血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂使用者在 COPDGene 队列中肺气肿进展和肺功能下降。
Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort.
机构信息
Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD.
Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD.
出版信息
Chest. 2021 Oct;160(4):1245-1254. doi: 10.1016/j.chest.2021.05.007. Epub 2021 May 21.
BACKGROUND
Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV progression in current smokers.
RESEARCH QUESTION
Is use of ACEi and ARB associated with less progression of emphysema and FEV decline among individuals with COPD or baseline emphysema?
METHODS
Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated.
RESULTS
Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV % predicted, 0.83; 95% CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.
INTERPRETATION
Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.
背景
通过阻断血管紧张素 II 来抑制转化生长因子 β 已被证明可减少小鼠模型中的肺气肿。人群研究表明，血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB）的使用与戒烟者肺气肿进展减少有关，ACEI 的使用与当前吸烟者的 FEV 进展减少有关。
研究问题
在 COPD 或基线肺气肿患者中，ACEI 和 ARB 的使用是否与肺气肿进展和 FEV 下降减少有关？
方法
参加基线和 5 年随访的来自 COPD 遗传流行病学研究的既往吸烟者和当前吸烟者，不改变吸烟状态，并接受胸部 CT 成像，包括在内。使用调整后的线性混合模型来评估调整后的肺密度（ALD）、肺气肿百分比（%-总肺体积<-950 亨氏单位 [HU]）、衰减直方图的第 15 百分位数（衰减[HU]低于 15%的体素位于何处加上 1000 HU）以及 5 年内 ACEI 和 ARB 使用者与非使用者之间的肺功能下降，以及所有参与者和基线肺气肿患者。还研究了吸烟状况的效应修饰。
结果
在 5 年的随访中，与非使用者相比，COPD 患者的 ACEI 和 ARB 使用者的 ALD 进展更慢（调整后的平均差异 [aMD]，1.6；95%CI，0.34-2.9）。基于第 1 阶段药物未观察到肺功能下降（FEV %预测的 aMD，0.83；95%CI，-0.62 至 2.3），但当分析仅限于一致的 ACEI 和 ARB 使用者时，观察到肺功能下降（FEV %预测的 aMD，1.9；95%CI，0.14-3.6）。吸烟状况对影像学结果无影响修饰，在既往吸烟者中，肺功能的影响更为明显。在基线肺气肿患者中，结果相似。
解释
在经过肺量计确诊的 COPD 或基线肺气肿患者中，ACEI 和 ARB 的使用与肺气肿和肺功能下降的进展较慢有关。
试验注册
ClinicalTrials.gov；编号：NCT00608764；网址：www.clinicaltrials.gov。
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