Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
Duke Clinical Research Institute, Durham, North Carolina, United States of America.
PLoS One. 2024 Oct 17;19(10):e0312044. doi: 10.1371/journal.pone.0312044. eCollection 2024.
We assessed the prognostic utility of circulating levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry.
MMP and TIMP concentrations were quantified by ELISA in plasma from 300 patients. A Cox proportional hazard regression model was used to assess associations between select MMPs and TIMPs and death and disease progression (absolute decline in forced vital capacity ≥10% predicted, death, or lung transplant).
Over a median follow-up of 30.4 months, 98 patients died and 182 patients had disease progression. In unadjusted analyses, higher concentrations of MMPs 2, 3, 8 and 9 and TIMPs 1, 2 and 4 were associated with an increased risk of death. MMPs 2 and 8 and TIMP1 remained associated with death after adjustment for clinical factors. In unadjusted analyses, higher concentrations of MMPs 8 and 9 and TIMPs 1 and 4 were associated with an increased risk of disease progression. MMPs 8 and 9 and TIMP1 remained associated with progression after adjustment for clinical factors.
Circulating levels of MMP8 and TIMP1 may provide information on the risk of outcomes in patients with IPF not captured by clinical measures.
我们在特发性肺纤维化（IPF）患者的 IPF-PRO 注册中心评估了循环基质金属蛋白酶（MMPs）和基质金属蛋白酶抑制剂（TIMPs）水平的预后价值。
通过 ELISA 定量检测 300 例患者血浆中的 MMP 和 TIMP 浓度。使用 Cox 比例风险回归模型评估选定的 MMP 和 TIMP 与死亡和疾病进展（用力肺活量绝对下降≥10%预测值、死亡或肺移植）之间的关联。
在中位随访 30.4 个月期间，98 例患者死亡，182 例患者疾病进展。在未调整分析中，MMPs 2、3、8 和 9 以及 TIMPs 1、2 和 4 的浓度较高与死亡风险增加相关。在调整临床因素后，MMPs 2 和 8 以及 TIMP1 仍与死亡相关。在未调整分析中，MMPs 8 和 9 以及 TIMPs 1 和 4 的浓度较高与疾病进展风险增加相关。在调整临床因素后，MMPs 8 和 9 以及 TIMP1 仍与进展相关。
MMP8 和 TIMP1 的循环水平可能提供了临床指标无法捕捉的 IPF 患者结局风险的信息。
