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Article(id=1198200257759769092, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198200256912519683, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.0113.2024.0717, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1705075200000, receivedDateStr=2024-01-13, revisedDate=null, revisedDateStr=null, acceptedDate=1714233600000, acceptedDateStr=2024-04-28, onlineDate=1763602802933, onlineDateStr=2025-11-20, pubDate=1732723200000, pubDateStr=2024-11-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763602802933, onlineIssueDateStr=2025-11-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763602802933, creator=13701087609, updateTime=1763602802933, updator=13701087609, issue=Issue{id=1198200256912519683, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='11', pageStart='1221', pageEnd='1342', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763602802732, creator=13701087609, updateTime=1763603918291, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1198204935973204862, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198200256912519683, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1198204935973204863, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198200256912519683, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1295, endPage=1301, ext={EN=ArticleExt(id=1198200257986261512, articleId=1198200257759769092, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=The clinical value of red blood cell volume distribution width coefficient of variation and serum IL-11 and IL-31 in the diagnosis of interstitial lung disease, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To explore the clinical value of red blood cell volume distribution width coefficient of variation (RDW-CV), serum interleukin-11 (IL-11) and interleukin-31 (IL-31) in the diagnosis of interstitial lung disease (ILD). Methods Prospectively selected 46 ILD patients admitted to the Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Chengde Medical University from November 2022 to October 2023 were set as ILD group, 40 patients with community-acquired pneumonia (CAP) as CAP group, and 35 healthy examiners as control group. The ILD group was further divided into idiopathic interstitial pneumonia (IIP) subgroup (n=30) and connective tissue disease-related ILD (CTD-ILD) subgroup (n=16) based on clinical diagnosis. General and clinical data of each group were recorded, and RDW-CV and serum IL-11 and IL-31 levels were detected in each group. The ILD group was tested for alveolar arterial oxygen pressure difference (AaDO2) and arterial blood oxygen pressure (PaO2), and calculated the oxygenation index (OI). The correlation between the levels of RDW-CV, IL-11 and IL-31 and the severity of ILD were analyzed to explore the value of the above indicators in the clinical diagnosis of ILD and the differential diagnosis of different types of ILD. Results Compared with control group, there was no statistically significant difference in general information such as age, gender, smoking history, and complications between the ILD and CAP groups (P<0.05); RDW-CV, absolute values of neutrophil count (NEUT), and serum IL-11 and IL-31 levels in ILD group were significantly increased (P>0.05). Compared with CAP group, the levels of RDW-CV and serum IL-11, IL-31 in ILD group were increased, while the level of serum C-reactive protein (CRP) was decreased, with statistically significant differences (P<0.05). Correlation analysis results showed that RDW-CV and serum IL-31 in ILD patients were negatively correlated with OI (P<0.05), and positively correlated with AaDO2 (P<0.05). The area under the ROC curves (AUC) of RDW-CV and serum IL-11, IL-31 single and combined applications for diagnosing ILD were 0.770, 0.666, 0.646, and 0.854, respectively (P<0.05). The AUC of serum IL-11 for differential diagnosis of CTD-ILD and IIP was 0.727(95%CI 0.580-0.874), with sensitivity of 62.5% and specificity of 73.3% (P<0.05). Conclusions RDW-CV and serum IL-31 have certain value in assessing the severity of ILD. RDW-CV and serum IL-11 and IL-31 have certain value in the diagnosis of ILD. Serum IL-11 has certain value in the differential diagnosis between CTD-ILD and IIP.

, correspAuthors=Lin-Ying Yang, authorNote=null, correspAuthorsNote=
E-mail:
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目的 探讨红细胞体积分布宽度变异系数(RDW-CV)和血清白细胞介素-11(IL-11)、IL-31在间质性肺疾病(ILD)诊断中的临床价值。方法 前瞻性选取2022年11月－2023年10月在承德医学院附属医院呼吸与危重症医学科住院的46例ILD患者设为ILD组，40例社区获得性肺炎(CAP)患者设为CAP组，以同期35名健康体检者作为对照组；其中ILD组依据临床诊断分为特发性间质性肺炎(IIP)亚组(n=30)、结缔组织病相关ILD(CTD-ILD)亚组(n=16)。记录各组的一般资料，检测各组RDW-CV和血清IL-11、IL-31水平；ILD组检测肺泡-动脉氧分压差(AaDO2)、动脉血氧分压(PaO2)，计算氧合指数(OI)；分析RDW-CV和血清IL-11、IL-31水平与ILD病情严重程度的相关性，探讨上述指标在ILD临床诊断及不同类型ILD鉴别诊断中的价值。结果 与对照组比较，ILD组、CAP组的年龄、性别、吸烟史、并发症等一般资料差异均无统计学意义(P>0.05)；ILD组的RDW-CV、中性粒细胞(NEUT)绝对值和血清IL-11、IL-31水平明显升高(P<0.05)。与CAP组比较，ILD组RDW-CV和血清IL-11、IL-31水平升高，血清C反应蛋白(CRP)水平降低，差异均有统计学意义(P<0.05)。相关分析结果显示，ILD患者RDW-CV、血清IL-31与OI呈负相关(P<0.05)，与AaDO2呈正相关(P<0.05)。RDW-CV和血清IL-11、IL-31单项及联合应用诊断ILD的ROC曲线下面积(AUC)分别为0.770、0.666、0.646、0.854(P<0.05)。血清IL-11鉴别诊断CTD-ILD和IIP的AUC为0.727(95%CI 0.580~0.874)，敏感度为62.5%，特异度为73.3%(P<0.05)。结论 RDW-CV和血清IL-31在评估ILD病情严重程度中有一定价值；RDW-CV和血清IL-11、IL-31诊断ILD有一定价值；血清IL-11鉴别诊断CTD-ILD与IIP有一定价值。

