首页 期刊 论文 学科刊群 资讯 加盟 关于
EN
image
Article(id=1322954164615127322, tenantId=1146029695717560320, journalId=1319373162502258839, issueId=1322954116858782668, articleNumber=null, orderNo=null, doi=10.16016/j.2097-0927.202510031, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1760457600000, receivedDateStr=2025-10-15, revisedDate=1764259200000, revisedDateStr=2025-11-28, acceptedDate=null, acceptedDateStr=null, onlineDate=1793346452143, onlineDateStr=2026-10-30, pubDate=1767024000000, pubDateStr=2025-12-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793346452143, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793346452143, creator=13701087609, updateTime=1793346452143, updator=13701087609, issue=Issue{id=1322954116858782668, tenantId=1146029695717560320, journalId=1319373162502258839, year='2025', volume='47', issue='24', pageStart='3009', pageEnd='3159', issueExtLink='null', onlineDate='null', pubDate='1767024000000', pubDateStr='2025-12-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793346440757, creator='13701087609', updateTime=1793346440757, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=3139, endPage=3149, ext={EN=ArticleExt(id=1322954166313820443, articleId=1322954164615127322, tenantId=1146029695717560320, journalId=1319373162502258839, language=EN, title=Association between asthma and endocrine diseases: A Mendelian randomization study and mediation analysis, columnId=1320435174995772212, journalTitle=Journal of Army Medical University, columnName=Clinical Medicine, runingTitle=null, highlight=null, articleAbstract=
Objective

To explore the bidirectional causal relationship between asthma and endocrine diseases and make a mediation analysis through Mendelian randomization (MR).

Methods

An MR analysis was performed on the statistical data from the published genome-wide association study (GWAS), and inverse variance weighting (IVW) was mainly used to study the relationship between asthma and endocrine diseases. To ensure the stability of the results, a series of sensitivity analyses were also performed. Mediated MR analysis was carried out with a two-step procedure, and multivariate MR analysis was employed to eliminate the interaction between endocrine diseases.

Results

Positive univariate MR results suggested that type 1 diabetes and autoimmune hyperthyroidism may be risk factors for asthma (OR=1.02, 95%CI: 1.01~1.04, P=0.001; OR=1.05, 95%CI: 1.02~1.08, P=0.001). Inverse univariate MR results suggested asthma as a possible risk factor for autoimmune hyperthyroidism (OR=1.36, 95%CI: 1.07~1.73, P=0.011). Multivariable MR analysis identified type 1 diabetes as the only positive predictor of asthma risk (OR=1.03, 95%CI: 1.01~1.04; P=0.002). Based on mediation MR analysis, C-reactive protein (CRP) played a mediating role in the causal association between type 1 diabetes and asthma.

Conclusion

This study suggests that type 1 diabetes may be a risk factor for asthma. Additionally, asthma may be a risk factor for autoimmune hyperthyroidism. CRP may mediate the causal relationship between type 1 diabetes and asthma.

, authors=Xi LU, Qiuling SU, Liangshan LIU, Yipeng SUN, Siqin JI, Zhenwei WANG, authorsList=Xi LU, Qiuling SU, Liangshan LIU, Yipeng SUN, Siqin JI, Zhenwei WANG, authorCompany=null, correspAuthors=Zhenwei WANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=© 2025 Journal of Army Medical University, copyrightOwner=Editorial Office of Journal of Army Medical University, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322954167274316066, articleId=1322954164615127322, tenantId=1146029695717560320, journalId=1319373162502258839, language=CN, title=哮喘与内分泌疾病的关联：孟德尔随机化研究与中介分析, columnId=1320435175822050102, journalTitle=陆军军医大学学报, columnName=论著·临床医学, runingTitle=null, highlight=null, articleAbstract=
目的

本研究旨在通过孟德尔随机化（Mendelian randomization，MR）探讨哮喘与内分泌疾病双向因果关系以及中介分析。

方法

在本研究中，通过公开发表的基因组关联研究（genome-wide association study, GWAS）统计数据进行了MR分析，并主要采用逆方差加权（inverse variance weighting, IVW）方法来研究哮喘与内分泌疾病之间的关系。为确保结果的稳定性，还进行了一系列敏感性分析。我们通过两步程序进行了中介 MR 分析，并采用多变量MR分析来消除内分泌疾病间的相互影响。

结果

正向单变量MR结果提示，1 型糖尿病可能是哮喘的危险因素（OR=1.02，95%CI：1.01~1.04，P=0.001），以及自身免疫性甲状腺功能亢进症可能是哮喘的危险因素（OR=1.05，95%CI：1.02~1.08，P=0.001）。反向单变量MR结果提示，哮喘是自身免疫性甲状腺功能亢进症的可能危险因素（OR=1.36，95%CI：1.07~1.73，P=0.011）。多变量 MR分析确定1型糖尿病是哮喘风险的唯一阳性预测因子（OR=1.03，95%CI：1.01~1.04；P=0.002）。基于中介MR分析，C反应蛋白（C-reactive protein, CRP）在1型糖尿病与哮喘的因果关系连接中起中介作用。

