Article(id=1240633248313831687, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240633237542851387, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202403140, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1709827200000, receivedDateStr=2024-03-08, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773719616249, onlineDateStr=2026-03-17, pubDate=1716566400000, pubDateStr=2024-05-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773719616249, onlineIssueDateStr=2026-03-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773719616249, creator=13701087609, updateTime=1773719616249, updator=13701087609, issue=Issue{id=1240633237542851387, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='10', pageStart='1729', pageEnd='1920', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773719613680, creator=13701087609, updateTime=1773720039302, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240635022806405370, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240633237542851387, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240635022806405371, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240633237542851387, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1914, endPage=1920, ext={EN=ArticleExt(id=1240633250025107744, articleId=1240633248313831687, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Study on associations of serum albumin levels with risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To provide reference for controlling or delaying the decline of pulmonary ventilation function in male pneumoconiosis patients by studying associations of serum albumin levels with the risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients.

Methods

A retrospective cohort design was adopted in this study. Male pneumoconiosis patients who were hospitalized in West China Fourth Hospital from January 2012 to December 2021 and did not have pulmonary ventilation dysfunction at baseline were selected as the study objects. Cox proportional hazard regression models were used to calculate HRs and 95% CIs to evaluate the association of baseline serum albumin levels and the risk of severe or very severe pulmonary ventilation dysfunction. Restricted cubic spline plot was used to explore whether there was a dose-response relationship between baseline serum albumin concentrations and the risk of severe or very severe pulmonary ventilation dysfunction.

Results

A total of 746 subjects were included in this study. Fully adjusted model results of Cox proportional hazard regression analysis showed that male pneumoconiosis patients with serum albumin higher than 40.8 g/L had a reduced risk of severe or very severe pulmonary ventilation dysfunction compared with male pneumoconiosis patients with serum albumin lower than 34.4g/L (HR=0.660, 95%CI: 0.439-0.992). The restricted cubic spline figure showed that the risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients gradually decreased with the gradual increase of serum albumin concentrations and there was a linear negative relationship between baseline serum albumin concentrations and the incidence risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients (P<0.05).

Conclusion

Higher serum albumin is a protective factor for severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients and maintaining the serum albumin concentrations above 40.8 g/L can reduce the risk of severe or very severe pulmonary ventilation dysfunction.

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目的

通过研究血清白蛋白水平与男性尘肺患者重度以上肺通气功能障碍发生风险的关联,为控制或延缓男性尘肺患者肺通气功能的下降提供参考依据。

方法

本研究采用回顾性队列设计,选取2012年1月—2021年12月间于华西第四医院住院,且基线未合并肺通气功能障碍的男性尘肺患者为研究对象,采用Cox比例风险回归模型计算HR及95%CI以评估基线血清白蛋白水平与重度以上肺通气功能障碍发生风险的关联,采用限制性立方样条图来探究基线血清白蛋白浓度与重度以上肺通气功能障碍发生风险是否存在剂量反应关系。

结果

本研究共纳入746名研究对象。Cox比例风险回归分析的完全调整模型结果显示,与血清白蛋白低于34.4 g/L的男性尘肺患者相比,血清白蛋白高于40.8g/L的男性尘肺患者发生重度以上肺通气功能障碍的风险降低(HR=0.660, 95%CI: 0.439~0.992)。限制性立方样条图显示,随着血清白蛋白浓度的逐渐增加,男性尘肺患者发生重度以上肺通气功能障碍的风险逐渐降低,男性尘肺患者的基线血清白蛋白浓度与重度以上肺通气功能障碍的发生风险呈线性负相关(P<0.05)。

结论

高血清白蛋白是男性尘肺患者发生重度以上肺通气功能障碍的保护因素,维持其血清白蛋白浓度高于40.8 g/L,可降低其重度以上肺通气功能障碍的发生风险。

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杜文,E-mail:
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魏宇豪(1998—),男,硕士在读,研究方向:流行病学

