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Article(id=1208073006027481250, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208073005197009056, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.05.0486, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1627315200000, receivedDateStr=2021-07-27, revisedDate=null, revisedDateStr=null, acceptedDate=1631635200000, acceptedDateStr=2021-09-15, onlineDate=1765956649546, onlineDateStr=2025-12-17, pubDate=1653667200000, pubDateStr=2022-05-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765956649546, onlineIssueDateStr=2025-12-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765956649546, creator=13701087609, updateTime=1765956649546, updator=13701087609, issue=Issue{id=1208073005197009056, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='5', pageStart='427', pageEnd='532', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1765956649350, creator=13701087609, updateTime=1765956710955, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208073263641633510, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208073005197009056, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208073263641633511, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208073005197009056, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=486, endPage=492, ext={EN=ArticleExt(id=1208073006295916710, articleId=1208073006027481250, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Diagnostic value of fractional exhaled nitric oxide combined with pulmonary function and the proportion of eosinophils in peripheral blood in cough variant asthma, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To explore the diagnostic value of screening cough variant asthma (CVA) by fractional exhaled nitric oxide (FeNO) combined with lung function and the proportion of peripheral blood eosinophils in patients with chronic cough. Methods Two hundred and sixty-seven patients with chronic cough diagnosed in the Respiratory Medicine Clinic of the Affiliated Hospital of North Sichuan Medical College from March 2016 to November 2017 were selected and divided into CVA group (n=60)and non-CVA group (n=207), and 30 healthy physical examiners in the same period served as the control group. All patients and health examiners were tested of FeNO, routine lung function, pulse oscillatory lung function, bronchodiastolic test, peripheral blood eosinophil proportion. Linear correlation was used to analyze the correlation of FeNO value to pulmonary function and the proportion of peripheral blood eosinophils in patients with CVA. Results The FeNO value and the proportion of peripheral blood eosinophils were obviously higher in CVA group than in non-CVA group and control group [45(34.3, 74.8) μg/L vs. 14(10.0,19.0) μg/L and 10(7.0, 18.0) μg/L, P<0.001; 5.9%±2.3% vs. 2.3%±1.6% and 2.6%±1.3%, P<0.001]. The MEF75pre, MEF50pre,MEF25pre, FEV1pre, PEFpre and MMEFpre were significantly lower in CVA group than the normal range and those in non-CVA group and control group (P<0.01), and the R20pre was significantly higher in CVA group (137.6%±40.7%) than in non-CVA group(127.5%±40.1%) and control group (128.5%±45.4%) (P<0.05). The improvement rates of FEV1, MEF75, MEF50, MEF25, MMEF were significantly higher after using bronchodilator in CVA group than in non-CVA group and control group (P<0.001). Linear correlation results showed that the FeNO value in CVA group showed no correlation with FEV1pre, FEV1/FVC, PEFpre, MEF75pre,Z5, X5, R5pre, R20pre, and Fres (P>0.05), while showed negative correlation with MEF50pre, MEF25pre and MMEFpre (P<0.05),and positive correlation with peripheral blood eosinophil proportion (r=0.863, P<0.001). Conclusion FeNO, pulmonary function and the proportion of peripheral blood eosinophils can be used as the index of screening CVA in patients with chronic cough. The combined effect of the three index may be better.

, correspAuthors=Xiao-Ju Chen, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 探讨呼出气一氧化氮(FeNO)联合肺功能及外周血嗜酸性粒细胞比例检测在咳嗽变异性哮喘(CVA)诊断中的价值。方法 选取2016年3月－2017年11月于川北医学院附属医院呼吸内科门诊诊断为慢性咳嗽的患者267例[分为CVA组(n=60)与非咳嗽变异性哮喘组(非CVA组，n=207)]，另选择同期该院健康体检者30名作为对照组。对所有受试者行FeNO、常规肺功能、脉冲振荡肺功能、支气管舒张试验、外周血嗜酸性粒细胞比例检测，并分析CVA患者FeNO值与肺功能及外周血嗜酸性粒细胞比例的相关性。结果 CVA组FeNO值、外周血嗜酸性粒细胞比例明显高于非CVA组及对照组[45(34.3，74.8) μg/L vs. 14(10.0，19.0) μg/L vs.10(7.0，18.0) μg/L，P<0.001；5.9%±2.3% vs. 2.3%±1.6% vs. 2.6%±1.3%，P<0.001]。CVA组MEF75pre、MEF50pre、MEF25pre、FEV1pre、PEFpre和MMEFpre均明显低于正常范围，且均低于非CVA组及对照组(P<0.01)，而R20pre较非CVA组和对照组明显增高(137.6%±40.7% vs. 127.5%±40.1% vs.128.5%±45.4%，P<0.05)。使用支气管扩张剂后CVA组FEV1、MEF75、MEF50、MEF25及MMEF的改善率较非CVA组和对照组明显增高(P<0.001)。直线相关分析显示，CVA组FeNO值与FEV1pre、FEV1/FVC、PEFpre、MEF75pre、Z5、X5、R5pre、R20pre、Fres无相关性(P>0.05)，而与MEF50pre、MEF25pre、MMEFpre呈负相关(P<0.05)，与外周血嗜酸性粒细胞比例呈正相关(r=0.863，P<0.001)。结论 FeNO、肺功能及外周血嗜酸性粒细胞比例检测均可作为慢性咳嗽患者筛选CVA的指标，三者联合效果更好。