结论

这项研究提示1型糖尿病可能是哮喘的危险因素。此外，哮喘可能是自身免疫性甲状腺功能亢进的危险因素。CRP 可能在1型糖尿病与哮喘之间的因果关系起中介作用。

, authors=陆曦, 苏秋玲, 刘良善, 孙亦鹏, 季思勤, 王振伟, authorsList=陆曦, 苏秋玲, 刘良善, 孙亦鹏, 季思勤, 王振伟, authorCompany=null, correspAuthors=王振伟, authorNote=null, correspAuthorsNote=
王振伟，E-mail：
WANG Zhenwei，Email：
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=0jNYS8faHpCZWjsGebf8bA==, magXml=9Eyv0PNQrkMhdqQ94jrcwg==, pdfUrl=null, pdf=CyhU5McPxVWW4sHO0JZrBg==, pdfFileSize=873059, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=bG94HPKkN15rc5xdBf1P8Q==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=b7Kppjur/o/BVdZepng2bA==, mapNumber=null, fund=null)}, authors=[Author(id=1322954167597277479, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954167681163561, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167597277479, language=EN, stringName=Xi LU, firstName=Xi, middleName=null, lastName=LU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954167794409770, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167597277479, language=CN, stringName=陆曦, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954167928627500, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954167995736366, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167928627500, language=EN, stringName=Qiuling SU, firstName=Qiuling, middleName=null, lastName=SU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168058650927, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167928627500, language=CN, stringName=苏秋玲, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168129954097, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954168239006003, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168129954097, language=EN, stringName=Liangshan LIU, firstName=Liangshan, middleName=null, lastName=LIU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168318697780, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168129954097, language=CN, stringName=刘良善, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168394195254, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954168494858552, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168394195254, language=EN, stringName=Yipeng SUN, firstName=Yipeng, middleName=null, lastName=SUN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168608104761, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168394195254, language=CN, stringName=孙亦鹏, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168691990843, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954168767488317, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168691990843, language=EN, stringName=Siqin JI, firstName=Siqin, middleName=null, lastName=JI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168834597182, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168691990843, language=CN, stringName=季思勤, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168931066176, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=luckytcm@126.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322954170612982082, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168931066176, language=EN, stringName=Zhenwei WANG, firstName=Zhenwei, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954170713645379, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168931066176, language=CN, stringName=王振伟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])])], keywords=[Keyword(id=1322954170856251716, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, orderNo=1, keyword=asthma), Keyword(id=1322954170935943493, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, orderNo=2, keyword=endocrine disease), Keyword(id=1322954170998858054, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, orderNo=3, keyword=Mendelian randomization), Keyword(id=1322954171086938439, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, orderNo=1, keyword=哮喘), Keyword(id=1322954171158241608, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, orderNo=2, keyword=内分泌疾病), Keyword(id=1322954171267293513, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, orderNo=3, keyword=孟德尔随机化)], refs=[Reference(id=1322954172546556246, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1172/JCI184316, pmid=null, pmcid=null, year=2025, volume=135, issue=4, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=1, rfOrder=0, authorNames=KIM Y J, BUNYAVANICH S, journalName=J Clin Invest, refType=null, unstructuredReference=KIM Y J，BUNYAVANICH S. Microbial influencers：the airway microbiome’s role in asthma［J］. J Clin Invest，2025，135（4）：e184316., articleTitle=Microbial influencers：the airway microbiome’s role in asthma, refAbstract=null), Reference(id=1322954172622053719, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.16016/j.2097-0927.202401018, pmid=null, pmcid=null, year=2024, volume=46, issue=12, pageStart=1395, pageEnd=1402, url=null, language=null, rfNumber=2, rfOrder=1, authorNames=李熙炫, 彭东红, journalName=陆军军医大学学报, refType=null, unstructuredReference=李熙炫，彭东红. NaNO2对HDM预处理的气道上皮细胞氧化损伤的影响及其机制［J］. 陆军军医大学学报，2024，46（12）：1395-1402., articleTitle=NaNO2对HDM预处理的气道上皮细胞氧化损伤的影响及其机制, refAbstract=null), Reference(id=1322954172701745496, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.16016/j.2097-0927.202401018, pmid=null, pmcid=null, year=2024, volume=46, issue=12, pageStart=1395, pageEnd=1402, url=null, language=null, rfNumber=2, rfOrder=2, authorNames=LI X X, PENG D H, journalName=J Army Med Univ, refType=null, unstructuredReference=LI X X，PENG D H. Effect of NaNO2 on oxidative damage in house dust mite pretreated airway epithelial cells and its underlying mechanism［J］. J Army Med Univ，2024，46（12）：1395-1402., articleTitle=Effect of NaNO2 on oxidative damage in house dust mite pretreated airway epithelial cells and its underlying mechanism, refAbstract=null), Reference(id=1322954172789825881, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1136/thoraxjnl-2020-216421, pmid=null, pmcid=null, year=2021, volume=76, issue=6, pageStart=624, pageEnd=631, url=null, language=null, rfNumber=3, rfOrder=3, authorNames=WANG R, MURRAY C S, FOWLER S J, journalName=Thorax, refType=null, unstructuredReference=WANG R，MURRAY C S，FOWLER S J，et al. Asthma diagnosis：into the fourth dimension［J］. Thorax，2021，76（6）：624-631., articleTitle=Asthma diagnosis：into the fourth dimension, refAbstract=null), Reference(id=1322954172894683482, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1016/j.ijbiomac.2024.129431, pmid=null, pmcid=null, year=2024, volume=260, issue=null, pageStart=129431, pageEnd=null, url=null, language=null, rfNumber=4, rfOrder=4, authorNames=LIU Y J, GAO K X, PENG X, journalName=Int J Biol Macromol, refType=null, unstructuredReference=LIU Y J，GAO K X，PENG X，et al. The great potential of polysaccharides from natural resources in the treatment of asthma：a review［J］. Int J Biol Macromol，2024，260：129431., articleTitle=The great potential of polysaccharides from natural resources in the treatment of asthma：a review, refAbstract=null), Reference(id=1322954172965986651, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1186/s12931-023-02475-6, pmid=null, pmcid=null, year=2023, volume=24, issue=1, pageStart=169, pageEnd=null, url=null, language=null, rfNumber=5, rfOrder=5, authorNames=WANG Z F, LI Y, GAO Y, journalName=Respir Res, refType=null, unstructuredReference=WANG Z F，LI Y，GAO Y，et al. Global，regional，and national burden of asthma and its attributable risk factors from 1990 to 2019：a systematic analysis for the Global Burden of Disease Study 2019［J］. Respir Res，2023，24（1）：169., articleTitle=Global，regional，and national burden of asthma and its attributable risk factors from 1990 to 2019：a systematic analysis for the Global Burden of Disease Study 2019, refAbstract=null), Reference(id=1322954173049872732, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1007/s12020-021-02973-x, pmid=null, pmcid=null, year=2022, volume=75, issue=3, pageStart=709, pageEnd=717, url=null, language=null, rfNumber=6, rfOrder=6, authorNames=ZENG R, WANG Z H, ZHANG J T, journalName=Endocrine, refType=null, unstructuredReference=ZENG R，WANG Z H，ZHANG J T，et al. Type 1 diabetes and asthma：a systematic review and meta-analysis of observational studies［J］. Endocrine，2022，75（3）：709-717., articleTitle=Type 1 diabetes and asthma：a systematic review and meta-analysis of observational studies, refAbstract=null), Reference(id=1322954173364445533, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1155/2021/8830439, pmid=null, pmcid=null, year=2021, volume=2021, issue=null, pageStart=8830439, pageEnd=null, url=null, language=null, rfNumber=7, rfOrder=7, authorNames=TORRES R M, DOS SANTOS SOUZA M, COELHO A C C, journalName=Can Respir J, refType=null, unstructuredReference=TORRES R M，DOS SANTOS SOUZA M，COELHO A C C，et al. Association between asthma and type 2 diabetes mellitus：mechanisms and impact on asthma control-a literature review［J］. Can Respir J，2021，2021：8830439., articleTitle=Association between asthma and type 2 diabetes mellitus：mechanisms and impact on asthma control-a literature review, refAbstract=null), Reference(id=1322954173439943006, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1016/j.jaip.2021.08.027, pmid=null, pmcid=null, year=2021, volume=9, issue=11, pageStart=3887, pageEnd=3897, url=null, language=null, rfNumber=8, rfOrder=8, authorNames=CARDET J C, BULKHI A A, LOCKEY R F, journalName=J Allergy Clin Immunol Pract, refType=null, unstructuredReference=CARDET J C，BULKHI A A，LOCKEY R F. Nonrespiratory comorbidities in asthma［J］. J Allergy Clin Immunol Pract，2021，9（11）：3887-3897., articleTitle=Nonrespiratory comorbidities in asthma, refAbstract=null), Reference(id=1322954175105081695, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1093/ije/dyq151, pmid=null, pmcid=null, year=2011, volume=40, issue=3, pageStart=740, pageEnd=752, url=null, language=null, rfNumber=9, rfOrder=9, authorNames=PIERCE B L, AHSAN H, VANDERWEELE T J, journalName=Int J Epidemiol, refType=null, unstructuredReference=PIERCE B L，AHSAN H，VANDERWEELE T J. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants［J］. Int J Epidemiol，2011，40（3）：740-752., articleTitle=Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants, refAbstract=null), Reference(id=1322954175184773472, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1002/gepi.21758, pmid=null, pmcid=null, year=2013, volume=37, issue=7, pageStart=658, pageEnd=665, url=null, language=null, rfNumber=10, rfOrder=10, authorNames=BURGESS S, BUTTERWORTH A, THOMPSON S G, journalName=Genet Epidemiol, refType=null, unstructuredReference=BURGESS S，BUTTERWORTH A，THOMPSON S G. Mendelian randomization analysis with multiple genetic variants using summarized data［J］. Genet Epidemiol，2013，37（7）：658-665., articleTitle=Mendelian randomization analysis with multiple genetic variants using summarized data, refAbstract=null), Reference(id=1322954175293825377, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=null, pmid=null, pmcid=null, year=1984, volume=null, issue=null, pageStart=1984, pageEnd=null, url=null, language=null, rfNumber=11, rfOrder=11, authorNames=Johnston J, journalName=McGraw-Hill Book Company, refType=null, unstructuredReference=Johnston J. Econometric methods 3rd ed.［J］. New York，New York，McGraw-Hill Book Company，1984，1984., articleTitle=Econometric methods 3rd ed, refAbstract=null), Reference(id=1322954175365128546, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=null, pmid=null, pmcid=null, year=2018, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=12, rfOrder=12, authorNames=贾俊平, journalName=统计学, refType=null, unstructuredReference=贾俊平. 统计学［M］. 7版. 北京：中国人民大学出版社，2018., articleTitle=null, refAbstract=null), Reference(id=1322954175440626019, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1016/S0140-6736（22）02125-0, pmid=null, pmcid=null, year=2023, volume=401, issue=10379, pageStart=858, pageEnd=873, url=null, language=null, rfNumber=13, rfOrder=13, authorNames=PORSBJERG C, MELÉN E, LEHTIMÄKI L, journalName=Lancet, refType=null, unstructuredReference=PORSBJERG C，MELÉN E，LEHTIMÄKI L，et al. Asthma［J］. Lancet，2023，401（10379）：858-873., articleTitle=Asthma, refAbstract=null), Reference(id=1322954175524512100, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1016/j.prrv.2019.08.002, pmid=null, pmcid=null, year=2020, volume=36, issue=null, pageStart=118, pageEnd=127, url=null, language=null, rfNumber=14, rfOrder=14, authorNames=GANS M D, GAVRILOVA T, journalName=Paediatr Respir Rev, refType=null, unstructuredReference=GANS M D，GAVRILOVA T. Understanding the immunology of asthma：Pathophysiology，biomarkers，and treatments for asthma endotypes［J］. Paediatr Respir Rev，2020，36：118-127., articleTitle=Understanding the immunology of asthma：Pathophysiology，biomarkers，and treatments for asthma endotypes, refAbstract=null), Reference(id=1322954175608398181, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1183/09031936.00077207, pmid=null, pmcid=null, year=2008, volume=32, issue=1, pageStart=77, pageEnd=84, url=null, language=null, rfNumber=15, rfOrder=15, authorNames=BUTLAND B K, STRACHAN D P, RUDNICKA A R, journalName=Eur Respir J, refType=null, unstructuredReference=BUTLAND B K，STRACHAN D P，RUDNICKA A R. C-reactive protein，obesity，atopy and asthma symptoms in middle-aged adults［J］. Eur Respir J，2008，32（1）：77-84., articleTitle=C-reactive protein，obesity，atopy and asthma symptoms in middle-aged adults, refAbstract=null), Reference(id=1322954175692284263, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1034/j.1398-9995.2001.00143.x, pmid=null, pmcid=null, year=2001, volume=56, issue=9, pageStart=825, pageEnd=840, url=null, language=null, rfNumber=16, rfOrder=16, authorNames=STIRLING R G, CHUNG K F, journalName=Allergy, refType=null, unstructuredReference=STIRLING R G，CHUNG K F. Severe asthma：definition and mechanisms［J］. Allergy，2001，56（9）：825-840., articleTitle=Severe asthma：definition and mechanisms, refAbstract=null), Reference(id=1322954175767781736, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1111/all.13370, pmid=null, pmcid=null, year=2018, volume=73, issue=7, pageStart=1369, pageEnd=1382, url=null, language=null, rfNumber=17, rfOrder=17, authorNames=TAY T R, HEW M, journalName=Allergy, refType=null, unstructuredReference=TAY T R，HEW M. Comorbid “treatable traits” in difficult asthma：Current evidence and clinical evaluation［J］. Allergy，2018，73（7）：1369-1382., articleTitle=Comorbid “treatable traits” in difficult asthma：Current evidence and clinical evaluation, refAbstract=null), Reference(id=1322954175839084905, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1146/annurev-genom-091212-153455, pmid=null, pmcid=null, year=2013, volume=14, issue=null, pageStart=301, pageEnd=323, url=null, language=null, rfNumber=18, rfOrder=18, authorNames=TROWSDALE J, KNIGHT J C, journalName=Annu Rev Genomics Hum Genet, refType=null, unstructuredReference=TROWSDALE