PDF(Pubmed)
Abstract：
BACKGROUND: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry.
METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3).
RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low.
CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.
METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3).
RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low.
CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.
摘要：
背景：肺纤维化是具有不同病因的各种间质性肺病（ILD）的特征。进行性肺纤维化（PPF）的临床试验根据先前描述的过去进展的临床标准招募患者，其中包括来自INBUILD试验的PPF分类和纳入标准的临床实践指南。在这项研究中,我们比较了PFF患者注册表中一组患者过去FVC(强迫肺活量)进展和基线生物标志物水平预测未来进展的能力.
方法：选择先前与肺纤维化病理生物学和/或进展相关的生物标志物来反映细胞衰老（端粒长度），肺上皮（SP-D，RAGE),骨髓激活（CXCL13，YKL40，CCL18，OPN）和成纤维细胞激活（POSTN，COMP,PROC3)。
结果：使用PFF或INBUILD样临床标准将患者分为过去进展组和非过去进展组，对于未来肺功能下降更大的患者，这两种临床标准似乎都不能丰富。与健康对照相比,所有测量的基线生物标志物在患者组中差异表达。SP-D和POSTN的基线水平在一年内与FVC斜率的相关性最高，尽管相关性很低。
结论：我们的研究结果提供了进一步的证据，表明先前的肺功能下降可能无法预测ILD患者未来的疾病进展。并提高了对进行性表型的分子定义的需求。在ILD亚型中，基于观察到的某些生物标志物组的分子谱,可能存在某些共有病理.特别是,SP-D可能是跨ILD的肺损伤和未来肺功能下降的常见标志物。
方法：选择先前与肺纤维化病理生物学和/或进展相关的生物标志物来反映细胞衰老（端粒长度），肺上皮（SP-D，RAGE),骨髓激活（CXCL13，YKL40，CCL18，OPN）和成纤维细胞激活（POSTN，COMP,PROC3)。
结果：使用PFF或INBUILD样临床标准将患者分为过去进展组和非过去进展组，对于未来肺功能下降更大的患者，这两种临床标准似乎都不能丰富。与健康对照相比,所有测量的基线生物标志物在患者组中差异表达。SP-D和POSTN的基线水平在一年内与FVC斜率的相关性最高，尽管相关性很低。
结论：我们的研究结果提供了进一步的证据，表明先前的肺功能下降可能无法预测ILD患者未来的疾病进展。并提高了对进行性表型的分子定义的需求。在ILD亚型中，基于观察到的某些生物标志物组的分子谱,可能存在某些共有病理.特别是,SP-D可能是跨ILD的肺损伤和未来肺功能下降的常见标志物。