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Journal of Tropical Medicine, 2023, 23(9): 1183-1187., articleTitle=COVID-19 risk factor analysis for post inflammatory pulmonary fibrosis, refAbstract=null)], funds=[Fund(id=1240633259990774518, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, awardId=U22A20359,U23A20495, language=CN, fundingSource=国家自然科学基金区域创新发展联合基金项目(U22A20359,U23A20495), fundOrder=null, country=null), Fund(id=1240633260057883384, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, awardId=2023NSFSC0647,2023NSFSC1729, language=CN, fundingSource=四川省科技厅自然科学基金项目(2023NSFSC0647,2023NSFSC1729), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240633251585388967, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, xref=null, ext=[AuthorCompanyExt(id=1240633251589583271, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, companyId=1240633251585388967, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=West China Occupational Pneumoconiosis Cohort Study (WCOPCS) workgroup, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China), AuthorCompanyExt(id=1240633251597971881, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, companyId=1240633251585388967, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=四川大学华西公共卫生学院/华西第四医院,华西职业性尘肺病队列工作组,四川 成都 610041)])], figs=[ArticleFig(id=1240633259068027609, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=EN, label=Fig.1, caption=Flow chart of enrolled population, figureFileSmall=TcDhxkE/PHGm5i03URrnnQ==, figureFileBig=X9p0hH9tGNXlYRpyFuhrEQ==, tableContent=null), ArticleFig(id=1240633259143525084, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=CN, label=图1, caption=研究对象纳入流程图, figureFileSmall=TcDhxkE/PHGm5i03URrnnQ==, figureFileBig=X9p0hH9tGNXlYRpyFuhrEQ==, tableContent=null), ArticleFig(id=1240633259349045987, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=EN, label=Fig.2, caption=Dose-response relationship between serum albumin concentrations and the risk of severe or very severe pulmonary ventilation dysfunction, figureFileSmall=R/SucexWMiP0r8E4umvLfQ==, figureFileBig=r6Yru+DWxTcovoZeWsDNig==, tableContent=null), ArticleFig(id=1240633259432932071, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=CN, label=图2, caption=基线血清白蛋白浓度与重度以上肺通气功能障碍发生风险的剂量反应关系, figureFileSmall=R/SucexWMiP0r8E4umvLfQ==, figureFileBig=r6Yru+DWxTcovoZeWsDNig==, tableContent=null), ArticleFig(id=1240633259529401065, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=EN, label=Table 1, caption=

Characteristics distribution among pneumoconiosis patients without lung function impairment under different serum albumin levels at baseline (n=746)

, figureFileSmall=null, figureFileBig=null, tableContent=
特征血清白蛋白水平分组(g/L)χ2/FP
≤34.434.5~37.637.7~40.7≥40.8
年龄(岁)55.2±12.252.2±11.549.1±10.045.1±8.431.24<0.001a
民族1.460.691b
汉族165(88.71)163(88.11)168(89.36)160(85.56)
少数民族21(11.29)22(11.89)20(10.64)27(14.44)
文化程度5.360.147b
小学及以下131(70.43)119(64.32)115(61.17)112(59.89)
初中及以上55(29.57)66(35.68)73(38.83)75(40.11)
吸烟状态3.330.767b
无吸烟史28(15.05)29(15.68)31(16.49)31(16.58)
既往吸烟者135(72.58)123(66.49)125(66.49)123(65.78)
当前吸烟者23(12.37)33(17.84)32(17.02)33(17.65)
吸烟量(包-年)18.2±19.814.7±15.114.2±12.711.7±12.24.540.004a
是否饮酒5.860.118b
116(62.37)102(55.14)109(57.98)94(50.27)
70(37.63)83(44.86)79(42.02)93(49.73)
尘肺类型3.110.376b
矽肺137(89.54)138(93.24)138(87.34)136(90.67)
其他16(10.46)10(6.76)20(12.66)14(9.33)
尘肺期别8.240.041c
Ⅰ期21(15.67)40(29.20)36(25.00)45(31.47)
Ⅱ期38(28.36)34(24.82)42(29.17)35(24.48)
Ⅲ期75(55.97)63(45.99)66(45.83)63(44.06)
接尘工龄(年)14.2±11.411.4±8.511.0±8.48.9±7.010.73<0.001a
BMI(kg/m220.9±2.722.3±3.223.2±3.323.5±3.420.47<0.001a
结核感染状态29.16<0.001b
141(75.81)161(87.03)170(90.43)175(93.58)
45(24.19)24(12.97)18(9.57)12(6.42)
), ArticleFig(id=1240633259655230188, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=CN, label=表1, caption=

