Department of Medicine, University of Virginia, Charlottesville, Virginia.
Department of Medicine.
Ann Am Thorac Soc. 2021 Nov;18(11):1839-1848. doi: 10.1513/AnnalsATS.202012-1557OC.
The coagulation cascade may play a role in the pathogenesis of interstitial lung disease through increased production of thrombin and fibrin deposition. Whether circulating coagulation cascade factors are linked to lung inflammation and scarring among community-dwelling adults is unknown. To test the hypothesis that higher baseline D-dimer concentrations are associated with markers of early lung injury and scarring. Using the MESA (Multi-Ethnic Study of Atherosclerosis) cohort ( = 6,814), we examined associations of baseline D-dimer concentrations with high attenuation areas from examination 1 (2000-2002; = 6,184) and interstitial lung abnormalities from examination 5 computed tomographic (CT) scans (2010-2012; = 2,227), and serum MMP-7 (matrix metalloproteinase-7) and SP-A (surfactant protein-A) from examination 1 ( = 1,098). We examined longitudinal change in forced vital capacity (FVC) from examinations 3-6 (2004-2018, = 3,562). We used linear logistic regression and linear mixed models to examine associations and adjust for potential confounders. The mean (standard deviation) age of the cohort was 62 (10) years, and the D-dimer concentration was 0.35 (0.69) ug/ml. For every 10% increase in D-dimer concentration, there was an increase in high attenuation area percentage of 0.27 (95% confidence interval (CI), 0.08-0.47) after adjustment for covariates. Associations were stronger among those older than 65 years ( values for interaction < 0.001). A 10% increase in D-dimer concentration was associated with an odds ratio of 1.05 for interstitial lung abnormalities (95% CI, 0.99-1.11). Higher D-dimer concentrations were associated with higher serum MMP-7 and a faster decline in FVC. D-dimer was not associated with SP-A. Higher D-dimer concentrations were associated with a greater burden of lung parenchymal abnormalities detected on CT scan, MMP-7, and FVC decline among community-dwelling adults.
凝血级联反应可能通过增加凝血酶和纤维蛋白沉积在特发性肺纤维化的发病机制中发挥作用。循环凝血级联反应因子是否与社区居住成年人的肺炎症和瘢痕形成有关尚不清楚。
为了检验以下假设,即较高的基线 D-二聚体浓度与早期肺损伤和瘢痕形成的标志物相关。
我们使用 MESA(多民族动脉粥样硬化研究)队列(n=6814),研究了基线 D-二聚体浓度与第一次检查(2000-2002 年;n=6184)中高衰减区域和第五次 CT 扫描(2010-2012 年;n=2227)中肺间质异常之间的关联,并研究了第一次检查(n=1098)中的血清 MMP-7(基质金属蛋白酶-7)和 SP-A(表面活性剂蛋白-A)。我们研究了第三次至第六次检查(2004-2018 年,n=3562)中用力肺活量(FVC)的纵向变化。我们使用线性逻辑回归和线性混合模型来研究关联,并调整潜在的混杂因素。
队列的平均(标准差)年龄为 62(10)岁,D-二聚体浓度为 0.35(0.69)μg/ml。在调整了混杂因素后,D-二聚体浓度每增加 10%,高衰减区域百分比增加 0.27(95%置信区间(CI),0.08-0.47)。在年龄大于 65 岁的人群中,关联更强(交互值<0.001)。D-二聚体浓度增加 10%,间质性肺异常的比值比为 1.05(95%CI,0.99-1.11)。较高的 D-二聚体浓度与更高的血清 MMP-7 和 FVC 下降速度更快相关。D-二聚体与 SP-A 无关。
较高的 D-二聚体浓度与 CT 扫描上检测到的肺实质异常、MMP-7 增加和 FVC 下降的负担增加有关,在社区居住的成年人中。