慢性阻塞性肺疾病合并骨质疏松患者血清肿瘤坏死因子α、转化生长因子β1、白细胞介素6水平的变化

背景:肿瘤坏死因子α、白细胞介素6、转化生长因子β是临床已明确与慢性阻塞性肺疾病发病发展有关的重要系统性炎症相关因子,但其与慢性阻塞性肺疾病合并骨质疏松间关系如何,鲜见报道。目的:探究慢性阻塞性肺疾病合并骨质疏松患者血清肿瘤坏死因子α、转化生长因子β、白细胞介素6水平变化的临床意义。方法:按照前瞻性病例对照原则选取120例慢性阻塞性肺疾病患者,根据骨量分为慢性阻塞性肺疾病骨量正常组40例,慢性阻塞性肺疾病合并骨量减少组40例,慢性阻塞性肺疾病合并骨质疏松组40例。比较3组临床资料、血清肿瘤坏死因子α、转化生长因子β1及白细胞介素6水平;分析骨质疏松组血清3种因子水平与肺功能、骨密度、骨代谢相关性;并采用偏相关性分析血清3种因子水平与慢性阻塞性肺疾病合并骨质疏松的关系;受试者工作特征(ROC)曲线评价血清肿瘤坏死因子α、转化生长因子β1、白细胞介素6的诊断价值。研究方案符合青海大学附属医院的相关伦理要求。结果与结论:①Pearson相关性分析,骨质疏松组血清肿瘤坏死因子α、白细胞介素6与第1秒用力呼气容积占预计值百分比(FEV1%Pre)、第1秒用力呼气量与用力肺活量比值(FEV1/FVC)、腰椎骨密度、股骨颈骨密度呈负相关,与骨保护素、Ⅰ型胶原交联羧基末端肽降解产物呈正相关;转化生长因子β1与FEV1%Pre、FEV1/FVC、腰椎骨密度、股骨颈骨密度呈正相关,与骨保护素、Ⅰ型胶原交联羧基末端肽降解产物呈负相关(P<0.05);②将肺功能、骨代谢、骨密度等其他因素控制后,血清肿瘤坏死因子α、转化生长因子β1、白细胞介素6仍与慢性阻塞性肺疾病合并骨质疏松显著相关(P<0.05);③血清肿瘤坏死因子α、转化生长因子β1、白细胞介素6联合对诊断慢性阻塞性肺疾病合并骨量减少及慢性阻塞性肺疾病合并骨质疏松的ROC曲线下的面积(AUC值)分别为0.870、0.850;④结果说明,血清肿瘤坏死因子α、转化生长因子β1、白细胞介素6水平与肺功能及骨代谢有关,三者联合检测可为临床评价慢性阻塞性肺疾病合并骨质疏松提供参考依据。

Changes in serum tumor necrosis factor alpha,transforming growth factor beta 1,and interleukin-6 levels in patients with chronic obstructive pulmonary disease combined with osteoporosis

BACKGROUND: Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) are important systemic inflammation-relatedfactors that have been clinically clearly related to the pathogenesis and development of chronic obstructive pulmonary disease (COPD). However, theirrelationship with COPD combined with osteoporosis is rarely reported.OBJECTIVE: To explore the clinical significance of serum TNF-α, TGF-β and IL-6 levels in patients with COPD combined with osteoporosis.METHODS: A total of 120 COPD patients were selected as the research subjects in accordance with the principle of prospective case control. According to theirbone mass, the patients were assigned into a COPD with normal bone mass group, a COPD with osteopenia group and a COPD with osteoporosis group (n=40per group). The clinical data, serum TNF-α, TGF-β1, and IL-6 levels were compared among three groups. A correlation analysis was conducted between serumTNF-α, TGF-β1, IL-6 and lung function, bone mineral density, and bone metabolism in the COPD with osteoporosis group. Partial correlation analysis was usedto analyze the relationship between serum TNF-α, TGF-β1, IL-6 and COPD combined with osteoporosis. The receiver operating characteristic curve was usedto evaluate the diagnostic value of serum TNF-α, TGF-β1, and IL-6. The study protocol was implemented in line with the relevant ethics requirements of theAffiliated Hospital of Qinghai University.RESULTS AND CONCLUSION: Pearson correlation analysis showed that serum TNF-α and IL-6 in COPD with osteoporosis group were negatively correlatedwith the forced expiratory volume in one second as a percentage of the predicted value (FEVl%Pre), the ratio of the forced expiratory volume in one secondto forced vital capacity (FEV1/FVC), and bone mineral density of the lumbar spine and femoral neck, as well as positively correlated with osteoprotegerin anddegradation product of β-cross linked C-telope-ptide of type I collagen. The level of TGF-β1 was positively correlated with FEV1%Pre, FEV1/FVC, and bonemineral density of the lumbar spine and femoral neck, and negatively correlated with steoprotegerin and degradation product of β-cross linked C-telope-ptideof type I collagen (P < 0.05). After controlling lung function, bone metabolism, bone mineral density and other factors, serum TNF-α, TGF-β1, and IL-6 were stillsignificantly correlated with COPD combined with osteoporosis (P < 0.05);the area under the receiver operating characteristic curve of serum TNF-α, TGF-β1,and IL-6 in the diagnosis of COPD with osteopenia and COPD with osteoporosis were 0.870 and 0.850, respectively. To conclude, serum levels of TNF-α, TGF-β1,and IL-6 are related to lung function and bone metabolism. The combined detection of the three can provide a reference for clinical evaluation of COPDcombined with osteoporosis.