J，KNIGHT J C. Major histocompatibility complex genomics and human disease［J］. Annu Rev Genomics Hum Genet，2013，14：301-323., articleTitle=Major histocompatibility complex genomics and human disease, refAbstract=null), Reference(id=1322954175910388074, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1126/science.1167728, pmid=null, pmcid=null, year=2009, volume=324, issue=5925, pageStart=387, pageEnd=389, url=null, language=null, rfNumber=19, rfOrder=19, authorNames=NEJENTSEV S, WALKER N, RICHES D, journalName=Science, refType=null, unstructuredReference=NEJENTSEV S，WALKER N，RICHES D，et al. Rare variants of IFIH1 a gene implicated in antiviral responses，protect against type 1 diabetes［J］. Science，2009，324（5925）：387-389., articleTitle=Rare variants of IFIH1 a gene implicated in antiviral responses，protect against type 1 diabetes, refAbstract=null), Reference(id=1322954176044605803, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1097/MD.0000000000001466, pmid=null, pmcid=null, year=2015, volume=94, issue=36, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=20, rfOrder=20, authorNames=HSIAO Y T, CHENG W C, LIAO W C, journalName=Medicine, refType=null, unstructuredReference=HSIAO Y T，CHENG W C，LIAO W C，et al. Type 1 diabetes and increased risk of subsequent asthma：a nationwide population-based cohort study［J］. Medicine，2015，94（36）：e1466., articleTitle=Type 1 diabetes and increased risk of subsequent asthma：a nationwide population-based cohort study, refAbstract=null), Reference(id=1322954176132686188, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1016/j.aller.2013.11.009, pmid=null, pmcid=null, year=2015, volume=43, issue=2, pageStart=157, pageEnd=161, url=null, language=null, rfNumber=21, rfOrder=21, authorNames=VILLA-NOVA H, SPINOLA-CASTRO A M, GARCIA F E, journalName=Allergol Immunopathol, refType=null, unstructuredReference=VILLA-NOVA H，SPINOLA-CASTRO A M，GARCIA F E，et al. Prevalence of allergic diseases and/or allergic sensitisation in children and adolescents with type 1 diabetes mellitus［J］. Allergol Immunopathol，2015，43（2）：157-161., articleTitle=Prevalence of allergic diseases and/or allergic sensitisation in children and adolescents with type 1 diabetes mellitus, refAbstract=null), Reference(id=1322954176195600749, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=null, pmid=null, pmcid=null, year=2006, volume=63, issue=9, pageStart=719, pageEnd=722, url=null, language=null, rfNumber=22, rfOrder=22, authorNames=PRZYBYLIK-MAZUREK E, KOTLINOWSKA B, KASZTELNIK M, journalName=Przegl Lek, refType=null, unstructuredReference=PRZYBYLIK-MAZUREK E，KOTLINOWSKA B，KASZTELNIK M，et al. Autoimmunological and allergic disorders with Hashimoto and Graves disease［J］. Przegl Lek，2006，63（9）：719-722., articleTitle=Autoimmunological and allergic disorders with Hashimoto and Graves disease, refAbstract=null), Reference(id=1322954176262709614, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1038/sj.gene.6364059, pmid=null, pmcid=null, year=2004, volume=5, issue=3, pageStart=203, pageEnd=208, url=null, language=null, rfNumber=23, rfOrder=23, authorNames=BAN Y, DAVIES T F, GREENBERG D A, journalName=Genes Immun, refType=null, unstructuredReference=BAN Y，DAVIES T F，GREENBERG D A，et al. Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves' disease［J］. Genes Immun，2004，5（3）：203-208., articleTitle=Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves' disease, refAbstract=null), Reference(id=1322954176329818479, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1038/jhg.2015.94, pmid=null, pmcid=null, year=2015, volume=60, issue=11, pageStart=657, pageEnd=664, url=null, language=null, rfNumber=24, rfOrder=24, authorNames=RAMOS P S, SHEDLOCK A M, LANGEFELD C D, journalName=J Hum Genet, refType=null, unstructuredReference=RAMOS P S，SHEDLOCK A M，LANGEFELD C D. Genetics of autoimmune diseases：insights from population genetics［J］. J Hum Genet，2015，60（11）：657-664., articleTitle=Genetics of autoimmune diseases：insights from population genetics, refAbstract=null), Reference(id=1322954176417898864, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1111/j.1398-9995.2010.02504.x, pmid=null, pmcid=null, year=2011, volume=66, issue=4, pageStart=562, pageEnd=568, url=null, language=null, rfNumber=25, rfOrder=25, authorNames=THOMSEN S F, DUFFY D L, KYVIK K O, journalName=Allergy, refType=null, unstructuredReference=THOMSEN S F，DUFFY D L，KYVIK K O，et al. Risk of asthma in adult twins with type 2 diabetes and increased body mass index［J］. Allergy，2011，66（4）：562-568., articleTitle=Risk of asthma in adult twins with type 2 diabetes and increased body mass index, refAbstract=null), Reference(id=1322954176497590641, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1111/j.1445-5994.2009.01976.x, pmid=null, pmcid=null, year=2009, volume=39, issue=10, pageStart=699, pageEnd=701, url=null, language=null, rfNumber=26, rfOrder=26, authorNames=HASHEMZADEH M, MOVAHED M R, journalName=Intern Med J, refType=null, unstructuredReference=HASHEMZADEH M，MOVAHED M R. The occurrence of asthma in hospitalized patients with type 2 diabetes mellitus［J］. Intern Med J，2009，39（10）：699-701., articleTitle=The occurrence of asthma in hospitalized patients with type 2 diabetes mellitus, refAbstract=null), Reference(id=1322954176568893810, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.2337/dc09-0880, pmid=null, pmcid=null, year=2010, volume=33, issue=1, pageStart=55, pageEnd=60, url=null, language=null, rfNumber=27, rfOrder=27, authorNames=EHRLICH S F, QUESENBERRY C P Jr, VAN DEN EEDEN S K, journalName=Diabetes Care, refType=null, unstructuredReference=EHRLICH S F，QUESENBERRY C P Jr，VAN DEN EEDEN S K，et al. Patients diagnosed with diabetes are at increased risk for asthma，chronic obstructive pulmonary disease，pulmonary fibrosis，and pneumonia but not lung cancer［J］. Diabetes Care，2010，33（1）：55-60., articleTitle=Patients diagnosed with diabetes are at increased risk for asthma，chronic obstructive pulmonary disease，pulmonary fibrosis，and pneumonia but not lung cancer, refAbstract=null), Reference(id=1322954176665362803, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.2174/1573399814666180711114859, pmid=null, pmcid=null, year=2019, volume=15, issue=2, pageStart=118, pageEnd=126, url=null, language=null, rfNumber=28, rfOrder=28, authorNames=RAYNER L, MCGOVERN A, CREAGH-BROWN B, journalName=Curr Diabetes Rev, refType=null, unstructuredReference=RAYNER L，MCGOVERN A，CREAGH-BROWN B，et al. Type 2 diabetes and asthma：systematic review of the bidirectional relationship［J］. Curr Diabetes Rev，2019，15（2）：118-126., articleTitle=Type 2 diabetes and asthma：systematic review of the bidirectional relationship, refAbstract=null), Reference(id=1322954176745054580, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=null, pmid=null, pmcid=null, year=2015, volume=44, issue=8, pageStart=1045, pageEnd=1052, url=null, language=null, rfNumber=29, rfOrder=29, authorNames=ZHENG Y S, ZHANG G L, CHEN Z L, journalName=Iran J Public Health, refType=null, unstructuredReference=ZHENG Y S，ZHANG G L，CHEN Z L，et al. Relationship between type 2 diabetes and inflammation diseases：cohort study in Chinese adults［J］. Iran J Public Health，2015，44（8）：1045-1052., articleTitle=Relationship between type 2 diabetes and inflammation diseases：cohort study in Chinese adults, refAbstract=null), Reference(id=1322954176816357749, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.3389/fmed.2024.1332664, pmid=null, pmcid=null, year=2024, volume=11, issue=null, pageStart=1332664, pageEnd=null, url=null, language=null, rfNumber=30, rfOrder=30, authorNames=CHEN J, ZHANG X F, SUN G Y, journalName=Front Med, refType=null, unstructuredReference=CHEN J，ZHANG X F，SUN G Y. Causal relationship between type 2 diabetes and common respiratory system diseases：a two-sample Mendelian randomization analysis［J］. Front Med，2024，11：1332664., articleTitle=Causal relationship between type 2 diabetes and common respiratory system diseases：a two-sample Mendelian randomization analysis, refAbstract=null), Reference(id=1322954176933798262, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1038/nri2873, pmid=null, pmcid=null, year=2010, volume=10, issue=12, pageStart=826, pageEnd=837, url=null, language=null, rfNumber=31, rfOrder=31, authorNames=CHEN G Y, NUÑEZ G, journalName=Nat Rev Immunol, refType=null, unstructuredReference=CHEN G Y，NUÑEZ G. Sterile inflammation：sensing and reacting to damage［J］. Nat Rev Immunol，2010，10（12）：826-837., articleTitle=Sterile inflammation：sensing and reacting to damage, refAbstract=null), Reference(id=1322954177093181815, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1074/jbc.R400025200, pmid=null, pmcid=null, year=2004, volume=279, issue=47, pageStart=48487, pageEnd=48490, url=null, language=null, rfNumber=32, rfOrder=32, authorNames=BLACK S, KUSHNER I, SAMOLS D, journalName=J Biol Chem, refType=null, unstructuredReference=BLACK S，KUSHNER I，SAMOLS D. C-reactive protein［J］. J Biol Chem，2004，279（47）：48487-48490., articleTitle=C-reactive protein, refAbstract=null), Reference(id=1322954177189650808, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1038/nature04672, pmid=null, pmcid=null, year=2006, volume=440, issue=7088, pageStart=1217, pageEnd=1221, url=null, language=null, rfNumber=33, rfOrder=33, authorNames=PEPYS M B, HIRSCHFIELD G M, TENNENT G A, journalName=Nature, refType=null, unstructuredReference=PEPYS M B，HIRSCHFIELD G M，TENNENT G A，et al. Targeting C-reactive protein for the treatment of cardiovascular disease［J］. Nature，2006，440（7088）：1217-1221., articleTitle=Targeting C-reactive protein for the treatment of cardiovascular disease, refAbstract=null), Reference(id=1322954177269342585, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1111/j.1440-1843.2008.01314.x, pmid=null, pmcid=null, year=2008, volume=13, issue=5, pageStart=664, pageEnd=669, url=null, language=null, rfNumber=34, rfOrder=34, authorNames=QIAN F H, ZHANG Q, ZHOU L F, journalName=Respirology, refType=null, unstructuredReference=QIAN F H，ZHANG Q，ZHOU L F，et al. High-sensitivity C-reactive protein：a predicative marker in severe asthma［J］. Respirology，2008，13（5）：664-669., articleTitle=High-sensitivity C-reactive protein：a predicative marker in severe asthma, refAbstract=null), Reference(id=1322954177512612218, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1016/j.biocel.2014.05.016, pmid=null, pmcid=null, year=2014, volume=53, issue=null, pageStart=77, pageEnd=88, url=null, language=null, rfNumber=35, rfOrder=35, authorNames=AGASSANDIAN M, SHURIN G V, MA Y, journalName=Int J Biochem Cell Biol, refType=null, unstructuredReference=AGASSANDIAN M，SHURIN G V，MA Y，et al. C-reactive protein and lung diseases［J］. Int J Biochem Cell Biol，2014，53：77-88., articleTitle=C-reactive protein and lung diseases, refAbstract=null), Reference(id=1322954177583915387, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.3389/fimmu.2018.00754, pmid=null, pmcid=null, year=2018, volume=9, issue=null, pageStart=754, pageEnd=null, url=null, language=null, rfNumber=36, rfOrder=36, authorNames=SPROSTON N R, ASHWORTH J J, journalName=Front Immunol, refType=null, unstructuredReference=SPROSTON N R，ASHWORTH J J. Role of C-reactive protein at sites of inflammation and infection［J］. Front Immunol，2018，9：754., articleTitle=Role of C-reactive protein at sites of inflammation and infection, refAbstract=null), Reference(id=1322954177671995772, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1152/ajplung.00325.2002, pmid=null, pmcid=null, year=2003, volume=284, issue=3, pageStart=L466, pageEnd=L472, url=null, language=null, rfNumber=37, rfOrder=37, authorNames=CASALS C, ARIAS-DIAZ J, VALINO F, journalName=Am J Physiol Lung Cell Mol Physiol, refType=null, unstructuredReference=CASALS C，ARIAS-DIAZ J，VALINO F，et al. Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release［J］. Am J Physiol Lung Cell Mol Physiol，2003，284（3）：L466-L472., articleTitle=Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release, refAbstract=null), Reference(id=1322954179634930045, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1183/09031936.00040708, pmid=null, pmcid=null, year=2009, volume=33, issue=2, pageStart=382, pageEnd=388, url=null, language=null, rfNumber=38, rfOrder=38, authorNames=RASMUSSEN F, MIKKELSEN D, HANCOX R J, journalName=Eur Respir J, refType=null, unstructuredReference=RASMUSSEN F，MIKKELSEN D，HANCOX R J，et al. High-sensitive C-reactive protein is associated with reduced lung function in young adults［J］. Eur Respir J，2009，33（2）：382-388., articleTitle=High-sensitive C-reactive protein is associated with reduced lung function in young adults, refAbstract=null), Reference(id=1322954179756564862, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.3349/ymj.2016.57.3.690, pmid=null, pmcid=null, year=2016, volume=57, issue=3, pageStart=690, pageEnd=697, url=null, language=null, rfNumber=39, rfOrder=39, authorNames=KO A R, KIM Y H, SOL I S, journalName=Yonsei Med J, refType=null, unstructuredReference=KO A R，KIM Y H，SOL I S，et al. High-sensitivity C-reactive protein can reflect small airway obstruction in childhood asthma［J］. Yonsei Med J，2016，57（3）：690-697., articleTitle=High-sensitivity C-reactive protein can reflect small airway obstruction in childhood asthma, refAbstract=null), Reference(id=1322954179878199679, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1073/pnas.88.6.2297, pmid=null, pmcid=null, year=1991, volume=88, issue=6, pageStart=2297, pageEnd=2301, url=null, language=null, rfNumber=40, rfOrder=40, authorNames=PINCUS S M, journalName=Proc Natl Acad Sci USA, refType=null, unstructuredReference=PINCUS S M. Approximate entropy as a measure of system complexity［J］. Proc Natl Acad Sci USA，1991，88（6）：2297-2301., articleTitle=Approximate entropy as a measure of system complexity, refAbstract=null), Reference(id=1322954180016611712, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, doi=10.1152/japplphysiol.00267.2011, pmid=null, pmcid=null, year=2011, volume=111, issue=2, pageStart=412, pageEnd=419, url=null, language=null, rfNumber=41, rfOrder=41, authorNames=VEIGA J, LOPES A J, JANSEN J M, journalName=J Appl Physiol, refType=null, unstructuredReference=VEIGA J，LOPES A J，JANSEN J M，et al. Airflow pattern complexity and airway obstruction in asthma［J］. J Appl Physiol （1985），2011，111（2）：412-419., articleTitle=Airflow pattern complexity and airway obstruction in asthma, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])], figs=[ArticleFig(id=1322954171409899850, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, label=Figure 1, caption=Results of forward univariate analysis, figureFileSmall=Y6ZK+UknXszPnrfaNKAuEw==, figureFileBig=bG94HPKkN15rc5xdBf1P8Q==, tableContent=null), ArticleFig(id=1322954171477008715, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, label=图1, caption=正向单变量分析结果