, correspAuthors=杨林瀛, authorNote=null, correspAuthorsNote=
杨林瀛，E-mail：
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郭鑫龙，硕士研究生，主要从事慢性呼吸系统疾病方面的研究

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郭鑫龙，硕士研究生，主要从事慢性呼吸系统疾病方面的研究

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郭鑫龙，硕士研究生，主要从事慢性呼吸系统疾病方面的研究

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RDW-CV. 红细胞体积分布宽度变异系数；IL-11. 白细胞介素-11；IL-31. 白细胞介素-31；ILD. 间质性肺疾病

, figureFileSmall=hqt288a5DQocf+62hUe7bg==, figureFileBig=1NpUQg5sfyBFuWap25gy4w==, tableContent=null), ArticleFig(id=1198318986724213714, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Fig.2, caption=ROC curves for differential diagnosis of different types of ILD using IL-11, figureFileSmall=//wd9vmxqrzDZASWTcBu3w==, figureFileBig=jGdT2okcau1OXi00AX/sOA==, tableContent=null), ArticleFig(id=1198318986837459927, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=图2, caption=IL-11鉴别诊断不同类型ILD的ROC曲线

IL-11. 白细胞介素-11； ILD. 间质性肺疾病

, figureFileSmall=//wd9vmxqrzDZASWTcBu3w==, figureFileBig=jGdT2okcau1OXi00AX/sOA==, tableContent=null), ArticleFig(id=1198318986929734618, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.1, caption=

Comparison of general information between three groups

, figureFileSmall=null, figureFileBig=null, tableContent=
项目

ILD组

(n=46)

CAP组

(n=40)

对照组

(n=35)

F/χ2P
年龄(岁, $\bar{x}±s$)65.7±10.462.1±12.661.4±11.31.7400.180
性别[例(%)]2.3800.304
男20(43.5)22(55.0)21(60.0)
女26(56.5)18(45.0)14(40.0)
吸烟史[例(%)]20(43.5)17(42.5)18(51.4)0.7170.699
并发症[例(%)]
高血压15(32.6)19(47.5)-1.9850.159
糖尿病7(15.2)12(30.0)-2.7160.099
冠心病5(10.9)3(7.5)-0.0270.869
), ArticleFig(id=1198318987017815006, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表1, caption=

三组一般资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目

ILD组

(n=46)

CAP组

(n=40)

对照组

(n=35)

F/χ2P
年龄(岁, $\bar{x}±s$)65.7±10.462.1±12.661.4±11.31.7400.180
性别[例(%)]2.3800.304
男20(43.5)22(55.0)21(60.0)
女26(56.5)18(45.0)14(40.0)
吸烟史[例(%)]20(43.5)17(42.5)18(51.4)0.7170.699
并发症[例(%)]
高血压15(32.6)19(47.5)-1.9850.159
糖尿病7(15.2)12(30.0)-2.7160.099
冠心病5(10.9)3(7.5)-0.0270.869
), ArticleFig(id=1198318987164615649, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.2, caption=

Comparison of inflammatory indicators, RDW-CV, IL-11 and IL-31 between three groups [M(Q1, Q3)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标ILD组(n=46)CAP组(n=40)对照组(n=35)Z/HP
CRP (mg/L)8.39(1.84, 47.20)31.32(7.70, 97.84)--2.6320.008
WBC (×109/L)6.31(5.62, 9.60)7.34(4.99, 9.57)6.22(5.23, 7.02)3.3180.190
NEUT (×109/L)4.36(3.39, 6.87)4.85(2.99, 7.69)3.64*(3.00, 4.51)6.6350.036
RDW-CV (%)13.30(12.90, 14.65)12.60*(11.90, 13.40)12.70*(12.40, 12.90)20.8500.001
IL-11 (pg/ml)8.04(3.14, 24.58)6.63*(2.32, 9.75)4.53*(2.43, 7.81)8.2810.016
IL-31 (pg/ml)17.38(11.12, 23.12)11.99*(4.38, 21.18)11.75*(8.28, 19.07)7.0740.029
), ArticleFig(id=1198318987240113124, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表2, caption=

三组患者炎症指标、RDW-CV和血清IL-11、IL-31水平比较[M(Q1，Q3)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标ILD组(n=46)CAP组(n=40)对照组(n=35)Z/HP
CRP (mg/L)8.39(1.84, 47.20)31.32(7.70, 97.84)--2.6320.008
WBC (×109/L)6.31(5.62, 9.60)7.34(4.99, 9.57)6.22(5.23, 7.02)3.3180.190
NEUT (×109/L)4.36(3.39, 6.87)4.85(2.99, 7.69)3.64*(3.00, 4.51)6.6350.036
RDW-CV (%)13.30(12.90, 14.65)12.60*(11.90, 13.40)12.70*(12.40, 12.90)20.8500.001
IL-11 (pg/ml)8.04(3.14, 24.58)6.63*(2.32, 9.75)4.53*(2.43, 7.81)8.2810.016
IL-31 (pg/ml)17.38(11.12, 23.12)11.99*(4.38, 21.18)11.75*(8.28, 19.07)7.0740.029
), ArticleFig(id=1198318987395302375, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.3, caption=

