骨硬化蛋白水平与 COPD 患者的身体成分、肺功能和加重的相关性。

Associations of serum sclerostin levels with body composition, pulmonary function, and exacerbations in COPD patients.

机构信息

Department of Pulmonology, Hospital Universitario Marqués de Valdecilla. Santander, Spain; University of Cantabria. Santander, Spain; IDIVAL (Instituto de Investigación Biomédica de Cantabria). Santander, Spain.

University of Cantabria. Santander, Spain; Department of Biochemistry, Hospital Universitario Marqués de Valdecilla. Santander, Spain.

出版信息

Pulmonology. 2024 Nov-Dec;30(6):512-521. doi: 10.1016/j.pulmoe.2022.06.003. Epub 2022 Aug 11.

DOI:10.1016/j.pulmoe.2022.06.003

PMID:35963832

Abstract

BACKGROUND

In COPD, the bronchial epithelium shows a pathologically activated Wnt pathway. Sclerostin (SOST) is a secreted glycoprotein that is associated with bone metabolism and blocks the Wnt pathway. We hypothesized that low sclerostin levels might be associated with lung function and COPD exacerbations in patients.

METHODS

We studied 139 outpatients with stable COPD and normal kidney function. We assessed the serum levels of SOST and bone metabolism parameters, body composition, clinical characteristics and lung function at baseline. We followed the patients prospectively for 12 months after enrolment. Moderate exacerbations and hospital admissions were recorded during follow-up.

RESULTS

The serum SOST levels were 23.98±7.6 pmol/l (men: 25.5±7.7 pmol/l, women: 20.3±5.9 pmol/l (p < 0.001)). SOST showed correlations with age (r = 0.36), FFMI (r = 0.38), FEV1 (r = 0.27), DLCO (r = 0.39), 6MWD (r = 0.19) and CAT (r = -0.24). In multivariate linear regression analysis, only age (beta=0.264) and FFMI (beta=1.241) remained significant. SOST showed a significant negative correlation with serum phosphorus (r = -0.29). Cox proportional risk analysis indicated that patients in the lower tertile of SOST levels were at higher risk of moderate COPD exacerbation (HR 2.015, CI95% 1.136-3.577, p = 0.017) and hospital admission due to COPD (HR 5.142, CI95% 1.380-19.158, p = 0.015) than the rest of the patients.

CONCLUSIONS

SOST levels are associated with body composition and lung function in patients with COPD. Furthermore, lower SOST levels predict a higher risk of exacerbations and hospitalization.

摘要

背景

在 COPD 中，支气管上皮表现出病理性激活的 Wnt 途径。骨硬化蛋白（SOST）是一种分泌型糖蛋白，与骨代谢有关，并阻断 Wnt 途径。我们假设低骨硬化蛋白水平可能与患者的肺功能和 COPD 加重有关。

方法

我们研究了 139 例稳定期 COPD 且肾功能正常的门诊患者。我们在基线时评估了 SOST 血清水平和骨代谢参数、身体成分、临床特征和肺功能。我们在入组后对患者进行了 12 个月的前瞻性随访。在随访期间记录了中度加重和住院情况。

结果

血清 SOST 水平为 23.98±7.6 pmol/l（男性：25.5±7.7 pmol/l，女性：20.3±5.9 pmol/l（p<0.001））。SOST 与年龄（r=0.36）、FFMI（r=0.38）、FEV1（r=0.27）、DLCO（r=0.39）、6MWD（r=0.19）和 CAT（r=-0.24）呈正相关。在多元线性回归分析中，只有年龄（β=0.264）和 FFMI（β=1.241）仍具有显著意义。SOST 与血清磷呈显著负相关（r=-0.29）。Cox 比例风险分析表明，SOST 水平较低的患者发生中度 COPD 加重的风险较高（HR 2.015，95%CI95%1.136-3.577，p=0.017）和因 COPD 住院的风险（HR 5.142，95%CI95%1.380-19.158，p=0.015）高于其余患者。