, correspAuthors=陈小菊, authorNote=null, correspAuthorsNote=
陈小菊，E-mail：
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蒋国路，硕士研究生，住院医师，主要从事慢性阻塞性肺疾病、哮喘、肺癌的基础与临床研究

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蒋国路，硕士研究生，住院医师，主要从事慢性阻塞性肺疾病、哮喘、肺癌的基础与临床研究

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蒋国路，硕士研究生，住院医师，主要从事慢性阻塞性肺疾病、哮喘、肺癌的基础与临床研究

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Med Sci Monit, 2019, 25: 3832-3838., articleTitle=Fractional exhaled nitric oxide(FeNO) combined with pulmonary function parameters shows increased sensitivity and specificity for the diagnosis of cough variant asthma in children, refAbstract=null), Reference(id=1208073018073522799, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, doi=null, pmid=null, pmcid=null, year=2021, volume=2021, issue=null, pageStart=9954411, pageEnd=null, url=null, language=null, rfNumber=[30], rfOrder=36, authorNames=Wang Y, Zhao L, Chen F, journalName=Can Respir J, refType=null, unstructuredReference=Wang Y, Zhao L, Chen F, et al. Diagnostic value of fractional exhaled nitric oxide and small airway function in differentiating cough-variant asthma from typical asthma[J]. Can Respir J, 2021, 2021: 9954411., articleTitle=Diagnostic value of fractional exhaled nitric oxide and small airway function in differentiating cough-variant asthma from typical asthma, refAbstract=null), Reference(id=1208073018190963318, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, doi=null, pmid=null, pmcid=null, year=2021, volume=14, issue=null, pageStart=1065, pageEnd=1073, url=null, language=null, rfNumber=[31], rfOrder=37, authorNames=Chen L, Wu L, Lu D, journalName=J Asthma Allergy, refType=null, unstructuredReference=Chen L, Wu L, Lu D, et al. The value of fractional exhaled nitric oxide and impulse oscillometric and spirometric parameters for predicting bronchial hyperresponsiveness in adults with chronic cough[J]. 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Comparison of the general data among the three groups

, figureFileSmall=null, figureFileBig=null, tableContent=
项目对照组(n=30)非CVA组(n=207)CVA组(n=60)χ2/FP
性别[例(%)]   1.2400.070
 男14(46.7)99(47.8)29(48.3)
 女16(53.3)108(52.2)31(51.7)
年龄(岁，$\bar{x}±s$)48.8±13.346.2±12.547.5±13.10.6450.520
体重指数(kg/m2, $\bar{x}±s$)25.5±3.124.8±3.424.9±4.00.5680.567
吸烟指数($\bar{x}±s$)152.0±19.7147.0±23.1158.0±20.00.6230.510
), ArticleFig(id=1208073011970810197, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=CN, label=表1, caption=

三组一般资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目对照组(n=30)非CVA组(n=207)CVA组(n=60)χ2/FP
性别[例(%)]   1.2400.070
 男14(46.7)99(47.8)29(48.3)
 女16(53.3)108(52.2)31(51.7)
年龄(岁，$\bar{x}±s$)48.8±13.346.2±12.547.5±13.10.6450.520
体重指数(kg/m2, $\bar{x}±s$)25.5±3.124.8±3.424.9±4.00.5680.567
吸烟指数($\bar{x}±s$)152.0±19.7147.0±23.1158.0±20.00.6230.510
), ArticleFig(id=1208073012100833629, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=EN, label=Tab.2, caption=

Comparison of the lung function indexes among the three groups (%, $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标对照组(n=30)非CVA组(n=207)CVA组(n=60)FP
FEV1pre101.0±15.0103.2±15.288.0±23.6(1)(2)18.3050.000
FEV1/FVC75.0±10.076.9±8.371.8±11.5(1)(2)7.2380.001
PEFpre74.0±22.880.9±24.568.4±20.6(1)(2)6.9480.001
MEF75pre74.5±26.780.8±25.566.8±28.8(1)(2)6.7220.001
MEF50pre70.1±31.076.0±27.258.8±31.9(1)(2)8.5170.000
MEF25pre59.5±30.160.8±23.948.3±24.2(1)(2)6.0000.003
MMEFpre62.9±28.667.4±23.646.8±22.5(1)(2)17.2350.000
), ArticleFig(id=1208073012184719719, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=CN, label=表2, caption=

三组常规肺功能指标比较(%, $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标对照组(n=30)非CVA组(n=207)CVA组(n=60)FP
FEV1pre101.0±15.0103.2±15.288.0±23.6(1)(2)18.3050.000
FEV1/FVC75.0±10.076.9±8.371.8±11.5(1)(2)7.2380.001
PEFpre74.0±22.880.9±24.568.4±20.6(1)(2)6.9480.001
MEF75pre74.5±26.780.8±25.566.8±28.8(1)(2)6.7220.001
MEF50pre70.1±31.076.0±27.258.8±31.9(1)(2)8.5170.000
MEF25pre59.5±30.160.8±23.948.3±24.2(1)(2)6.0000.003
MMEFpre62.9±28.667.4±23.646.8±22.5(1)(2)17.2350.000
), ArticleFig(id=1208073012365074801, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=EN, label=Tab.3, caption=

