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首页> 外文期刊>EBioMedicine >Endotype–phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease
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Endotype–phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease

机译：内型-表型可能预测进行性纤维化间质性肺疾病的治疗反应

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Background Some interstitial lung disease (ILD) patients develop a progressive fibrosing-ILD phenotype (PF-ILD), with similar persistent lung function decline suggesting common molecular pathways involved. Nintedanib, a tyrosine kinase inhibitor targeting the PDGF, FGF, VEGF and M-CSF pathways, has shown comparable efficacy in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated ILD (SSc-ILD). We hypothesize that Nintedanib targeted molecular pathways will be augmented to a similar degree across PF-ILD regardless of aetiology. Methods We collected explanted lung tissue at the time of lung transplantation from 130 PF-ILD patients (99 (76%) IPF, 14 (11%) SSc-ILD, 17 (13%) other PF-ILD), and wedge biopsies from 200 donor lungs and measured PDGF, FGF, VEGF and M-CSF concentrations by Luminex. Findings The concentrations of PDGF-AA, PDGF-BB, FGF-2, VEGF and M-CSF were significantly increased in PF-ILD lungs compared to donor lungs (PDGF-AA 93·0?pg/ml [±97·2] vs. 37·5?pg/ml [±35·4], p ??0·001; PDGF-BB 102·5?pg/ml [±78·8] vs. 61·9?pg/ml [±47·0], p ??0·001; FGF-2 1442·4?pg/ml [±426·6] vs. 1201·7?pg/ml [±535·2], p ?=?0·009; VEGF 40·6?pg/ml [±20·1] vs. 24·9?pg/ml [±29·5], p ??0·001; and M-CSF 25526?pg/ml [±24,799] vs. 6120?pg/ml [±7245], p ??0·001). There were no significant differences in these growth factor/angiogenic molecules/cytokine concentrations when segregated by IPF, SSc-ILD and other PF-ILDs. Interpretation Nintedanib specific targeted molecular pathways are augmented to a similar magnitude in all PF-ILD lung tissue as compared to controls, suggesting that Nintedanib treatment may be efficacious in PF-ILD regardless of aetiology. We speculate that clinical trials using Nintedanib for PF-ILD with or without IPF or SSc-ILD should show a similar relative reduction in FVC decline as seen in IPF and SSc-ILD (～45–50%). Funding Health Grant P01-HL108793 (JAB), South-Eastern Norway Regional Health Authority Grant 2018072 (AMHV).
机译：背景技术一些间质性肺疾病（ILD）患者会发展为进行性纤维化-ILD表型（PF-ILD），并伴有相似的持续肺功能下降，提示涉及的常见分子途径。 Nintedanib是一种靶向PDGF，FGF，VEGF和M-CSF途径的酪氨酸激酶抑制剂，在特发性肺纤维化（IPF）和全身性硬化相关性ILD（SSc-ILD）中显示出可比的疗效。我们假设，无论病因如何，Nintedanib靶向的分子途径将在整个PF-ILD中以相似的程度增加。方法我们收集了130例PF-ILD患者（99（76％）IPF，14（11％）SSc-ILD，17（13％）其他PF-ILD）的肺移植后的肺组织，并从200个供体肺，并通过Luminex测量PDGF，FGF，VEGF和M-CSF浓度。发现与供体肺相比，PF-ILD肺中PDGF-AA，PDGF-BB，FGF-2，VEGF和M-CSF的浓度显着增加（PDGF-AA 93·0？pg / ml [±97·2]相对于37·5？pg / ml [±35·4]，p？<？0·001; PDGF-BB 102·5？pg / ml [±78·8]与61·9？pg / ml [ ±47·0]，p≤＜0·001; FGF-2 1442·4μpg/ ml [±426·6]相对于1201·7μpg/ ml [±535·2]，p≤＝ 3。 0·009; VEGF 40·6？pg / ml [±20·1]与24·9？pg / ml [±29·5]，p？<？0·001;和M-CSF 25526？pg / ml [±24,799]对6120μpg/ ml [±7245]，p≤<0·001）。当通过IPF，SSc-ILD和其他PF-ILD进行分离时，这些生长因子/血管生成分子/细胞因子浓度无显着差异。解释与所有对照组相比，在所有PF-ILD肺组织中Nintedanib特异的靶向分子途径均增加了相似的幅度，这表明Nintedanib治疗可能在PF-ILD中有效，无论病因如何。我们推测，在使用或不使用IPF或SSc-ILD的情况下，使用Nintedanib进行PF-ILD的临床试验应显示出FVC下降的相对减少程度与IPF和SSc-ILD相似（〜45-50％）。资助健康补助金P01-HL108793（JAB），挪威东南部区域卫生局补助金2018072（AMHV）。

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