measure peripheral resistance directly at the site of inflammation may become an asset of the endobronchial instillation method. Causality can be proved only by selectively adding or removing certain inflammatory mediators through the use of leukotriene synthesis inhibitors, human grade eicosanoids, specific antagonists, agonists, and humanized antibodies. Of these examples, only leukotriene modulation has been evaluated with BAL in studies with human subjects. Whether inflammation and obstruction in patients with asthma result from the lack of certain mediators and/or an excess of others is unknown.
即使在轻度哮喘患者中,炎症细胞数量增加及其激活状态也是典型表现。炎症加重期的特征是有进一步变化,如夜间哮喘患者嗜酸性粒细胞数量增加、变应原激发后淋巴细胞和嗜碱性粒细胞数量增加,以及接触甲苯二异氰酸酯后中性粒细胞数量增加。支气管肺泡灌洗(BAL)结果与哮喘患者生理变化之间的相关性虽有帮助,但在灌洗中细胞和介质绝对定量存在困难的情况下必须加以分析。已报道BAL肥大细胞、嗜酸性粒细胞、嗜酸性阳离子蛋白与乙酰甲胆碱PC20和第一秒用力呼气量(FEV1)之间存在相关性。其他细胞类型或介质与生理变化的相关性要么存在争议(如淋巴细胞及其激活情况),要么不存在(如大多数已检测的介质)。体外介质产生情况可能是一项有用的指标。能在炎症部位直接测量外周阻力可能成为支气管内滴注法的一个优点。只有通过使用白三烯合成抑制剂、人级类二十烷酸、特异性拮抗剂、激动剂和人源化抗体选择性地添加或去除某些炎症介质,才能证明因果关系。在这些例子中,只有白三烯调节在人体研究中通过BAL进行了评估。哮喘患者的炎症和阻塞是否由某些介质缺乏和/或其他介质过量所致尚不清楚。