不同血清白蛋白水平下,研究对象的基线特征分布(n=746)

, figureFileSmall=null, figureFileBig=null, tableContent=
特征血清白蛋白水平分组(g/L)χ2/FP
≤34.434.5~37.637.7~40.7≥40.8
年龄(岁)55.2±12.252.2±11.549.1±10.045.1±8.431.24<0.001a
民族1.460.691b
汉族165(88.71)163(88.11)168(89.36)160(85.56)
少数民族21(11.29)22(11.89)20(10.64)27(14.44)
文化程度5.360.147b
小学及以下131(70.43)119(64.32)115(61.17)112(59.89)
初中及以上55(29.57)66(35.68)73(38.83)75(40.11)
吸烟状态3.330.767b
无吸烟史28(15.05)29(15.68)31(16.49)31(16.58)
既往吸烟者135(72.58)123(66.49)125(66.49)123(65.78)
当前吸烟者23(12.37)33(17.84)32(17.02)33(17.65)
吸烟量(包-年)18.2±19.814.7±15.114.2±12.711.7±12.24.540.004a
是否饮酒5.860.118b
116(62.37)102(55.14)109(57.98)94(50.27)
70(37.63)83(44.86)79(42.02)93(49.73)
尘肺类型3.110.376b
矽肺137(89.54)138(93.24)138(87.34)136(90.67)
其他16(10.46)10(6.76)20(12.66)14(9.33)
尘肺期别8.240.041c
Ⅰ期21(15.67)40(29.20)36(25.00)45(31.47)
Ⅱ期38(28.36)34(24.82)42(29.17)35(24.48)
Ⅲ期75(55.97)63(45.99)66(45.83)63(44.06)
接尘工龄(年)14.2±11.411.4±8.511.0±8.48.9±7.010.73<0.001a
BMI(kg/m220.9±2.722.3±3.223.2±3.323.5±3.420.47<0.001a
结核感染状态29.16<0.001b
141(75.81)161(87.03)170(90.43)175(93.58)
45(24.19)24(12.97)18(9.57)12(6.42)
), ArticleFig(id=1240633259781059312, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=EN, label=Table 2, caption=

Association of baseline serum albumin levels with risk of severe or very severe pulmonary ventilatory defect

, figureFileSmall=null, figureFileBig=null, tableContent=
白蛋白水平分组(g/L)随访人年数结局发生人数发病密度/100人年模型1HR(95%CI)模型2HR(95%CI)
≤34.4375.76818.101.000(Ref)1.000(Ref)
34.5~37.6549.37613.840.834(0.597~1.164)0.919(0.654~1.292)
37.7~40.7589.56210.520.649 (0.453~0.930)a0.730(0.504~1.058)
≥40.8616.3508.110.570(0.384~0.847)a0.660(0.439~0.992)a
), ArticleFig(id=1240633259873334002, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240633248313831687, language=CN, label=表2, caption=