Correlation analysis between RDW-CV, IL-11, IL-31 and the severity of ILD disease

, figureFileSmall=null, figureFileBig=null, tableContent=
参数RDW-CVIL-11IL-31
rPrPrP
CRP0.4660.0010.0110.9430.2000.183
OI-0.5230.0010.1980.186-0.3130.034
AaDO20.5900.001-0.0500.7430.3400.021
), ArticleFig(id=1198318987516937198, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表3, caption=

ILD患者RDW-CV和血清IL-11、IL-31水平与疾病严重程度的相关性分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
参数RDW-CVIL-11IL-31
rPrPrP
CRP0.4660.0010.0110.9430.2000.183
OI-0.5230.0010.1980.186-0.3130.034
AaDO20.5900.001-0.0500.7430.3400.021
), ArticleFig(id=1198318987642766323, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.4, caption=

Logistic regression analysis on the predictive indicators for ILD

, figureFileSmall=null, figureFileBig=null, tableContent=
指标βSEWald χ2POR95%CI
性别-0.9370.9440.9840.3210.3920.062~2.495
吸烟史0.1890.9430.0400.8411.2080.190~7.672
RDW-CV1.1730.3968.7730.0033.2311.487~7.022
IL-110.0980.0454.6470.0311.1031.009~1.205
IL-310.1000.0454.9750.0261.1051.012~1.207
), ArticleFig(id=1198318987756012536, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表4, caption=

ILD预测指标的logistic回归分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
指标βSEWald χ2POR95%CI
性别-0.9370.9440.9840.3210.3920.062~2.495
吸烟史0.1890.9430.0400.8411.2080.190~7.672
RDW-CV1.1730.3968.7730.0033.2311.487~7.022
IL-110.0980.0454.6470.0311.1031.009~1.205
IL-310.1000.0454.9750.0261.1051.012~1.207
), ArticleFig(id=1198318987881841661, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.5, caption=

The value of single and combined application of RDW-CV, IL-11, IL-31 in the clinical diagnosis of ILD

, figureFileSmall=null, figureFileBig=null, tableContent=
指标

敏感度

(%)

特异度

(%)

约登

指数

AUC95%CIP
RDW-CV69.677.10.4670.7700.666~0.8730.001
IL-1143.591.40.3490.6660.548~0.7830.011
IL-3173.954.30.2820.6460.526~0.7660.025
联合应用60.994.30.5520.8540.776~0.9320.001
), ArticleFig(id=1198318987986699264, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表5, caption=

RDW-CV和血清IL-11、IL-31单项及联合应用在ILD临床诊断中的价值

, figureFileSmall=null, figureFileBig=null, tableContent=
指标

敏感度

(%)

特异度

(%)

约登

指数

AUC95%CIP
RDW-CV69.677.10.4670.7700.666~0.8730.001
IL-1143.591.40.3490.6660.548~0.7830.011
IL-3173.954.30.2820.6460.526~0.7660.025
联合应用60.994.30.5520.8540.776~0.9320.001
), ArticleFig(id=1198318988087361538, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.6, caption=

Comparison of general information between IIP group and CTD-ILD group

, figureFileSmall=null, figureFileBig=null, tableContent=
指标IIP(n=30)CTD-ILD(n=16)t/χ2P
年龄(岁, $\bar{x}±s$)66.57±10.6264.19±10.020.7380.465
性别[例(%)]6.1050.013
男17(56.7)3(18.8)
女13(43.3)13(81.2)
吸烟史[例(%)]17(56.7)3(18.8)6.1050.013
并发症[例(%)]
高血压11(36.7)4(25.0)0.6460.421
糖尿病7(23.3)0(0.0)2.7810.095
冠心病4(13.3)1(6.3)0.0570.812
), ArticleFig(id=1198318988259328008, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表6, caption=

IIP亚组和CTD-ILD亚组一般资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标IIP(n=30)CTD-ILD(n=16)t/χ2P
年龄(岁, $\bar{x}±s$)66.57±10.6264.19±10.020.7380.465
性别[例(%)]6.1050.013
男17(56.7)3(18.8)
女13(43.3)13(81.2)
吸烟史[例(%)]17(56.7)3(18.8)6.1050.013
并发症[例(%)]
高血压11(36.7)4(25.0)0.6460.421
糖尿病7(23.3)0(0.0)2.7810.095
冠心病4(13.3)1(6.3)0.0570.812
), ArticleFig(id=1198318988385157133, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.7, caption=

