支气管热成形术治疗严重难治性哮喘的临床和组织病理学预测因素。
Clinical and histopathologic predictors of therapeutic response to bronchial thermoplasty in severe refractory asthma.
机构信息
Inserm UMR1152, Physiopathologie et Epidémiologie des Maladies Respiratoires, Université de Paris, Faculté de Médicine, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité and DHU FIRE, Paris, France.
Inserm UMR1152, Physiopathologie et Epidémiologie des Maladies Respiratoires, Université de Paris, Faculté de Médicine, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité and DHU FIRE, Paris, France; Département de Pneumologie A, Hôpital Bichat-Claude Bernard, Paris, France; Assistance Publique des Hôpitaux de Paris, Paris, France.
出版信息
J Allergy Clin Immunol. 2021 Nov;148(5):1227-1235.e6. doi: 10.1016/j.jaci.2020.12.642. Epub 2021 Jan 13.
BACKGROUND
Phenotypes and endotypes predicting optimal response to bronchial thermoplasty (BT) in patients with severe asthma remain elusive.
OBJECTIVE
Our aim was to compare the clinical characteristics and hallmarks of airway inflammation and remodeling before and after BT in responder and partial responder patients with severe asthma refractory to oral steroids and to omalizumab.
METHODS
In all, 23 patients with severe refractory asthma 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 remodeling were analyzed by immunohistochemistry in bronchial biopsy specimens before and 3 months after BT.
RESULTS
At baseline, the BT responders were around 8 years younger than the BT partial responders (P = .02) and they had a greater incidence of atopy, higher numbers of blood eosinophils (both P = .03) and IgE levels, higher epithelial IFN-α expression, and higher numbers of mucosal eosinophils and IL-33-positive cells (P ≤ .05). A reduction in blood eosinophil count, serum IgE level, type 2 airway inflammation, and numbers of mucosal IL-33-positive cells and mast cells associated with augmented epithelial MUC5AC and IFN-α/β immunostaining was noted after BT in responders, whereas the numbers of mucosal IL-33-positive cells were augmented in BT partial responders. Most of these changes were correlated with clinical parameters. Subepithelial membrane thickening and airway smooth muscle area were similar in the 2 patient groups at baseline and after BT.
CONCLUSION
By reducing allergic type 2 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 BT responders. Instead, targeting IL-33 may provide a clinical benefit in BT partial responders.
背景
预测严重哮喘患者对支气管热成形术（BT）反应的表型和内型仍然难以捉摸。
目的
我们旨在比较对口服类固醇和奥马珠单抗难治的严重哮喘患者中 BT 反应者和部分反应者在 BT 前后气道炎症和重塑的临床特征和标志。
方法
所有 23 例严重难治性哮喘患者根据 BT 后 12 个月哮喘加重的减少分为 BT 反应者（n=15）和 BT 部分反应者（n=8）。在 BT 前后和 BT 后 3 个月通过支气管活检分析气道炎症和重塑的标志，并比较基线和 BT 后 12 个月的临床参数。
结果
在基线时，BT 反应者比 BT 部分反应者年轻约 8 岁（P=0.02），并且他们更易发生过敏，血嗜酸性粒细胞计数更高（均 P=0.03），IgE 水平更高，上皮 IFN-α表达更高，黏膜嗜酸性粒细胞和 IL-33 阳性细胞计数更高（P≤0.05）。BT 后反应者血嗜酸性粒细胞计数、血清 IgE 水平、2 型气道炎症以及黏膜 IL-33 阳性细胞和肥大细胞计数减少，上皮 MUC5AC 和 IFN-α/β免疫染色增强，而 BT 部分反应者黏膜 IL-33 阳性细胞计数增加。这些变化大多与临床参数相关。在基线和 BT 后，2 组患者的黏膜下膜增厚和气道平滑肌面积相似。
结论
通过减少过敏性 2 型炎症并增加上皮 MUC5AC 和抗病毒 IFN-α/β表达，BT 可能增强宿主免疫反应，从而减轻 BT 反应者的恶化和症状。相反，靶向 IL-33 可能为 BT 部分反应者提供临床获益。
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