基线血清白蛋白水平与重度以上肺通气功能障碍发生风险的关联

, figureFileSmall=null, figureFileBig=null, tableContent=
白蛋白水平分组(g/L)随访人年数结局发生人数发病密度/100人年模型1HR(95%CI)模型2HR(95%CI)
≤34.4375.76818.101.000(Ref)1.000(Ref)
34.5~37.6549.37613.840.834(0.597~1.164)0.919(0.654~1.292)
37.7~40.7589.56210.520.649 (0.453~0.930)a0.730(0.504~1.058)
≥40.8616.3508.110.570(0.384~0.847)a0.660(0.439~0.992)a
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魏宇豪 , 彭姗姗 , 刘丽芳 , 喻文鳌 , 周丁子 , 廖加强 , 张勤 , 姚于勤 , 张本 , 杜文
现代预防医学 | 临床与预防 2024,51(10): 1914-1920
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现代预防医学 | 临床与预防 2024, 51(10): 1914-1920
血清白蛋白水平与男性尘肺患者重度以上肺通气功能障碍发生风险的关联研究
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魏宇豪, 彭姗姗, 刘丽芳, 喻文鳌, 周丁子, 廖加强, 张勤, 姚于勤, 张本, 杜文
作者信息
  • 四川大学华西公共卫生学院/华西第四医院,华西职业性尘肺病队列工作组,四川 成都 610041
  • 魏宇豪(1998—),男,硕士在读,研究方向:流行病学

通讯作者:

杜文,E-mail:
Study on associations of serum albumin levels with risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients
Yu-hao WEI, Shan-shan PENG, Li-fang LIU, Wen-ao YU, Ding-zi ZHOU, Jia-qiang LIAO, Qin ZHANG, Yu-qin YAO, Ben ZHANG, Wen DU
Affiliations
  • West China Occupational Pneumoconiosis Cohort Study (WCOPCS) workgroup, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, China
出版时间: 2024-05-25 doi: 10.20043/j.cnki.MPM.202403140
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目的

通过研究血清白蛋白水平与男性尘肺患者重度以上肺通气功能障碍发生风险的关联,为控制或延缓男性尘肺患者肺通气功能的下降提供参考依据。

方法

本研究采用回顾性队列设计,选取2012年1月—2021年12月间于华西第四医院住院,且基线未合并肺通气功能障碍的男性尘肺患者为研究对象,采用Cox比例风险回归模型计算HR及95%CI以评估基线血清白蛋白水平与重度以上肺通气功能障碍发生风险的关联,采用限制性立方样条图来探究基线血清白蛋白浓度与重度以上肺通气功能障碍发生风险是否存在剂量反应关系。

结果

本研究共纳入746名研究对象。Cox比例风险回归分析的完全调整模型结果显示,与血清白蛋白低于34.4 g/L的男性尘肺患者相比,血清白蛋白高于40.8g/L的男性尘肺患者发生重度以上肺通气功能障碍的风险降低(HR=0.660, 95%CI: 0.439~0.992)。限制性立方样条图显示,随着血清白蛋白浓度的逐渐增加,男性尘肺患者发生重度以上肺通气功能障碍的风险逐渐降低,男性尘肺患者的基线血清白蛋白浓度与重度以上肺通气功能障碍的发生风险呈线性负相关(P<0.05)。

结论

高血清白蛋白是男性尘肺患者发生重度以上肺通气功能障碍的保护因素,维持其血清白蛋白浓度高于40.8 g/L,可降低其重度以上肺通气功能障碍的发生风险。

高血清白蛋白  /  男性尘肺患者  /  重度以上  /  肺通气功能障碍  /  保护因素
Objective

To provide reference for controlling or delaying the decline of pulmonary ventilation function in male pneumoconiosis patients by studying associations of serum albumin levels with the risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients.

Methods

A retrospective cohort design was adopted in this study. Male pneumoconiosis patients who were hospitalized in West China Fourth Hospital from January 2012 to December 2021 and did not have pulmonary ventilation dysfunction at baseline were selected as the study objects. Cox proportional hazard regression models were used to calculate HRs and 95% CIs to evaluate the association of baseline serum albumin levels and the risk of severe or very severe pulmonary ventilation dysfunction. Restricted cubic spline plot was used to explore whether there was a dose-response relationship between baseline serum albumin concentrations and the risk of severe or very severe pulmonary ventilation dysfunction.

