嗜酸性细胞过氧化物酶作为哮喘嗜酸性细胞炎症生物标志物的作用
2024/05/28
摘要
背景：嗜酸性粒细胞过氧化物酶（EPX）和血液和痰嗜酸性粒计数作为哮喘疾病生物标志物的相对效用尚不确定。
目的：确定EPX作为哮喘全身和气道嗜酸性粒细胞炎症的生物标志物的效用。
方法：通过免疫测定法测定110名健康对照者的血清和痰液中的EPX蛋白，以建立正常参考范围，并在480名严重哮喘研究计划（SARP）-3参与者的三年观察期间收集的血清和痰的重复样本中测定EPX蛋白。
结果：在三年多的时间里，哮喘患者27-31%的血清样本和36-53%的痰样本中EPX水平高于正常水平。血中嗜酸性粒细胞和EPX的相关性比痰中好（rs值分别为0.74和0.43），27%的血中嗜酸粒细胞计数<150个细胞/uL的参与者和42%的血中酸性粒细胞计数150-299个细胞/uL的参与者出现高痰EPX水平。三年来持续高痰EPX值的患者表现为严重的气流阻塞、频繁的加重和高粘液塞评分。在59名在观察期间开始使用美泊利珠单抗的哮喘患者中，96%的患者血清EPX水平正常，但只有49%的患者痰液EPX正常。即使痰中EPX正常，肺功能仍然异常。
结论：血清EPX是哮喘全身性嗜酸性粒细胞炎症的有效蛋白质生物标志物，痰EPX水平是气道嗜酸性粒炎症的一个比痰嗜酸性粒计数更敏感的生物标志物。血液中的嗜酸性粒细胞测量经常忽略气道嗜酸性粒炎症，而美泊利珠单抗经常无法使气道嗜酸性炎症正常化，尽管它使全身嗜酸性粒炎正常化。
Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma
Monica Tang, Annabelle R Charbit, Mats W Johansson, Nizar N Jarjour, Loren C Denlinger, Wilfred W Raymond, Michael C Peters, Eleanor M Dunican, Mario Castro, Kaharu Sumino, Serpil C Erzurum, Suzy A Comhair, Wendy C Moore, Bruce D Levy, Elliot Israel, Wanda Phipatanakul, Brenda R Phillips, David T Mauger, Eugene R Bleecker, Sally E Wenzel, Merritt L Fajt, Prescott G Woodruff, Annette T Hastie, John V Fahy; National Heart Lung and Blood Institute Severe Asthma Research Program
Abstract
Background: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.
Objective: To determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma.
Methods: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during three years of observation in 480 participants in the Severe Asthma Research Program (SARP)-3.
Results: Over three years, EPX levels in asthma patients were higher than normal in 27-31% of serum samples and 36-53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (rs values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts < 150 cells/uL and 42% of participants with blood eosinophil counts 150-299 cells/uL. Patients with persistently high sputum EPX values for three years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 asthma patients who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized.
Conclusion: Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation.
背景：嗜酸性粒细胞过氧化物酶（EPX）和血液和痰嗜酸性粒计数作为哮喘疾病生物标志物的相对效用尚不确定。
目的：确定EPX作为哮喘全身和气道嗜酸性粒细胞炎症的生物标志物的效用。
方法：通过免疫测定法测定110名健康对照者的血清和痰液中的EPX蛋白，以建立正常参考范围，并在480名严重哮喘研究计划（SARP）-3参与者的三年观察期间收集的血清和痰的重复样本中测定EPX蛋白。
结果：在三年多的时间里，哮喘患者27-31%的血清样本和36-53%的痰样本中EPX水平高于正常水平。血中嗜酸性粒细胞和EPX的相关性比痰中好（rs值分别为0.74和0.43），27%的血中嗜酸粒细胞计数<150个细胞/uL的参与者和42%的血中酸性粒细胞计数150-299个细胞/uL的参与者出现高痰EPX水平。三年来持续高痰EPX值的患者表现为严重的气流阻塞、频繁的加重和高粘液塞评分。在59名在观察期间开始使用美泊利珠单抗的哮喘患者中，96%的患者血清EPX水平正常，但只有49%的患者痰液EPX正常。即使痰中EPX正常，肺功能仍然异常。
结论：血清EPX是哮喘全身性嗜酸性粒细胞炎症的有效蛋白质生物标志物，痰EPX水平是气道嗜酸性粒炎症的一个比痰嗜酸性粒计数更敏感的生物标志物。血液中的嗜酸性粒细胞测量经常忽略气道嗜酸性粒炎症，而美泊利珠单抗经常无法使气道嗜酸性炎症正常化，尽管它使全身嗜酸性粒炎正常化。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2024 Apr 23:S0091-6749(24)00365-8. doi: 10.1016/j.jaci.2024.03.023.)
(J Allergy Clin Immunol. 2024 Apr 23:S0091-6749(24)00365-8. doi: 10.1016/j.jaci.2024.03.023.)
Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma
Monica Tang, Annabelle R Charbit, Mats W Johansson, Nizar N Jarjour, Loren C Denlinger, Wilfred W Raymond, Michael C Peters, Eleanor M Dunican, Mario Castro, Kaharu Sumino, Serpil C Erzurum, Suzy A Comhair, Wendy C Moore, Bruce D Levy, Elliot Israel, Wanda Phipatanakul, Brenda R Phillips, David T Mauger, Eugene R Bleecker, Sally E Wenzel, Merritt L Fajt, Prescott G Woodruff, Annette T Hastie, John V Fahy; National Heart Lung and Blood Institute Severe Asthma Research Program
Abstract
Background: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.
Objective: To determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma.
Methods: EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during three years of observation in 480 participants in the Severe Asthma Research Program (SARP)-3.
Results: Over three years, EPX levels in asthma patients were higher than normal in 27-31% of serum samples and 36-53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (rs values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts < 150 cells/uL and 42% of participants with blood eosinophil counts 150-299 cells/uL. Patients with persistently high sputum EPX values for three years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 asthma patients who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized.
Conclusion: Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation.
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