Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Respir Med. 2011 Jun;105(6):939-45. doi: 10.1016/j.rmed.2011.02.016. Epub 2011 Mar 12.
Obstructive sleep apnea (OSA) has both systemic and local effects partly through the increased oxidative stress caused by intermittent hypoxia and reoxygenation. However, lung-specific biomarkers in OSA have not been fully assessed in comparison with systemic biomarkers such as C-reactive protein (CRP), although results of a recent study having a small sample size indicated KL-6 as one candidate.
Subjects of the present study were 197 patients suspected to have OSA. In addition to polysomnography, we also measured serum levels of KL-6, surfactant protein-D (SP-D) and CRP and pulmonary function. We examined the relationships of different biomarkers with OSA severity and pulmonary function.
The apnea/hypopnea index (AHI) was significantly positively correlated with serum KL-6 levels even after adjustment for body mass index (BMI) and smoking (p = 0.03), but not with SP-D and CRP. Also, a significant trend for an increase in serum KL-6 was noted in accordance with the severity of OSA even after adjustment for BMI and smoking (β coefficient = 0.18, p = 0.02). Additionally, elevated KL-6 levels were significantly associated with restrictive lung function disturbance and gas exchange derangement after adjustment for obesity and smoking, which contrasted with CRP whose elevations were significantly associated with worsened airflow limitation and increased lung volume.
Serum KL-6 levels may reflect the degree of subclinical lung injury associated with OSA independently of obesity or smoking, unlike CRP. We consider that KL-6 can be a potential candidate as a lung-specific biomarker of OSA and might provide complementary information on systemic biomarkers in assessing OSA.
阻塞性睡眠呼吸暂停（OSA）既有全身性影响，也有局部影响，部分原因是间歇性低氧和再氧合引起的氧化应激增加。然而，与 C 反应蛋白（CRP）等系统性生物标志物相比，OSA 中的肺部特异性生物标志物尚未得到充分评估，尽管最近一项样本量较小的研究结果表明 KL-6 是候选标志物之一。
本研究的受试者为 197 名疑似 OSA 的患者。除了多导睡眠图外，我们还测量了血清 KL-6、表面活性蛋白-D（SP-D）和 CRP 水平以及肺功能。我们检查了不同生物标志物与 OSA 严重程度和肺功能的关系。
即使在调整体重指数（BMI）和吸烟后，呼吸暂停/低通气指数（AHI）与血清 KL-6 水平仍呈显著正相关（p=0.03），但与 SP-D 和 CRP 无关。此外，即使在调整 BMI 和吸烟后，血清 KL-6 水平也随着 OSA 的严重程度呈显著升高趋势（β系数=0.18，p=0.02）。此外，调整肥胖和吸烟因素后，升高的 KL-6 水平与限制性肺功能障碍和气体交换障碍显著相关，而 CRP 的升高与气流受限加重和肺容积增加显著相关。
与 CRP 不同，血清 KL-6 水平可能独立于肥胖或吸烟反映与 OSA 相关的亚临床肺损伤程度。我们认为 KL-6 可以作为 OSA 的一种潜在肺部特异性生物标志物，为评估 OSA 提供补充的系统性生物标志物信息。