Comparison of the pulse oscillation pulmonary function index among the three groups ($\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标对照组(n=30)非CVA组(n=207)CVA组(n=60)FP
Z5[cmH2O/(L.s)]6.9±5.66.0±3.65.5±3.21.4710.231
R5pre(%)155.3±62.7150.8±64.0147.1±60.00.1500.861
R20pre(%)128.5±45.4127.5±40.1137.6±40.7(1)(2)1.3360.025
X5[cmH2O/(L.s)]–2.1±2.6–2.1±2.5–2.2±2.72.2990.102
Fres(L/s)27.5±30.820.2±15.818.7±7.13.0290.482
), ArticleFig(id=1208073012516069756, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=CN, label=表3, caption=

三组脉冲振荡肺功能指标比较($\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标对照组(n=30)非CVA组(n=207)CVA组(n=60)FP
Z5[cmH2O/(L.s)]6.9±5.66.0±3.65.5±3.21.4710.231
R5pre(%)155.3±62.7150.8±64.0147.1±60.00.1500.861
R20pre(%)128.5±45.4127.5±40.1137.6±40.7(1)(2)1.3360.025
X5[cmH2O/(L.s)]–2.1±2.6–2.1±2.5–2.2±2.72.2990.102
Fres(L/s)27.5±30.820.2±15.818.7±7.13.0290.482
), ArticleFig(id=1208073012658676100, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=EN, label=Tab.4, caption=

Comparison of the improvement rates of MEF75, MEF50, MEF25, MMEF FEV1 among the three groups (%, $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标对照组(n=30)非CVA组(n=207)CVA组(n=60)FP
MEF75改善率14.5±10.815.4±10.632.2±14.6(1)(2)52.1820.000
MEF50改善率17.7±10.617.4±11.734.8±16.9(1)(2)44.1420.000
MEF25改善率20.0±10.120.1±13.235.7±12.2(1)(2)35.7000.000
MMEF改善率17.8±8.317.2±10.632.6±10.9(1)(2)51.5060.000
FEV1改善率17.2±9.117.6±10.133.5±11.8(1)(2)50.4510.000
), ArticleFig(id=1208073012801282442, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208073006027481250, language=CN, label=表4, caption=

三组MEF75、MEF50、MEF25、MMEF及FEV1的改善率比较(%, $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标对照组(n=30)非CVA组(n=207)CVA组(n=60)FP
MEF75改善率14.5±10.815.4±10.632.2±14.6(1)(2)52.1820.000
MEF50改善率17.7±10.617.4±11.734.8±16.9(1)(2)44.1420.000
MEF25改善率20.0±10.120.1±13.235.7±12.2(1)(2)35.7000.000
MMEF改善率17.8±8.317.2±10.632.6±10.9(1)(2)51.5060.000
FEV1改善率17.2±9.117.6±10.133.5±11.8(1)(2)50.4510.000
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呼出气一氧化氮联合肺功能及外周血嗜酸性粒细胞比例检测在咳嗽变异性哮喘诊断中的价值
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蒋国路 1 , 陈小菊 2, * , 蒋莉 1 , 刘琴 1 , 李奉玲 3
解放军医学杂志 | 临床研究 2022,47(5): 486-492
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解放军医学杂志 | 临床研究 2022, 47(5): 486-492
呼出气一氧化氮联合肺功能及外周血嗜酸性粒细胞比例检测在咳嗽变异性哮喘诊断中的价值
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蒋国路1, 陈小菊2, * , 蒋莉1, 刘琴1, 李奉玲3
作者信息
  • 1川北医学院附属医院呼吸与危重症医学科，四川南充 637000
  • 2成都大学附属医院呼吸内科，成都 610000
  • 3川北医学院附属医院产科，四川南充 637000

    • 蒋国路，硕士研究生，住院医师，主要从事慢性阻塞性肺疾病、哮喘、肺癌的基础与临床研究

通讯作者:

