Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine (KPUM), Kyoto, Japan.
Department of Pediatric Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine (KPUM), Kyoto, Japan.
Pediatr Pulmonol. 2020 Jul;55(7):1771-1780. doi: 10.1002/ppul.24799. Epub 2020 May 5.
Pulmonary hypoplasia is an important cause of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). This study aimed to verify our hypothesis that the abnormal development of bronchial cartilage as well as alveolar immaturity, might play a central role in hypoplasia of the lung in human CDH.
We retrospectively analyzed autopsied lungs from 10 CDH cases and compared with nine age-matched controls to assess the bronchial cartilage and alveolar maturity using morphological techniques.
Ki-67 and thyroid transcription factor-1 (TTF-1) expression in the alveoli significantly increased in bilateral lungs with CDH. The shortest distance from the bronchial cartilage to the pleura was significantly shorter in ipsilateral (left) lungs with CDH, showing a positive correlation with the radial alveolar count (RAC). Regarding the small bronchial cartilages less than 20 000 μm , the average cartilage area significantly decreased in left lungs with CDH, and tended to decrease in right lungs with CDH. In addition, cartilage around the bronchi less than 200 μm in diameter tended to be smaller in left lungs with CDH. In contrast, regarding the cartilage around the bronchi 200 to 400 μm in diameter, the ratio of the total cartilage area relative to the bronchial diameter tended to be higher in left lungs with CDH, although there was a large variation.
These opposite directional cartilage abnormalities around the distal and more proximal bronchi support our hypothesis that abnormal development of bronchial cartilage might play an important role in the hypoplastic lung in CDH.
肺发育不全是先天性膈疝（CDH）患儿发病率和死亡率的重要原因。本研究旨在验证我们的假设，即支气管软骨的异常发育以及肺泡不成熟可能在 CDH 中肺发育不全中起核心作用。
我们回顾性分析了 10 例 CDH 尸检肺，并与 9 例年龄匹配的对照组进行比较，使用形态学技术评估支气管软骨和肺泡成熟度。
Ki-67 和甲状腺转录因子-1（TTF-1）在 CDH 双侧肺中的肺泡表达显著增加。CDH 同侧（左侧）肺的支气管软骨到胸膜的最短距离明显缩短，与肺泡计数（RAC）呈正相关。对于小于 20000μm 的小支气管软骨，左侧 CDH 肺中的平均软骨面积明显减小，右侧 CDH 肺中的软骨面积也有减小的趋势。此外，小于 200μm 直径的支气管周围软骨在左侧 CDH 肺中趋于较小。相比之下，对于直径为 200 至 400μm 的支气管周围软骨，左侧 CDH 肺中总软骨面积与支气管直径的比值趋于较高，尽管存在较大的变异性。
远端和更近端支气管周围相反方向的软骨异常支持我们的假设，即支气管软骨的异常发育可能在 CDH 中的肺发育不全中起重要作用。
