利用透射电子显微镜观察纤维化间质性肺疾病患者经支气管肺冷冻活检样本——血管内皮变化的可行性与意义

Transmission electron microscopy of transbronchial lung cryobiopsy samples in a cohort of fibrotic interstitial lung disease patients - feasibility and implications of endothelial alterations

RESPIRATORY RESEARCH

影响因子:5

分区:医学2区 / 呼吸系统2区

发表日期:2024 Oct 09

作者: David Lang, Walter Stoiber, Sylvia Lohfink-Schumm, Astrid Obermayer, Guangyu Shao, Bernhard Kaiser, Rupert Langer, Bernd Lamprecht

DOI: 10.1186/s12931-024-02981-1

摘要

我们评估了在16名连续接受纤维化间质性肺疾病（ILD）常规评估的患者中使用透射电子显微镜（TEM）分析经支气管肺冷冻活检（TBLC）样本的实用性。除了常规病理检查外，对1至2个TBLC样本进行TEM分析，并使用蔡司LEO EM 910进行评估。以非ILD肺癌患者的肺叶切除新鲜组织的亚肺膜冷冻样本和未冷冻的切除活检作为对照。TEM提供了高质量的图像，只有少量冷冻伪影。并且，在几位ILD患者中观察到明显的微血管内皮异常，如腔内拟突起和内表面缺损。这些异常在25%的患者中广泛存在，在43.8%的患者中中度存在，在31.3%的患者中几乎不存在。血管内皮异常的严重程度与年龄较小、非特异性间质性肺炎模式、支气管肺泡灌洗淋巴细胞计数升高、自身抗体阳性，以及呼吸测定、弥散能力和氧合指标较低有关。我们得出结论，TEM评估ILD患者TBLC样本是可行的，但观察到的微血管变化仍需进一步研究。

Abstract

We evaluated the utility of transmission electron microscopy (TEM) in transbronchial lung cryobiopsy (TBLC) samples from 16 consecutive patients undergoing routine evaluation of fibrotic interstitial lung disease (ILD). Next to routine pathology examination, 1 to 2 TBLC samples were prepared for TEM analysis and evaluated using a Zeiss LEO EM 910. Subpleural cryobiopsies and unfrozen excision biopsies from fresh lobectomy tissue of non-ILD lung cancer patients served as controls. TEM provided high-quality images with only minor cryoartifacts as compared to controls. Furthermore, in several ILD patients we found marked microvascular endothelial abnormalities like luminal pseudopodia-like protrusions and inner surface defects. These were extensively present in four (25%), moderately present in seven (43.8%), and largely absent in five (31.3%) patients. A higher degree of TEM endothelial abnormalities was associated with younger age, non-specific interstitial pneumonia pattern, higher broncho-alveolar lavage lymphocyte count, positive autoantibodies, and lower spirometry, diffusion capacity and oxygenation biomarkers. We conclude that TEM evaluation of TBLC samples from ILD patients is feasible, while the observed microvascular alterations warrant further evaluation.