Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, Australia.
Institute for Respiratory Health Inc., Nedlands, Australia.
Eur Respir J. 2022 Mar 31;59(3). doi: 10.1183/13993003.01181-2021. Print 2022 Mar.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).
In the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations.
189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts.
A panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.
特发性肺纤维化(IPF)是一种进行性肺部疾病,循环生物标志物有可能在临床实践中指导管理。我们评估了三个独立的 IPF 队列中的血清生物标志物的预后作用:澳大利亚特发性肺纤维化登记处(AIPFR)、特伦特肺纤维化(TLF)和前瞻性观察肺纤维化临床终点(PROFILE)。
在 AIPFR 队列中,通过 ELISA 以及无偏蛋白组学方法评估候选蛋白。LASSO(最小绝对收缩和选择算子)回归用于限制标记物的选择,这些标记物在 AIPFR 队列中 1 年内最佳地解释了进展表型,随后在验证性 TLF 队列中前瞻性选择,并在 PROFILE 队列中回顾性评估。四个显著复制的生物标志物根据循环浓度的三分位数聚集到一个进展指数模型中。
AIPFR 队列纳入 189 名参与者,TLF 队列纳入 205 名参与者,PROFILE 队列纳入 122 名参与者。通过 ELISA 观察到差异生物标志物表达,并在 AIPFR 队列中复制了骨桥蛋白、基质金属蛋白酶-7、细胞间黏附分子-1 和骨膜蛋白在 1 年内具有进展表型的患者。蛋白质组学数据未复制。AIPFR、TLF 和 PROFILE 队列中的进展指数预测了进展风险、死亡率和无进展生存率。一个包含进展指数的统计模型证明了区分 12 个月疾病进展的能力,在所有队列中,这一能力超过了临床 GAP(性别、年龄和生理学)评分模型,在基于发病率的 TLF 和 PROFILE 队列中更为显著。
一组循环生物标志物可以为 IPF 患者的预后提供潜在有价值的临床帮助。