陈小菊，E-mail：
Diagnostic value of fractional exhaled nitric oxide combined with pulmonary function and the proportion of eosinophils in peripheral blood in cough variant asthma
Guo-Lu Jiang1, Xiao-Ju Chen2, * , Li Jiang1, Qin Liu1, Feng-Ling Li3
Affiliations
  • 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China
  • 2Department of Respiratory, Affiliated Hospital of Chengdu University, Chengdu 610000, China
  • 3Department of Obstetrics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China
出版时间: 2022-05-28 doi: 10.11855/j.issn.0577-7402.2022.05.0486
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摘要
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目的 探讨呼出气一氧化氮(FeNO)联合肺功能及外周血嗜酸性粒细胞比例检测在咳嗽变异性哮喘(CVA)诊断中的价值。方法 选取2016年3月－2017年11月于川北医学院附属医院呼吸内科门诊诊断为慢性咳嗽的患者267例[分为CVA组(n=60)与非咳嗽变异性哮喘组(非CVA组，n=207)]，另选择同期该院健康体检者30名作为对照组。对所有受试者行FeNO、常规肺功能、脉冲振荡肺功能、支气管舒张试验、外周血嗜酸性粒细胞比例检测，并分析CVA患者FeNO值与肺功能及外周血嗜酸性粒细胞比例的相关性。结果 CVA组FeNO值、外周血嗜酸性粒细胞比例明显高于非CVA组及对照组[45(34.3，74.8) μg/L vs. 14(10.0，19.0) μg/L vs.10(7.0，18.0) μg/L，P<0.001；5.9%±2.3% vs. 2.3%±1.6% vs. 2.6%±1.3%，P<0.001]。CVA组MEF75pre、MEF50pre、MEF25pre、FEV1pre、PEFpre和MMEFpre均明显低于正常范围，且均低于非CVA组及对照组(P<0.01)，而R20pre较非CVA组和对照组明显增高(137.6%±40.7% vs. 127.5%±40.1% vs.128.5%±45.4%，P<0.05)。使用支气管扩张剂后CVA组FEV1、MEF75、MEF50、MEF25及MMEF的改善率较非CVA组和对照组明显增高(P<0.001)。直线相关分析显示，CVA组FeNO值与FEV1pre、FEV1/FVC、PEFpre、MEF75pre、Z5、X5、R5pre、R20pre、Fres无相关性(P>0.05)，而与MEF50pre、MEF25pre、MMEFpre呈负相关(P<0.05)，与外周血嗜酸性粒细胞比例呈正相关(r=0.863，P<0.001)。结论 FeNO、肺功能及外周血嗜酸性粒细胞比例检测均可作为慢性咳嗽患者筛选CVA的指标，三者联合效果更好。

慢性咳嗽  /  咳嗽变异性哮喘  /  呼出气一氧化氮  /  肺功能  /  外周血嗜酸性粒细胞比例

Objective To explore the diagnostic value of screening cough variant asthma (CVA) by fractional exhaled nitric oxide (FeNO) combined with lung function and the proportion of peripheral blood eosinophils in patients with chronic cough. Methods Two hundred and sixty-seven patients with chronic cough diagnosed in the Respiratory Medicine Clinic of the Affiliated Hospital of North Sichuan Medical College from March 2016 to November 2017 were selected and divided into CVA group (n=60)and non-CVA group (n=207), and 30 healthy physical examiners in the same period served as the control group. All patients and health examiners were tested of FeNO, routine lung function, pulse oscillatory lung function, bronchodiastolic test, peripheral blood eosinophil proportion. Linear correlation was used to analyze the correlation of FeNO value to pulmonary function and the proportion of peripheral blood eosinophils in patients with CVA. Results The FeNO value and the proportion of peripheral blood eosinophils were obviously higher in CVA group than in non-CVA group and control group [45(34.3, 74.8) μg/L vs. 14(10.0,19.0) μg/L and 10(7.0, 18.0) μg/L, P<0.001; 5.9%±2.3% vs. 2.3%±1.6% and 2.6%±1.3%, P<0.001]. The MEF75pre, MEF50pre,MEF25pre, FEV1pre, PEFpre and MMEFpre were significantly lower in CVA group than the normal range and those in non-CVA group and control group (P<0.01), and the R20pre was significantly higher in CVA group (137.6%±40.7%) than in non-CVA group(127.5%±40.1%) and control group (128.5%±45.4%) (P<0.05). The improvement rates of FEV1, MEF75, MEF50, MEF25, MMEF were significantly higher after using bronchodilator in CVA group than in non-CVA group and control group (P<0.001). Linear correlation results showed that the FeNO value in CVA group showed no correlation with FEV1pre, FEV1/FVC, PEFpre, MEF75pre,Z5, X5, R5pre, R20pre, and Fres (P>0.05), while showed negative correlation with MEF50pre, MEF25pre and MMEFpre (P<0.05),and positive correlation with peripheral blood eosinophil proportion (r=0.863, P<0.001). Conclusion FeNO, pulmonary function and the proportion of peripheral blood eosinophils can be used as the index of screening CVA in patients with chronic cough. The combined effect of the three index may be better.

