Department of Respiratory Medicine, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, 734-8551, Japan.
Orphanet J Rare Dis. 2021 Jul 3;16(1):298. doi: 10.1186/s13023-021-01926-x.
Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction.
One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p < 0.001 for each). Next, the fractions of lymphocytes with small areas, short perimeters, low radius ratios, and increased roundness, which were determined based on receiver operating characteristic (ROC) analyses-based thresholds, were demonstrated to be higher in sarcoidosis patients than in the other ILD patients (p < 0.001 for each). Furthermore, when we combined size-representing parameters with shape-representing parameters, the fraction of lymphocytes with small and round nuclei showed approximately 0.90 of area under the ROC curve in discriminating sarcoidosis both in the development cohort and the validation cohort.
This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis.
支气管肺泡灌洗（BAL）是间质性肺疾病（ILDs）鉴别诊断的基本检查之一，淋巴细胞增多强烈提示替代诊断而不是特发性肺纤维化。然而，几种 ILD 中均可观察到 BALF 淋巴细胞增多。我们认为，定量评估 BALF 淋巴细胞核形态对于鉴别 BALF 淋巴细胞分数增加的 ILD 具有重要意义。
共招募了 121 名 BALF 淋巴细胞分数增加的 ILD 患者（发展队列 68 例，验证队列 53 例）。在发展队列中，结节病患者的 BALF 淋巴细胞核面积明显较小，周长较短，半径比较低，圆形度增加，与其他 ILD 患者相比差异具有统计学意义（p<0.001）。接下来，基于接收者操作特征（ROC）分析的阈值确定了小面积、短周长、低半径比和高圆形度的淋巴细胞分数，这些分数在结节病患者中均高于其他 ILD 患者（p<0.001）。此外，当我们将大小代表参数与形状代表参数结合时，在发展队列和验证队列中，具有小而圆核的淋巴细胞分数在鉴别结节病方面的 ROC 曲线下面积约为 0.90。
本研究首次证明了 BALF 淋巴细胞核形态的定量参数作为鉴别结节病的新型生物标志物的有用性。
