在严重难治性哮喘中支气管热成形术治疗反应的临床和组织病理学预测因素
2021/02/09
摘要
背景：表型和内型预测严重哮喘患者对支气管热成形术(BT)的最佳反应仍不明确。
目的：客观的比较有应答者和部分应答者口服类固醇和奥玛珠单抗难治性重度哮喘患者在BT治疗前后气道炎症和气道重塑的临床特征和特征。
方法：根据在BT术后12个月哮喘发作的减少次数，23位严重难治性哮喘患者被分为BT-应答组(n = 15)和BT-部分应答组(n = 8)。在基线时和BT后12个月比较临床参数，并在BT之前和3个月后通过免疫组织化学分析免疫支气管活检的气道炎症和重塑标志。
结果：基线时，bt应答者比bt部分应答者年轻约8岁(P=0.02)，特异反应发生率更高，血液嗜酸性粒细胞数量(均P=0.03)和IgE水平更高，上皮干扰素(IFN)-α表达更高，粘膜嗜酸性粒细胞和IL-33阳性细胞更高(P≤0.05)。血清IgE、2型(T2)气道炎症、黏膜il -33阳性细胞和肥大细胞的减少，与上皮MUC5AC和IFN-α/β免疫染色增强相关，而在BT部分应答者中黏膜IL-33阳性细胞增强。这些变化大多与临床参数相关。上皮下膜增厚和气道平滑肌面积在两组患者基线和BT后相似。
结论：通过减少变态反应T2炎症、增加上皮MUC5AC和抗病毒IFN-α/β的表达，BT可能增强宿主的免疫应答，从而减轻加重和症状。相反，靶向IL-33可能为部分应答者提供临床益处。
Clinical and histopathological predictors of therapeutic response to bronchial thermoplasty in severe refractory asthma
Ladjemi MZ, Di Candia L, Heddebaut N, et al.
Abstract
Background:Phenotypes and endotypes predicting optimal response to bronchial thermoplasty (BT) in severe asthmatics remain elusive.
Objective:To compare clinical characteristics and hallmarks of airway inflammation and remodelling before and after BT in responders and partial responders severe asthmatics refractory to oral steroids and to omalizumab.
Methods:Twenty-three severe refractory asthmatics were divided into BT-responders (n=15) and BT-partial responders (n=8), according to the decrease in asthma exacerbations at 12 months after BT. Clinical parameters were compared at baseline and 12 months after BT and hallmarks of airway inflammation and remodelling were analysed by immunohistochemistry in bronchial biopsies before and 3 months after BT.
Results:At baseline, BT-responders were around 8 years younger (P=0.02), had greater incidence of atopy, higher numbers of blood eosinophils (both P=0.03) and IgE levels, higher epithelial interferon (IFN)-α expression, higher mucosal eosinophils and IL-33-positive cells (P≤0.05) than BT-partial responders. A reduction in blood eosinophils, serum IgE, type 2 (T2) airway inflammation, mucosal IL-33-positive cells and mast cells, associated with an augmented epithelial MUC5AC and IFN-α/β immunostaining were noted after BT in responders, whereas mucosal IL-33-positive cells were augmented in BT-partial responders. Most of these changes correlated with clinical parameters. Sub-epithelial membrane thickening and airway smooth muscle area were similar in the two patient groups at baseline and after BT.
Conclusion:By reducing allergic T2 inflammation and increasing epithelial MUC5AC and anti-viral IFN-α/β expression, BT may enhance host immune responses and thus attenuate exacerbations and symptoms in responders. Instead, targeting IL-33 may provide a clinical benefit in partial responders.
背景：表型和内型预测严重哮喘患者对支气管热成形术(BT)的最佳反应仍不明确。
目的：客观的比较有应答者和部分应答者口服类固醇和奥玛珠单抗难治性重度哮喘患者在BT治疗前后气道炎症和气道重塑的临床特征和特征。
方法：根据在BT术后12个月哮喘发作的减少次数，23位严重难治性哮喘患者被分为BT-应答组(n = 15)和BT-部分应答组(n = 8)。在基线时和BT后12个月比较临床参数，并在BT之前和3个月后通过免疫组织化学分析免疫支气管活检的气道炎症和重塑标志。
结果：基线时，bt应答者比bt部分应答者年轻约8岁(P=0.02)，特异反应发生率更高，血液嗜酸性粒细胞数量(均P=0.03)和IgE水平更高，上皮干扰素(IFN)-α表达更高，粘膜嗜酸性粒细胞和IL-33阳性细胞更高(P≤0.05)。血清IgE、2型(T2)气道炎症、黏膜il -33阳性细胞和肥大细胞的减少，与上皮MUC5AC和IFN-α/β免疫染色增强相关，而在BT部分应答者中黏膜IL-33阳性细胞增强。这些变化大多与临床参数相关。上皮下膜增厚和气道平滑肌面积在两组患者基线和BT后相似。
结论：通过减少变态反应T2炎症、增加上皮MUC5AC和抗病毒IFN-α/β的表达，BT可能增强宿主的免疫应答，从而减轻加重和症状。相反，靶向IL-33可能为部分应答者提供临床益处。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol, 2021.）
（J Allergy Clin Immunol, 2021.）
Clinical and histopathological predictors of therapeutic response to bronchial thermoplasty in severe refractory asthma
Ladjemi MZ, Di Candia L, Heddebaut N, et al.
Abstract
Background:Phenotypes and endotypes predicting optimal response to bronchial thermoplasty (BT) in severe asthmatics remain elusive.
Objective:To compare clinical characteristics and hallmarks of airway inflammation and remodelling before and after BT in responders and partial responders severe asthmatics refractory to oral steroids and to omalizumab.
Methods:Twenty-three severe refractory asthmatics were divided into BT-responders (n=15) and BT-partial responders (n=8), according to the decrease in asthma exacerbations at 12 months after BT. Clinical parameters were compared at baseline and 12 months after BT and hallmarks of airway inflammation and remodelling were analysed by immunohistochemistry in bronchial biopsies before and 3 months after BT.
Results:At baseline, BT-responders were around 8 years younger (P=0.02), had greater incidence of atopy, higher numbers of blood eosinophils (both P=0.03) and IgE levels, higher epithelial interferon (IFN)-α expression, higher mucosal eosinophils and IL-33-positive cells (P≤0.05) than BT-partial responders. A reduction in blood eosinophils, serum IgE, type 2 (T2) airway inflammation, mucosal IL-33-positive cells and mast cells, associated with an augmented epithelial MUC5AC and IFN-α/β immunostaining were noted after BT in responders, whereas mucosal IL-33-positive cells were augmented in BT-partial responders. Most of these changes correlated with clinical parameters. Sub-epithelial membrane thickening and airway smooth muscle area were similar in the two patient groups at baseline and after BT.
Conclusion:By reducing allergic T2 inflammation and increasing epithelial MUC5AC and anti-viral IFN-α/β expression, BT may enhance host immune responses and thus attenuate exacerbations and symptoms in responders. Instead, targeting IL-33 may provide a clinical benefit in partial responders.
上一篇：
缺氧的hUCMSC产生的细胞外囊泡减轻了慢性哮喘小鼠的过敏性气道炎症和气道重塑
下一篇：
支气管热成形术对严重哮喘气道平滑肌减少及临床反应的影响。塔斯马随机试验
