Mukhtar Saima, Choudhry Nakhshab, Saeed Saqib, Hanif Asif, Gondal Aamir J, Yasmin Nighat
Department of Physiology, Rahbar Medical and Dental College, Lahore, Pakistan.
Department of Biomedical Sciences, King Edward Medical University, Lahore, Pakistan.
Front Pharmacol. 2024 Jul 18;15:1376394. doi: 10.3389/fphar.2024.1376394. eCollection 2024.
Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on patients and healthcare systems. Spirometry is the most widely used test to diagnose the disease; however, a surrogate marker is required to predict the disease pattern and progression. The aim of the current study was to explore the association of elevated levels of plasma surfactant protein D (SP-D) with gene expression of osteoclast-associated receptor (OSCAR) and lung functions as potential diagnostic biomarkers of COPD. This cross-sectional study employed convenience sampling. As men compose the majority of patients in the outpatient department and with smoking being common among Pakistani men, choosing men offered a representative sample. Using a post-bronchodilator forced expiratory volume in the first second (FEV1) to a forced vital capacity (FVC) of less than 0.70 (FEV1/FVC <0.7), COPD patients were diagnosed on spirometry (n = 41). Controls were healthy individuals with FEV1/FVC >0.7 (n = 41). Plasma SP-D levels were measured using an enzyme-linked immunosorbent assay (ELISA). The gene expression of OSCAR was determined by real-time polymerase chain reaction (qPCR) and subsequently analyzed by the threshold cycle (Ct) method. Statistical Package for Social Sciences (SPSS) version 20 was used for statistical analysis. The mean BMI of controls (25.66 ± 4.17 kg/m) was higher than that of cases (23.49 ± 2.94 kg/m ( = .008)). The median age of controls was 49 years (interquartile range (IQR) 42.0-65.0 years) and that of cases was 65 years (IQR = 57.50-68.50). SP-D concentration was not significantly higher in COPD patients [4.96 ng/mL (IQR 3.26-7.96)] as compared to controls [3.64 ng/mL (IQR 2.60-8.59)] ( = .209). The forced expiratory ratio (FEV1/FVC) and FEV1 were related to gene expression of OSCAR ( = <.001). The gene expression of OSCAR was significantly related to SP-D ( = .034). A multiple regression model found FEV1 and FVC to have a significant effect on the gene expression of OSCAR (-values <0.001 and 0.001, respectively). Gene expression of OSCAR was increased in COPD patients and related directly to SP-D levels and inversely to lung functions in cohort of this study, suggesting that OSCAR along with SP-D may serve as a diagnostic biomarker of COPD.
慢性阻塞性肺疾病(COPD)给患者和医疗系统带来了沉重负担。肺活量测定是诊断该疾病最广泛使用的检测方法;然而,需要一种替代标志物来预测疾病模式和进展。本研究的目的是探讨血浆表面活性蛋白D(SP-D)水平升高与破骨细胞相关受体(OSCAR)基因表达及肺功能之间的关联,将其作为COPD潜在的诊断生物标志物。这项横断面研究采用了便利抽样。由于男性占门诊患者的大多数,且吸烟在巴基斯坦男性中很常见,选择男性提供了一个具有代表性的样本。使用支气管扩张剂后第一秒用力呼气量(FEV1)与用力肺活量(FVC)之比小于0.70(FEV1/FVC<0.7),通过肺活量测定诊断COPD患者(n = 41)。对照组为FEV1/FVC>0.7的健康个体(n = 41)。使用酶联免疫吸附测定(ELISA)测量血浆SP-D水平。通过实时聚合酶链反应(qPCR)测定OSCAR的基因表达,随后通过阈值循环(Ct)方法进行分析。使用社会科学统计软件包(SPSS)20版进行统计分析。对照组的平均体重指数(25.66±4.17kg/m²)高于病例组(23.49±2.94kg/m²,P = 0.008)。对照组的年龄中位数为49岁(四分位间距(IQR)42.0 - 65.0岁),病例组为65岁(IQR = 57.50 - 68.50)。与对照组[3.64ng/mL(IQR 2.60 - 8.59)]相比,COPD患者的SP-D浓度[4.96ng/mL(IQR 3.26 - 7.96)]没有显著升高(P = 0.209)。用力呼气比(FEV1/FVC)和FEV1与OSCAR的基因表达相关(P<0.001)。OSCAR的基因表达与SP-D显著相关(P = 0.034)。多元回归模型发现FEV1和FVC对OSCAR的基因表达有显著影响(P值分别<0.001和0.001)。在本研究队列中,COPD患者的OSCAR基因表达增加,与SP-D水平直接相关,与肺功能呈负相关,这表明OSCAR与SP-D可能作为COPD的诊断生物标志物。