Background

Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib.

Methods

This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment.

Results

The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range: [-25%–-5%], vs. -3% [-7%–0%], P = 0.004) and reticular shadow (7% [3%–13%], vs. 0% [0%–5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval: [5.9–25.3], vs. event <50%, [12.1–Not available], P = 0.0009, and 6.1 months, [5.2–6.6] vs. 14.5 months [7.8–not available], P<0.0001).

Conclusions

Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.

中文翻译：

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辛达尼布治疗特发性肺纤维化患者的组织学因素

背景

尚未研究预测Nintedanib在特发性肺纤维化中的功效的组织病理学因素。我们旨在描述对nintedanib有反应和无反应的特发性肺纤维化患者的特征，重点是组织病理学。

方法

这项研究回顾性检查了连续40例接受nintedanib治疗的经手术肺活检证实为特发性肺纤维化的患者的临床放射病理学特征。此外，我们比较了在治疗12个月内有功能或影像学进展的患者与无进展的患者之间21个微观特征的组织病理学评分。

结果

组织病理学评估显示，小叶间隔水肿改变是功能和放射学进展患者中唯一见到的组织学发现，而无功能和放射学进展者则更为常见（58％vs. 14％，P = 0.007和50％vs. 0％，P分别为0.003）。对于每年的变化，小叶间隔水肿变化的患者在备用区中位变化的进展更大（-12％，四分位间距：[-25％-5％]，而-3％[-7％ –0％]，P = 0.004）和计算机断层扫描上的网状阴影（7％[3％–13％]，而0％[0％–5％]，P = 0.041）。小叶间隔水肿改变的患者的功能和影像学无进展生存期短于无叶间隔水肿变化的患者（6.6个月，置信区间95％：[5.9–25.3]，而事件<50％，[12.1–无资料] ，P = 0.0009和6.1个月，

结论

小叶间隔的水肿变化可能表明尼达尼布在特发性肺纤维化中的疗效较差。需要进一步研究以验证这些发现并解决ECIS背后的机制。