Th2型生物标志物在重症哮喘中的分离；主要由FeNO作为恶化的预测因子，骨膜蛋白作为肺功能降低的预测因子
2018/10/23
摘要
背景:Th2型炎症的生物标志物可预测哮喘控制水平和恶化风险。然而严重哮喘患者的Th2生物标志物与肺功能之间的关系仍不确定。
目标：探讨Th2型生物标志物在严重哮喘临床预后预测中的作用。
方法：未经选择的重度哮喘患者被纳入此横断面真实世界研究。获得参与者的进行临床特征及以下测量数据：需要口服糖皮质激素（OCS）的加重次数、哮喘控制（Juniper ACQ6-7）、肺功能、呼出气一氧化氮（FeNO）、外周血嗜酸性粒细胞（PBE）和血清骨膜蛋白。
结果：共招募115名患者，平均年龄45岁（18-70岁），女性80名（69.6%），预测第一秒平均呼气量（FEV1）为68%±24.7，平均吸入皮质类固醇（ICS）为1.96±0.82_mg/天。FeNO与PBE显著相关(r=0.35,p=0.0004),与骨膜素(r=0.22,p=0.065)无显著相关性。FENO与病情加重相关（r＝0.42，P＝0.0008）明显强于PBE和PieloSin。3项生物标志物的综合评分与病情加重呈剂量依赖关系，但多元回归分析未证实有额外的益处。结果表明，仅骨膜蛋白与FEV1%预测值呈显著正相关（r＝-0.34，P＝0.004），ROC-AUC为0.7.。
结论：FeNO与哮喘恶化的相关性比PBE或骨膜素更强，而三种生物标志物的综合评分没有明确增加预测哮喘病情加重的益处。只有骨膜蛋白与降低的肺功能显著相关，从而提高其作为气道重塑的生物标志物的潜力。
Disconnect of type 2 biomarkers in severe asthma; dominated by FeNO as a predictor of exacerbations and periostin as predictor of reduced lung function.
Mansur AH, Srivastava S, Sahal A.
Abstract
BACKGROUND: biomarkers of Type 2 (T2) inflammation may predict asthma control and exacerbation risk. However, the relationships between individual T2 biomarkers to exacerbations and lung function in severe asthma remain uncertain.
OBJECTIVES: to explore the roles played by T2 biomarkers individually and as a composite score in predicting clinical outcomes in severe asthma.
METHODS: unselected severe asthma patients were enrolled in this cross sectional real life study. Participants were clinically characterised and the following measurements were obtained: the frequency of exacerbations requiring oral corticosteroids (OCS), asthma control (Juniper ACQ6-7), lung function, Fraction exhaled Nitric Oxide (FeNO), peripheral blood eosinophils (PBE), and serum periostin.
RESULTS: A total of 115 patients were recruited [mean age 45 years (range 18-70), 80 (69.6%) females, mean forced expiratory volume in first second (FEV1) %predicted was 68% ± 24.7, mean inhaled corticosteroids (ICS) 1.96 ± 0.82 mg/day. FeNO correlated significantly with PBE (r = 0.35, p = 0.0004), but not with periostin (r = 0.22, p = 0.065) and there was no significant correlation between PBE and periostin. FeNO correlation with exacerbations (r = 0.42, p = 0.0008) was stronger than PBE and periostin. A composite score of the 3 biomarkers correlated with exacerbations in a dose-dependent manner but multiple regression analysis did not confirm an added benefit. Only periostin demonstrated a significant correlation with FEV1%predicted (r = -0.34, p = 0.004) with ROC-AUC 0.7.
CONCLUSION: FeNO demonstrated stronger correlation with asthma exacerbations than PBE or periostin with no definite added benefit from a composite score of the 3 biomarkers. Only periostin showed significant association with reduced lung function raising its potential as a biomarker of airway remodeling.