Comparison of inflammatory markers, RDW-CV, IL-11 and IL-31 between IIP group and CTD-ILD group [M(Q1, Q3)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标IIP(n=30)CTD-ILD(n=16)ZP
CRP(mg/L)5.75(1.76, 30.74)22.40(2.57, 82.34)-1.3720.170
WBC(×109/L)6.17(5.54, 9.08)6.43(5.74, 10.88)-0.5770.564
NEUT(×109/L)4.36(3.33, 6.72)4.94(3.41, 8.52)-0.2310.818
RDW-CV(%)13.05(12.85, 14.68)13.40(13.13, 14.75)-1.0740.283
IL-11(pg/ml)6.75(2.39, 14.50)14.41(7.26, 58.15)-2.5140.012
IL-31(pg/ml)15.66(12.07, 22.85)19.40(10.93, 53.30)-0.9340.350
), ArticleFig(id=1198318988523569169, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表7, caption=

IIP亚组和CTD-ILD亚组炎性指标、RDW-CV及血清IL-11、IL-31水平比较[M(Q1，Q3)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标IIP(n=30)CTD-ILD(n=16)ZP
CRP(mg/L)5.75(1.76, 30.74)22.40(2.57, 82.34)-1.3720.170
WBC(×109/L)6.17(5.54, 9.08)6.43(5.74, 10.88)-0.5770.564
NEUT(×109/L)4.36(3.33, 6.72)4.94(3.41, 8.52)-0.2310.818
RDW-CV(%)13.05(12.85, 14.68)13.40(13.13, 14.75)-1.0740.283
IL-11(pg/ml)6.75(2.39, 14.50)14.41(7.26, 58.15)-2.5140.012
IL-31(pg/ml)15.66(12.07, 22.85)19.40(10.93, 53.30)-0.9340.350
), ArticleFig(id=1198318988636815380, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=EN, label=Tab.8, caption=

Analysis of differences in IL-11 level between CTD-ILD group and IIP group

, figureFileSmall=null, figureFileBig=null, tableContent=
指标βSEWald χ2PRR95%CI
性别-0.8360.7691.1820.2770.4340.096~1.956
吸烟史-0.8600.7701.2460.2640.4230.094~1.915
IL-110.0030.00120.3550.0011.0031.002~1.004
), ArticleFig(id=1198318988733284375, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198200257759769092, language=CN, label=表8, caption=

CTD-ILD亚组和IIP亚组血清IL-11水平差异分析

, figureFileSmall=null, figureFileBig=null, tableContent=
指标βSEWald χ2PRR95%CI
性别-0.8360.7691.1820.2770.4340.096~1.956
吸烟史-0.8600.7701.2460.2640.4230.094~1.915
IL-110.0030.00120.3550.0011.0031.002~1.004
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红细胞体积分布宽度变异系数和血清IL-11、IL-31在间质性肺疾病诊断中的应用价值
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郭鑫龙 , 赵志伟 , 庞桂芬 , 杨林瀛 *
解放军医学杂志 | 临床研究 2024,49(11): 1295-1301
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解放军医学杂志 | 临床研究 2024, 49(11): 1295-1301
红细胞体积分布宽度变异系数和血清IL-11、IL-31在间质性肺疾病诊断中的应用价值
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郭鑫龙, 赵志伟, 庞桂芬, 杨林瀛*
作者信息
  • 承德医学院附属医院呼吸与危重症医学科，河北承德 067000

    • 郭鑫龙，硕士研究生，主要从事慢性呼吸系统疾病方面的研究

通讯作者:

杨林瀛，E-mail：
The clinical value of red blood cell volume distribution width coefficient of variation and serum IL-11 and IL-31 in the diagnosis of interstitial lung disease
Xin-Long Guo, Zhi-Wei Zhao, Gui-Fen Pang, Lin-Ying Yang*
Affiliations
  • Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, China
出版时间: 2024-11-28 doi: 10.11855/j.issn.0577-7402.0113.2024.0717
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摘要
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目的 探讨红细胞体积分布宽度变异系数(RDW-CV)和血清白细胞介素-11(IL-11)、IL-31在间质性肺疾病(ILD)诊断中的临床价值。方法 前瞻性选取2022年11月－2023年10月在承德医学院附属医院呼吸与危重症医学科住院的46例ILD患者设为ILD组，40例社区获得性肺炎(CAP)患者设为CAP组，以同期35名健康体检者作为对照组；其中ILD组依据临床诊断分为特发性间质性肺炎(IIP)亚组(n=30)、结缔组织病相关ILD(CTD-ILD)亚组(n=16)。记录各组的一般资料，检测各组RDW-CV和血清IL-11、IL-31水平；ILD组检测肺泡-动脉氧分压差(AaDO2)、动脉血氧分压(PaO2)，计算氧合指数(OI)；分析RDW-CV和血清IL-11、IL-31水平与ILD病情严重程度的相关性，探讨上述指标在ILD临床诊断及不同类型ILD鉴别诊断中的价值。结果 与对照组比较，ILD组、CAP组的年龄、性别、吸烟史、并发症等一般资料差异均无统计学意义(P>0.05)；ILD组的RDW-CV、中性粒细胞(NEUT)绝对值和血清IL-11、IL-31水平明显升高(P<0.05)。与CAP组比较，ILD组RDW-CV和血清IL-11、IL-31水平升高，血清C反应蛋白(CRP)水平降低，差异均有统计学意义(P<0.05)。相关分析结果显示，ILD患者RDW-CV、血清IL-31与OI呈负相关(P<0.05)，与AaDO2呈正相关(P<0.05)。RDW-CV和血清IL-11、IL-31单项及联合应用诊断ILD的ROC曲线下面积(AUC)分别为0.770、0.666、0.646、0.854(P<0.05)。血清IL-11鉴别诊断CTD-ILD和IIP的AUC为0.727(95%CI 0.580~0.874)，敏感度为62.5%，特异度为73.3%(P<0.05)。结论 RDW-CV和血清IL-31在评估ILD病情严重程度中有一定价值；RDW-CV和血清IL-11、IL-31诊断ILD有一定价值；血清IL-11鉴别诊断CTD-ILD与IIP有一定价值。

