在轻到中度哮喘中，停用皮质类固醇引起的哮喘失控与经典的粒细胞激活无关
2020/02/11
摘要
背景：哮喘失去控制和急性加重与痰嗜酸性粒细胞计数增加有关。但是，到底是嗜酸性粒细胞还是存在的中性粒细胞积极促成伴随的炎症还没有广泛的研究。
方法：23例轻度至中度哮喘患者纳入了一项标准前瞻性吸入皮质类固醇(ICS)戒断研究;22例患者哮喘症状失去控制。该研究评估了各种免疫、炎症和氧化应激参数，以及在三个阶段(基线、失控期和恢复期)收集的呼出气冷凝液、血浆和痰液中嗜酸性粒细胞和中性粒细胞活性的标记物。
结果：哮喘症状的失控以痰嗜酸性粒细胞增多为特征，而炎症和氧化应激反应的三个阶段之间未发现差异。活化的嗜酸性粒细胞(嗜酸性粒细胞阳离子蛋白和溴酪氨酸)和中性粒细胞(髓过氧化物酶和氯酪氨酸)的标记物也没有差异。然而，游离的嗜酸粒细胞颗粒和瓜氨酸化的组蛋白H，提示嗜酸细胞溶解和潜在的嗜酸细胞外陷阱形成的增强。研究发现，血浆中不对称二甲基精氨酸(一种一氧化氮合酶抑制剂)的基线血嗜酸性粒细胞和变化与ICS停药后预测的FEV百分比下降相关(两者r = 0.46;P = 03)。
结论：中断ICS治疗对轻度至中度哮喘的临床效果与典型的嗜酸性粒细胞和中性粒细胞炎症激活无关。然而，它可能反映了在哮喘症状失去控制或急性发作开始时的另一种潜在的通路。
Corticosteroid Withdrawal-Induced Loss of Control in Mild to Moderate Asthma Is Independent of Classic Granulocyte Activation.
de Groot LES, van de Pol MA, Fens N, Dierdorp BS, Dekker T, Kulik W, Majoor CJ,
Hamann J, Sterk PJ, Lutter R
Chest 2020 Jan;157(1)
Abstract
BACKGROUND:Loss of asthma control and asthma exacerbations are associated with increased sputum eosinophil counts. However, whether eosinophils, or the also present neutrophils, actively contribute to the accompanying inflammation has not been extensively investigated.
METHODS:Twenty-three patients with mild to moderate asthma were included in a standardized prospective inhaled corticosteroid (ICS) withdrawal study; 22 of the patients experienced loss of asthma control. The study assessed various immune, inflammatory, and oxidative stress parameters, as well as markers of eosinophil and neutrophil activity, in exhaled breath condensate, plasma, and sputum collected at three phases (baseline, during loss of control, and following recovery).
RESULTS:Loss of asthma control was characterized by increased sputum eosinophils, whereas no differences were detected between the three phases for most inflammatory and oxidative stress responses. There were also no differences detected for markers of activated eosinophils (eosinophil cationic protein and bromotyrosine) and neutrophils (myeloperoxidase and chlorotyrosine). However, free eosinophilic granules and citrullinated histone H, suggestive of eosinophil cytolysis and potentially eosinophil extracellular trap formation, were enhanced. Baseline blood eosinophils and changes in asymmetric dimethylarginine (an inhibitor of nitric oxide synthase) inplasma were found to correlate with the decrease in FEV percent predicted upon ICS withdrawal (both, r = 0.46; P = .03).
CONCLUSIONS:The clinical effect in mild to moderate asthma upon interruption of ICS therapy is not related to the classic inflammatory activation of eosinophils and neutrophils. It may, however, reflect another pathway underlying the onset of loss of disease control and asthma exacerbations.
背景：哮喘失去控制和急性加重与痰嗜酸性粒细胞计数增加有关。但是，到底是嗜酸性粒细胞还是存在的中性粒细胞积极促成伴随的炎症还没有广泛的研究。
方法：23例轻度至中度哮喘患者纳入了一项标准前瞻性吸入皮质类固醇(ICS)戒断研究;22例患者哮喘症状失去控制。该研究评估了各种免疫、炎症和氧化应激参数，以及在三个阶段(基线、失控期和恢复期)收集的呼出气冷凝液、血浆和痰液中嗜酸性粒细胞和中性粒细胞活性的标记物。
结果：哮喘症状的失控以痰嗜酸性粒细胞增多为特征，而炎症和氧化应激反应的三个阶段之间未发现差异。活化的嗜酸性粒细胞(嗜酸性粒细胞阳离子蛋白和溴酪氨酸)和中性粒细胞(髓过氧化物酶和氯酪氨酸)的标记物也没有差异。然而，游离的嗜酸粒细胞颗粒和瓜氨酸化的组蛋白H，提示嗜酸细胞溶解和潜在的嗜酸细胞外陷阱形成的增强。研究发现，血浆中不对称二甲基精氨酸(一种一氧化氮合酶抑制剂)的基线血嗜酸性粒细胞和变化与ICS停药后预测的FEV百分比下降相关(两者r = 0.46;P = 03)。
结论：中断ICS治疗对轻度至中度哮喘的临床效果与典型的嗜酸性粒细胞和中性粒细胞炎症激活无关。然而，它可能反映了在哮喘症状失去控制或急性发作开始时的另一种潜在的通路。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Chest 2020 Jan;157(1))
(Chest 2020 Jan;157(1))
Corticosteroid Withdrawal-Induced Loss of Control in Mild to Moderate Asthma Is Independent of Classic Granulocyte Activation.
de Groot LES, van de Pol MA, Fens N, Dierdorp BS, Dekker T, Kulik W, Majoor CJ,
Hamann J, Sterk PJ, Lutter R
Chest 2020 Jan;157(1)
Abstract
BACKGROUND:Loss of asthma control and asthma exacerbations are associated with increased sputum eosinophil counts. However, whether eosinophils, or the also present neutrophils, actively contribute to the accompanying inflammation has not been extensively investigated.
METHODS:Twenty-three patients with mild to moderate asthma were included in a standardized prospective inhaled corticosteroid (ICS) withdrawal study; 22 of the patients experienced loss of asthma control. The study assessed various immune, inflammatory, and oxidative stress parameters, as well as markers of eosinophil and neutrophil activity, in exhaled breath condensate, plasma, and sputum collected at three phases (baseline, during loss of control, and following recovery).
RESULTS:Loss of asthma control was characterized by increased sputum eosinophils, whereas no differences were detected between the three phases for most inflammatory and oxidative stress responses. There were also no differences detected for markers of activated eosinophils (eosinophil cationic protein and bromotyrosine) and neutrophils (myeloperoxidase and chlorotyrosine). However, free eosinophilic granules and citrullinated histone H, suggestive of eosinophil cytolysis and potentially eosinophil extracellular trap formation, were enhanced. Baseline blood eosinophils and changes in asymmetric dimethylarginine (an inhibitor of nitric oxide synthase) inplasma were found to correlate with the decrease in FEV percent predicted upon ICS withdrawal (both, r = 0.46; P = .03).
CONCLUSIONS:The clinical effect in mild to moderate asthma upon interruption of ICS therapy is not related to the classic inflammatory activation of eosinophils and neutrophils. It may, however, reflect another pathway underlying the onset of loss of disease control and asthma exacerbations.
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嗜酸性肉芽肿性多血管炎：长期哮喘严重程度的临床预测指标
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急性喘息特异性基因模块显示维生素D和哮喘药物治疗相关
