Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Korean J Intern Med. 2023 Nov;38(6):934-944. doi: 10.3904/kjim.2023.090. Epub 2023 Oct 5.
BACKGROUND/AIMS: Obstructive sleep apnea (OSA) is prevalent in older patients with idiopathic pulmonary fibrosis (IPF); however, it is underrecognized. OSA is characterized by intermittent hypoxia (IH) and sleep fragmentation. In this study, we evaluated the effects of IH in an older mouse model of bleomycin-induced lung fibrosis.
Bleomycin-induced mice (C57BL/6, female) were randomly divided into four groups of young vs. old and room air (RA)-exposed vs. IH-exposed. Mice were exposed to RA or IH (20 cycles/h, FiO2 nadir 7 ± 0.5%, 8 h/day) for four weeks. The mice were sacrificed on day 28, and blood, bronchoalveolar lavage (BAL) fluid, and lung tissue samples were obtained.
The bleomycin-induced IH-exposed (EBI) older group showed more severe inflammation, fibrosis, and oxidative stress than the other groups. The levels of inflammatory cytokines in the serum and BAL fluid increased in the EBI group. Hydroxyproline levels in the lung tissue increased markedly in the EBI group.
This study demonstrates the possible harmful impact of OSA in an elderly mouse model of lung fibrosis. This study further suggests that older patients with IPF and OSA may be more of a concern than younger patients with IPF. Further research is required in this area.
背景/目的：阻塞性睡眠呼吸暂停（OSA）在特发性肺纤维化（IPF）的老年患者中很常见，但认识不足。OSA 的特征是间歇性低氧（IH）和睡眠碎片化。在这项研究中，我们评估了 IH 在老年博来霉素诱导的肺纤维化小鼠模型中的作用。
博来霉素诱导的小鼠（C57BL/6，雌性）随机分为年轻组与老年组，以及常氧（RA）暴露组与 IH 暴露组。小鼠接受 RA 或 IH（20 个循环/小时，FiO2 最低 7±0.5%，每天 8 小时）暴露四周。第 28 天处死小鼠，获取血液、支气管肺泡灌洗液（BAL）和肺组织样本。
博来霉素诱导的 IH 暴露（EBI）老年组比其他组表现出更严重的炎症、纤维化和氧化应激。EBI 组血清和 BAL 液中的炎症细胞因子水平升高。EBI 组肺组织中的羟脯氨酸水平明显增加。
本研究表明 OSA 在老年肺纤维化小鼠模型中可能产生有害影响。这进一步表明，患有 OSA 的老年 IPF 患者比年轻 IPF 患者更值得关注。需要在这一领域开展进一步研究。