间质性肺疾病  /  红细胞体积分布宽度变异系数  /  白细胞介素-11  /  白细胞介素-31

Objective To explore the clinical value of red blood cell volume distribution width coefficient of variation (RDW-CV), serum interleukin-11 (IL-11) and interleukin-31 (IL-31) in the diagnosis of interstitial lung disease (ILD). Methods Prospectively selected 46 ILD patients admitted to the Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Chengde Medical University from November 2022 to October 2023 were set as ILD group, 40 patients with community-acquired pneumonia (CAP) as CAP group, and 35 healthy examiners as control group. The ILD group was further divided into idiopathic interstitial pneumonia (IIP) subgroup (n=30) and connective tissue disease-related ILD (CTD-ILD) subgroup (n=16) based on clinical diagnosis. General and clinical data of each group were recorded, and RDW-CV and serum IL-11 and IL-31 levels were detected in each group. The ILD group was tested for alveolar arterial oxygen pressure difference (AaDO2) and arterial blood oxygen pressure (PaO2), and calculated the oxygenation index (OI). The correlation between the levels of RDW-CV, IL-11 and IL-31 and the severity of ILD were analyzed to explore the value of the above indicators in the clinical diagnosis of ILD and the differential diagnosis of different types of ILD. Results Compared with control group, there was no statistically significant difference in general information such as age, gender, smoking history, and complications between the ILD and CAP groups (P<0.05); RDW-CV, absolute values of neutrophil count (NEUT), and serum IL-11 and IL-31 levels in ILD group were significantly increased (P>0.05). Compared with CAP group, the levels of RDW-CV and serum IL-11, IL-31 in ILD group were increased, while the level of serum C-reactive protein (CRP) was decreased, with statistically significant differences (P<0.05). Correlation analysis results showed that RDW-CV and serum IL-31 in ILD patients were negatively correlated with OI (P<0.05), and positively correlated with AaDO2 (P<0.05). The area under the ROC curves (AUC) of RDW-CV and serum IL-11, IL-31 single and combined applications for diagnosing ILD were 0.770, 0.666, 0.646, and 0.854, respectively (P<0.05). The AUC of serum IL-11 for differential diagnosis of CTD-ILD and IIP was 0.727(95%CI 0.580-0.874), with sensitivity of 62.5% and specificity of 73.3% (P<0.05). Conclusions RDW-CV and serum IL-31 have certain value in assessing the severity of ILD. RDW-CV and serum IL-11 and IL-31 have certain value in the diagnosis of ILD. Serum IL-11 has certain value in the differential diagnosis between CTD-ILD and IIP.