背景:Th2型炎症的生物标志物可预测哮喘控制水平和恶化风险。然而严重哮喘患者的Th2生物标志物与肺功能之间的关系仍不确定。
目标：探讨Th2型生物标志物在严重哮喘临床预后预测中的作用。
方法：未经选择的重度哮喘患者被纳入此横断面真实世界研究。获得参与者的进行临床特征及以下测量数据：需要口服糖皮质激素（OCS）的加重次数、哮喘控制（Juniper ACQ6-7）、肺功能、呼出气一氧化氮（FeNO）、外周血嗜酸性粒细胞（PBE）和血清骨膜蛋白。
结果：共招募115名患者，平均年龄45岁（18-70岁），女性80名（69.6%），预测第一秒平均呼气量（FEV1）为68%±24.7，平均吸入皮质类固醇（ICS）为1.96±0.82_mg/天。FeNO与PBE显著相关(r=0.35,p=0.0004),与骨膜素(r=0.22,p=0.065)无显著相关性。FENO与病情加重相关（r＝0.42，P＝0.0008）明显强于PBE和PieloSin。3项生物标志物的综合评分与病情加重呈剂量依赖关系，但多元回归分析未证实有额外的益处。结果表明，仅骨膜蛋白与FEV1%预测值呈显著正相关（r＝-0.34，P＝0.004），ROC-AUC为0.7.。
结论：FeNO与哮喘恶化的相关性比PBE或骨膜素更强，而三种生物标志物的综合评分没有明确增加预测哮喘病情加重的益处。只有骨膜蛋白与降低的肺功能显著相关，从而提高其作为气道重塑的生物标志物的潜力。
(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)
(Respir Med. 2018 Oct;143:31-38. doi: 10.1016/j.rmed.2018.08.005. Epub 2018 Aug 9.)
(Respir Med. 2018 Oct;143:31-38. doi: 10.1016/j.rmed.2018.08.005. Epub 2018 Aug 9.)
Disconnect of type 2 biomarkers in severe asthma; dominated by FeNO as a predictor of exacerbations and periostin as predictor of reduced lung function.
Mansur AH, Srivastava S, Sahal A.
Abstract
BACKGROUND: biomarkers of Type 2 (T2) inflammation may predict asthma control and exacerbation risk. However, the relationships between individual T2 biomarkers to exacerbations and lung function in severe asthma remain uncertain.
OBJECTIVES: to explore the roles played by T2 biomarkers individually and as a composite score in predicting clinical outcomes in severe asthma.
METHODS: unselected severe asthma patients were enrolled in this cross sectional real life study. Participants were clinically characterised and the following measurements were obtained: the frequency of exacerbations requiring oral corticosteroids (OCS), asthma control (Juniper ACQ6-7), lung function, Fraction exhaled Nitric Oxide (FeNO), peripheral blood eosinophils (PBE), and serum periostin.
RESULTS: A total of 115 patients were recruited [mean age 45 years (range 18-70), 80 (69.6%) females, mean forced expiratory volume in first second (FEV1) %predicted was 68% ± 24.7, mean inhaled corticosteroids (ICS) 1.96 ± 0.82 mg/day. FeNO correlated significantly with PBE (r = 0.35, p = 0.0004), but not with periostin (r = 0.22, p = 0.065) and there was no significant correlation between PBE and periostin. FeNO correlation with exacerbations (r = 0.42, p = 0.0008) was stronger than PBE and periostin. A composite score of the 3 biomarkers correlated with exacerbations in a dose-dependent manner but multiple regression analysis did not confirm an added benefit. Only periostin demonstrated a significant correlation with FEV1%predicted (r = -0.34, p = 0.004) with ROC-AUC 0.7.
CONCLUSION: FeNO demonstrated stronger correlation with asthma exacerbations than PBE or periostin with no definite added benefit from a composite score of the 3 biomarkers. Only periostin showed significant association with reduced lung function raising its potential as a biomarker of airway remodeling.
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哮喘-慢阻肺重叠在中低等收入国家的流行病学及危险因素
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Toll样受体4通路多态性与环境污染相互作用影响哮喘的诊断和严重程度
