激素戒断引起轻中度哮喘控制不佳独立于经典中性粒激活途径
2019/11/12
摘要
背景：哮喘控制不佳及急性发作与痰嗜酸粒细胞具有相关性。然而无论是嗜酸粒细胞还是中性粒细胞占主导地位，其导致相伴行的炎症反应仍未被广泛研究。
方法：一项标准化前瞻性吸入性糖皮质激素（ICS）戒断研究纳入了23例轻度至中度哮喘患者。 其中22名患者哮喘控制不佳。这项研究评通过收集三个阶段（基线水平、控制不佳以及随后恢复期）的呼出气冷凝物、血浆和痰液，以评估各种免疫性、炎性和氧化应激参数，及嗜酸性粒细胞和中性粒细胞活性指标。
结果：哮喘控制不佳的特征是痰嗜酸性粒细胞增多，而对于大多数炎症和氧化应激反应，这三个阶段之间均未发现差异。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）和嗜中性粒细胞（髓过氧化物酶和氯酪氨酸）的标记物也没有发现差异。然而，可见观察到游离嗜酸性颗粒和瓜氨酸化组蛋白H3增强，提示嗜酸性细胞溶解和潜在嗜酸性细胞外捕获。发现基线血嗜酸性粒细胞和血浆中不对称二甲基精氨酸（一氧化氮合酶的抑制剂）变化与ICS停药时FEV1％pred下降相关（均为rs = 0.46；P = .03）。
结论：ICS治疗中断对轻中度哮喘临床疗效与嗜酸性粒细胞和中性粒细胞的经典炎症激活途径无关。 但是，它可能反映了哮喘控制不佳和急性发作的另一种潜在途径。
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.
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 H3, 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) in plasma were found to correlate with the decrease in FEV1 percent predicted upon ICS withdrawal (both, rs = 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：哮喘控制不佳及急性发作与痰嗜酸粒细胞具有相关性。然而无论是嗜酸粒细胞还是中性粒细胞占主导地位，其导致相伴行的炎症反应仍未被广泛研究。
方法：一项标准化前瞻性吸入性糖皮质激素（ICS）戒断研究纳入了23例轻度至中度哮喘患者。 其中22名患者哮喘控制不佳。这项研究评通过收集三个阶段（基线水平、控制不佳以及随后恢复期）的呼出气冷凝物、血浆和痰液，以评估各种免疫性、炎性和氧化应激参数，及嗜酸性粒细胞和中性粒细胞活性指标。
结果：哮喘控制不佳的特征是痰嗜酸性粒细胞增多，而对于大多数炎症和氧化应激反应，这三个阶段之间均未发现差异。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）和嗜中性粒细胞（髓过氧化物酶和氯酪氨酸）的标记物也没有发现差异。然而，可见观察到游离嗜酸性颗粒和瓜氨酸化组蛋白H3增强，提示嗜酸性细胞溶解和潜在嗜酸性细胞外捕获。发现基线血嗜酸性粒细胞和血浆中不对称二甲基精氨酸（一氧化氮合酶的抑制剂）变化与ICS停药时FEV1％pred下降相关（均为rs = 0.46；P = .03）。
结论：ICS治疗中断对轻中度哮喘临床疗效与嗜酸性粒细胞和中性粒细胞的经典炎症激活途径无关。 但是，它可能反映了哮喘控制不佳和急性发作的另一种潜在途径。
（中日友好医院呼吸与危重症医学科 张鑫 摘译 林江涛 审校）
（Chest. 2019 Oct 14. pii: S0012-3692(19)34009-7. doi: 10.1016/j.chest.2019.09.027.）
（Chest. 2019 Oct 14. pii: S0012-3692(19)34009-7. doi: 10.1016/j.chest.2019.09.027.）
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.
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 H3, 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) in plasma were found to correlate with the decrease in FEV1 percent predicted upon ICS withdrawal (both, rs = 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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气道G-CSF可识别中性粒细胞炎症并促进哮喘进展
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