Analysis in related factors of cognitive impairment in patients with overlap syndrome of chronic obstructive pulmonary disease complicated with obstructive sleep apnea hypopnea syndrome
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摘要:目的
探讨慢性阻塞性肺疾病-阻塞性睡眠呼吸暂停低通气综合征(COPD-OSAHS)重叠综合征患者认知功能障碍(CI)与内皮素-1(ET-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平的关系。
方法选取2021年1月—2022年1月河北省张家口市第一医院收治的87例COPD-OSAHS重叠综合征患者为COPD-OSAHS组，根据CI情况分为CI组41例、非CI组46例; 另选取62例COPD患者为COPD组。采用酶联免疫吸附测定检测血清ET-1、NGAL水平。比较COPD-OSAHS组与COPD组蒙特利尔认知评估量表(MoCA)评分和血清ET-1、NGAL水平。采用Pearson相关系数分析COPD-OSAHS重叠综合征患者血清ET-1、NGAL水平与MoCA评分的相关性; 采用多因素Logistic回归模型分析COPD-OSAHS重叠综合征患者CI的影响因素; 采用受试者工作特征(ROC)曲线分析血清ET-1、NGAL水平对COPD-OSAHS重叠综合征患者CI的预测价值。
结果COPD-OSAHS组MoCA各项评分及总分均低于COPD组，差异有统计学意义(P < 0.01)。COPD-OSAHS组血清ET-1、NGAL水平分别为(52.81±9.95) pg/mL、(7.63±1.62) ng/mL, 高于COPD组的(27.84±6.98) pg/mL、(3.13±1.19) ng/mL, 差异有统计学意义(P < 0.01)。Pearson相关系数显示, COPD-OSAHS重叠综合征患者血清ET-1、NGAL水平与MoCA评分呈负相关(r=-0.622、-0.613, P < 0.001)。与非CI组患者比较, CI组患者年龄更大，体质量指数(BMI)≥28 kg/m2、吸烟、COPD病程≥5年、重度COPD、OSAHS病程≥5年、重度OSAHS患者比率更高, ET-1、NGAL水平更高，差异有统计学意义(P < 0.05)。多因素Logistic回归模型分析显示，年龄、BMI≥28 kg/m2、重度COPD、OSAHS病程≥5年、重度OSAHS、ET-1、NGAL是COPD-OSAHS重叠综合征患者CI的独立危险因素(P < 0.05)。ROC曲线显示，血清ET-1、NGAL联合预测COPD-OSAHS重叠综合征患者CI的曲线下面积(AUC)大于2个指标单独预测的AUC, 差异有统计学意义(Z=2.039、2.347, P=0.041、0.019)。
结论COPD-OSAHS重叠综合征患者存在明显的CI, 血清ET-1、NGAL水平升高与CI密切相关，并有助于CI预测。
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关键词:
- 慢性阻塞性肺疾病 /
- 阻塞性睡眠呼吸暂停低通气综合征 /
- 内皮素-1 /
- 中性粒细胞明胶酶相关脂质运载蛋白 /
- 认知功能障碍
Abstract:ObjectiveTo investigate the relationships of cognitive impairment (CI) with levels of endothelin-1 (ET-1) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with overlap syndrome of chronic obstructive pulmonary disease complicated with obstructive sleep apnea hypopnea syndrome (COPD-OSAHS).
MethodsA total of 87 patients with overlap syndrome of COPD-OSAHS in the Zhangjiakou City First Hospital of Hebei Province from January 2021 to January 2022 were selected as COPD-OSAHS group, and these patients were divided into CI group with 41 cases and non-CI group with 46 cases according to the condition of CI; another 62 COPD patients were selected as COPD group. Serum ET-1 and NGAL levels were detected by enzyme-linked immunosorbent assay. Scores of the Montreal Cognitive Assessment (MoCA) and the levels of serum ET-1 and NGAL were compared between COPD-OSAHS group and COPD group. Pearson correlation coefficient was used to analyze the correlations of the MoCA score with serum ET-1 and NGAL levels in patients with overlap syndrome of COPD-OSAHS; the multivariate Logistic regression model was used to analyze the influencing factors of CI in patients with overlap syndrome of COPD-OSAHS; the receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum ET-1 and NGAL levels for CI in patients with overlap syndrome of COPD-OSAHS.
ResultsThe score of each item in MoCA and total score in the COPD-OSAHS group were significantly lower than those in the COPD group (P < 0.01). The levels of serum ET-1 and NGAL in the COPD-OSAHS group were (52.81±9.95) pg/mL and (7.63±1.62) ng/mL respectively, which were significantly higher than (27.84±6.98) pg/mL and (3.13±1.19) ng/mL in the COPD group (P < 0.01). Pearson correlation coefficient showed that the levels of serum ET-1 and NGAL in patients with overlap syndrome of COPD-OSAHS were negatively correlated with the MoCA score (r=-0.622, -0.613, P < 0.001). Compared with the patients in the non-CI group, the patients in the CI group were older, the ratios of patients with body mass index (BMI) ≥ 28 kg/m2, smoking, COPD duration ≥ 5 years, severe COPD, OSAHS duration≥ 5 years, and severe OSAHS were significantly higher, and the levels of ET-1 and NGAL were significantly higher in the CI group (P < 0.05). Multivariate Logistic regression model analysis showed that age, BMI≥ 28 kg/m2, severe COPD, OSAHS duration≥ 5 years, severe OSAHS, ET-1 and NGAL were the independent risk factors for CI in patients with overlap syndrome of COPD-OSAHS (P < 0.05). ROC curve showed that the area under curve (AUC) of CI predicted by serum ET-1 and NGAL in patients with overlap syndrome of COPD-OSAHS was significantly greater than that predicted by one indicator alone (Z=2.039, 2.347, P=0.041, 0.019).
