严重哮喘支气管热成形术后的气道炎症
2015/10/30
摘要
背景:支气管热成形术是针对重度哮喘未控制患者的治疗方式之一,运用射频消融术切除气道平滑肌。虽然这项新的治疗方式效果确切,但其对气道炎症的影响尚不明确。本文研究了支气管热成形术前及术后几周,患者气道促炎性细胞因子浓度及平滑肌肌动蛋白丰度。
方法:11例重度哮喘患者于首次支气管热成形术前及术后3-6周行支气管活检并收集右下页支气管肺泡灌洗样本。分析支气管肺泡灌洗液样本细胞比例及细胞因子浓度,及支气管内活检中是否存在α-平滑肌肌动蛋白。
结果:11例患者中有7例在6周时支气管内活检平滑肌肌动蛋白表达下降。支气管肺泡灌洗液中,所有患者TGFβ1 和RANTES/CCL5在支气管热成形术后3周及6周时均大量减少。能诱导多种类型细胞凋亡的肿瘤坏死因子相关细胞凋亡诱导配体(TRAIL)在术后3周和6周浓度均有所增加。
结论:重度哮喘未控制患者支气管热成形术后平滑肌肌动蛋白的临床改善和减少与主要炎症介质的变化有关。数据证实,在人哮喘气道中,热成形术后气道平滑肌大幅消除。数据同时表明了热成形术后前几周内气道炎症显著改变的首要特征。
(杨冬 审校)
Ann Am Thorac Soc. 2015 Jul 31. [Epub ahead of print]
Airway Inflammation after Bronchial Thermoplasty for Severe Asthma.
Denner DR1, Doeing DC2, Hogarth DK3, Dugan K4, Naureckas ET5, White SR6.
Abstract
BACKGROUND:Bronchial thermoplasty is an alternative treatment for patients with severe, uncontrolledasthma in which the airway smooth muscle is eliminated using radio-ablation. While this emerging therapy shows promising outcomes, little is known about its effects on airway inflammation. We examined the concentration of pro-inflammatory airway cytokines and factors, and of smooth muscle actin abundance, in patients before and in the weeks after bronchial thermoplasty.
METHODS:Endobronchial biopsies and bronchoalveolar lavage samples from 11 patients with severe asthmawere collected from the right lower lobe prior to, and 3 and 6 weeks post, initial bronchial thermoplasty. Samples were analyzed for cell proportions and cytokine concentrations in bronchoalveolar lavage, and for the presence of alpha-smooth muscle actin in endobronchial biopsies.
RESULTS:Smooth muscle actin expression was decreased in endobronchial biopsies of 7 of 11 subjects by week 6. In bronchoalveolar lavage fluid, both TGFβ1 and RANTES/CCL5 were substantially decreased 3 and 6 weeks post bronchial thermoplasty in all patients. The cytokine tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in several cell types, was increased in concentration both 3 and 6 weeks post bronchial thermoplasty.
CONCLUSION:Clinical improvement and reduction in smooth muscle actin after bronchial thermoplasty in severe, uncontrolled asthma is associated with substantial changes in key mediators of inflammation. These data confirm the substantial elimination of airway smooth muscle post thermoplasty in the human asthmatic airway, and represent the first characterization of significant changes in airway inflammation in the first weeks after thermoplasty.
Ann Am Thorac Soc. 2015 Jul 31. [Epub ahead of print]