T1D：Type 1 diabetes； T2D：Type 2 diabetes； SNP：Single nucleotide polymorphism； MR：Mendelian randomization

, figureFileSmall=Y6ZK+UknXszPnrfaNKAuEw==, figureFileBig=bG94HPKkN15rc5xdBf1P8Q==, tableContent=null), ArticleFig(id=1322954171686723916, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, label=Figure 2, caption=Scatter plot of MR analysis from 4 endocrine diseases and asthma, figureFileSmall=Lm2j3bMSGN7AqAPUAiYk/A==, figureFileBig=Bo48jNza6g0d7ziAw6NHYw==, tableContent=null), ArticleFig(id=1322954171758027085, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, label=图2, caption=四种内分泌疾病与哮喘的孟德尔随机化散点图

A~D：Scatter plots of MR analysis from Type 1 diabetes （A），Type 2 diabetes （B），autoimmune hyperthyroidism （C），and autoimmune hypothyroidism （D） to asthma. Each point in the graph represents a single nucleotide polymorphism （SNP） as an instrumental variable. The abscissa represents the genetic effect value （odds ratio，OR） of SNP on exposure （ie，4 endocrine diseases）； The ordinate represents the genetic effect value （OR） of SNP on outcome （asthma）. The slope of the fitted line represents the direction of the causal effect. A straight line from lower left to upper right indicates that the exposure has a positive causal effect on the outcome. MR：Mendelian randomization

, figureFileSmall=Lm2j3bMSGN7AqAPUAiYk/A==, figureFileBig=Bo48jNza6g0d7ziAw6NHYw==, tableContent=null), ArticleFig(id=1322954171820941646, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, label=Figure 3, caption=Leave-one-out analysis of MR analysis from 4 endocrine diseases and asthma, figureFileSmall=Yhcslpf3MTdnOWqR+Gytbg==, figureFileBig=pZH9rhHqfru4Dqba4jsbeQ==, tableContent=null), ArticleFig(id=1322954171883856207, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, label=图3, caption=四种内分泌疾病与哮喘的孟德尔随机化留一图

A：Leave-one-out analysis of MR analysis from Type 1 diabetes （A），Type 2 diabetes （B），autoimmune hyperthyroidism （C），and autoimmune hypothyroidism （D） to asthma. MR：Mendelian randomization

, figureFileSmall=Yhcslpf3MTdnOWqR+Gytbg==, figureFileBig=pZH9rhHqfru4Dqba4jsbeQ==, tableContent=null), ArticleFig(id=1322954171955159376, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, label=Table 1, caption=

Data summary

, figureFileSmall=null, figureFileBig=null, tableContent=
DiseaseGWAS IDCase/ControlNumber of SNPs
Type 1diabetesfinn-b-T1D_STRICT2 542/182 57316 380 230
Type 2 diabetesfinn-b-E4_DM232 469/183 18516 380 440
Autoimmune hyperthyroidismfinn-b-AUTOIMMUNE_HYPERTHYROIDISM962/172 97616 380 189
Autoimmune hypothyroidismfinn-b-E4_HYTHY_AI_STRICT22 997/175 47516 380 353
Asthmaebi-a-GCST9001432556 167/352 25534 551 291
), ArticleFig(id=1322954172093571409, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, label=表1, caption=

数据汇总

, figureFileSmall=null, figureFileBig=null, tableContent=
DiseaseGWAS IDCase/ControlNumber of SNPs
Type 1diabetesfinn-b-T1D_STRICT2 542/182 57316 380 230
Type 2 diabetesfinn-b-E4_DM232 469/183 18516 380 440
Autoimmune hyperthyroidismfinn-b-AUTOIMMUNE_HYPERTHYROIDISM962/172 97616 380 189
Autoimmune hypothyroidismfinn-b-E4_HYTHY_AI_STRICT22 997/175 47516 380 353
Asthmaebi-a-GCST9001432556 167/352 25534 551 291
), ArticleFig(id=1322954172164874578, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, label=Table 2, caption=

Summary of instrumental variable intensity of each exposure factor

, figureFileSmall=null, figureFileBig=null, tableContent=
ExposurenSNPTotal variance explained （%）Mean F-statisticMinimum F-statistic
Type 1 diabetes373.832192.4831.00
Type 2 diabetes732.02559.8529.79
Autoimmune hyperthyroidism100.30753.3730.90
Autoimmune hypothyroidism772.78371.7929.94
Asthma1051.64363.9229.79
), ArticleFig(id=1322954172252954963, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, label=表2, caption=

各暴露因素工具变量强度汇总

, figureFileSmall=null, figureFileBig=null, tableContent=
ExposurenSNPTotal variance explained （%）Mean F-statisticMinimum F-statistic
Type 1 diabetes373.832192.4831.00
Type 2 diabetes732.02559.8529.79
Autoimmune hyperthyroidism100.30753.3730.90
Autoimmune hypothyroidism772.78371.7929.94
Asthma1051.64363.9229.79
), ArticleFig(id=1322954172332646740, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=EN, label=Table 3, caption=

Results of multivariate MR analysis

, figureFileSmall=null, figureFileBig=null, tableContent=
ExposureOutcomenSNPP.valOR95%CIVIF
Type 1 diabetesAsthma70.0021.031.01~1.041.10
Type 2 diabetes500.4600.990.95~1.031.04
Autoimmune hyperthyroidism40.7721.010.97~1.041.12
Autoimmune hypothyroidism410.8931.000.96~1.051.11
), ArticleFig(id=1322954172466864469, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, language=CN, label=表3, caption=

多变量MR分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
ExposureOutcomenSNPP.valOR95%CIVIF
Type 1 diabetesAsthma70.0021.031.01~1.041.10
Type 2 diabetes500.4600.990.95~1.031.04
Autoimmune hyperthyroidism40.7721.010.97~1.041.12
Autoimmune hypothyroidism410.8931.000.96~1.051.11
)], attaches=null, journal=Journal(id=1319372634082869396, delFlag=0, nameCn=陆军军医大学学报, nameEn=Journal of Army Medical University, nameHistory1=null, nameHistory2=null, issn=2097-0927, eissn=null, cn=50-1223/R, coden=null, periodic=3, language=CN, oaType=null, ccby=null, superviseOffice=null, ownerOffice=null, pubOffice=null, editorOffice=null, officeType=null, aims=null, clcCode=null, officeProv=null, officeCity=null, officeAddr=null, officeZip=null, officeEmail=null, officePhone=null, editDirector=null, officeDirector=null, officeDirectorPhone=null, officeStaffNum=null, officeEmpNum=null, coverPicUrl=zdiTazv9TbsMJqLaCJ/k7A==, journalPrice=null, startedYear=null, abbrevIsoEn=Journal of Army Medical University, journalRemark=null, publicationField=null, createdTime=1792492548725, updatedTime=1792745216517, createdBy=18614031015, updatedBy=13701087609, firstLetterCn=L, firstLetterEn=L, subjectCode=Medical and Pharmaceutical Sciences, subjectName=null, subjectCodeEn=Medical and Pharmaceutical Sciences, subjectNameEn=null, picCn=zdiTazv9TbsMJqLaCJ/k7A==, picEn=931BgeD2k9AIsc7QjHoQKg==, jcr=null, cjcr=null, exts=[JournalExt(id=1320432400862135101, language=CN, name=陆军军医大学学报, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1792745216813, updatedTime=1792745216813, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ljjydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn, submissionReviewUrl=https://ljjydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""}), JournalExt(id=1320432400933438270, language=EN, name=Journal of Army Medical University, nameHistory1=null, nameHistory2=null, managedBy=, sponsoredBy=, publishedBy=, editorOffice=, officeProv=null, officeCity=null, officeAddr=, officeZip=, editDirector=, officeDirector=null, officePhone=null, coverPicUrl=null, journalRemark=, submitArticleUrl=null, websiteUrl=, createdTime=1792745216830, updatedTime=1792745216830, createdBy=13701087609, updatedBy=13701087609, submissionGuidelinesUrl=, submissionAuthorUrl=https://ljjydx.portal.founderss.cn, submissionEditorUrl=https://journal.ids.fzyun.cn, submissionReviewUrl=https://ljjydx.portal.founderss.cn, submissionCeEditorUrl=, submissionAeEditorUrl=, option={"copyright":""})], databaseList=null, tenantJournalId=1319373162502258839, websiteList=[Website(id=1319376331821925278, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1319373162502258839, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN, language=CN, createTime=1792493430333, createBy=18614031015, updateTime=1792493552921, updateBy=18614031015, name=陆军军医大学学报-中文, tplId=1146099689490845704, title=陆军军医大学学报, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1319376971570729589, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=articleTextType, value=kx, createTime=1792493582861, updateTime=1792493582861, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971549758066, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=banner, value=null, createTime=1792493582856, updateTime=1792493582856, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971591701112, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=grayFlag, value=0, createTime=1792493582866, updateTime=1792493582866, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971541369457, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=logo, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/file/pic?fileId=Mmvh7crXM7dcUwf9n9+ehg==, createTime=1792493582854, updateTime=1792493582854, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971608478330, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=minRunFlag, value=0, createTime=1792493582870, updateTime=1792493582870, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971562340980, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/file/pic, createTime=1792493582859, updateTime=1792493582859, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971600089721, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=silenceFlag, value=0, createTime=1792493582868, updateTime=1792493582868, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971558146675, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_cn_619/, createTime=1792493582858, updateTime=1792493582858, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971574923894, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=themeColor, value=null, createTime=1792493582862, updateTime=1792493582862, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376971583312503, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331821925278, code=themeStyle, value=null, createTime=1792493582864, updateTime=1792493582864, creator=18614031015, updator=18614031015)]), Website(id=1319376331905811365, webName=null, webTitle=null, webDomain=null, webCopyrigh=null, webIpcNo=null, seoTitle=null, seoKeywords=null, seoDescription=null, tenantJournalId=null, journalId=1319373162502258839, journalNameCn=null, journalNameEn=null, grayFlag=null, tenantId=1146029695717560320, platformId=null, journalGroupId=null, journalGroupNameCn=null, journalGroupNameEn=null, type=1, domain=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN, language=EN, createTime=1792493430353, createBy=18614031015, updateTime=1792493548158, updateBy=18614031015, name=陆军军医大学学报-英文, tplId=1146101810881728533, title=Journal of Army Medical University, delFlag=0, indexPage=/home, props=[WebsiteProps(id=1319376935873008230, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=articleTextType, value=kx, createTime=1792493574350, updateTime=1792493574350, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935843648099, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=banner, value=null, createTime=1792493574343, updateTime=1792493574343, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935902368361, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=grayFlag, value=0, createTime=1792493574357, updateTime=1792493574357, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935835259490, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=logo, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/file/pic?fileId=Mmvh7crXM7dcUwf9n9+ehg==, createTime=1792493574341, updateTime=1792493574341, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935914951275, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=minRunFlag, value=0, createTime=1792493574360, updateTime=1792493574360, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935864619621, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=picServerUrl, value=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/file/pic, createTime=1792493574348, updateTime=1792493574348, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935906562666, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=silenceFlag, value=0, createTime=1792493574358, updateTime=1792493574358, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935856231012, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=staticResourcePath, value=https://castjournals.cast.org.cn/joweb/cast_kjdb_en_623/, createTime=1792493574346, updateTime=1792493574346, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935881396839, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=themeColor, value=null, createTime=1792493574352, updateTime=1792493574352, creator=18614031015, updator=18614031015), WebsiteProps(id=1319376935889785448, tenantId=1146029695717560320, journalId=null, journalGroupId=null, siteId=1319376331905811365, code=themeStyle, value=null, createTime=1792493574354, updateTime=1792493574354, creator=18614031015, updator=18614031015)])], journalTitle=陆军军医大学学报, weixinUrl=null, journalUrl=https://aammt.tmmu.edu.cn/, iacademicId=null, status=1, seqNo=null, journalTitleEn=Journal of Army Medical University, journalPhotoCn=zdiTazv9TbsMJqLaCJ/k7A==, journalPhotoEn=931BgeD2k9AIsc7QjHoQKg==, journalFirstLetter=L, journalRecommend=null, journalNew=null, journalCollection=null, jcrJf=null, cjcrJf=null, jcrJfStr=null, cjcrJfStr=null, submissionFirstDecision=null, sciSubjectClassification=null, casSubjectClassification=null, citeScore=null, totalCitationFrequency=null, icpCode=null, psCode=null, advertisingLicenseCode=null, copyrightInformation=null, country=null, option=, provinceCode=null, provinceName=null, collectFlag=false, interPubPlatform=, interPubPlatformUrl=null), detailUrlCn=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/10.16016/j.2097-0927.202510031, detailUrlEn=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/10.16016/j.2097-0927.202510031, pdfUrlCn=https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/PDF/10.16016/j.2097-0927.202510031, pdfUrlEn=https://castjournals.cast.org.cn/joweb/ljjydxxb/EN/PDF/10.16016/j.2097-0927.202510031, aliStartDate=0, aliEndDate=0, collectionFlag=false, citedCount=null, citedUrl=null, previewStatus=0, delFlag=0, hasFullText=1, orderTime=1767024000000, fullTextJson=null, articleText=null, reference=null)
收藏切换
哮喘与内分泌疾病的关联：孟德尔随机化研究与中介分析
收藏切换
PDF下载
陆曦 , 苏秋玲 , 刘良善 , 孙亦鹏 , 季思勤 , 王振伟
陆军军医大学学报 | 论著·临床医学 2025,47(24): 3139-3149
收起
收藏切换
陆军军医大学学报 |论著·临床医学 2025 , 47 (24) : 3139 -3149
哮喘与内分泌疾病的关联：孟德尔随机化研究与中介分析
全屏
[Author(id=1322954167597277479, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954167681163561, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167597277479, language=EN, stringName=Xi LU, firstName=Xi, middleName=null, lastName=LU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954167794409770, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167597277479, language=CN, stringName=陆曦, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954167928627500, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=1, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954167995736366, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167928627500, language=EN, stringName=Qiuling SU, firstName=Qiuling, middleName=null, lastName=SU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168058650927, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954167928627500, language=CN, stringName=苏秋玲, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168129954097, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=2, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954168239006003, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168129954097, language=EN, stringName=Liangshan LIU, firstName=Liangshan, middleName=null, lastName=LIU, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168318697780, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168129954097, language=CN, stringName=刘良善, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168394195254, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=3, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954168494858552, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168394195254, language=EN, stringName=Yipeng SUN, firstName=Yipeng, middleName=null, lastName=SUN, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168608104761, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168394195254, language=CN, stringName=孙亦鹏, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168691990843, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=4, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1322954168767488317, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168691990843, language=EN, stringName=Siqin JI, firstName=Siqin, middleName=null, lastName=JI, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954168834597182, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168691990843, language=CN, stringName=季思勤, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])]), Author(id=1322954168931066176, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, orderNo=5, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=luckytcm@126.com, emailSecond=null, emailThird=null, correspondingAuthor=1, authorType=1, ext={EN=AuthorExt(id=1322954170612982082, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168931066176, language=EN, stringName=Zhenwei WANG, firstName=Zhenwei, middleName=null, lastName=WANG, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null), CN=AuthorExt(id=1322954170713645379, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, authorId=1322954168931066176, language=CN, stringName=王振伟, firstName=null, middleName=null, lastName=null, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=null, address=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海, bio=null, bioImg=null, bioContent=null, aboutCorrespAuthor=null)}, companyList=[AuthorCompany(id=1322954167500808483, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, xref=1, ext=[AuthorCompanyExt(id=1322954167509197092, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China), AuthorCompanyExt(id=1322954167517585701, tenantId=1146029695717560320, journalId=1319373162502258839, articleId=1322954164615127322, companyId=1322954167500808483, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海)])])]
陆曦, 苏秋玲, 刘良善, 孙亦鹏, 季思勤, 王振伟
作者信息
  • 1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海
通讯作者:
王振伟，E-mail：
WANG Zhenwei，Email：
Association between asthma and endocrine diseases: A Mendelian randomization study and mediation analysis
Xi LU, Qiuling SU, Liangshan LIU, Yipeng SUN, Siqin JI, Zhenwei WANG
Affiliations
  • 1Department of Respiratory Medicine，Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai，China
出版时间: 2025-12-30 doi: 10.16016/j.2097-0927.202510031
文章导航
收藏切换
摘要
收起
目的