interstitial lung disease  /  red blood cell volume distribution width  /  interleukin-11  /  interleukin-31
郭鑫龙, 赵志伟, 庞桂芬, 杨林瀛. 红细胞体积分布宽度变异系数和血清IL-11、IL-31在间质性肺疾病诊断中的应用价值. 解放军医学杂志, 2024 , 49 (11) : 1295 -1301 . DOI: 10.11855/j.issn.0577-7402.0113.2024.0717
Xin-Long Guo, Zhi-Wei Zhao, Gui-Fen Pang, Lin-Ying Yang. The clinical value of red blood cell volume distribution width coefficient of variation and serum IL-11 and IL-31 in the diagnosis of interstitial lung disease[J]. Medical Journal of Chinese People’s Liberation Army, 2024 , 49 (11) : 1295 -1301 . DOI: 10.11855/j.issn.0577-7402.0113.2024.0717
正文
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间质性肺疾病(interstitial lung disease，ILD)是一类弥漫性肺部疾病，目前多采用2002年美国胸科学会/欧洲呼吸学会共识推荐的分类方案[1]将其分为已知病因的ILD、特发性间质性肺炎(idiopathic interstitial pneumonia，IIP)、肉芽肿性ILD及其他少见的ILD。ILD的分类不同，预后也不尽相同；部分患者的病情可稳定或经治疗后缓解，但也有部分患者持续进展为终末期纤维化甚至死亡，因此早诊断、早治疗可明显改善患者预后。ILD的临床诊断主要依据患者的症状、体征、胸部高分辨CT、肺功能测定、肺活检等，但部分检查手段由于费用较高、重复性差或有创等缺点，难以广泛应用。
血清生物标志物是近年来相关研究的热点。红细胞体积分布宽度变异系数(coefficient of variation of red blood cell volume distribution width，RDW-CV)可反映外周红细胞体积的离散程度。有研究显示，相比于单纯结缔组织病(connective tissue disease，CTD)，CTD相关的ILD(connective tissue disease-interstitial lung disease，CTD-ILD)中红细胞体积分布宽度(RDW)明显升高且与疾病严重程度呈正相关[2]。白细胞介素(interleukin，IL)-11、IL-31作为IL-6细胞因子家族成员，可通过与特异受体结合而激活JAK-STAT信号通路[3]，导致纤维化疾病的发生。研究显示，在博来霉素诱导的肺纤维化模型小鼠肺组织中，IL-11、IL-31表达水平明显升高[4-5]；ILD患者血清IL-6水平升高并可用于评估其疾病严重程度[6-7]。但采用血清IL-11、IL-31水平评估ILD严重程度的相关报道少见。本研究分析RDW-CV及血清IL-11、IL-31与ILD的相关性，旨在通过血清学指标辅助诊断ILD并评估其疾病严重程度，为ILD的临床诊治提供帮助。
1 资料与方法
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1.1 研究对象
前瞻性选取2022年11月－2023年10月在承德医学院附属医院呼吸与危重症医学科住院的46例ILD患者设为ILD组；依据临床诊断再分为两个亚组：IIP亚组30例、CTD-ILD亚组16例(包括类风湿关节炎7例，系统性硬化症3例，干燥综合征2例，抗合成酶综合征2例，混合性结缔组织病1例，系统性红斑狼疮1例)。另选择同期住院的社区获得性肺炎(community acquired pneumonia，CAP)患者40例设为CAP组，以及同期体检的健康人员35名设为对照组。纳入标准：(1)依据《成人特发性肺纤维化(更新)和进展性肺纤维化——ATS/ERS/JRS/ALAT临床实践指南(2022版)》[8]和《结缔组织病相关间质性肺疾病诊疗规范》[9]诊断为ILD，或依据中华医学会呼吸病学分会的《成人社区获得性肺炎基层诊疗指南(实践版2018)》[10]诊断为CAP；(2)年龄40岁；(3)入院前未使用抗生素或使用抗生素治疗无效者。排除标准：(1)合并恶性肿瘤或血液系统恶性疾病；(2)合并严重的肝、肾等重要脏器功能不全；(3)入院前1个月内使用糖皮质激素或免疫抑制剂；(4)合并慢性阻塞性肺疾病、支气管哮喘、肺结核或肺癌等肺部疾病；(5)临床资料不完整。本研究获承德医学院附属医院医学伦理委员会审批(第CYFYLL2022605号)。
1.2 方法
1.2.1 资料收集
收集研究对象的一般资料，包括年龄、性别、吸烟史、高血压病史、糖尿病史、冠心病史，以及血常规检查结果和C反应蛋白(C-reactive protein，CRP)。记录ILD患者的动脉血气分析指标，包括肺泡-动脉氧分压差(arterial alveolar oxygen gradient，AaDO2)、动脉血氧分压(arterial partial pressure of oxygen，PaO2)、吸入氧浓度(fraction of inspired oxygen，FiO2)，计算氧合指数(oxygenation index，OI=PaO2/FiO2)。
1.2.2 实验室检查
采集ILD患者入院次日清晨空腹肘静脉血5 ml，于室温下静置2 h后以3000 r/min的速度离心15 min，移取上清液备用。采用UniCel DxH800 血细胞分析仪(美国贝克曼库尔特公司)进行血细胞分析，记录白细胞(white blood cells，WBC)计数、中性粒细胞(neutrophils，NEUT)绝对值、RDW-CV；采用IMMAGE 800 特定蛋白分析仪(美国贝克曼库尔特公司)及配套试剂检测CRP水平；采用双抗体夹心酶联免疫吸附试验法检测血清IL-11、IL-31水平，试剂盒购自武汉爱博泰克生物科技有限公司，所有操作严格遵循试剂盒说明书。抽取肘动脉血1 ml检测动脉血气分析。CAP患者于入院次日相同条件下检测上述指标(动脉血气分析除外)；健康体检者于体检时相同条件下检测上述指标(动脉血气分析除外)。
