成人中-重度哮喘对肠外糖皮质激素的应答及肺功能纵向变化曲线
2021/03/25
摘要
背景：中-重度哮喘患者即使接受治疗肺功能仍然会继续下降，其原因尚不清楚。我们假设对肠外糖皮质激素应答最小的受试者导致肺功能严重下降的风险最大。
目的：评估糖皮质激素应答表型作为肺功能下降的纵向预测指标。
方法：在美国心肺血液研究所（NHLBI）的重症哮喘研究项目（SARP3 ;（1，2））中，在基线时接受了一个疗程的曲安奈德肌注治疗，且完成每年≥2次随访的受试者纳入评估。计算每个受试者的支气管扩张剂后FEV1％预计值的纵向斜率受试者的FEV1斜率分类定义如下：重度下降组，年下降率>2.0%; 轻度下降组，0.5%<年下降率≤2.0% ; 无变化组，年下降率<0.5 %且年增长率<1.0%；改善组，年增长率≥1.0% 。回归模型用来筛选肺功能重度下降的预测指标。
测量与主要结果：在396例受试者中，78例有重度下降，91例有轻度下降，114例无变化，113例显示肺功能改善。曲安奈德诱导的支气管扩张剂后FEV1% 预计值的变化（tdFEV1; 由基线减法导出）与单变量模型中4年后肺功能或斜率分类的变化相关(p <0.001)。校正基线FEV1，急性发作病史，血嗜酸粒细胞计数和BMI后，tdFEV1每下降5%，重度下降组发生概率增加50%(OR 1.5, 95% CI 1.3 to 1.8)。
结论：肠外类固醇激素刺激后未能改善支气管扩张剂后FEV1，它可作为患者肺功能重度下降风险的诱发生物标志物。
关键词：重症哮喘 糖皮质激素敏感性 纵向 急性发作
Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory
in Adults with Moderate to Severe Asthma
AJRCCM Articles in Press. Published December 08, 2020 as 10.1164/rccm.202002-0454OC. Pii :33290668
Denlinger LC, Phillips BR, Sorkness RL, Bleecker ER, Castro M, DeBoer MD, Fitzpatrick AM, Hastie AT, Gaffin JM, Moore WC, Peters MC, Peters SP, Phipatanakul W, Cardet JC, Erzurum SC, Fahy JV, Fajt ML, Gaston B, Levy BD, Meyers DA, Ross K, Teague WG, Wenzel SE, Woodruff PG, Zein J, Jarjour NN, Mauger DT, and Israel E; for the National Heart, Lung and Blood Institute’s Severe Asthma Research Program-3 Investigators.
Abstract
Rationale: It is unclear why select patients with moderate to severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of severe decline in lung function.
Objective: To evaluate corticosteroid response phenotypes as longitudinal predictors of lung decline.
Methods: Adults with in the NHLBI Severe Asthma Research Program (SARP3; (1, 2)) who had undergone a course of intramuscular triamcinolone at baseline and ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant’s post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/year; mild decline, >0.5 to 2.0% loss/year; no change, 0.5% loss/year to <1% gain/year; improve, ≥1% gain/year. Regression models were used to develop predictors of severe decline.
Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (tdFEV1; derived by baseline subtraction) was related to the 4-yr change in lung function or slope category in univariable models (p <0.001). For each 5% decrement in the tdFEV1, there was a 50% increase in the odds of being in the severe decline group (OR 1.5, 95% CI 1.3 to 1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and BMI.
Conclusions: Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk of severe decline in lung function.
Key Words: severe asthma, corticosteroid sensitivity, longitudinal, lung function, exacerbations
背景：中-重度哮喘患者即使接受治疗肺功能仍然会继续下降，其原因尚不清楚。我们假设对肠外糖皮质激素应答最小的受试者导致肺功能严重下降的风险最大。
目的：评估糖皮质激素应答表型作为肺功能下降的纵向预测指标。
方法：在美国心肺血液研究所（NHLBI）的重症哮喘研究项目（SARP3 ;（1，2））中，在基线时接受了一个疗程的曲安奈德肌注治疗，且完成每年≥2次随访的受试者纳入评估。计算每个受试者的支气管扩张剂后FEV1％预计值的纵向斜率受试者的FEV1斜率分类定义如下：重度下降组，年下降率>2.0%; 轻度下降组，0.5%<年下降率≤2.0% ; 无变化组，年下降率<0.5 %且年增长率<1.0%；改善组，年增长率≥1.0% 。回归模型用来筛选肺功能重度下降的预测指标。
测量与主要结果：在396例受试者中，78例有重度下降，91例有轻度下降，114例无变化，113例显示肺功能改善。曲安奈德诱导的支气管扩张剂后FEV1% 预计值的变化（tdFEV1; 由基线减法导出）与单变量模型中4年后肺功能或斜率分类的变化相关(p <0.001)。校正基线FEV1，急性发作病史，血嗜酸粒细胞计数和BMI后，tdFEV1每下降5%，重度下降组发生概率增加50%(OR 1.5, 95% CI 1.3 to 1.8)。
结论：肠外类固醇激素刺激后未能改善支气管扩张剂后FEV1，它可作为患者肺功能重度下降风险的诱发生物标志物。
关键词：重症哮喘 糖皮质激素敏感性 纵向 急性发作
(蒋玉才1 张红萍2 王刚1 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（AJRCCM Articles in Press. Published December 08, 2020 as 10.1164/rccm.202002-0454OC. Pii :33290668.）
（AJRCCM Articles in Press. Published December 08, 2020 as 10.1164/rccm.202002-0454OC. Pii :33290668.）
Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory
in Adults with Moderate to Severe Asthma
AJRCCM Articles in Press. Published December 08, 2020 as 10.1164/rccm.202002-0454OC. Pii :33290668
Denlinger LC, Phillips BR, Sorkness RL, Bleecker ER, Castro M, DeBoer MD, Fitzpatrick AM, Hastie AT, Gaffin JM, Moore WC, Peters MC, Peters SP, Phipatanakul W, Cardet JC, Erzurum SC, Fahy JV, Fajt ML, Gaston B, Levy BD, Meyers DA, Ross K, Teague WG, Wenzel SE, Woodruff PG, Zein J, Jarjour NN, Mauger DT, and Israel E; for the National Heart, Lung and Blood Institute’s Severe Asthma Research Program-3 Investigators.
Abstract
Rationale: It is unclear why select patients with moderate to severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of severe decline in lung function.
Objective: To evaluate corticosteroid response phenotypes as longitudinal predictors of lung decline.
Methods: Adults with in the NHLBI Severe Asthma Research Program (SARP3; (1, 2)) who had undergone a course of intramuscular triamcinolone at baseline and ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant’s post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/year; mild decline, >0.5 to 2.0% loss/year; no change, 0.5% loss/year to <1% gain/year; improve, ≥1% gain/year. Regression models were used to develop predictors of severe decline.
Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (tdFEV1; derived by baseline subtraction) was related to the 4-yr change in lung function or slope category in univariable models (p <0.001). For each 5% decrement in the tdFEV1, there was a 50% increase in the odds of being in the severe decline group (OR 1.5, 95% CI 1.3 to 1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and BMI.
Conclusions: Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk of severe decline in lung function.
Key Words: severe asthma, corticosteroid sensitivity, longitudinal, lung function, exacerbations
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重症哮喘研究中混合痰粒细胞对肺功能的纵向影响
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