本研究旨在通过孟德尔随机化（Mendelian randomization，MR）探讨哮喘与内分泌疾病双向因果关系以及中介分析。

方法

在本研究中，通过公开发表的基因组关联研究（genome-wide association study, GWAS）统计数据进行了MR分析，并主要采用逆方差加权（inverse variance weighting, IVW）方法来研究哮喘与内分泌疾病之间的关系。为确保结果的稳定性，还进行了一系列敏感性分析。我们通过两步程序进行了中介 MR 分析，并采用多变量MR分析来消除内分泌疾病间的相互影响。

结果

正向单变量MR结果提示，1 型糖尿病可能是哮喘的危险因素（OR=1.02，95%CI：1.01~1.04，P=0.001），以及自身免疫性甲状腺功能亢进症可能是哮喘的危险因素（OR=1.05，95%CI：1.02~1.08，P=0.001）。反向单变量MR结果提示，哮喘是自身免疫性甲状腺功能亢进症的可能危险因素（OR=1.36，95%CI：1.07~1.73，P=0.011）。多变量 MR分析确定1型糖尿病是哮喘风险的唯一阳性预测因子（OR=1.03，95%CI：1.01~1.04；P=0.002）。基于中介MR分析，C反应蛋白（C-reactive protein, CRP）在1型糖尿病与哮喘的因果关系连接中起中介作用。

结论

这项研究提示1型糖尿病可能是哮喘的危险因素。此外，哮喘可能是自身免疫性甲状腺功能亢进的危险因素。CRP 可能在1型糖尿病与哮喘之间的因果关系起中介作用。

哮喘  /  内分泌疾病  /  孟德尔随机化
Objective

To explore the bidirectional causal relationship between asthma and endocrine diseases and make a mediation analysis through Mendelian randomization (MR).

Methods

An MR analysis was performed on the statistical data from the published genome-wide association study (GWAS), and inverse variance weighting (IVW) was mainly used to study the relationship between asthma and endocrine diseases. To ensure the stability of the results, a series of sensitivity analyses were also performed. Mediated MR analysis was carried out with a two-step procedure, and multivariate MR analysis was employed to eliminate the interaction between endocrine diseases.

Results

Positive univariate MR results suggested that type 1 diabetes and autoimmune hyperthyroidism may be risk factors for asthma (OR=1.02, 95%CI: 1.01~1.04, P=0.001; OR=1.05, 95%CI: 1.02~1.08, P=0.001). Inverse univariate MR results suggested asthma as a possible risk factor for autoimmune hyperthyroidism (OR=1.36, 95%CI: 1.07~1.73, P=0.011). Multivariable MR analysis identified type 1 diabetes as the only positive predictor of asthma risk (OR=1.03, 95%CI: 1.01~1.04; P=0.002). Based on mediation MR analysis, C-reactive protein (CRP) played a mediating role in the causal association between type 1 diabetes and asthma.

Conclusion

This study suggests that type 1 diabetes may be a risk factor for asthma. Additionally, asthma may be a risk factor for autoimmune hyperthyroidism. CRP may mediate the causal relationship between type 1 diabetes and asthma.

