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通讯作者:

孙培莉,E-mail: plisun9419@njmu.edu.cn

中图分类号:R563

文献标识码:A

文章编号:1007-4368(2024)08-1082-10

DOI:10.7655/NYDXBNSN240229

参考文献 1
GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE(GOLD).Global Strategy for Prevention,Diagnosis and Management of chronic obstructive pulmonary disease 2022 report[EB/OL][.2021⁃ 11 ⁃ 15].https://goldcopd.org/wp-content/uploads/2021/12/GOLD⁃REPORT⁃2022⁃v1.1⁃22Nov2021_WMV.pdf
参考文献 2
JANJUA S,PIKE K C,CARR R,et al.Interventions to improve adherence to pharmacological therapy for chronic obstructive pulmonary disease(COPD)[J].Cochrane Database Syst Rev,2021,9(9):CD013381
参考文献 3
PIRES I M,DENYSYUK H V,VILLASANA M V,et al.Development technologies for the monitoring of six-min⁃ ute walk test:a systematic review[J].Sensors(Basel),2022,22(2):581
参考文献 4
中华医学会老年医学分会.老年患者6分钟步行试验临床应用中国专家共识[J].中华老年医学杂志,2020,39(11):1241-1250
参考文献 5
中华医学会心血管病学分会,中国康复医学会心肺预防与康复专业委员会,中华心血管病杂志编辑委员会.6分钟步行试验临床规范应用中国专家共识[J].中华心血管病杂志,2022,50(5):432-442
参考文献 6
SUNJAYA A,POULOS L,REDDEL H,et al.Qualitative validation of the modified Medical Research Council(mMRC)dyspnoea scale as a patient⁃reported measure of breathlessness severity[J].Respir Med,2022,203:106984
参考文献 7
GIL H I,ZO S,JONES P W,et al.Clinical characteristics of COPD patients according to COPD assessment test(CAT)score level:cross⁃sectional study[J].Int J Chron Obstruct Pulmon Dis,2021,16:1509-1517
参考文献 8
GRAHAM B L,STEENBRUGGEN I,MILLER M R,et al.Standardization of spirometry 2019 update.An official american thoracic society and european respiratory society technical statement[J].Am J Respir Crit Care Med,2019,200(8):e70-e88
参考文献 9
HEINICKE G,CLAY R,DECATO T W.Six⁃minute⁃walk testing[J].Am J Respir Crit Care Med,2021,204(3):P5-P6
参考文献 10
ENRIGHT P L,SHERRILL D L.Reference equations for the six-minute walk in healthy adults[J].Am J Respir Crit Care Med,1998,158(5 Pt 1):1384-1387
参考文献 11
SANTOS C D,SANTOS A F,DAS N R,et al.Telemonitor-ing of daily activities compared to the six-minute walk test further completes the puzzle of oximetry⁃guided interventions[J].Sci Rep,2021,11(1):16600
参考文献 12
DELBRESSINE J M,JENSEN D,VAES A W,et al.Reference values for six ⁃minute walk distance and six ⁃minute walk work in Caucasian adults[J].Pulmonology,2023,29(5):399-409
参考文献 13
ADELOYE D,SONG P,ZHU Y,et al.Global,regional,and national prevalence of,and risk factors for,chronic obstructive pulmonary disease(COPD)in 2019:a systematic review and modelling analysis[J].Lancet Respir Med,2022,10(5):447-458
参考文献 14
ZHOU M,WANG H,ZENG X,et al.Mortality,morbidity,and risk factors in China and its provinces,1990⁃2017:a systematic analysis for the global burden of disease study 2017[J].Lancet,2019,394(10204):1145-1158
参考文献 15
KIM T,KIM H,KONG S,et al.Association between regular moderate to vigorous physical activity initiation following COPD diagnosis and mortality:an emulated target trial using nationwide cohort data[J].Chest,2024,165(1):84-94
参考文献 16
VOGELMEIER C F,FRIEDRICH F W,TIMPEL P,et al.Impact of COPD on mortality:an 8⁃year observational retrospective healthcare claims database cohort study[J].Respir Med,2024,222:107506
参考文献 17
KIM C,KO Y,LEE J S,et al.Predicting long⁃term mortality with two different criteria of exercise ⁃induced desaturation in COPD[J].Respir Med,2021,182:106393
参考文献 18
AGARWAL M,ANAND S,PATRO M,et al.Early versus non⁃early desaturation during 6MWT in COPD patients:a follow⁃up study[J].Lung India,2023,40(3):235-241
参考文献 19
GARCIA⁃TALAVERA I,FIGUEIRA⁃GONCALVES J M,GOLPE R,et al.Early desaturation during 6⁃minute walk test is a predictor of mortality in COPD[J].Lung,2023,201(2):217-224
参考文献 20
ANDRIANOPOULOS V,CELLI B R,FRANSSEN F M,et al.Determinants of exercise ⁃induced oxygen desaturation including pulmonary emphysema in COPD:results from the ECLIPSE study[J].Respir Med,2016,119:87-95
参考文献 21
PEREZ T,DESLÉE G,BURGEL P R,et al.Predictors in routine practice of 6⁃min walking distance and oxygen desaturation in patients with COPD:impact of comorbidi-ties[J].Int J Chron Obstruct Pulmon Dis,2019,14:1399-1410
参考文献 22
GUPTA R,RUPPEL G L,ESPIRITU J.Exercise⁃induced oxygen desaturation during the 6 ⁃ minute walk test[J].Med Sci(Basel),2020,8(1):8
