van Dalen Christine J, Aldridge Ruth E, Chan Timothy, Senthilmohan Revathy, Hancox Robert J, Cowan Jan O, Taylor D Robin, Town G Ian, Kettle Anthony J
Centre for Public Health Research, Massey University, Wellington, New Zealand.
Ann Allergy Asthma Immunol. 2009 Oct;103(4):348-53. doi: 10.1016/S1081-1206(10)60536-4.
Inhaled corticosteroids are widely used in the treatment of persistent asthma, usually combined with inhaled beta2-agonists. Previous research suggests that short-acting beta2-agonists (SABAs) may downregulate the anti-inflammatory effects of inhaled corticosteroids, thereby increasing asthma morbidity.
To determine whether 3-bromotyrosine and 3,5-dibromotyrosine levels, specific markers of eosinophil activation, reflect treatment effects on airway inflammation of inhaled corticosteroids and SABAs and support previous conclusions.
Levels of 3-bromotyrosine and 3,5-dibromotyrosine were measured in sputum supernatants using stable isotope dilution gas chromatography-mass spectrometry in a randomized, placebo-controlled, crossover study of treatment with terbutaline, budesonide, and their combination in patients with persistent asthma. Thirty-four individuals were randomized, and 28 completed the study.
Treatment with budesonide lowered median 3-bromotyrosine levels compared with treatment with placebo, terbutaline, and budesonide-terbutaline (0.24 vs 0.64, 0.62, and 0.43 3-bromotyosine/tyrosine [mmol/mol]; P < .05) and lowered median 3,5-dibromotyrosine levels compared with placebo and terbutaline treatments (0.04 vs 0.11 and 0.07 3,5-dibromotyrosine/ tyrosine [mmol/mol], P < .05). Unlike eosinophil numbers, 3-bromotyrosine and 3,5-dibromotyrosine levels did not increase with terbutaline treatment compared with placebo treatment but were significantly raised when terbutaline was added to budesonide treatment. 3-Bromotyrosine levels correlated significantly with eosinophil cationic protein levels in all groups.
3-Bromotyrosine and 3,5-dibromotyrosine levels reflect treatment effects in asthma and support previous findings that SABAs impair the anti-inflammatory effects of inhaled corticosteroids. In addition to eosinophil numbers and eosinophil cationic protein levels, these modified tyrosine residues provide useful information about the inflammatory state of the airways.
吸入性糖皮质激素广泛用于治疗持续性哮喘，通常与吸入性β2受体激动剂联合使用。先前的研究表明，短效β2受体激动剂（SABAs）可能会下调吸入性糖皮质激素的抗炎作用，从而增加哮喘发病率。
确定嗜酸性粒细胞活化的特异性标志物3-溴酪氨酸和3,5-二溴酪氨酸水平是否反映吸入性糖皮质激素和SABAs对气道炎症的治疗效果，并支持先前的结论。
在一项随机、安慰剂对照、交叉研究中，使用稳定同位素稀释气相色谱-质谱法测量持续性哮喘患者痰液上清液中3-溴酪氨酸和3,5-二溴酪氨酸的水平，该研究使用特布他林、布地奈德及其组合进行治疗。34名个体被随机分组，28名完成了研究。
与安慰剂、特布他林和布地奈德-特布他林治疗相比，布地奈德治疗降低了3-溴酪氨酸的中位数水平（0.24对0.64、0.62和0.43 3-溴酪氨酸/酪氨酸[mmol/mol]；P<.05），与安慰剂和特布他林治疗相比，降低了3,5-二溴酪氨酸的中位数水平（0.04对0.11和0.07 3,5-二溴酪氨酸/酪氨酸[mmol/mol]，P<.05）。与嗜酸性粒细胞数量不同，与安慰剂治疗相比，特布他林治疗时3-溴酪氨酸和3,5-二溴酪氨酸水平没有增加，但当特布他林添加到布地奈德治疗中时显著升高。在所有组中，3-溴酪氨酸水平与嗜酸性粒细胞阳离子蛋白水平显著相关。
3-溴酪氨酸和3,5-二溴酪氨酸水平反映了哮喘的治疗效果，并支持先前的发现，即SABAs会损害吸入性糖皮质激素的抗炎作用。除了嗜酸性粒细胞数量和嗜酸性粒细胞阳离子蛋白水平外，这些修饰的酪氨酸残基还提供了有关气道炎症状态的有用信息。