asthma  /  endocrine disease  /  Mendelian randomization
陆曦, 苏秋玲, 刘良善, 孙亦鹏, 季思勤, 王振伟. 哮喘与内分泌疾病的关联：孟德尔随机化研究与中介分析. 陆军军医大学学报, 2025 , 47 (24) : 3139 -3149 . DOI: 10.16016/j.2097-0927.202510031
Xi LU, Qiuling SU, Liangshan LIU, Yipeng SUN, Siqin JI, Zhenwei WANG. Association between asthma and endocrine diseases: A Mendelian randomization study and mediation analysis[J]. Journal of Army Medical University, 2025 , 47 (24) : 3139 -3149 . DOI: 10.16016/j.2097-0927.202510031
正文
收起
哮喘是一种影响所有年龄组的临床综合症。它影响全球数百万人，对全球健康产生广泛影响［1］。哮喘是一种高度节律性的疾病，其特征是可逆性气流受限并伴有气道炎症和高反应性，发病机制具有昼夜变化。哮喘也具有每日、季节性和年度变化，这种变异性也给哮喘诊断带来了重大挑战［2-3］。在治疗方面，哮喘仍然是一个严重的公共卫生挑战。传统的哮喘治疗药物通常有副作用且临床疗效不理想［4］。此外，哮喘在早逝或生活质量下降方面的负担仍然是一个主要问题［5］。因此，确定哮喘的病因并加以预防对我们来说非常重要。
内分泌疾病可能与哮喘之间存在关联。一项显示哮喘诊断先于1型糖尿病发病的荟萃分析表明，哮喘患者后续患1型糖尿病的风险增加，合并优势比为1.23（95%CI，1.04~1.44），调整后优势比为1.58（95%CI，1.11~2.24）［6］。此外，哮喘和2型糖尿病是两种常见的慢性疾病，患病率不断上升，且常在同一患者中并存。这种并存可能使哮喘控制恶化［7］。此外，一份报告显示，自身免疫性甲状腺疾病患者患哮喘的概率是正常对照的3倍［8］。然而，现有的观察性研究容易受到混杂因素的影响，荟萃分析尚未揭示这种关联。目前没有研究揭示哮喘与内分泌疾病之间的因果关系。
孟德尔随机化（Mendelian randomization，MR）是一种常用于探索因果关系的方法。MR原理基于孟德尔的第二定律，并使用单核苷酸多态性（SNPs）作为工具变量。这种方法有许多优点。首先，MR可以克服观察性研究中固有的偏倚，更好地揭示关联。此外，基因变量在个体出生前就已确定，出生后不受外部环境因素的影响；因此，MR 可以有效解决由缺失变量引起的内生性问题，并逆转因果关系。最后，MR在某些方面类似于随机对照试验（RCTs），但MR研究可以调查那些预计会不利影响疾病风险的暴露因素，而这些因素在RCTs中从伦理上讲是无法研究的。
迄今为止，没有MR研究评估过哮喘与内分泌疾病之间的关系。因此，本研究使用MR来解释疾病之间的因果关系，以促进相关临床研究。最终，这些研究结果为临床实践提供了预防建议。
1　材料与方法
收起
1.1　研究设计
为了研究每种内分泌疾病（包括1型糖尿病、2型糖尿病、自身免疫性甲状腺功能亢进和自身免疫性甲状腺功能减退）与哮喘之间可能的因果关系，我们首先进行了双向单变量孟德尔随机化分析。在正向单变量MR分析中，以4种内分泌疾病作为暴露，哮喘作为结局；在反向单变量MR分析中，以哮喘作为暴露，4种内分泌疾病作为结局。
对正向MR分析的结果进一步验证，为排除上述四种内分泌代谢疾病在遗传基础和生理病理上可能存在的相关性的影响，评估其中任何一种疾病对哮喘（即相互校正后）的独立遗传效应，我们将四种暴露同时纳入同一模型，进行了多变量孟德尔随机化分析。
最后，我们进行了孟德尔随机化中介分析，并通过两步孟德尔随机化分析研究了内分泌疾病与哮喘之间的各种潜在中介因素。孟德尔随机化分析基于三个基本假设：①关联性假设：工具变量（IV）应与暴露因素有强关联；②排他性假设：IV只能通过暴露因素影响结局，而不能通过其他路径；③独立性假设：IV 必须与暴露-结局关系中的混杂因素无关。
1.2　数据来源
本研究使用的数据来自 OpenGWAS 数据库（https://gwas.mrcieu.ac.uk/）和欧洲 FinnGen 项目（https://www.finngen.fi/en）。所有数据的人群均为欧洲人，性别为男或女。统计数据如下：哮喘（病例/对照：56 167/352 255）、1型糖尿病（病例/对照：2 542/182 573）、2型糖尿病（病例/对照：32 469/183 185）、自身免疫性甲状腺功能亢进（病例/对照：962/172 976）和自身免疫性甲状腺功能减退（病例/对照：22 997/175 475）。暴露和结局的数据从不同数据库中提取可以去除样本重叠的影响，即内分泌疾病取自FinnGen 项目，哮喘取自OpenGWAS 数据库，具体见表1。
我们使用的数据来自公开数据集，因此无需获得伦理批准或知情同意。
1.3　工具变量选择
在 MR 分析中，我们选择单核苷酸多态性作为工具变量（IVs），它们与暴露密切相关（P<5×10-8）。然后，我们排除了连锁不平衡（LD），其阈值设置为kb=10 000，r²<0.001。结果数据集中缺失的SNP数量较少，因此我们直接移除它们，而不是使用代理 SNP。为确保工具变量的强度，我们使用F统计量来评估它们。计算公式如下：F=R2×（N-k-1）/（1-R2）×k，其中N代表GWAS分析中的样本量，K代表工具变量的数量，R2代表工具变量对暴露因素的解释。R2=2×β2×（1-EAF）×EAF，其中EAF代表效应等位基因的频率，β代表SNP对暴露因素的影响值。当F>10［9-10］时，SNP被认为与暴露密切相关。
1.4　统计分析
1.4.1　单变量MR分析
在本研究中，首先进行了单变量MR分析。研究内分泌疾病与哮喘之间关系的主要方法是逆方差加权（IVW）方法。然而，IVW 方法要求所有IVSs都有效且具有平衡的多效性［11］。因此，为了证明结果的稳健性，我们在此分析中同时采用了加权中位数方法和MR-Egger方法。当P值小于Bonferroni 校正阈值（P<0.05/4=0.012 5）且三种方法的方向一致时，因果效应具有显著性。0.012 5≤P<0.05 被认为具有显著性。为评估异质性，首先使用Cochran’s Q统计量检验异质性并计算I²统计量；若检测到显著异质性（P<0.05），则采用MR-PRESSO方法检测离群SNP；若MR-PRESSO无法返回有效结果，则使用标准化残差分析（阈值>2.5 SD）识别潜在离群值；剔除离群SNP后重新进行MR分析并比较结果稳定性。此外，使用 MR-Egger截距评估多效性。P<0.05 提示存在多效性，这意味着未建立因果关系。为了进一步确定结果的稳定性，即没有SNP对结果有显著影响，我们还进行了留一法敏感性分析。
1.4.2　多变量MR分析
由于1型糖尿病、2型糖尿病、自身免疫性甲状腺功能亢进和自身免疫性甲状腺功能减退之间可能在遗传背景上存在相关性，我们采用基于逆方差加权法的多变量MR框架，在模型中同时纳入上述四种疾病作为暴露因素，以哮喘作为结局，进行回归分析，以估计每种疾病对哮喘的直接因果效应。为保证结果的可靠性，我们进行了以下敏感性分析：多效性检验：我们使用了MR-Egger回归方法评估潜在的水平多效性（即工具变量是否通过非暴露途径影响结局）。通过MR-Egger回归的截距项进行检验，若截距项的P值≥0.05，则认为不存在显著的水平多效性。共线性检验：为评估并量化暴露因素之间因遗传相关性导致的共线性问题，我们计算了每个暴露因素的方差膨胀因子（VIF）。VIF衡量了由于共线性导致的回归系数估计值的方差增大了多少。其计算公式为：VIF=1/（1-R²）。其中，R²是将一个暴露因素作为因变量，其他所有暴露因素作为自变量进行线性回归所得到的决定系数。我们采用最常用的判断标准［11-12］，VIF<10表明不存在严重的多重共线性；VIF≥10 则表明存在严重的多重共线性，可能会影响模型结果的稳定性和解释。
1.4.3　中介分析
哮喘作为一种复杂的异质性疾病，涉及多种免疫炎症通路和生物标志物。暴露与结局之间的生物学中介机制，目前仍不甚明确。孟德尔随机化方法为推断暴露与结局间的因果关系提供了强大工具，而中介MR分析则能进一步将这种“黑箱”因果关联分解为直接效应和通过特定中介物的间接效应，从而为阐明其内在机制提供一定的帮助。
PORSBJERG等［13］在《The Lancet》中指出，哮喘的临床生物标志物包括血液和气道嗜酸性粒细胞，这些主要由IL-5、IL-13等Th2细胞因子驱动诱导。此外，炎症介质如IL-5、IL-13和IL-8会加剧气道炎症和重塑过程。上皮细胞因子（被称为警报素）如胸腺基质淋巴生成素，能够激活多种免疫细胞，导致嗜酸性气道炎症、黏液过度分泌和支气管痉挛等，进而促使哮喘加重［13］。在哮喘的免疫学机制中，Th1和Th2细胞反应的平衡至关重要。GANS等［14］研究强调，Th1反应通常在感染中激活，病毒上调干扰素-γ和白介素27，这些物质在清除病原体的同时也参与了气道炎症。而Th2细胞因子如IL-4、IL-5、IL-9和IL-13通过刺激B细胞释放IgE，进而引发肥大细胞脱颗粒和介质释放导致支气管收缩，从而加重哮喘。此外，BUTLAND等［15］的研究发现，在调整了性别、过敏史、地区、BMI、吸烟史和父亲的社会阶层后，哮喘患病率与CRP之间仍然存在显著的分级关系。基于哮喘发病机制的关键通路和既往研究证据［13-17］，我们建立了以下筛选标准：纳入标准：①生物学合理性：在哮喘发病机制中具有明确作用的生物标志物；②数据可及性：在大型GWAS数据库中有可用的高质量遗传工具变量；③通路覆盖全面性：涵盖免疫调节、炎症效应、组织结构改变和功能表型等。排除标准：①生物学特异性不足：在哮喘中证据有限或缺乏特异性的炎症因子（如IL-6）；②数据质量限制：测量方法不统一或样本量不足的标志物；③通路冗余性：功能高度重叠的细胞因子中选择最具代表性的成员。最终纳入的24种中介物包括：干扰素-γ、IL-4、IL-5、IL-8、IL-9、IL-10、IL-11、IL-12、IL-13、IL-17、IL-22、IL-27、IgE、胸腺基质淋巴生成素、嗜酸性粒细胞计数、骨膜蛋白、GM-CSF、ECP、谷胱甘肽S-转移酶、PEF、FEV1、淋巴细胞百分比和CRP。采用两步MR方法进行中介MR分析，以阐明上述物质是否在暴露与结局之间介导因果关系。首先，我们计算了暴露对中介物的因果效应（β₁）及其标准误（SE₁），并估计了中介物对哮喘的因果效应（β₂）及其标准误（SE₂）。随后，我们计算了中介效应值（β₁×β₂）以及中介效应在总效应中的比例。最后，采用Sobel检验评估该中介效应的统计学显著性，通过计算中介效应的标准误SE=sqrt（β₁²×SE₂²+β₂²×SE₁²）和Z统计量Z=（β₁×β₂）/SE，进而得到对应的P值。
2　结果
收起
2.1　工具变量
对于工具变量的选择，我们以P<5×10-8为条件进行相关性设置，再以kb=10 000，r²<0.001为阈值进行独立性设置去除连锁不平衡，剔除部分SNPs，得到：以1型糖尿病为暴露共有37个SNPs；以2型糖尿病为暴露共有73个SNPs；以自身免疫性甲状腺功能亢进症为暴露共有10个SNPs；以自身免疫性甲状腺功能减退症为暴露共有77个SNPs，以哮喘为暴露共有105个SNPs，最后以F=R2×（N-k-1）/（1-R2）×k，计算每个工具变量的F统计量，在本研究中，所有F统计量均大于10。各暴露因素的工具变量强度汇总见表2。
2.2　双向单变量MR 分析
以4种内分泌疾病作为暴露，哮喘作为结局，其结果显示：1型糖尿病与哮喘之间存在显著关联（OR=1.02，95%CI：1.01~1.04，P=0.001），自身免疫性甲状腺功能亢进症与哮喘之间存在显著关联（OR=1.05，95%CI：1.02~1.08，P=0.001），自身免疫性甲状腺功能减退症与哮喘之间存在显著关联（OR=1.07，95%CI：1.02~1.13，P=0.005），见图1。2型糖尿病与哮喘之间可能不存在因果关系（P=0.927）。加权中位数法和MR-Egger法的结果与 IVW 法的结果相似。散点图也显示了相似的结果，见图2。异质性检验显示所有暴露存在异质性（I²=65.3%~85.9%）。MR-PRESSO未返回有效结果。标准化残差分析识别出离群SNP（1型糖尿病11个、2型糖尿病9个、自身免疫性甲亢1个、自身免疫性甲减19个），剔除后所有暴露的IVW估计方向均保持一致，1型糖尿病（P从0.001变为0.000 6）和自身免疫性甲亢（P从0.001变为0.000 3）的显著性未改变，提示结果稳健。值得注意的是，对离群SNP的初步分析揭示，它们并非随机分布，而是富集于免疫相关通路。例如，rs9271365（根据NCBI dbSNP数据库，位于6p21.3的HLA区域内）位于主要组织相容性复合体（HLA）区域，该区域是自身免疫最重要的遗传决定因素［18］；rs1990760（根据NCBI dbSNP数据库，位于IFIH1基因内）位于先天免疫传感器基因IFIH1中，其与1型糖尿病等自身免疫疾病的关联已被广泛证实［19］。这些离群SNP在免疫通路中的非随机分布提示，暴露与结局之间可能共享部分免疫学基础，这为观察到的异质性提供了一个合理的生物学解释。此外，MR-Egger 截距检验显示不存在水平多效性（所有P>0.05）。最后，我们进行了留一法敏感性分析。我们发现，在 1 型糖尿病与哮喘以及自身免疫性甲状腺功能亢进症与哮喘的因果关联中，没有单个核苷酸多态性（SNP）对结果有显著影响。然而，在自身免疫性甲状腺功能减退症与哮喘的因果关联中，有一个SNP（rs9271365）对结果有显著影响。因此，我们认为这个SNP使得自身免疫性甲状腺功能减退症与哮喘的因果关联的P值小于0.05，见图3。1型糖尿病和自身免疫性甲状腺功能亢进症可能是哮喘的危险因素。