参考文献 23
CHANG C H,LIN H C,YANG C H,et al.Factors associated with exercise ⁃induced desaturation in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:2643-2652
参考文献 24
WAATEVIK M,FRISK B,REAL F G,et al.CT ⁃defined emphysema in COPD patients and risk for change in desaturation status in 6 ⁃ min walk test[J].Respir Med,2021,187:106542
参考文献 25
ANDRIANOPOULOS V,FRANSSEN F M,PEETERS J P,et al.Exercise⁃induced oxygen desaturation in COPD patients without resting hypoxemia[J].Respir Physiol Neu-robiol,2014,190:40-46
参考文献 26
肖心儒,施宇佳,张倩.慢性阻塞性肺疾病生物学标志物的研究进展[J].南京医科大学学报(自然科学版),2023,43(7):1011-1016
参考文献 27
NEDER J A.Exercise ventilation and dyspnea in the obese patient with chronic obstructive pulmonary disease:“how much”versus“how well”[J].Chron Respir Dis,2021,18:241483804
参考文献 28
OMAR M,OMOTE K,SORIMACHI H,et al.Hypoxaemia in patients with heart failure and preserved ejection fraction[J].Eur J Heart Fail,2023,25(9):1593-1603
参考文献 29
FERMOYLE C C,STEWART G M,BORLAUG B A,et al.Simultaneous measurement of lung diffusing capacity and pulmonary hemodynamics reveals exertional alveolar⁃capillary dysfunction in heart failure with preserved ejection fraction[J].J Am Heart Assoc,2021,10(16):e019950
参考文献 30
BUEKERS J,STAS M,AERTS R,et al.Daily allergy burden and heart rate characteristics in adults with allergic rhinitis based on a wearable telemonitoring system[J].Clin Transl Allergy,2023,13(4):e12242
参考文献 31
OMLOR A J,TRUDZINSKI F C,ALQUDRAH M,et al.Time-updated resting heart rate predicts mortality in patients with COPD[J].Clin Res Cardiol,2020,109(6):776-786
参考文献 32
FERMONT J M,MASCONI K L,JENSEN M T,et al.Biomarkers and clinical outcomes in COPD:a systematic review and meta⁃analysis[J].Thorax,2019,74(5):439-446
参考文献 33
LAGE V,DE PAULA F A,LIMA L P,et al.Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia[J].Exp Gerontol,2022,164:111834
参考文献 34
SPRUIT M A,WATKINS M L,EDWARDS L D,et al.Determinants of poor 6⁃min walking distance in patients with COPD:the ECLIPSE cohort[J].Respir Med,2010,104(6):849-857
参考文献 35
RA F,CL G,PB S,et al.Association of right ventricle diastolic diameter with pulmonary function,exercise tolerance and exacerbation period in patients with chronic obstructive pulmonary disease:a prospective study[J].Heart Lung,2022,55:11-15
参考文献 36
WASHKO G R,NARDELLI P,ASH S Y,et al.Smaller left ventricle size at noncontrast CT is associated with lower mortality in COPD gene participants[J].Radiology,2020,296(1):208-215
参考文献 37
MASSON S J,TANNUS S D,FURTADO R G,et al.Correlation between 2D strain and classic echocardiographic indices in the diagnosis of right ventricular dysfunction in COPD[J].Int J Chron Obstruct Pulmon Dis,2021,16:1967-1976
参考文献 38
ANTWI⁃BOASIAKO C,KOLLIE M F,KYEREMEH K A,et al.Associations between spirometric measures and exercise capacity in type 2 diabetes[J].Diabetes Metab Syndr,2023,17(8):102831
参考文献 39
ZHANG R H,ZHOU J B,CAI Y H,et al.Non⁃linear association between diabetes mellitus and pulmonary function:a population⁃based study[J].Respir Res,2020,21(1):292
参考文献 40
LIU W,LIU Y,LI X.Impact of exercise capacity upon respiratory functions,perception of dyspnea,and quality of life in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2021,16:1529-1534
参考文献 41
CAMARGO P F,DITOMASO-LUPORINI L,DE CARV-ALHO L J,et al.Association between the predictors of functional capacity and heart rate off⁃kinetics in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:1977-1986
参考文献 42
COX N S,DAL CORSO S,HANSEN H,et al.Telerehabil-itation for chronic respiratory disease[J].Cochrane Database Syst Rev,2021,1(1):CD013040
参考文献 43
FUJIMOTO Y,OKI Y,KANEKO M,et al.Usefulness of the desaturation-distance ratio from the six ⁃minute walk test for patients with COPD[J].Int J Chron Obstruct Pul-mon Dis,2017,12:2669-2675
参考文献 44
ZOU H,ZHANG J,ZOU Y,et al.Six⁃minute walking distance in healthy Chinese people older than 60 years[J].BMC Pulm Med,2020,20(1):177
参考文献 45
GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE(GOLD).Global Strategy for Prevention,Diagnosis and Management of chronic obstructive pulmonary disease 2024 report[EB/OL][.2023⁃ 11⁃15].https://goldcopd.org/2024⁃gold⁃report/
目录contents