Results

A total of 746 subjects were included in this study. Fully adjusted model results of Cox proportional hazard regression analysis showed that male pneumoconiosis patients with serum albumin higher than 40.8 g/L had a reduced risk of severe or very severe pulmonary ventilation dysfunction compared with male pneumoconiosis patients with serum albumin lower than 34.4g/L (HR=0.660, 95%CI: 0.439-0.992). The restricted cubic spline figure showed that the risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients gradually decreased with the gradual increase of serum albumin concentrations and there was a linear negative relationship between baseline serum albumin concentrations and the incidence risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients (P<0.05).

Conclusion

Higher serum albumin is a protective factor for severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients and maintaining the serum albumin concentrations above 40.8 g/L can reduce the risk of severe or very severe pulmonary ventilation dysfunction.

Higher serum albumin  /  Male pneumoconiosis patients  /  Severe or very severe  /  Pulmonary ventilation dysfunction  /  Protective factor
魏宇豪, 彭姗姗, 刘丽芳, 喻文鳌, 周丁子, 廖加强, 张勤, 姚于勤, 张本, 杜文. 血清白蛋白水平与男性尘肺患者重度以上肺通气功能障碍发生风险的关联研究. 现代预防医学, 2024 , 51 (10) : 1914 -1920 . DOI: 10.20043/j.cnki.MPM.202403140
Yu-hao WEI, Shan-shan PENG, Li-fang LIU, Wen-ao YU, Ding-zi ZHOU, Jia-qiang LIAO, Qin ZHANG, Yu-qin YAO, Ben ZHANG, Wen DU. Study on associations of serum albumin levels with risk of severe or very severe pulmonary ventilation dysfunction in male pneumoconiosis patients[J]. Modern Preventive Medicine, 2024 , 51 (10) : 1914 -1920 . DOI: 10.20043/j.cnki.MPM.202403140
尘肺病是一种由于在职业活动中吸入并沉积于肺部的生产性粉尘引起的职业性间质性肺疾病,其主要病理特征为慢性肺部炎症和进行性肺纤维化,尘肺可分为矽肺、石棉肺、金属尘肺等多种类型,在脱离了粉尘源后,其仍可继续进展[1-3]。尘肺不仅在世界范围内是一个重大的公共卫生问题,而且在中国尘肺也是最常见的职业病。根据中国卫生健康事业发展统计公报公布的结果,2022年全国共报告7 577例职业性尘肺病新发病例以及9 613例尘肺病死亡病例,尘肺病新发病例占各类职业病新发病例的68.2%[4]