在反向单变量 MR分析中，我们以哮喘作为暴露，4种内分泌疾病作为结局，其结果显示：哮喘和自身免疫性甲状腺功能亢进的分析提示存在显著的因果关系（OR=1.36，95%CI：1.07~1.73，P=0.011）。然而，哮喘与1型糖尿病（OR=1.25，95%CI：0.95~1.66，P=0.114）、哮喘与 2 型糖尿病（OR=1.01，95%CI：0.95~1.07，P=0.705）以及哮喘与自身免疫性甲状腺功能减退（OR=1.07，95%CI：0.97~1.19，P=0.180）之间可能没有因果关系。对上述结果，我们进行异质性和水平多效性的检测。结果显示存在异质性，我们仍以IVW 作为主要方法。不存在水平多效性。留一法敏感性分析也未发现存在某个SNP对结果产生影响。哮喘可能是自身免疫性甲状腺功能亢进的危险因素。
2.3　多变量MR分析
将四种内分泌疾病同时纳入模型，作为暴露，进行MVMR分析，旨在消除四种内分泌疾病之间的可能存在的相互影响，探究独立的直接影响。当同时评估这四种疾病时，1型糖尿病和哮喘仍然维持着显著的因果关系（OR=1.03，95%CI：1.01~1.04，P=0.002）。其余结果均不显著（P>0.05）。见表3。为保证结果可靠性，我们进行了一系列敏感性分析。首先，通过MR-Egger回归进行多效性检验，其截距项的P值为0.839，提示在我们的模型中未检测到显著的水平多效性，支持了工具变量假设的有效性。其次，我们计算了各暴露因素的方差膨胀因子以评估共线性，其值介于1.04至1.12之间（见表2）。根据预设的评判标准（VIF<10表示不存在严重共线性，VIF值1.04-1.12均远低于10的阈值），提示四种内分泌疾病作为暴露因素在遗传工具变量层面不存在严重的多重共线性问题，确保了模型估计的稳定性。此外，对遗传工具变量的分析显示，自身免疫性甲亢与1型糖尿病（T1D）的工具变量在基因组上存在一定重复。这可能导致在多变量模型中同时校正T1D的效应后，甲亢工具变量所能提供的独立遗传信息相对减弱。这一现象为理解其独立效应在多变量框架中未达到显著提供了信息。
2.4　中介分析
MR 分析旨在探究IL-4、IL-5、IL-8、IL-9、IL-10、IL-11、IL-12、IL-13、IL-17、IL-22、IL-27、干扰素-γ、IgE、胸腺基质淋巴生成素、嗜酸性粒细胞计数、中性粒细胞计数、骨桥蛋白、GM-CSF、ECP、谷胱甘肽S-转移酶、PEF、FEV1、淋巴细胞百分比和CRP是否介导了1型糖尿病与哮喘之间的因果关系。首先，我们计算了1型糖尿病对上述24种可能中介的因果效应。数据显示，1型糖尿病与IL-5（OR=0.97，95%CI：0.95~0.99，P=0.002）、IL-8（OR=0.98，95%CI：0.96~0.99，P=0.020）、IL-9（OR=1.03，95%CI：1.01~1.05，P=0.006）、IL-12（OR=1.03，95%CI：1.01~1.05，P=0.001）、骨桥蛋白（OR=0.98，95%CI：0.96~0.99，P=0.033）、FEV1（OR=0.99，95%CI：0.98~1.00，P=0.044）、淋巴细胞百分比（OR=0.99，95%CI：0.99~1.00，P=0.035）和CRP（OR=1.03，95%CI：1.01~1.04，P=0.001）相关。随后，我们计算了24种可能中介对哮喘的因果效应。嗜酸性粒细胞计数（OR=1.69，95%CI：1.60~1.79，P=7.78E-77）、中性粒细胞计数（OR=1.14，95%CI：1.08~1.21，P=7.52E-06）、谷胱甘肽S-转移酶（OR=1.04，95%CI：1.01~1.08，P=0.029）、PEF（OR=0.56，95%CI：0.47~0.67，P=9.78E-11）、FEV1（OR=0.66，95%CI：0.59~0.74，P=1.14E-13）、淋巴细胞百分比（OR=0.85，95%CI：0.79~0.90，P=7.71E-07）和 CRP（OR=1.05，95%CI：1.01~1.08，P=0.009）与哮喘相关。根据上述结果，FEV1、淋巴细胞百分比和 CRP 水平与 1 型糖尿病和哮喘相关。我们计算了它们的中介效应。FEV1的中介效应为 0.15%（95%CI：2.14%~2.45%）。淋巴细胞百分比的中介效应为0.06%（95%CI：0.50%~0.63%）。CRP 的中介效应为0.11%（95%CI：0.03%~0.19%），其中介比例为5.2%，对应P值为0.049 1只有 CRP 满足中介的要求。这一发现提示，1型糖尿病和哮喘之间的因果效应可能通过 CRP 介导。
3　讨论
收起
正向单变量MR分析结果提示1型糖尿病和自身免疫性甲状腺功能亢进症是哮喘的风险因素。然而，自身免疫性甲状腺功能亢进与哮喘之间的因果关系可能受到1型糖尿病的影响。反向MR分析显示：哮喘可能是自身免疫性甲状腺功能亢进症的风险因素。1型糖尿病和哮喘之间的因果效应可能通过CRP介导。
哮喘和内分泌疾病的成因和影响一直受到越来越多的关注。一项包含3 545名1型糖尿病患者和14 180名对照者的全国性基于人群的队列研究提示，1型糖尿病组中哮喘的累积发病率显著高于对照组（对数秩检验，P<0.001）［20］。类似地，另一项研究也发现，1型糖尿病患者的哮喘患病率高于一般预期［21］。这些结果与我们的单变量MR分析结果一致，在随后的MVMR分析中，1型糖尿病和哮喘仍然显著正相关。先前研究提示，急诊就诊次数或住院次数确实会增加1型糖尿病患者患哮喘的风险。这一发现可能表明血糖控制不佳与哮喘风险相关。血糖控制不佳会引发慢性炎症，可能破坏Th1和Th2细胞反应的平衡。此外，与没有糖尿病的人相比，糖尿病患者肺功能较差［20］，可能会进一步加重哮喘患者的症状。这些发现提醒医生要警惕1型糖尿病患者的哮喘发生的可能性。
在一项观察性研究中，由255名自身免疫性甲状腺功能亢进症患者组成的实验组中有13人患有哮喘，而对照组中只有2名患者患有哮喘［22］。自身免疫性甲状腺功能亢进症会加剧哮喘的风险，这与单变量 MR 分析的结果一致。然而，在 MVMR 分析中，自身免疫性甲状腺功能亢进症与哮喘之间没有因果关系。甲亢效应的消失，主要源于其与T1D共享关键的HLA遗传易感性。研究已证实，HLA-DR3等位基因，特别是其DRβ1链第74位的精氨酸（Arg74），通过改变抗原呈递结构，是共同predispose至甲亢与T1D的关键功能性变异［23］。在多变量MR中，T1D的工具变量捕获了这部分共享的致病通路，从而削弱了甲亢所贡献的独立遗传信息。此外，非HLA基因的广泛多效性也是重要原因。全基因组关联研究的荟萃分析已反复证实，T1D与自身免疫性甲状腺疾病等在全基因组水平上存在显著的遗传相关性，并共享大量非HLA风险位点。这些免疫基因富集了自然选择的信号，其当前频率很可能是过去为增强抗病原体感染（即拮抗多效性）而被选择留存的结果［24］。因此，单变量MR中甲亢与哮喘的关联，在很大程度上反映了这种通用的自身免疫易感背景；多变量MR通过校正T1D，有效剥离了此背景，从而凸显出T1D特异的因果路径。基于这些发现，并结合 MVMR 分析，甲亢效应的消失提示其与哮喘的关联非独立因果关系，更大程度上源于与T1D共享的、由进化选择塑造的遗传背景。这强调了在剖析自身免疫共病时，采用多变量框架以区分共享与特异通路的重要性。自身免疫性甲状腺功能亢进症与哮喘的独立因果关系需要进一步研究。
先前研究提示，2 型糖尿病（T2D）患者不仅哮喘风险更高［25-26］，其哮喘发病率也呈上升趋势［27］。然而，这些观察性研究常受肥胖、吸烟等多种混杂因素干扰，部分研究仅基于出院数据，亦缺乏糖尿病与哮喘诊断时长信息，因此难以评估两者关系的时效性与方向性［28］。值得注意的是，一项中国成年人群队列研究甚至发现T2D患者的哮喘发病率降低，其比值比为0.23（95%CI：0.12~0.47，P<0.001）［29］，这进一步凸显了观察性研究结果的不一致。孟德尔随机化（MR）研究为厘清该关系提供了新视角，但现有结论尚不一致。例如，一项两样本MR分析指出，T2D与支气管哮喘之间存在负向因果关系（OR=0.85；95%CI=0.81~0.89；P<0.05）［30］。在本研究中，我们的MR分析结果显示T2D与哮喘之间可能不存在因果关系（P=0.927）。不同MR研究结论的差异，可能源于遗传工具变量的选择、人群种族背景、样本规模以及哮喘表型定义的不同；此外，潜在的水平多效性也可能对因果估计造成干扰。因此，当前关于T2D与哮喘之间独立因果关系的证据仍不充分，未来需要在更广泛、更具代表性的人群中开展深入研究，并严格控制遗传工具的有效性与特异性，以最终澄清二者关系。
这项研究提示，自身免疫性甲状腺功能减退与哮喘没有因果关系，其因果关系此前未曾报道。在反向 MR分析中，我们还发现哮喘可能是自身免疫性甲状腺功能亢进的风险因素。然而，这两种疾病的前瞻性研究不足、同类的MR分析缺失，因果关系机制需要进一步研究。
通过两步孟德尔随机化分析，本研究结果提示：在1型糖尿病（T1D）对哮喘的因果效应中，C反应蛋白（CRP）承担了的中介作用。但必须强调的是，CRP中介效应比例较低（0.11%），其所介导的通路在T1D导致哮喘的整体因果机制中贡献有限。尽管如此，这一较小的中介效应仍具有一定的生物学提示意义。从机制上看，1型糖尿病驱动CRP升高的过程，核心在于其自身免疫本质触发的系统性无菌炎症状态，这种状态会释放内源性损伤相关分子模式（DAMPs）［32］。而这些DAMPs作为危险信号，被肝脏的Kupffer细胞（肝内巨噬细胞）及循环中的单核细胞等天然免疫细胞识别，激活关键的NF-κB炎症信号通路［31］，驱动肝细胞大量合成与释放C反应蛋白（CRP）［32］。CRP与哮喘的关联不仅限于其作为炎症标志物的角色，更涉及主动参与疾病病理过程的分子机制。在气道微环境中，CRP可通过其固有免疫效应直接加剧炎症：一方面，CRP通过与补体片段C1q结合，有效激活经典补体途径，补体成分可直接作用于气道中的肥大细胞与平滑肌，促进其脱颗粒与收缩，是诱发支气管高反应性（BHR）并驱动哮喘症状的关键机制之一［33-35］。另一方面，CRP可作为免疫细胞调节剂，通过与其受体（如FcγR）相互作用，直接刺激巨噬细胞并激活核因子κB （NF-κB） 信号通路，进而诱导多种蛋白酶与促炎因子的释放，形成正反馈循环，持续放大气道的慢性炎症反应［36-37］。此外，CRP水平与整体肺功能密切相关。研究证实，血清CRP水平升高与肺功能的下降及小气道阻塞的加重显著相关［38-39］。这种功能性损害在气流动力学上表现为气流模式复杂性的降低（即近似熵ApEnQ值下降），反映了气道在应对生理挑战时适应能力的减退，构成了哮喘严重度增加的病理生理基础［40-41］。
值得注意的是，尽管中介比例较低，但本研究首次从遗传学角度为T1D、CRP与哮喘三者间的因果链条提供了客观证据，具有一定的理论提示价值。微小的中介效应可能源于以下因素：孟德尔随机化工具变量的保守性、人群异质性稀释了主效应，或存在其他更重要的并行中介通路尚未被揭示。因此，CRP这条通路不应被完全忽视，而应在未来研究中进一步探索其实际效应以及更重要的通路。综上，本研究揭示了一条真实但微弱的中介通路，为理解T1D与哮喘的共病机制提供了新的遗传学视角。
本研究系统地评估了四种内分泌疾病与哮喘的因果关系。双样本MR设计使我们能够利用大规模公开数据库，最大限度地提高统计效能，并有效避免反向因果关联。多变量MR模型则允许我们在估计单一疾病效应时，有效控制其他相关疾病的遗传混杂，从而揭示了1型糖尿病对哮喘的独立直接效应。进一步的中介分析初步探索了其内在生物学通路，为理解其机制提供了新的视角。
本研究也存在若干局限性。首先，双样本MR依赖于公开的GWAS汇总数据，我们无法获得个体水平数据，这限制了我们进行更精细的亚组分析或验证某些假设。其次，孟德尔随机化分析固有的局限性仍应注意，尽管我们已采用多种方法评估，但潜在的残留多效性（即遗传变异通过未测途径影响结局）以及SNP选择带来的偏差，仍可能对因果估计构成影响，同时，尽管多变量MR控制了共暴露因素，但我们仍无法完全排除所有未知或未测量的混杂因素。第三，本分析的遗传数据均源于欧洲血统人群。这虽然保障了MR分析所需的人群同质性，但不可避免地限制了研究结论在全球其他人群（如亚洲、非洲人群）中的普适性。最后，中介分析存在两方面局限：在筛选标准上，我们排除了在哮喘中生物学特异性不足的因子（如IL-6）；在数据层面，部分理论上相关的标志物因缺乏强效的遗传工具变量而未能纳入。未来的研究应致力于在包含亚洲（如中国）等多民族人群中验证我们的核心结论，并利用个体水平数据、涵盖更广泛中介物的遗传资源以及实验生物学方法，系统地探索和验证连接内分泌疾病与哮喘的潜在因果通路。此外，本研究为保障统计效力而采用广泛定义的哮喘表型，这虽能提示整体因果关联，但无法解析其在不同亚型（如过敏性哮喘）中的异质性，这构成了未来研究的重要方向。
总体而言，1 型糖尿病是哮喘的危险因素之一。CRP 可能在 1 型糖尿病和哮喘之间起中介作用。根据反向因果关系研究，哮喘可能促进自身免疫性甲状腺功能亢进的发展。基于上述发现，本研究确立了临床转化路径与研究优先级：①在临床实践层面，本研究结果为将1型糖尿病本身确立为哮喘筛查的一个指征提供了证据。我们建议，应将针对“反复喘息、气促、胸闷及慢性咳嗽”等典型哮喘症状的主动问询，整合至1型糖尿病患者的常规随访方案中。对于存在相关症状的患者，及时转诊至呼吸科并进行肺功能检查，是实现哮喘早期诊断与规范管理的可行路径。②在患者管理层面，应加强对1型糖尿病患者及其家属的呼吸道健康教育，使其了解共病风险并学会识别早期症状，从而促进及时就医。③在未来研究层面，本结果为探索连接内分泌与呼吸系统疾病的机制确立了优先级。后续工作应致力于：在不同人群中验证本研究的核心发现；寻找并验证在1型糖尿病-哮喘关系中效应量更大的核心介质与通路，以弥补CRP解释力不足的现状；通过前瞻性研究，最终确立针对高风险人群的精准筛查频率与干预阈值。