1.2.3 各组相关指标比较
比较ILD组、CAP组和对照组间以及ILD组中两个亚组(IIP亚组和CTD-ILD亚组)间一般资料、RDW-CV和血清IL-11、IL-31水平，分析ILD组RDW-CV和血清IL-11、IL-31水平与OI、AaDO2的相关性，探讨血清RDW-CV、IL-11、IL-31在ILD临床诊断中的价值以及在IIP和CTD-ILD鉴别诊断中的价值。
1.3 统计学处理
采用SPSS 25.0软件进行统计分析，Graphpad Pism9.5软件绘图。符合正态分布的计量资料以$\bar{x}±s$表示，两组间比较采用独立样本t检验，多组间比较采用方差分析，进一步两两比较采用LSD-t检验；非正态分布的计量资料以M(Q1，Q3)表示，两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Dunn's检验。计数资料以例(%)表示，组间比较采用χ2检验或校正χ2检验，多组间比较采用R×C列联表χ2检验。采用Spearman相关性分析RDW-CV和血清IL-11、IL-31水平与ILD严重程度的相关性；采用二元logistic回归建立血清RDW-CV、IL-11、IL-31的联合预测因子，采用修正Poisson回归分析不同类型ILD中血清IL-11水平的差异，采用受试者操作特征(receiver operator characteristic，ROC)曲线分析各指标在ILD临床诊断中的价值，以及血清IL-11水平在CTD-ILD和IIP鉴别诊断中的价值。P<0.05为差异有统计学意义。
2 结果
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2.1 三组一般资料比较
与对照组比较，ILD组、CAP组的年龄、性别、吸烟史及并发症发生情况差异均无统计学意义(P>0.05，表1)。
2.2 三组炎性指标、RDW-CV和血清IL-11、IL-31水平比较
与对照组比较，ILD组血清RDW-CV、IL-11、IL-31、NEUT水平均明显升高，差异有统计学意义(P<0.05)；两组血清WBC水平比较，差异无统计学意义(P>0.05)。与CAP组比较，ILD组RDW-CV和血清IL-11、IL-31水平均升高，血清CRP水平降低，差异均有统计学意义(P<0.05)；两组血清WBC、NEUT水平比较，差异无统计学意义(P>0.05，表2)。
2.3 ILD患者RDW-CV和血清IL-11、IL-31水平与疾病严重程度的相关性分析
Spearman相关分析结果显示，ILD患者的RDW-CV与OI呈负相关(P<0.05)，与AaDO2、CRP呈正相关(P<0.05)；血清IL-31水平与OI呈负相关(P<0.05)，与AaDO2呈正相关(P<0.05)，与CRP不相关(P>0.05)；血清IL-11水平与CRP、OI、AaDO2均不相关(P<0.05，表3)。
2.4 ILD的预测指标分析
以是否发生ILD为因变量(0=对照组，1=ILD组)，经过共线性诊断，将可能影响ILD临床诊断的因素(性别、吸烟史、RDW-CV、血清IL-11、IL-31水平)作为自变量纳入二元logistic回归，结果显示，RDW-CV和血清IL-11、IL-31水平预测ILD发生的效能较高(P<0.05，表4)。
2.5 RDW-CV和血清IL-11、IL-31单项及联合应用对ILD的诊断价值
ROC曲线分析显示，RDW-CV和血清IL-11、IL-31联合诊断ILD的曲线下面积(AUC)为0.854，敏感度为60.9%，特异度为94.3%，其诊断价值明显优于各指标单独应用(表5、图1)。
2.6 IIP亚组与CTD-ILD亚组一般资料比较
与IIP亚组比较，CTD-ILD亚组的男性占比和吸烟史比例较低，差异有统计学意义(P<0.05)；两亚组的年龄、高血压病史、糖尿病史、冠心病史比较，差异无统计学意义(P>0.05，表6)。
2.7 IIP亚组与CTD-ILD亚组炎性指标、RDW-CV及血清IL-11、IL-31水平比较
与IIP亚组比较，CTD-ILD亚组患者血清IL-11水平较高，差异有统计学意义(P<0.05)；两亚组WBC、NEUT、RDW-CV和血清CRP、IL-31水平比较，差异无统计学意义(P>0.05，表7)。
2.8 CTD-ILD亚组与IIP亚组血清IL-11水平差异分析
采用修正Poisson回归校正CTD-ILD亚组与IIP亚组性别、吸烟史的差异，结果显示，CTD-ILD亚组血清IL-11水平高于IIP亚组，差异有统计学意义(P<0.05，表8)。
2.9 血清IL-11在CTD-ILD和IIP鉴别诊断中的价值
ROC曲线分析结果显示，血清IL-11在CTD-ILD和IIP鉴别诊断中的AUC为0.727，敏感度为62.5%，特异度为73.3%(P<0.05，图2)。
3 讨论
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3.1 ILD的发病机制
ILD是一组以肺间质炎症和纤维化为基本病变特征的异质性疾病。肺是与外界相通的呼吸器官，正常情况下肺泡上皮凭借出色的修复能力可快速修复受损的结构与功能；当反复的炎症刺激和(或)上皮修复能力低下等因素叠加于遗传易感或衰老个体时，可触发肺泡上皮细胞纤维化的表观遗传学重编程机制[11]，引起成纤维细胞持续激活、过度增殖及细胞外基质分泌增多，导致肺结构损伤、功能丧失及肺组织纤维化的形成。因此，ILD患者在临床上主要表现为进行性加重的呼吸困难、低氧血症及影像学上的双肺弥漫性病变。
3.2 RDW-CV水平在ILD患者中升高且与疾病严重程度相关
RDW-CV作为衡量红细胞大小异质性的指标，早期常被用于血液系统疾病的鉴别诊断；但目前越来越多的证据显示，RDW-CV与机体的炎症状态、缺氧和氧化应激等因素相关[12-13]。CRP是常用的临床炎症指标之一，在炎症反应过程中快速升高，特异性不强，但敏感度较高[14]。本研究结果显示，ILD组血清RDW-CV水平明显高于CAP组和对照组，血清CRP水平明显低于CAP组，ILD患者与CAP患者RDW-CV和CRP水平呈现出一种“相反现象”，考虑ILD患者RDW-CV升高不仅与疾病本身的炎症水平相关，还与其体内组织缺氧有关。究其原因，ILD患者的肺泡上皮损伤和组织缺氧导致机体发生氧化应激，释放大量氧自由基并激活补体系统，使体内的自身抗体或补体吸附在红细胞表面，从而使红细胞体积增大、破坏，导致RDW-CV升高。另外，本研究Spearman相关分析结果显示，ILD组RDW-CV与炎性指标CRP相关性较弱(|r|0.5)，而与组织缺氧指标OI、AaDO2相关性较强(|r|0.5)。这不仅与上述观点一致，也提示RDW-CV有望作为判断ILD严重程度的指标。