chronic cough  /  cough variant asthma  /  fractional exhaled nitric oxide  /  lung function  /  peripheral blood eosinophil proportion
蒋国路, 陈小菊, 蒋莉, 刘琴, 李奉玲. 呼出气一氧化氮联合肺功能及外周血嗜酸性粒细胞比例检测在咳嗽变异性哮喘诊断中的价值. 解放军医学杂志, 2022 , 47 (5) : 486 -492 . DOI: 10.11855/j.issn.0577-7402.2022.05.0486
Guo-Lu Jiang, Xiao-Ju Chen, Li Jiang, Qin Liu, Feng-Ling Li. Diagnostic value of fractional exhaled nitric oxide combined with pulmonary function and the proportion of eosinophils in peripheral blood in cough variant asthma[J]. Medical Journal of Chinese People’s Liberation Army, 2022 , 47 (5) : 486 -492 . DOI: 10.11855/j.issn.0577-7402.2022.05.0486
正文
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咳嗽是呼吸内科门诊最常见的临床症状之一[1]，其病因复杂，尤其是胸部影像正常的慢性咳嗽。慢性咳嗽常见的病因有上气道咳嗽综合征(upper airway cough syndrome，UACS)、嗜酸性粒细胞支气管炎(eosinophilic bronchitis，EB)、胃食管反流性咳嗽(gastroesophageal reflux-related cough，GERC)、变应性咳嗽(atopic cough，AC)、咳嗽变异性哮喘(cough variant asthma，CVA)等[2]。国内统计数据显示，CVA是慢性咳嗽最常见的病因之一，约占慢性咳嗽的1/3[3]。CVA是一种以持续存在的慢性气道炎症及气道高反应性为特征的慢性肺部炎症性疾病[4]，其发病机制复杂，涉及多个环节，具体发病机制尚不明确。长期慢性气道炎症与CVA的发生发展密切相关，CVA气道炎症以嗜酸性粒细胞为主，且嗜酸性粒细胞炎症程度与病情严重程度呈正相关[5]，故检测、评估气道嗜酸性粒细胞炎症对控制CVA进展具有重要的临床意义。
呼出气一氧化氮(fractional exhaled nitric oxide，FeNO)检测是近年来发现的一种新的气道炎症检测方法，具有简便易行、重复性高且无创高效的特点。FeNO主要反映气道嗜酸性粒细胞炎症程度，其水平与嗜酸性粒细胞炎症程度呈正相关，对FeNO进行监测可评估气道嗜酸性粒细胞炎症控制情况[6]。2011年美国胸科协会(American Thoracic Society，ATS)颁布的《FeNO临床应用指南》指出，FeNO检测可用于哮喘的诊断、治疗、监测、管理等多个方面[7]。对于慢性咳嗽患者，肺功能检查是诊断CVA的金标准，但因其操作复杂、费时费力，且存在一定的假阳性及假阴性率，临床应用受到一定限制。哮喘作为一种异质性疾病，病变主要累及大气道和小气道，为此，本研究旨在探讨FeNO联合肺功能和外周血嗜酸性粒细胞比例检测在CVA诊断中的价值。
1 资料与方法
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1.1 研究对象
选取2016年3月－2017年11月就诊于川北医学院附属医院呼吸内科门诊的慢性咳嗽患者267例，其中男128例，女139例；年龄(46.5±12.6)岁。纳入标准：(1)年龄14~75岁；(2)慢性咳嗽超过8周，无咳脓痰、发热、痰中带血、气促、喘息等症状；(3)肺部影像学(X线或CT)检查未见异常；(4)非吸烟者或已戒烟6个月以上；(5)既往无哮喘或其他慢性肺部疾病，如慢性支气管炎、慢性阻塞性肺疾病、支气管扩张、肺纤维化等；(6)能配合相关检查。排除标准：(1)有精神疾病和意识障碍；(2)伴有严重心脑血管疾病、糖尿病、肝肾功能损害、身体极度虚弱的患者；(3)就诊前4周有急性上、下呼吸道感染；(4)近1个月内使用过糖皮质激素、孟鲁司特或2 d前使用过扩张支气管的药物；(5)FeNO测定前2 h食用含氮量高的食物如香肠、动物内脏等。
另选择同期该院门诊健康体检者30名作为对照，其中男14名，女16名；年龄(44.6±13.1)岁。纳入标准：(1)年龄14~75岁；(2)非吸烟者或已戒烟6个月以上；(3)近2个月无咳嗽、咳脓痰、发热、痰中带血、气促、喘息等症状；(4)无心、肝、肾、消化道、呼吸、血液、神经系统等疾病及相关病史；(5)体格检查未发现有临床意义的阳性体征；(6)能配合相关检查。排除标准：(1)妊娠或哺乳期女性；(2)精神或躯体残疾者；(3)近1个月内使用过糖皮质激素、孟鲁司特或2 d前使用过扩张支气管的药物；(4)FeNO测定前2 h食用含氮量高的食物如香肠、动物内脏等。本研究通过川北医学院伦理委员会审批(2016ERA021)。所有研究对象均签署知情同意书。
1.2 方法
1.2.1 FeNO检测
按照2005年欧洲呼吸协会(European Respiratory Society，ERS)、ATS推荐的成人FeNO标准化测定指南[8]，采用Exhaled NO分析仪(NIOX，瑞典尼尔斯公司)测定FeNO。受试者安静休息5 min，排空肺部气体，然后用力吸气直到肺总量，以50 ml/s恒定流速平稳缓慢呼气10 s以上。