文献
收起
参考文献 引证文献
排序方式：
1
KIM Y J，BUNYAVANICH S. Microbial influencers：the airway microbiome’s role in asthma［J］. J Clin Invest，2025，135（4）：e184316.
2
李熙炫，彭东红. NaNO2对HDM预处理的气道上皮细胞氧化损伤的影响及其机制［J］. 陆军军医大学学报，2024，46（12）：1395-1402.
LI X X，PENG D H. Effect of NaNO2 on oxidative damage in house dust mite pretreated airway epithelial cells and its underlying mechanism［J］. J Army Med Univ，2024，46（12）：1395-1402.
3
WANG R，MURRAY C S，FOWLER S J，et al. Asthma diagnosis：into the fourth dimension［J］. Thorax，2021，76（6）：624-631.
4
LIU Y J，GAO K X，PENG X，et al. The great potential of polysaccharides from natural resources in the treatment of asthma：a review［J］. Int J Biol Macromol，2024，260：129431.
5
WANG Z F，LI Y，GAO Y，et al. Global，regional，and national burden of asthma and its attributable risk factors from 1990 to 2019：a systematic analysis for the Global Burden of Disease Study 2019［J］. Respir Res，2023，24（1）：169.
6
ZENG R，WANG Z H，ZHANG J T，et al. Type 1 diabetes and asthma：a systematic review and meta-analysis of observational studies［J］. Endocrine，2022，75（3）：709-717.
7
TORRES R M，DOS SANTOS SOUZA M，COELHO A C C，et al. Association between asthma and type 2 diabetes mellitus：mechanisms and impact on asthma control-a literature review［J］. Can Respir J，2021，2021：8830439.
8
CARDET J C，BULKHI A A，LOCKEY R F. Nonrespiratory comorbidities in asthma［J］. J Allergy Clin Immunol Pract，2021，9（11）：3887-3897.
9
PIERCE B L，AHSAN H，VANDERWEELE T J. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants［J］. Int J Epidemiol，2011，40（3）：740-752.
10
BURGESS S，BUTTERWORTH A，THOMPSON S G. Mendelian randomization analysis with multiple genetic variants using summarized data［J］. Genet Epidemiol，2013，37（7）：658-665.
11
Johnston J. Econometric methods 3rd ed.［J］. New York，New York，McGraw-Hill Book Company，1984，1984.
12
贾俊平. 统计学［M］. 7版. 北京：中国人民大学出版社，2018.
13
PORSBJERG C，MELÉN E，LEHTIMÄKI L，et al. Asthma［J］. Lancet，2023，401（10379）：858-873.
14
GANS M D，GAVRILOVA T. Understanding the immunology of asthma：Pathophysiology，biomarkers，and treatments for asthma endotypes［J］. Paediatr Respir Rev，2020，36：118-127.
15
BUTLAND B K，STRACHAN D P，RUDNICKA A R. C-reactive protein，obesity，atopy and asthma symptoms in middle-aged adults［J］. Eur Respir J，2008，32（1）：77-84.
16
STIRLING R G，CHUNG K F. Severe asthma：definition and mechanisms［J］. Allergy，2001，56（9）：825-840.
17
TAY T R，HEW M. Comorbid “treatable traits” in difficult asthma：Current evidence and clinical evaluation［J］. Allergy，2018，73（7）：1369-1382.
18
TROWSDALE J，KNIGHT J C. Major histocompatibility complex genomics and human disease［J］. Annu Rev Genomics Hum Genet，2013，14：301-323.
19
NEJENTSEV S，WALKER N，RICHES D，et al. Rare variants of IFIH1 a gene implicated in antiviral responses，protect against type 1 diabetes［J］. Science，2009，324（5925）：387-389.
20
HSIAO Y T，CHENG W C，LIAO W C，et al. Type 1 diabetes and increased risk of subsequent asthma：a nationwide population-based cohort study［J］. Medicine，2015，94（36）：e1466.
21
VILLA-NOVA H，SPINOLA-CASTRO A M，GARCIA F E，et al. Prevalence of allergic diseases and/or allergic sensitisation in children and adolescents with type 1 diabetes mellitus［J］. Allergol Immunopathol，2015，43（2）：157-161.
22
PRZYBYLIK-MAZUREK E，KOTLINOWSKA B，KASZTELNIK M，et al. Autoimmunological and allergic disorders with Hashimoto and Graves disease［J］. Przegl Lek，2006，63（9）：719-722.
23
BAN Y，DAVIES T F，GREENBERG D A，et al. Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves' disease［J］. Genes Immun，2004，5（3）：203-208.
24
RAMOS P S，SHEDLOCK A M，LANGEFELD C D. Genetics of autoimmune diseases：insights from population genetics［J］. J Hum Genet，2015，60（11）：657-664.
25
THOMSEN S F，DUFFY D L，KYVIK K O，et al. Risk of asthma in adult twins with type 2 diabetes and increased body mass index［J］. Allergy，2011，66（4）：562-568.
26
HASHEMZADEH M，MOVAHED M R. The occurrence of asthma in hospitalized patients with type 2 diabetes mellitus［J］. Intern Med J，2009，39（10）：699-701.
27
EHRLICH S F，QUESENBERRY C P Jr，VAN DEN EEDEN S K，et al. Patients diagnosed with diabetes are at increased risk for asthma，chronic obstructive pulmonary disease，pulmonary fibrosis，and pneumonia but not lung cancer［J］. Diabetes Care，2010，33（1）：55-60.
28
RAYNER L，MCGOVERN A，CREAGH-BROWN B，et al. Type 2 diabetes and asthma：systematic review of the bidirectional relationship［J］. Curr Diabetes Rev，2019，15（2）：118-126.
29
ZHENG Y S，ZHANG G L，CHEN Z L，et al. Relationship between type 2 diabetes and inflammation diseases：cohort study in Chinese adults［J］. Iran J Public Health，2015，44（8）：1045-1052.
30
CHEN J，ZHANG X F，SUN G Y. Causal relationship between type 2 diabetes and common respiratory system diseases：a two-sample Mendelian randomization analysis［J］. Front Med，2024，11：1332664.
31
CHEN G Y，NUÑEZ G. Sterile inflammation：sensing and reacting to damage［J］. Nat Rev Immunol，2010，10（12）：826-837.
32
BLACK S，KUSHNER I，SAMOLS D. C-reactive protein［J］. J Biol Chem，2004，279（47）：48487-48490.
33
PEPYS M B，HIRSCHFIELD G M，TENNENT G A，et al. Targeting C-reactive protein for the treatment of cardiovascular disease［J］. Nature，2006，440（7088）：1217-1221.
34
QIAN F H，ZHANG Q，ZHOU L F，et al. High-sensitivity C-reactive protein：a predicative marker in severe asthma［J］. Respirology，2008，13（5）：664-669.
35
AGASSANDIAN M，SHURIN G V，MA Y，et al. C-reactive protein and lung diseases［J］. Int J Biochem Cell Biol，2014，53：77-88.
36
SPROSTON N R，ASHWORTH J J. Role of C-reactive protein at sites of inflammation and infection［J］. Front Immunol，2018，9：754.
37
CASALS C，ARIAS-DIAZ J，VALINO F，et al. Surfactant strengthens the inhibitory effect of C-reactive protein on human lung macrophage cytokine release［J］. Am J Physiol Lung Cell Mol Physiol，2003，284（3）：L466-L472.
38
RASMUSSEN F，MIKKELSEN D，HANCOX R J，et al. High-sensitive C-reactive protein is associated with reduced lung function in young adults［J］. Eur Respir J，2009，33（2）：382-388.
39
KO A R，KIM Y H，SOL I S，et al. High-sensitivity C-reactive protein can reflect small airway obstruction in childhood asthma［J］. Yonsei Med J，2016，57（3）：690-697.
40
PINCUS S M. Approximate entropy as a measure of system complexity［J］. Proc Natl Acad Sci USA，1991，88（6）：2297-2301.
41
VEIGA J，LOPES A J，JANSEN J M，et al. Airflow pattern complexity and airway obstruction in asthma［J］. J Appl Physiol （1985），2011，111（2）：412-419.
2025年第47卷第24期
PDF下载
20
7
引用本文
BibTeX
文章信息
doi: 10.16016/j.2097-0927.202510031
  • 接收时间：2025-10-15
  • 首发时间：2026-10-30
  • 出版时间：2025-12-30
补充材料
相关文章
文章信息
作者
出版历史
  • 收稿日期：2025-10-15
  • 修回日期：2025-11-28
基金
作者信息
    1上海中医药大学附属岳阳中西医结合医院呼吸内科，上海

通讯作者:

王振伟，E-mail：
WANG Zhenwei，Email：
参考文献
分享链接
https://castjournals.cast.org.cn/joweb/ljjydxxb/CN/10.16016/j.2097-0927.202510031
分享至
全文二维码

扫描看全文

引用本文
BibTeX
本文的引用情况
2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
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
关闭全屏
相关链接
论文
最新文章
热读文章
热点专题
内参
蓝皮书
产业发展报告
传播力报告
期刊分级目录
资讯
学术新闻
行业新闻
学术会议
行业会议
关于
关于我们
联系我们
北京市海淀区学院南路86号
100081
010-62662699（运营及技术支持）
qkjq@cast.org.cn

中国科学技术协会版权所有 京ICP 备10216604号-4 海淀分局备案 1101084647
科技导报社主办 中国科协信息中心技术支持