既往烟草暴露对重症哮喘患者气道嗜酸性粒细胞活化及自身免疫的影响
2022/03/17
摘要
背景：重度嗜酸性粒细胞性哮喘的特点为频繁发作且对类固醇激素的敏感性相对降低。既往实验发现，吸烟可诱发嗜酸性气道炎症，但对重症哮喘的影响尚不明确。
目的：研究重症哮喘患者中烟草暴露与嗜酸性粒细胞炎症和活化、气道自身免疫和类固醇激素反应性之间的关系。
方法：根据ERS/ATS标准对重症哮喘患者的痰标本进行评估，包括细胞分类计数分析及游离嗜酸性粒细胞颗粒（FEG）、抗嗜酸性粒细胞过氧化物酶（EPX）自身抗体和具有胶原结构的巨噬细胞受体（MARCO） 水平。对有嗜酸性气道炎症的患者，在泼尼松龙治疗2周后进行重新评估。
结果：本研究共纳入132例重症哮喘患者；39例（29.5%）吸烟史≥10包年，其中36例（27.3%）仅既往吸烟，3例（2.3%）目前仍吸烟，93例（70.5%），93例（70.5%）吸烟史＜10包年。与吸烟史＜10包年的患者（38.7%）相比，嗜酸性气道炎症在吸烟史≥10包年患者（66.7%）中更为普遍（p=0.03），FEG 水平、抗EPX 和抗 MARCO水平也更高（分别为 p=0.001，p<0.05 和 p<0.0001）。删去目前吸烟者并不影响上述关联性。此外，泼尼松龙可减少吸烟史≥10包年患者痰中嗜酸性粒细胞数量，但并未使其降至正常。
结论：在重症哮喘患者中，既往吸烟史与气道嗜酸性粒细胞炎症和活化、类固醇激素敏感性相对降低及气道自身免疫相关。
Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma
Klein DK, Silberbrandt A, Frøssing L, Hvidtfeldt M, von Bülow A, Nair P, Mukherjee M, Porsbjerg C
Abstract
INTRODUCTION:Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids., Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear.
OBJECTIVE:To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness.
METHODS:Patients with severe asthma according to ERS/ATS criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-weeks course of prednisolone.
RESULTS:A total of 132 severe asthmatics were included in the study; 39 patients (29.5%) had ≥10 pack years of smoking history; 36 (27.3%) were former smokers and 3 (2.3%) current smokers, and 93 (70.5%) had <10 pack years exposure. Eosinophilic airway inflammation was more prevalent among patients with ≥10 pack years (66.7%), compared to patients with <10 pack years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO(p<0.05 and p<0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a ≥10 pack years smoking history.
CONCLUSION:In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation, relative insensitivity to steroids, as well as airway autoimmunity.
背景：重度嗜酸性粒细胞性哮喘的特点为频繁发作且对类固醇激素的敏感性相对降低。既往实验发现，吸烟可诱发嗜酸性气道炎症，但对重症哮喘的影响尚不明确。
目的：研究重症哮喘患者中烟草暴露与嗜酸性粒细胞炎症和活化、气道自身免疫和类固醇激素反应性之间的关系。
方法：根据ERS/ATS标准对重症哮喘患者的痰标本进行评估，包括细胞分类计数分析及游离嗜酸性粒细胞颗粒（FEG）、抗嗜酸性粒细胞过氧化物酶（EPX）自身抗体和具有胶原结构的巨噬细胞受体（MARCO） 水平。对有嗜酸性气道炎症的患者，在泼尼松龙治疗2周后进行重新评估。
结果：本研究共纳入132例重症哮喘患者；39例（29.5%）吸烟史≥10包年，其中36例（27.3%）仅既往吸烟，3例（2.3%）目前仍吸烟，93例（70.5%），93例（70.5%）吸烟史＜10包年。与吸烟史＜10包年的患者（38.7%）相比，嗜酸性气道炎症在吸烟史≥10包年患者（66.7%）中更为普遍（p=0.03），FEG 水平、抗EPX 和抗 MARCO水平也更高（分别为 p=0.001，p<0.05 和 p<0.0001）。删去目前吸烟者并不影响上述关联性。此外，泼尼松龙可减少吸烟史≥10包年患者痰中嗜酸性粒细胞数量，但并未使其降至正常。
结论：在重症哮喘患者中，既往吸烟史与气道嗜酸性粒细胞炎症和活化、类固醇激素敏感性相对降低及气道自身免疫相关。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Eur Respir J. 2022 Mar 2;2102446. doi: 10.1183/13993003.02446-2021.)
(Eur Respir J. 2022 Mar 2;2102446. doi: 10.1183/13993003.02446-2021.)
Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma
Klein DK, Silberbrandt A, Frøssing L, Hvidtfeldt M, von Bülow A, Nair P, Mukherjee M, Porsbjerg C
Abstract
INTRODUCTION:Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids., Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear.
OBJECTIVE:To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness.
METHODS:Patients with severe asthma according to ERS/ATS criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-weeks course of prednisolone.
RESULTS:A total of 132 severe asthmatics were included in the study; 39 patients (29.5%) had ≥10 pack years of smoking history; 36 (27.3%) were former smokers and 3 (2.3%) current smokers, and 93 (70.5%) had <10 pack years exposure. Eosinophilic airway inflammation was more prevalent among patients with ≥10 pack years (66.7%), compared to patients with <10 pack years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO(p<0.05 and p<0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a ≥10 pack years smoking history.
CONCLUSION:In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation, relative insensitivity to steroids, as well as airway autoimmunity.
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