1.2.2 外周血常规检查
选择前臂肘正中静脉为穿刺血管，抽取2~3 ml血液，采用全自动血液分析仪(BC-6900，深圳迈瑞医疗电子股份有限公司)进行检测，记录外周血嗜酸性粒细胞比例。
1.2.3 常规肺功能检查
采用Masterscreen型肺功能测定仪(德国耶格公司)进行常规肺功能检查，检查指标包括第一秒用力呼气容积占预计值的百分比(FEV1pre)、FEV1/用力肺活量(FVC)、最大呼气流速占预计值的百分比(PEFpre)、最大呼气中段流速占预计值的百分比(MMEFpre)、75%肺活量时最大呼气流速占预计值的百分比(MEF75pre)、50%肺活量时最大呼气流速占预计值的百分比(MEF50pre)、25%肺活量时最大呼气流速占预计值的百分比(MEF25pre)等。受试者至少测试2次，2次之间误差<5%，并且保持流量-容积曲线无异常，取最佳值。
1.2.4 脉冲振荡肺功能检测
采用Masterscreen型肺功能测定仪进行脉冲振荡肺功能测定，测定指标包括呼吸总阻抗(Z5)、总气道阻力(R5)、中心气道阻力(R20)、外周弹性阻力(X5)和共振频率(Fres)等。嘱受试者全身放松，自主用口呼吸平稳后开始记录，记录至少3个稳定的呼吸周期，时间60 s，取最佳值。
1.2.5 支气管舒张试验
采用Masterscreen型肺功能测定仪进行支气管舒张试验，在受试者完成常规肺功能和脉冲振荡肺功能检查后，通过喷射雾化器(AXD-302，广州爱芯达电子有限公司)吸入沙丁胺醇溶液400 μg，吸入药物后15 min复查肺功能。记录吸入药物后的肺功能指标，包括FEV1改善率、MMEF改善率、MEF75改善率、MEF50改善率、MEF25改善率。结果判断：舒张试验阳性标准为用药后FEV1较用药前增高12%或以上，且其绝对值增加200 ml或以上。
1.2.6 CVA诊断标准及分组
结合《咳嗽的诊断与治疗指南(2015)》[9]中的诊断标准，制定本研究CVA的诊断标准：(1)慢性咳嗽(超过8周)，多呈发作性，常伴明显的夜间刺激性咳嗽，多与接触变应原、冷空气、物理化学刺激有关；(2)无明显肺部阳性体征；(3)支气管舒张试验阳性；(4)支气管扩张剂治疗有效；(5)使用抗生素或止咳药物治疗无效；(6)排除其他原因引起的慢性咳嗽。依据上述标准将慢性咳嗽患者分为CVA组(n=60)与非咳嗽变异性哮喘组(非CVA组，n=207)。
1.2.7 CVA患者FeNO值与肺功能指标、外周血嗜酸性粒细胞比例的相关性分析
采用直线相关分析CVA患者FeNO值与肺功能指标、外周血嗜酸性粒细胞比例的相关性。
1.3 统计学处理
采用SPSS 17.0软件进行统计分析。符合正态分布的计量资料以$\bar{x}±s$表示，不符合正态分布的计量资料以M(Q1，Q3)表示，多组间比较采用非参数检验，进一步两两比较采用K-S法；计数资料以例(%)表示。P<0.05为差异有统计学意义。
2 结果
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2.1 一般资料
共纳入慢性咳嗽患者267例，其中CVA患者60例[男29例，女31例，年龄(47.5±13.1)岁]，非CVA患者207例[男99例，女108例，年龄(46.2±12.5)岁]。对照组、CVA组、非CVA组性别、年龄等一般资料比较差异无统计学意义(P>0.05)，有可比性(表1)。
2.2 三组FeNO值、外周血嗜酸性粒细胞比例比较
FeNO检测及血常规检查结果显示，CVA组、非CVA组和对照组的FeNO值分别为45(34.3，74.8) μg/L、14(10.0，19.0) μg/L、10(7.0，18.0) μg/L，外周血嗜酸性粒细胞比例分别为5.9%±2.3%、2.3%±1.6%、2.6%±1.3%。CVA组FeNO值、外周血嗜酸性粒细胞比例明显高于非CVA组和对照组，差异有统计学意义(P<0.001)，但非CVA组与对照组差异无统计学意义(P>0.05)。
2.3 三组常规肺功能指标比较
常规肺功能检查结果显示，CVA组FEV1pre、FEV1/FVC、PEFpre、MEF75pre、MEF50pre、MEF25pre、MMEFpre均明显低于非CVA组和对照组，差异有统计学意义(P<0.01)。其中CVA组MEF75pre、MEF50pre、MEF25pre、FEV1pre、PEFpre和MMEFpre均明显低于正常范围下限，FEV1/FVC稍低于正常范围下限；非CVA组MEF50pre、FEV1/FVC、MEF25pre和MMEFpre均低于正常范围下限，而FEV1pre、PEFpre和MEF75pre均在正常范围内(表2)。
2.4 三组脉冲振荡肺功能指标比较
脉冲振荡肺功能测定结果显示，CVA组、非CVA组和对照组Z5、R5pre、X5、Fres比较差异均无统计学意义(P>0.05)；CVA组R20pre明显高于非CVA组和对照组，差异有统计学意义(P<0.05，表3)。
2.5 三组使用支气管扩张剂后MEF75、MEF50、MEF25、MMEF及FEV1的改善率比较
CVA患者持续雾化吸入支气管扩张剂后，除代表大气道功能指标的FEV1较用药前明显增高(P<0.001)，代表小气道功能的指标MEF75、MEF50、MEF25、MMEF也较用药前明显增高(P<0.001)。支气管舒张试验结果显示，CVA组患者用药后FEV1、MEF75、MEF50、MEF25及MMEF的改善率均在30%以上，且明显高于非CVA组和对照组的改善率，差异有统计学意义(P<0.001，表4)。
2.6 CVA患者FeNO值与肺功能指标、外周血嗜酸性粒细胞比例的相关性
