重症哮喘患者生物标记物的前瞻性、单臂、纵向研究
2020/05/14
摘要
背景：ARIETTA是一项前瞻性、单臂、非干预性、多中心的重症哮喘研究。
目的：探讨2型生物标志物对重症哮喘预后的预测能力。
方法：成人重症哮喘患者，每日吸入糖皮质激素（丙酸氟替卡松≥500μg或等效物）和≥1种的对照药物。在52周内收集生物标志物、临床和安全性数据。主要终点是血清骨膜蛋白高组（基线时≥50ng/mL）与骨膜蛋白低组（低于50ng/mL）在52周后哮喘发作率。评估生物标记物水平（骨膜蛋白、血嗜酸性粒细胞、免疫球蛋白E[IgE]和呼出一氧化氮[FeNO]）之间以及中心和局部实验室测量（血嗜酸性粒细胞和IgE）之间的相关性。
结果：465例患者中，女性占66.5%，口服皮质类固醇者占13.3%，前年1次以上发作者占42.4%，骨膜蛋白增高者占52.0%，2型炎症患者占87.5%（血嗜酸性粒细胞≥150细胞/μL和/或FeNO≥25ppb和/或皮肤过敏原试验阳性）。生物标志物水平相互之间相关性很差。中央和地方实验室的血嗜酸性粒细胞和IgE测量结果基本一致。在52周内，高骨膜蛋白患者和低骨膜蛋白患者的恶化率没有差异（比率为0.93[95%CI，0.67-1.28]；P=0.642）。结果提示血嗜酸性粒细胞≥300细胞/μL和FeNO≥25ppb的患者病情恶化率较高。
结论：血清骨膜素对病情恶化无预后价值。高血嗜酸性粒细胞和高FeNO可能与急性发作率有关。
Prospective, single-arm, longitudinal study of biomarkers in real-world patients with severe asthma.
Buhl R, Korn S, Menzies-Gow A, Aubier M, Chapman KR, Canonica GW, Picado C, Donica M, Kuhlbusch K, Korom S, Hanania NA.
Abstract
BACKGROUND: ARIETTA was a prospective, single-arm, noninterventional, multicenter study in patients with severe asthma.
OBJECTIVE:To examine the predictive and prognostic abilities of Type 2 biomarkers for severe asthma outcomes.
METHODS: Adult patients with severe asthma receiving daily inhaled corticosteroids (fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled. Biomarker, clinical, and safety data were collected over 52 weeks. The primary endpoint was the asthma exacerbation rate over 52 weeks in serum periostin-high (≥50 ng/mL at baseline) vs periostin-low subgroups (<50 ng/mL). Correlations between biomarker levels (periostin, blood eosinophils, immunoglobulin E [IgE], and fractional exhaled nitric oxide [FeNO]) and between central and local laboratory measurements (blood eosinophils and IgE) were assessed. The study was terminated before planned enrollment was completed.
RESULTS: Of 465 patients, 66.5% were female, 13.3% were receiving oral corticosteroids, 42.4% had ≥1 exacerbation in the previous year, 52.0% were periostin-high, and 87.5% had Type 2 inflammation (blood eosinophils ≥150 cells/μL and/or FeNO ≥25 ppb and/or positive skin allergen test). Biomarker levels correlated poorly with each other. Central and local laboratory blood eosinophil and IgE measurements generally agreed. No difference was observed in exacerbation rates over 52 weeks between periostin-high and periostin-low patients (rate ratio, 0.93 [95% CI, 0.67-1.28]; P=0.642). Results suggested higher exacerbation rates in patients with blood eosinophils ≥300 cells/μL and FeNO ≥25 ppb.
CONCLUSIONS: No prognostic value for serum periostin related to exacerbations was detected. Higher blood eosinophils combined with increased FeNO were potentially associated with increased exacerbation rates.