人血清白蛋白(human serum albumin,HSA)是由肝脏合成的,人类血液中含量最高的蛋白质,其正常浓度为35~50 g/L之间[5-6]。查阅国内外相关文献发现,人血清白蛋白与肺通气功能具有一定关联。例如,在一般人群中血清白蛋白水平与用力肺活量(forced vital capacity,FVC)呈线性正相关。当浓度在36 g/L以上时,血清白蛋白与第一秒用力呼气量(forced expiratory volume in one second,FEV1)呈正相关[7]。一些研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)的队列研究还发现,低HSA是COPD以及COPD加重的独立危险因素[8-10]。通气功能障碍可分为阻塞性通气功能障碍、限制性通气功能障碍和混合性通气功能障碍[11],COPD患者表现为阻塞性的通气功能障碍[12],尘肺患者由于其特殊的病理特征,可表现为阻塞性和限制性通气功能障碍同时存在的混合性通气功能障碍[13-14]。在一般人群中,血清白蛋白水平与用力肺活量呈正相关,低血清白蛋白是COPD的危险因素,但这不代表血清白蛋白水平与尘肺患者重度肺通气功能障碍的发生风险一定呈负相关。首先,当气道阻力较大时,胃肠道可处于长期缺氧状态,并出现血液循环不良的现象,从而影响人的食欲[15],食欲降低则可能导致血清白蛋白的水平降低。卢新卫等[16]的研究还指出,COPD不仅能使患者的食欲减退,还可增加患者机体的能量基础消耗率,最后导致患者营养不良。因此横断面研究的结果只能证明血清白蛋白水平与肺通气功能之间存在关联,而无法证明两者中谁为因、谁为果;其次,与一般人群相比,尘肺患者肺部的炎症更加严重。血清白蛋白因其抗炎和抗氧化应激的特性可抑制气流阻塞的进展[17-20],但当研究对象肺部的炎症较重时,人体内的血清白蛋白是否足以拮抗炎症的影响是一个值得思考的问题;最后,尚未有队列研究证明过高血清白蛋白对纤维化导致的肺通气功能下降有保护作用。因此为了给预防尘肺患者发生重度以上肺通气功能障碍提供科学依据,进行队列研究来探究血清白蛋白与尘肺患者重度以上肺通气功能障碍发生风险的关联是必要的。
本研究采用回顾性队列设计,最长观察期限为10年。本研究的数据均来自于四川大学华西第四医院的住院病案系统,选取2012年1月到2021年12月间于该院住院的尘肺病人为研究对象。尘肺的诊断依据为GBZ 70-2009 《尘肺病诊断标准》/GBZ 70-2015《职业性尘肺病的诊断》[21-22]。基线为研究对象首次住院的时间,随访从2012年1月开始至2021年12月结束。研究对象的纳排标准如下,纳入标准:经华西第四医院确诊为尘肺的住院患者。排除标准:(1)只有单次住院记录的患者;(2)2012—2021年间的首次住院记录的出院诊断包括肿瘤和HIV的患者;(3)女性(女性尘肺患者数量太少);(4)基线血清白蛋白或人口统计学数据缺失的患者;(5)基线体重为离群值的患者;(6)基线合并肺通气功能障碍的患者。经过上述纳排流程后,共有746名研究对象被纳入本研究,研究对象的总纳入流程如图1。本研究已获得四川大学华西第四医院伦理委员会的批准 (HXSY-EC-2021053),研究对象的知情同意已获得。
基于四川大学华西第四医院住院病案系统,提取研究对象2012—2021年间首次住院时的血清白蛋白浓度、年龄、民族、受教育程度、吸烟史、每日吸烟量、烟龄、是否戒烟、饮酒史、尘肺类型、尘肺期别、接尘工龄、结核感染状态、身高、体重等数据。其中血清白蛋白浓度为主要研究的自变量,根据746名研究对象血清白蛋白的上四分位数、中位数和下四分位数将研究对象分为4组。根据每日吸烟量(支)和烟龄(年)计算累计吸烟量,累计吸烟量(包-年)=每日吸烟量(包)× 烟龄(年),1标准包等于20支香烟,若无吸烟史则累计吸烟量赋值为0。根据有无吸烟史及是否戒烟将吸烟状态分为无吸烟史、既往吸烟者和当前吸烟者。根据身高和体重计算研究对象的身体质量指数(body mass index,BMI),BMI=weight(kg)/height(m)2。对于累计吸烟量、烟龄、尘肺类型、尘肺期别、BMI等具有缺失值的变量采用多重插补法生成20个插补数据集来补充缺失值。年龄、民族、受教育程度、累计吸烟量、吸烟状态、饮酒史、尘肺类型、尘肺期别、接尘工龄、结核感染状态、BMI等为需要调整的潜在混杂因素。