直线相关分析结果显示，CVA患者FeNO值与FEV1pre、FEV1/FVC、PEFpre、MEF75pre无明显相关性(r=–0.210、–0.020、0.007、–0.101，P>0.05)，而与MEF50pre、MEF25pre、MMEFpre呈明显负相关(r=–0.310、–0.277、–0.270，P<0.05)，与外周血嗜酸性粒细胞比例呈明显正相关(r=0.863，P<0.001)。CVA患者FeNO值与Z5、X5、R5pre、R20pre、Fres无明显相关性(r=–0.036、0.004、–0.079、–0.052、–0.128，P>0.05)。
3 讨论
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CVA是由多种炎性细胞及炎性介质参与的慢性气道炎症性疾病，其特征性改变是可逆性气流受限和气道高反应性[10]，目前诊断CVA的方法有支气管激发试验、支气管舒张试验和PEF日变异率检测等肺功能检查，但这些方法均有一定的局限性。本研究纳入267例慢性咳嗽患者，评估FeNO联合肺功能及外周血嗜酸性粒细胞比例检测在CVA中的诊断价值。
本研究结果显示，CVA组FeNO值明显高于非CVA组及对照组(P<0.001)，与既往研究结果一致[11-12]。张永明等[13]的研究纳入了106例慢性咳嗽患者，分析FeNO对慢性咳嗽病因的诊断价值，结果显示，CVA组(采用支气管激发试验或舒张试验诊断)FeNO值为(54±21) μg/L，非CVA组为(21±10) μg/L，本研究中CVA组(单纯采用支气管舒张试验诊断)FeNO值为45(34.3，74.8) μg/L，非CVA组为14(10.0，19.0) μg/L，两项研究中CVA组FeNO值均明显高于非CVA组。FeNO值增高也见于EB患者，张永明等[13]的研究发现，EB患者的FeNO值[(34±17) μg/L]明显高于除CVA、EB外的其他慢性咳嗽患者，但明显低于CVA患者，进一步分析发现，以FeNO≥40 μg/L为CVA的诊断标准，其敏感度为75%、特异度为86%、准确度为81%、阳性预测值为77%、阴性预测值为86%。结合近几年其他类似研究的结果[14-16]，提示FeNO在CVA诊断中具有较高的临床价值。
3.1 肺功能与CVA的关系
本研究发现，CVA组肺功能各指标(FEV1pre、FEV1/FVC、PEFpre、MEF75pre、MEF50pre、MEF25pre、MMEFpre)均明显低于非CVA组和对照组(P<0.01)；其中CVA组MEF75pre、MEF50pre、MEF25pre、FEV1pre、PEFpre和MMEFpre均明显低于正常范围下限，F E V1/F VC稍低于正常范围下限；非C VA组MEF50pre、FEV1/FVC、MEF25pre和MMEFpre均低于正常范围下限，而FEV1pre、PEFpre和MEF75pre在正常范围内。CVA组患者大小气道功能指标较非CVA组均有下降，两组患者的大气道功能指标(FEV1)虽有差别，但均接近正常范围，而CVA组患者的小气道功能指标(MEF75、MEF50、MEF25、MMEF)明显低于正常范围下限，提示CVA患者大气道通气功能受到的影响较小，而小气道通气功能出现明显下降。这与孙晓远[17]的研究结果一致，该研究以支气管激发试验阳性为CVA的诊断标准，发现CVA组FEV1/FVC、MMEF、MEF75、MEF50及MEF25均低于非CVA组，但CVA组的FEV1/FVC在正常范围内，而MMEF、MEF75、MEF50则明显低于正常范围下限。Chen等[18]收集在中山大学附属第一医院接受气道高反应性(bronchial hyperresponsiveness，BHR)及FeNO检测的慢性咳嗽患者，以BHR阳性为CVA的诊断标准，筛选出150例CVA患者及300例非CVA患者，发现两组FEV1pre、FEV1/FVC、PEFpre无明显差异，MEF50、MEF25、MMEF存在明显差异。以上研究结果表明，CVA气流受限主要累及小气道，大气道通气功能基本正常，因此，慢性咳嗽患者小气道功能下降对早期诊断CVA有较高的参考价值。
本研究发现，CVA患者除了反映大气道功能的指标FEV1较用药前明显增高，反映小气道功能的指标MEF75、MEF50、MEF25、MMEF也较用药前明显增高；CVA患者使用支气管扩张剂后MEF75、MEF50、MEF25及MMEF的改善率较非CVA患者明显增高，且均在30%以上，提示使用支气管扩张剂后，CVA患者的小气道气流阻塞改善明显，且小气道功能较大气道功能下降早，因此，临床上可将小气道功能指标改善率用于诊断CVA，以降低CVA的漏诊率。但MEF75、MEF50、MEF25及MMEF的改善率达到何种程度才能诊断为CVA，尚需通过大样本、多中心的临床研究进一步探讨。
脉冲振荡肺功能是判断气道阻力的敏感性指标。本研究发现，CVA组与非CVA组和对照组的Z5、R5pre、X5、Fres无明显差异(P>0.05)，而CVA组R20pre较非CVA组和对照组明显升高(P<0.05)。R20pre是反映中心气道阻力的指标，其升高提示CVA患者中心气道阻力高于非CVA患者。这与李珊珊等[19]的研究结果类似，该研究中CVA患者的R20、R20pre均高于非CVA患者，但R5、R5pre也高于非CVA患者，而本研究中两组患者的R5pre无明显差异，这可能与两项研究采用不同的肺功能检查方法诊断CVA及样本量差异较大有关。两项研究中CVA患者的R20pre均较非CVA患者明显升高，提示R20pre对临床鉴别CVA与非CVA具有一定的参考价值。