背景：ARIETTA是一项前瞻性、单臂、非干预性、多中心的重症哮喘研究。
目的：探讨2型生物标志物对重症哮喘预后的预测能力。
方法：成人重症哮喘患者，每日吸入糖皮质激素（丙酸氟替卡松≥500μg或等效物）和≥1种的对照药物。在52周内收集生物标志物、临床和安全性数据。主要终点是血清骨膜蛋白高组（基线时≥50ng/mL）与骨膜蛋白低组（低于50ng/mL）在52周后哮喘发作率。评估生物标记物水平（骨膜蛋白、血嗜酸性粒细胞、免疫球蛋白E[IgE]和呼出一氧化氮[FeNO]）之间以及中心和局部实验室测量（血嗜酸性粒细胞和IgE）之间的相关性。
结果：465例患者中，女性占66.5%，口服皮质类固醇者占13.3%，前年1次以上发作者占42.4%，骨膜蛋白增高者占52.0%，2型炎症患者占87.5%（血嗜酸性粒细胞≥150细胞/μL和/或FeNO≥25ppb和/或皮肤过敏原试验阳性）。生物标志物水平相互之间相关性很差。中央和地方实验室的血嗜酸性粒细胞和IgE测量结果基本一致。在52周内，高骨膜蛋白患者和低骨膜蛋白患者的恶化率没有差异（比率为0.93[95%CI，0.67-1.28]；P=0.642）。结果提示血嗜酸性粒细胞≥300细胞/μL和FeNO≥25ppb的患者病情恶化率较高。
结论：血清骨膜素对病情恶化无预后价值。高血嗜酸性粒细胞和高FeNO可能与急性发作率有关。
(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 Pract. 2020 Apr 15. pii: S2213-2198(20)30338-X. doi: 10.1016/j.jaip.2020.03.038.)
(J Allergy Clin Immunol Pract. 2020 Apr 15. pii: S2213-2198(20)30338-X. doi: 10.1016/j.jaip.2020.03.038.)
Prospective, single-arm, longitudinal study of biomarkers in real-world patients with severe asthma.
Buhl R, Korn S, Menzies-Gow A, Aubier M, Chapman KR, Canonica GW, Picado C, Donica M, Kuhlbusch K, Korom S, Hanania NA.
Abstract
BACKGROUND: ARIETTA was a prospective, single-arm, noninterventional, multicenter study in patients with severe asthma.
OBJECTIVE:To examine the predictive and prognostic abilities of Type 2 biomarkers for severe asthma outcomes.
METHODS: Adult patients with severe asthma receiving daily inhaled corticosteroids (fluticasone propionate ≥500 μg or equivalent) and ≥1 second controller medication were enrolled. Biomarker, clinical, and safety data were collected over 52 weeks. The primary endpoint was the asthma exacerbation rate over 52 weeks in serum periostin-high (≥50 ng/mL at baseline) vs periostin-low subgroups (<50 ng/mL). Correlations between biomarker levels (periostin, blood eosinophils, immunoglobulin E [IgE], and fractional exhaled nitric oxide [FeNO]) and between central and local laboratory measurements (blood eosinophils and IgE) were assessed. The study was terminated before planned enrollment was completed.
RESULTS: Of 465 patients, 66.5% were female, 13.3% were receiving oral corticosteroids, 42.4% had ≥1 exacerbation in the previous year, 52.0% were periostin-high, and 87.5% had Type 2 inflammation (blood eosinophils ≥150 cells/μL and/or FeNO ≥25 ppb and/or positive skin allergen test). Biomarker levels correlated poorly with each other. Central and local laboratory blood eosinophil and IgE measurements generally agreed. No difference was observed in exacerbation rates over 52 weeks between periostin-high and periostin-low patients (rate ratio, 0.93 [95% CI, 0.67-1.28]; P=0.642). Results suggested higher exacerbation rates in patients with blood eosinophils ≥300 cells/μL and FeNO ≥25 ppb.
CONCLUSIONS: No prognostic value for serum periostin related to exacerbations was detected. Higher blood eosinophils combined with increased FeNO were potentially associated with increased exacerbation rates.
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加工肉制品摄入与哮喘症状的关系：法国健康营养网队列研究
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重症嗜酸粒细胞性哮喘患者血嗜酸粒细胞计数变化及动力学研究