结局的定义为:2012—2021年间,研究对象除基线外的出院诊断首次包括重度或极重度的肺通气功能障碍。肺通气功能障碍的诊断标准为:FEV1/VC(用力肺活量)小于预测值的第5百分位数或TLC(肺总量)小于预测值的第5百分位数,肺通气功能障碍的严重程度的分类标准为:FEV1% pred>70,轻度;60≤FEV1% pred≤69,中度;50≤FEV1% pred≤59,中重度;35≤FEV1% pred≤49,重度;FEV1% pred<35,极重度,其中FEV1 % pred为FEV1占预计值的百分比[11]
将研究对象按基线血清白蛋白浓度的上四分位数、中位数和下四分位数分为4组,描述其余基线特征在各组间的分布并进行组间比较。采用频数和百分比对分类变量如民族、文化程度、尘肺期别等进行统计描述,其中无序分类变量的组间比较采用χ2检验,而等级变量的组间比较采用Kruskal-Wallis检验;定量变量如年龄、累积吸烟量等的统计描述采用的指标为(均数±标准差),其组间比较采用方差分析。采用Cox比例风险回归模型计算HRs及95% CIs 分析基线血清白蛋白水平与重度以上肺通气功能障碍发生风险之间的关联。人口统计学指标、行为因素、尘肺类型、尘肺期别、接尘工龄、结核感染状态、BMI等变量作为潜在的混杂因素被逐步纳入模型中进行调整。另外我们还采用了限制性立方样条图进一步探讨基线血清白蛋白浓度与重度以上肺通气功能障碍发生风险之间是否存在剂量反应关系,限制性立方样条图的节点数设为4。采用SAS 9.4(SAS Institute, Inc., Cary, North Carolina, USA),R 4.2.2(R Foundation for Statistical Computing, Vienna, Austria)和SPSS 26(IBM Corporation)进行数据分析,所有统计学检验均采用双侧检验,检验水准α=0.05。
表1,高血清白蛋白组的平均年龄(P<0.001)、平均吸烟量(P<0.05)和平均接尘工龄(P<0.001)更低,平均BMI更高(P<0.001),而低血清白蛋白组的结核感染率(P<0.001)及高期别尘肺(P<0.05)所占的比例更高。
基线746名研究对象的中位随访时间为2.2年,研究终止时共256人发生结局事件,发病率为34.3%。如表2所示,从血清白蛋白水平分组的第1组到第4组,重度以上肺通气功能障碍的发病密度逐渐降低。第4组的发病密度最低,为8.11 /100人年,第1组的发病最高,为18.10/100人年。Cox比例风险回归分析的结果显示,在完全调整模型即模型2中,与基线血清白蛋白浓度≤34.4 g/L组相比,34.5~37.6 g/L,37.7~40.7 g/L组的重度以上肺通气功能障碍的发生风险的差异无统计学意义,但≥40.8 g/L组的重度以上肺通气功能障碍的发生风险降低(HR=0.660, 95%CI:0.439~0.992)。根据Supremum检验结果,模型1和模型2中除BMI外的所有变量均符合等比例风险假定。BMI不符合等比例风险假定(P<0.05),因此在模型2中纳入了BMI与随访时间的交互项。
基于多因素Cox模型绘制限制性立方样条图,该模型中血清白蛋白浓度为定量变量,并对所有基线特征进行了调整。如图2所示,男性尘肺患者的基线血清白蛋白浓度与重度以上肺通气功能障碍的发生风险呈线性负相关(P<0.05)。
本研究的结果表明,高血清白蛋白是男性尘肺患者发生重度以上肺通气功能障碍的保护因素,维持血清白蛋白浓度高于40.8 g/L,可降低其重度以上肺通气功能障碍的发生风险。
白蛋白与肺通气功能的关联已在许多横断面研究中得到验证。例如,Hu等[7]的研究发现,在一般人群中血清白蛋白水平与FVC呈线性正相关,当浓度在36 g/L以上时,血清白蛋白与FEV1呈正相关。Ju等[23]的研究发现与正常血清白蛋白组相比,低血清白蛋白组的支气管扩张患者的FEV1更低。Zinellu等[24]基于26篇文献的meta分析的结果表明稳定型COPD患者的血清白蛋白浓度显著低于无COPD者。但是横断面研究的结果只能证明两者存在关联,不能证明两者具有因果关联。那么低血清白蛋白是否是以肺通气功能降低为特征的相关疾病的危险因素呢?一系列回顾性队列研究对此问题给出了答案。例如,Muro等[8]和Lu等[9]的研究发现低血清白蛋白是COPD的危险因素,而Yamaya等[10]的研究则进一步发现低白蛋白血症是COPD加重的危险因素。这些研究仅揭示了血清白蛋白与COPD发生风险之间的关联,然而尘肺患者可发生混合性的肺通气功能障碍。本研究以重度或极重度肺通气功能障碍为结局,发现当血清白蛋白高于40.8 g/L时,男性尘肺患者发生重度以上肺通气功能障碍的风险明显降低。这说明不仅是在一般人群中,即使是在以炎症和进行性纤维化为主要特征的疾病中,较高的血清白蛋白水平仍能对肺通气功能的降低有显著的保护作用。