本研究中，CVA组患者外周血嗜酸性粒细胞比例明显高于非CVA组和对照组(P<0.001)。有研究发现，嗜酸性粒细胞在CVA患者中表达增加，参与了CVA的发生[20-21]。提示外周血嗜酸性粒细胞增加结合小气道功能下降、R20pre增高以及FeNO值明显高于正常范围上限等综合指标可提高CVA诊断的阳性率。
3.2 FeNO值与外周血嗜酸性粒细胞比例、肺功能的相关性
本研究发现，CVA患者FeNO值与外周血嗜酸性粒细胞比例呈正相关(r=0.863，P<0.001)，与既往研究结果一致[22-23]，进一步证实了FeNO主要反映嗜酸性粒细胞炎症。2017年全球哮喘防治创议(Global Initiative for Asthma，GINA)指南指出，FeNO和外周血嗜酸性粒细胞均为哮喘急性发作的独立预测因子，二者的增高均提示短期内哮喘急性发作的可能性大[24]。定期对二者进行联合检测有助于更准确地监测气道嗜酸性粒细胞炎症，预测哮喘急性发作，以及评估对包括CVA在内的哮喘的治疗效果。
本研究发现，CVA患者FeNO值与小气道功能指标MEF50pre、MEF25pre、MMEFpre均呈负相关(P<0.05)，与Chen等[18]的研究结果一致，提示气道嗜酸性粒细胞炎症与早期小气道功能下降存在一定相关性。此外，CVA患者FeNO值与大气道功能指标FEV1pre、FEV1/FVC、PEFpre无明显相关性(P>0.05)，表明气道嗜酸性粒细胞炎症程度与大气道阻塞的程度并不同步，二者从不同的角度反映了CVA的病情，故在CVA的诊断中FeNO检测尚不能取代传统的支气管激发试验及舒张试验等检查方法，但可用于CVA辅助诊断及与其他呼吸道疾病的鉴别。目前有关CVA患者FeNO值与大小气道功能的相关性研究较少，且多项研究结果并不一致，存在较大争议[25-30]，推测其原因可能是：(1)哮喘的气道炎症分为不同细胞类型，FeNO值在嗜酸性粒细胞型哮喘中升高，而在其他细胞类型中正常甚至偏低，故可能因为各研究纳入患者气道炎症类型的比例存在差异，造成FeNO值高低不一，从而导致FeNO值与大小气道功能的相关性存在差异，最终使研究结果不一致。(2)各研究纳入的哮喘患者病情严重程度不一致也可能导致研究结果不一致。故FeNO值与CVA患者大小气道功能的相关性有待进一步研究证实。
本研究发现，CVA患者的FeNO值与Z5、X5、R5pre、R20pre、Fres无明显相关性(P>0.05)，与Chen等[31]的研究结果一致，表明气道嗜酸性粒细胞炎症程度与气道阻抗大小无关，FeNO检测尚无法取代脉冲振荡肺功能检测用于评估气道阻力。临床上可考虑联合FeNO、气道阻力等检查在慢性咳嗽患者中鉴别CVA，以提高诊断率及评估治疗效果。
综上所述，本研究结果表明，小气道气流受限是CVA的重要特征，FeNO联合外周血嗜酸性粒细胞比例、小气道功能指标和肺阻抗检测有助于CVA的诊断。采用FeNO联合肺功能及外周血嗜酸性粒细胞比例检测对CVA患者进行气道评估，可较全面地了解其气道炎症及阻塞情况，制定更合理的CVA控制方案，提高CVA诊治精准度。但本研究存在一定的局限性：(1)由于支气管激发试验有诱发哮喘急性发作的可能，以及部分门诊患者难以配合等原因，本研究未行支气管激发试验用于CVA的诊断，故存在一定的漏诊率；(2)未监测CVA治疗后FeNO、肺功能及外周血嗜酸性粒细胞比例的变化情况，有待在今后的研究中进一步完善。
基金
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  • 南充市科技局应用技术研究与开发专项项目(20YFZJ0100)
  • 川北医学院2020年度校级科研发展计划项目(CBY20-QB-Z02)
文献
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2022年第47卷第5期
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doi: 10.11855/j.issn.0577-7402.2022.05.0486
  • 接收时间：2021-07-27
  • 首发时间：2025-12-17
  • 出版时间：2022-05-28
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  • 收稿日期：2021-07-27
  • 录用日期：2021-09-15
基金
Application Technology Research and Development Special Project of Nanchong Science and Technology Bureau(20YFZJ0100)
南充市科技局应用技术研究与开发专项项目(20YFZJ0100)
Scientific Research and Development Plan of North Sichuan Medical College in 2020(CBY20-QB-Z02)
川北医学院2020年度校级科研发展计划项目(CBY20-QB-Z02)
作者信息
    1川北医学院附属医院呼吸与危重症医学科，四川南充 637000
    2成都大学附属医院呼吸内科，成都 610000
    3川北医学院附属医院产科，四川南充 637000

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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
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