ConclusionPatients with overlap syndrome of COPD-OSAHS have obvious CI, the increased levels of serum ET-1 and NGAL are closely associated with CI, which is also helpful for CI prediction.
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表 1 COPD-OSAHS组与COPD组MoCA评分比较(x±s)
分 项目 COPD-OSAHS组(n=87) COPD组(n=62) 定向力 4.67±1.28** 5.77±1.21 计算 2.55±0.61** 3.02±0.76 抽象思维 2.31±0.96** 2.71±0.76 视结构技能 2.26±1.01** 2.68±0.65 语言 2.41±0.77** 2.77±0.84 记忆 2.54±0.61** 3.10±1.11 执行功能 2.47±0.55** 3.15±1.02 注意与集中 3.23±1.09** 4.84±1.16 总分 22.45±4.49** 28.03±2.14 OSAHS: 阻塞性睡眠呼吸暂停低通气综合征;
COPD: 慢性阻塞性肺疾病。与COPD组比较, * * P < 0.01。
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表 2 COPD-OSAHS重叠综合征患者CI的单因素分析(x±s)[n(%)]
因素 分类 CI组(n=41) 非CI组(n=46) χ2/t/Z P 性别 男 28(68.29) 28(60.87) 0.521 0.470 女 13(31.71) 18(39.13) 年龄/岁 70.59±10.37 60.48±12.08 4.163 < 0.001 BMI≥28 kg/m2 13(31.71) 5(10.87) 5.736 0.017 文化程度 高中及以上 18(43.90) 27(58.70) 1.900 0.168 高中以下 23(56.10) 19(41.30) 吸烟史 14(34.15) 7(15.22) 4.242 0.039 既往史 高血压 21(51.22) 17(36.96) 1.793 0.181 糖尿病 6(14.63) 5(10.87) 0.278 0.598 血脂异常 6(14.63) 3(6.52) 0.788 0.375 COPD病程≥5年 33(80.49) 25(54.35) 6.666 0.010 COPD程度 轻度 8(19.51) 16(34.78) 6.512 0.039 中度 17(41.46) 21(45.65) 重度 16(39.02) 9(19.57) OSAHS病程≥5年 28(68.29) 20(43.48) 5.397 0.020 OSAHS程度 轻度 10(24.39) 19(41.30) 8.214 0.016 中度 21(51.22) 25(54.35) 重度 10(24.39) 2(4.35) ET-1/(pg/mL) 57.87±8.74 48.30±8.79 5.084 < 0.001 NGAL/(ng/mL) 8.34±1.53 7.00±1.44 4.178 < 0.001 COPD: 慢性阻塞性肺疾病; OSAHS: 阻塞性睡眠呼吸暂停低通气综合征; CI: 认知功能障碍; BMI: 体质量指数;
ET-1: 内皮素-1; NGAL: 中性粒细胞明胶酶相关脂质运载蛋白。
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表 3 COPD-OSAHS重叠综合征患者CI的多因素Logistic回归分析
因素 β SE Wald χ2 P OR(95%CI) 年龄 0.083 0.039 4.627 0.031 1.087(1.007~1.173) BMI≥28 kg/m2 1.717 0.848 4.100 0.043 5.568(1.057~29.343) 吸烟史 1.057 0.747 2.004 0.157 2.879(0.666~12.447) COPD病程≥5年 1.395 0.945 2.178 0.140 4.034(0.633~25.715) 重度COPD 1.727 0.729 5.609 0.018 5.624(1.347~23.480) OSAHS病程≥5年 1.571 0.633 6.157 0.013 4.810(1.391~16.634) 重度OSAHS 1.377 0.672 4.195 0.041 3.963(1.061~14.804) ET-1 0.248 0.088 7.928 0.005 1.281(1.078~1.523) NGAL 1.012 0.418 5.863 0.015 2.750(1.213~6.237) COPD: 慢性阻塞性肺疾病; OSAHS: 阻塞性睡眠呼吸暂停低通气综合征; CI: 认知功能障碍; BMI: 体质量指数;
ET-1: 内皮素-1; NGAL: 中性粒细胞明胶酶相关脂质运载蛋白。
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表 4 血清ET-1、NGAL水平预测COPD-OSAHS重叠综合征患者CI的价值
指标 AUC(95%CI) Cut-off 敏感度/% 特异度/% Youden ET-1 0.779(0.677~0.861) 50.16 pg/mL 87.80 58.70 0.465 NGAL 0.745(0.640~0.832) 7.04 ng/mL 85.37 56.52 0.419 ET-1联合NGAL 0.858(0.767~0.924) — 80.49 76.09 0.566
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