Unit of Experimental Asthma and Allergy Research, The National Institute of Environmental Medicine, Stockholm, Sweden.
Int Arch Allergy Immunol. 2012;158(3):299-306. doi: 10.1159/000331433. Epub 2012 Mar 6.
There is no in vitro test to diagnose aspirin-intolerant asthma (AIA). The aim of this study was to test if challenge with aspirin of sputum cells from subjects with AIA triggers the release of cysteinyl leukotrienes (CysLTs), known to be mediators of bronchoconstriction in AIA.
Sputum induction was performed at baseline and at another visit 2 h after a lysine-aspirin bronchoprovocation in 10 subjects with AIA and 9 subjects with aspirin-tolerant asthma (ATA). The isolated sputum cells were incubated for ex vivo challenge.
Release of CysLTs by sputum cells from patients with AIA was not induced by lysine-aspirin ex vivo, neither when cells were collected at baseline nor in sputum cells recovered after lysine-aspirin-induced bronchoconstriction, whereas release of CysLTs from sputum cells was triggered by an ionophore on both occasions. However, the CysLT levels elicited by the ionophore were higher in the AIA group both at baseline (AIA vs. ATA: 3.3 vs. 1.6 ng/million cells; p < 0.05) and after the lysine-aspirin bronchoprovocation (3.9 vs. 1.7 ng/million cells; p < 0.05). This difference in the amount of CysLTs released between the groups appeared to be related to the number of eosinophils.
Intolerance to aspirin could not be triggered in sputum cells isolated from subjects with AIA. Together with the previous inability to demonstrate intolerance to non-steroidal anti-inflammatory drugs in isolated blood cells, these results support the requirement of tissue-resident cells in the adverse reaction. However, ex vivo stimulation of sputum cells may be developed into a new test of capacity for LT release in inflammatory cells recovered from airways.
目前尚无体外检测方法可用于诊断阿司匹林不耐受型哮喘（AIA）。本研究旨在检测 AIA 患者痰液细胞在接受阿司匹林激发后是否会释放半胱氨酰白三烯（CysLTs），已知 CysLTs 是 AIA 支气管收缩的介质。
10 例 AIA 患者和 9 例阿司匹林耐受型哮喘（ATA）患者在接受赖氨酸-阿司匹林支气管激发试验 2 小时后，分别于基线和另一次就诊时进行痰液诱导。分离的痰液细胞进行体外挑战。
AIA 患者的痰液细胞在体外用赖氨酸-阿司匹林激发后并未释放 CysLTs，无论是在基线时收集细胞还是在赖氨酸-阿司匹林诱导的支气管收缩后回收的痰液细胞中均未诱导出 CysLTs 的释放，而两种情况下，细胞离子载体均能触发 CysLTs 的释放。然而，在 AIA 组中，离子载体诱导的 CysLTs 水平在基线时（AIA 组与 ATA 组相比：3.3 比 1.6 ng/百万细胞；p < 0.05）和赖氨酸-阿司匹林支气管激发后（3.9 比 1.7 ng/百万细胞；p < 0.05）均更高。两组之间释放的 CysLTs 量的差异似乎与嗜酸性粒细胞的数量有关。
无法在从 AIA 患者中分离的痰液细胞中引发对阿司匹林的不耐受。与之前在分离的血液细胞中未能证明对非甾体抗炎药不耐受的结果一致，这些结果支持组织驻留细胞在不良反应中的作用。然而，体外刺激痰液细胞可能会发展成为一种新的检测方法，用于检测从气道中回收的炎症细胞中 LTs 释放能力。
