痰液基因表达特征预测哮喘患者口服糖皮质激素治疗反应
2017/09/29
摘要
预测口服糖皮质激素（OCS）治疗反应的生物标志物有助于病人选择更佳的方案治疗哮喘。我们假设，哮喘患者会对OCS治疗的不同反应，可用生物标志物和炎症标记物来预测。
哮喘稳定期的成年人接受了为期10天的每日口服50毫克泼尼松龙的随机对照交叉试验（n＝55）。对诱导痰中6个基因生物标记物（CLC，CPA3，DNASE1L3，IL1B，ALPL和CXCR2），及血液和痰中嗜酸性粒细胞进行了评估，并进行了预测响应变化研究（1秒钟用力呼气量变化值（ΔFEV1），六项控制哮喘问卷评分（ΔACQ6）或呼出的一氧化氮（ΔFENO）。
在基线时，对OCS应答显著的这部分患者（n = 25）肥大细胞表达的CPA3基因上调，有较差的肺功能及痰及嗜酸性粒细胞增高。经继续治疗后，CLC和CPA3基因表达减少，而DNASE1L3，IL1B，ALPL和CXCR2的表达保持不变。受试者工作特性曲线（ROC）分析表明，六种基因生物标记物比血及痰嗜酸粒细胞更能作为临床显著反应的预测因子。
六种基因表现的特征包括嗜酸性粒细胞和Th2相关的肥大细胞生物标志物，在稳定哮喘患者中对OCS反应预测性精度更高。因此，一种新的突出显示肥大细胞在哮喘中的作用的痰液基因表达标志物，可能是指导哮喘OCS治疗的有效方法。
A sputum gene expression signature predicts oral corticosteroid response in asthma
Bronwyn S. Berthon, Peter G. Gibson, Lisa G. Wood, Lesley K. MacDonald-Wicks and Katherine J. Baines
ABSTRACT
Biomarkers that predict responses to oral corticosteroids (OCS) facilitate patient selection for asthma treatment. We hypothesised that asthma patients would respond differently to OCS therapy, with biomarkers and inflammometry predicting response.
Adults with stable asthma underwent a randomised controlled cross-over trial of 50 mg prednisolone daily for 10 days (n=55). A six-gene expression biomarker signature (CLC, CPA3, DNASE1L3, IL1B, ALPL and CXCR2) in induced sputum, and eosinophils in blood and sputum were assessed and predictors of response were investigated (changes in forced expiratory volume in 1 s (ΔFEV1), six-item Asthma Control Questionnaire score (ΔACQ6) or exhaled nitric oxide fraction (ΔFeNO)).
At baseline, responders to OCS (n=25) had upregulated mast cell CPA3 gene expression, poorer lung function, and higher sputum and blood eosinophils. Following treatment, CLC and CPA3 gene expression was reduced, whereas DNASE1L3, IL1B, ALPL and CXCR2 expression remained unchanged. Receiver operating characteristic (ROC) analysis showed the six-gene expression biomarker signature as a better predictor of clinically significant responses to OCS than blood and sputum eosinophils.
The six-gene expression signature including eosinophil and Th2 related mast cell biomarkers showed greater precision in predicting OCS response in stable asthma. Thus, a novel sputum gene expression signature highlights an additional role of mast cells in asthma, and could be a useful measurement to guide OCS therapy in asthma.
预测口服糖皮质激素（OCS）治疗反应的生物标志物有助于病人选择更佳的方案治疗哮喘。我们假设，哮喘患者会对OCS治疗的不同反应，可用生物标志物和炎症标记物来预测。
哮喘稳定期的成年人接受了为期10天的每日口服50毫克泼尼松龙的随机对照交叉试验（n＝55）。对诱导痰中6个基因生物标记物（CLC，CPA3，DNASE1L3，IL1B，ALPL和CXCR2），及血液和痰中嗜酸性粒细胞进行了评估，并进行了预测响应变化研究（1秒钟用力呼气量变化值（ΔFEV1），六项控制哮喘问卷评分（ΔACQ6）或呼出的一氧化氮（ΔFENO）。
在基线时，对OCS应答显著的这部分患者（n = 25）肥大细胞表达的CPA3基因上调，有较差的肺功能及痰及嗜酸性粒细胞增高。经继续治疗后，CLC和CPA3基因表达减少，而DNASE1L3，IL1B，ALPL和CXCR2的表达保持不变。受试者工作特性曲线（ROC）分析表明，六种基因生物标记物比血及痰嗜酸粒细胞更能作为临床显著反应的预测因子。
六种基因表现的特征包括嗜酸性粒细胞和Th2相关的肥大细胞生物标志物，在稳定哮喘患者中对OCS反应预测性精度更高。因此，一种新的突出显示肥大细胞在哮喘中的作用的痰液基因表达标志物，可能是指导哮喘OCS治疗的有效方法。
（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）
（Eur Respir J 2017;49:1700180doi.10.1183/13993003.00180-2017 March 21 2017）
（Eur Respir J 2017;49:1700180doi.10.1183/13993003.00180-2017 March 21 2017）
A sputum gene expression signature predicts oral corticosteroid response in asthma
Bronwyn S. Berthon, Peter G. Gibson, Lisa G. Wood, Lesley K. MacDonald-Wicks and Katherine J. Baines
ABSTRACT
Biomarkers that predict responses to oral corticosteroids (OCS) facilitate patient selection for asthma treatment. We hypothesised that asthma patients would respond differently to OCS therapy, with biomarkers and inflammometry predicting response.
Adults with stable asthma underwent a randomised controlled cross-over trial of 50 mg prednisolone daily for 10 days (n=55). A six-gene expression biomarker signature (CLC, CPA3, DNASE1L3, IL1B, ALPL and CXCR2) in induced sputum, and eosinophils in blood and sputum were assessed and predictors of response were investigated (changes in forced expiratory volume in 1 s (ΔFEV1), six-item Asthma Control Questionnaire score (ΔACQ6) or exhaled nitric oxide fraction (ΔFeNO)).
At baseline, responders to OCS (n=25) had upregulated mast cell CPA3 gene expression, poorer lung function, and higher sputum and blood eosinophils. Following treatment, CLC and CPA3 gene expression was reduced, whereas DNASE1L3, IL1B, ALPL and CXCR2 expression remained unchanged. Receiver operating characteristic (ROC) analysis showed the six-gene expression biomarker signature as a better predictor of clinically significant responses to OCS than blood and sputum eosinophils.
The six-gene expression signature including eosinophil and Th2 related mast cell biomarkers showed greater precision in predicting OCS response in stable asthma. Thus, a novel sputum gene expression signature highlights an additional role of mast cells in asthma, and could be a useful measurement to guide OCS therapy in asthma.
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气道直径的变化是呼出气一氧化氮评估哮喘控制能力的主要决定因素
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可以应用CT和一氧化碳弥散系数诊断具有哮喘特点的COPD患者吗？
