Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania.
Am J Respir Crit Care Med. 2021 Apr 1;203(7):841-852. doi: 10.1164/rccm.202002-0454OC.
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 undergoing a severe decline in lung function. To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline. Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV% predicted. Categories of participant FEV slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline. 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 FEV% predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models ( < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3-1.8), when adjusted for baseline FEV, exacerbation history, blood eosinophils and body mass index. Failure to improve the post-bronchodilator FEV after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.
目前尚不清楚为何一些中重度哮喘患者尽管接受了治疗，但仍会持续出现肺功能下降。我们假设，对皮质激素治疗反应最小的患者，其肺功能严重下降的风险最大。为了评估皮质激素反应表型作为肺功能下降的纵向预测因子。评估了 NHLBI SARP III（重度哮喘研究计划 III）中基线和至少 2 次年度随访时接受肌内曲安奈德治疗的成年人。为每位参与者的支气管扩张后 FEV%预测值计算了纵向斜率。参与者 FEV 斜率的分类如下：严重下降，>2%/年的损失；轻度下降，>0.5-2.0%/年的损失；无变化，0.5%/年至<1%/年的增益；改善，≥1%/年的增益。使用回归模型来建立严重下降的预测因子。在 396 名参与者中，78 人出现严重下降，91 人出现轻度下降，114 人无变化，113 人改善。支气管扩张后 FEV%预测值的（通过基线减去）的曲安奈德诱导差异与 4 年的肺功能变化或斜率类别有关在单变量模型中（ < 0.001）。对于曲安奈德诱导差异的每 5%下降，FEV1%预测值的严重下降组的比值比（OR）增加 50%（OR，1.5；95%置信区间，1.3-1.8），调整了基线 FEV、加重史、血嗜酸性粒细胞和体重指数。皮质激素治疗后支气管扩张后 FEV 未改善是肺功能严重下降风险患者的一个有价值的预测生物标志物。
