嗜酸性粒细胞过氧化物酶作为哮喘嗜酸性粒细胞炎症生物标志物的效用
2024/07/31
摘要
背景：嗜酸性粒细胞过氧化物酶（EPX）与血液和痰嗜酸性粒细胞计数作为哮喘疾病生物标志物的相对效用尚不确定。
目的：我们试图确定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了110名健康对照者血清和痰中的EPX蛋白，以建立正常参考范围，并对480名重度哮喘研究项目3（SARP-3）参与者3年随访期间重复收集的血清和痰样本进行了检测。
结果：在3年内，哮喘患者27%至31%的血清样本和36%至53%的痰液样本的EPX水平高于正常水平。血液中嗜酸性粒细胞与EPX的相关性优于痰液中的相关性
，血液嗜酸性粒细胞计数低于150个细胞/μL的受试者中有27%出现高痰液EPX水平，血液嗜酸性粒细胞计数在150至299个细胞/μL之间的受试者中有42%出现高痰液EPX水平。痰液EPX值持续高3年的患者，表现为严重气流阻塞、频繁急性发作、高粘液堵塞评分。在观察期间开始使用美泊利单抗治疗的59例哮喘患者中，96%的患者血清EPX水平恢复正常，但仅49%的患者痰EPX水平恢复正常。即使痰EPX恢复正常，肺功能仍然异常。
结论：血清EPX是哮喘全身嗜酸性粒细胞炎症的有效蛋白质生物标志物，痰EPX水平是比痰嗜酸性粒细胞计数更敏感的气道嗜酸性粒细胞炎症生物标志物。血液中的嗜酸性粒细胞计数经常漏诊气道嗜酸性粒细胞炎症，而美泊利单抗常常不能使气道嗜酸性粒细胞炎症正常化，尽管它总是能使全身性嗜酸性粒细胞炎症正常化。
Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma
Tang M, Charbit AR, Johansson MW, Jarjour NN, Denlinger LC, Raymond WW, Peters MC, Dunican EM, Castro M, Sumino K, Erzurum SC, Comhair SA, Moore WC, Levy BD, Israel E, Phipatanakul W, Phillips BR, Mauger DT, Bleecker ER, Wenzel SE, Fajt ML, Woodruff PG, Hastie AT, Fahy JV; National Heart Lung and Blood Institute Severe Asthma Research Program.
J Allergy Clin Immunol. 2024 Apr 23:S0091-6749(24)00365-8. doi: 10.1016/j.jaci.2024.03.023. Epub ahead of print. PMID: 38663815.
Abstrast
Background: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.
Objective: We sought 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 3 years of observation in 480 participants in the Severe Asthma Research Program 3.
Results: Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum
, and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/μL and 42% of participants with blood eosinophil counts between 150 and 299 cells/μL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma 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.
Conclusions: 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）与血液和痰嗜酸性粒细胞计数作为哮喘疾病生物标志物的相对效用尚不确定。
目的：我们试图确定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了110名健康对照者血清和痰中的EPX蛋白，以建立正常参考范围，并对480名重度哮喘研究项目3（SARP-3）参与者3年随访期间重复收集的血清和痰样本进行了检测。
结果：在3年内，哮喘患者27%至31%的血清样本和36%至53%的痰液样本的EPX水平高于正常水平。血液中嗜酸性粒细胞与EPX的相关性优于痰液中的相关性
，血液嗜酸性粒细胞计数低于150个细胞/μL的受试者中有27%出现高痰液EPX水平，血液嗜酸性粒细胞计数在150至299个细胞/μL之间的受试者中有42%出现高痰液EPX水平。痰液EPX值持续高3年的患者，表现为严重气流阻塞、频繁急性发作、高粘液堵塞评分。在观察期间开始使用美泊利单抗治疗的59例哮喘患者中，96%的患者血清EPX水平恢复正常，但仅49%的患者痰EPX水平恢复正常。即使痰EPX恢复正常，肺功能仍然异常。结论：血清EPX是哮喘全身嗜酸性粒细胞炎症的有效蛋白质生物标志物，痰EPX水平是比痰嗜酸性粒细胞计数更敏感的气道嗜酸性粒细胞炎症生物标志物。血液中的嗜酸性粒细胞计数经常漏诊气道嗜酸性粒细胞炎症，而美泊利单抗常常不能使气道嗜酸性粒细胞炎症正常化，尽管它总是能使全身性嗜酸性粒细胞炎症正常化。
(四川大学华西医院呼吸与危重症医学科 杨倩1 王霁1 王刚1 译)
(J Allergy Clin Immunol. 2024 Apr 23:S0091-6749(24)00365-8. doi: 10.1016/j.jaci.2024.03.023. Epub ahead of print. PMID: 38663815.)
(J Allergy Clin Immunol. 2024 Apr 23:S0091-6749(24)00365-8. doi: 10.1016/j.jaci.2024.03.023. Epub ahead of print. PMID: 38663815.)
Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma
Tang M, Charbit AR, Johansson MW, Jarjour NN, Denlinger LC, Raymond WW, Peters MC, Dunican EM, Castro M, Sumino K, Erzurum SC, Comhair SA, Moore WC, Levy BD, Israel E, Phipatanakul W, Phillips BR, Mauger DT, Bleecker ER, Wenzel SE, Fajt ML, Woodruff PG, Hastie AT, Fahy JV; National Heart Lung and Blood Institute Severe Asthma Research Program.
J Allergy Clin Immunol. 2024 Apr 23:S0091-6749(24)00365-8. doi: 10.1016/j.jaci.2024.03.023. Epub ahead of print. PMID: 38663815.
Abstrast
Background: The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.
Objective: We sought 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 3 years of observation in 480 participants in the Severe Asthma Research Program 3.
Results: Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum
, and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/μL and 42% of participants with blood eosinophil counts between 150 and 299 cells/μL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma 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.Conclusions: 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.
上一篇：
血嗜酸性粒细胞计数与FEV1下降的关联：一项队列研究
下一篇：
通过生物信息学分析和机器学习识别哮喘和抑郁症的共同潜在诊断标志物