那么高血清白蛋白对男性尘肺患者发生重度以上肺通气功能障碍具有保护作用的机制是什么呢?一方面HSA由于其特殊结构可通过与活性氧、活性氮、前列腺素等相结合来调节炎症反应,也可与多种配体结合和捕获自由基而发挥抗氧化的作用[19-20,25]。而炎症与氧化应激和气流阻塞的发展相关[17-18]。Hackett等[26]的研究发现与肺功能正常者相比,COPD患者肺实质中的HSA降低,但作为氧化测量指标的碳基残基的数量升高。HSA可能是肺部抗氧化系统的重要组成部分。而在Wang等[27]的研究中,经肠内和肠外营养支持后,COPD合并呼吸衰竭的老年患者的HSA水平升高,炎症因子和氧化应激标志物的水平降低,FEV1和FEV1/FVC上升,且这3项指标的变化幅度均大于仅经肠内和仅经肠外营养支持的患者。这提示研究人员可以通过给尘肺患者补充HSA来提升其抗炎和抗氧化系统的储备水平,从而抑制气流阻塞的发展。另一方面持续性的低血清白蛋白也可能引起持续性的炎症,炎症反应中单核细胞和粒细胞释放的白细胞介素-6(IL-6)可抑制白蛋白的合成以及促进成纤维细胞的增殖,从而导致纤维化[28]。因此,血清白蛋白水平越高,炎症反应的强度越低,则成纤维细胞的增殖会得到抑制。白蛋白与肺纤维化的关联在一些研究中已得到了证实,比如姚玲等[29]的研究发现,给予急性呼吸窘迫综合征家兔模型注射20%白蛋白后可明显改善家兔的氧合,氧合的改善机制可能与肺纤维化程度的降低有关。此外,孙红波等[30]的病例对照研究的结果也显示高血清白蛋白是新型冠状病毒肺炎患者发生肺纤维化的保护因素,但该研究并未探讨白蛋白与纤维化的关联机制,而是将结果归因于低血清白蛋白会加重患者感染的严重程度。综上,高血清白蛋白可通过抑制气流阻塞和纤维化的进展来改善男性尘肺患者的肺通气功能。
本研究的不足在于,首先研究对象均为住院患者且矽肺患者占比为73.6%,其他类型的尘肺患者占比较少,所以之后的研究应注意纳入门诊病人及更多其他类型的尘肺患者。其次本回顾性队列研究中,研究对象于2012年1月至2021年12月的除基线以外的每次住院的病案记录即为1次随访记录,因此病情较轻的尘肺患者的住院次数较少会导致其随访时间的不足。本研究中研究对象的中位随访时间为2.2年。所以之后的研究应基于前瞻性队列设计并制定足够长的随访年限。最后,通气功能障碍的类型包括阻塞性、限制性和混合性,但本研究的结局仅基于病人的出院诊断中通气功能障碍的严重程度,无法对结局进行分型,之后的研究应重点研究血清白蛋白与不同类型的重度以上通气功能障碍发生风险之间的关联。
  • 国家自然科学基金区域创新发展联合基金项目(U22A20359,U23A20495)
  • 四川省科技厅自然科学基金项目(2023NSFSC0647,2023NSFSC1729)
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2024年第51卷第10期
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doi: 10.20043/j.cnki.MPM.202403140
  • 接收时间:2024-03-08
  • 首发时间:2026-03-17
  • 出版时间:2024-05-25
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  • 收稿日期:2024-03-08
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国家自然科学基金区域创新发展联合基金项目(U22A20359,U23A20495)
四川省科技厅自然科学基金项目(2023NSFSC0647,2023NSFSC1729)
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    四川大学华西公共卫生学院/华西第四医院,华西职业性尘肺病队列工作组,四川 成都 610041

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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