3.3 血清IL-11水平在ILD患者中升高
IL-11是gp130/IL-6细胞因子家族中的一员，可与IL-11受体的α亚基[15]结合，然后通过gp130受体激活JAK-STAT3信号通路[16]，进而将信号传递到平滑肌细胞、上皮细胞和成纤维细胞内。这些细胞在IL-11刺激后分泌促炎细胞因子和趋化因子，导致纤维化的发生。Ng等[17]对特发性肺纤维化(idiopathic pulmonary fibrosis，IPF)患者和健康个体的肺组织样本使用的RNA微阵列进行IL-11基因表达分析，并通过免疫组化检测IPF患者肺组织IL-11蛋白的表达水平，发现IPF患者的IL-11表达水平明显高于健康人群。Arai等[18]报道，与健康体检者比较，IPF患者血清IL-11水平明显升高，而单纯血清IL-11水平与IPF疾病严重程度的相关性不明显。本研究中，ILD组血清IL-11水平明显高于对照组，且血清IL-11与OI、AaDO2不相关，与上述研究结果一致。值得注意的是，一项针对IL-11与细菌性肺炎的研究指出，在未感染大肠埃希菌时小鼠肺部IL-11即保持在一定水平，而发生肺部感染后IL-11水平仅略有改变，因此认为IL-11在急性呼吸道感染中并没有突出的作用[19]。本研究发现，与CAP组比较，ILD组血清IL-11水平明显升高；但在炎性指标方面，ILD组与CAP组WBC、NEUT差异不明显，且ILD组血清CRP水平明显低于CAP组，提示ILD患者血清IL-11水平升高可能与感染关系不大，可能更多地与肺间质纤维化本身的病理过程有关。
3.4 血清IL-31水平在ILD患者中升高且与疾病严重程度相关
IL-31作为近年来发现的IL-6细胞因子家族的一员，可与IL-31受体结合，激活JAK-STAT1信号通路[20]，进而将信号传递到免疫细胞、上皮细胞和成纤维细胞。这些细胞在IL-31刺激后分泌促炎细胞因子和趋化因子，导致细胞纤维化的发生。Yombo等[21]在博来霉素诱导的肺纤维化小鼠模型中发现，IL-31可促进细胞纤维化；对IPF患者和健康受试者进行的肺组织切片免疫荧光染色结果显示，IPF患者的IL-31表达水平明显升高。本研究发现，ILD组血清IL-31水平明显高于CAP组和对照组，与上述研究结果一致。本研究还发现，ILD组血清IL-31水平与OI呈负相关，与AaDO2呈正相关，提示IL-31可用于评估ILD的疾病严重程度。此外，本研究ROC曲线分析显示，血清IL-31、IL-11和RDW-CV诊断ILD的价值逐渐降低，三者联合应用的诊断价值明显高于各指标单独应用，提示联合应用RDW-CV和血清IL-11、IL-31可提高ILD的临床诊断效能。
3.5 血清IL-11水平在不同类型的ILD患者中存在差异
本研究依据临床诊断将ILD组分为IIP亚组与CTD-ILD亚组，其中IIP亚组男性占比更高，而CTD-ILD组女性占比更高，这与目前ILD的流行病学调查结果一致[22-23]。本研究在校正上述两组患者的性别及吸烟史后，分析结果显示，CTD-ILD亚组血清IL-11水平明显高于IIP亚组；ROC曲线分析结果显示，血清IL-11鉴别CTD-ILD和IIP的AUC为0.727(95%CI 0.580~0.874)，提示ILD患者血清IL-11水平升高时，更需要警惕CTD-ILD的可能。虽然有临床研究指出，与健康人群比较，血清IL-11在类风湿关节炎、系统性硬化症患者中明显升高，且在合并ILD的患者中升高更明显，但此两项研究未纳入IIP患者以进行不同类型ILD的比较[24-25]。
本研究为单中心小样本研究，未将ILD患者肺功能参数及影像学结果纳入分析，有待将来进行更广泛的前瞻性、多中心临床研究，以进一步验证RDW-CV和血清IL-11、IL-31水平在ILD诊断中的应用价值。
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  • 河北省泛血管疾病重点实验室项目(SZX202306)
  • 河北省政府资助临床医学人才培养项目[翼卫办科教(2021)9号]()
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参考文献 引证文献
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2024年第49卷第11期
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doi: 10.11855/j.issn.0577-7402.0113.2024.0717
  • 接收时间：2024-01-13
  • 首发时间：2025-11-20
  • 出版时间：2024-11-28
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  • 收稿日期：2024-01-13
  • 录用日期：2024-04-28
基金
Project of Hebei Key Laboratory of Panvascular Diseases(SZX202306)
河北省泛血管疾病重点实验室项目(SZX202306)
Talent Training Program on Clinical Medicine Founded by Government of Hebei Province [Ji Health (2021) No.9]()
河北省政府资助临床医学人才培养项目[翼卫办科教(2021)9号]()
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    承德医学院附属医院呼吸与危重症医学科，河北承德 067000

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杨林瀛，E-mail：
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species		 占总种数比例
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total species (%)		 属
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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