    摘要

    目的:研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期患者在6 min步行试验(6-minute walk test,6MWT)下脉搏血氧饱和度(pulse oxygen saturation,SpO2)和运动耐力的特点及相关因素,为COPD患者提供简便有效的客观评估方法。方法:纳入COPD稳定期患者58例和对照组患者21例,收集一般资料、改良版英国医学研究委员会呼吸困难问卷(modified medical research council dyspnoea scale,mMRC)评分、COPD自我评估测试(COPD assessment test,CAT)评分、肺功能参数(如FEV1%Pred、FVC%Pred、DLCO%Pred、DLCO/VA%Pred)和6MWT相关参数,分析SpO2和运动耐力指标的组间差异及其与COPD常用评估指标的相关性。结果:COPD患者在6MWT出现运动SpO2下降,表现为运动性低氧(exercise-induced de- saturation,EID),最低SpO2( SpO2min)和平均SpO2( SpO2mean)下降,运动SpO2低于88%、90%、92%的时间百分比(T88、T90、T92)和低氧面积(desaturation area,DA)增加;6 min 步行距离占预计值百分比(6MWD%Pred)和低氧距离比(desaturation distance ratio, DDR)在组间有差异;SpO2mean、DA、DDR、6MWD%Pred 均分别与mMRC评分、FEV1%Pred、FVC%Pred、静息SpO2( SpO2rest)相关, DDR还与DLCO%Pred、DLCO/VA%Pred相关,但是,多因素线性回归分析显示只有mMRC评分、DLCO%Pred和SpO2rest与DDR独立相关。结论:稳定期COPD患者6MWT同步持续脉搏指脉氧检测,其检测参数SpO2mean、DA、DDR和6MWD%Pred能有效反映 COPD患者肺功能和症状,提示该评估方法有效,有助于COPD患者的评估和管理。

    Abstract

    Objective:To study the characteristics and correlative factors of pulse oxygen saturation(SpO2)and exercise tolerance during the 6-min walk test(6MWT)in the stable chronic obstructive pulmonary disease(COPD)patients,aiming to provide a simple and effective objective assessment method for COPD patients. Methods:A total of 58 stable COPD patients and 21 control subjects were enrolled. General data,modified Medical Research Council dyspnoea scale(mMRC)score,COPD assessment test(CAT)score, pulmonary function parameters(such as FEV1%Pred,FVC%Pred,DLCO%Pred,DLCO/VA%Pred),and 6MWT-related parameters were collected. The study analyzed the differences in SpO2 and exercise tolerance indicators between groups,and their correlation with commonly used COPD assessment indicators. Results:COPD patients exhibited a decline in exercise SpO2 during the 6MWT, characterized by the occurrence of exercise-induced desaturation(EID),a decline in minimum SpO2( SpO2min)and mean SpO2( SpO2mean), an increase in the percentage of time with SpO2 below 88%,90%,and 92%(T88,T90,T92)and desaturation area(DA). There were differences in the 6 - minute walk distance(6 MWD)as a percentage of the predicted value(6MWD% Pred)and the desaturation distance ratio(DDR)between the two groups. SpO2mean,DA,DDR and 6MWD%Pred were correlated with mMRC scores,FEV1%Pred, FVC%Pred,and resting SpO2( SpO2rest). DDR was also correlated with DLCO%Pred and DLCO/VA%Pred. However,multivariable linear regression analysis showed that only mMRC scores,DLCO%Pred,and SpO2rest were independently associated with DDR. Conclusion: Continuous SpO2 monitoring during the 6MWT,with parameters such as SpO2mean,DA,DDR,and 6MWD%Pred,can effectively reflect pulmonary function and symptoms of stable COPD patients,suggesting its efficacy in assessment and management of COPD patients.

  • 慢性阻塞性肺疾病(chronic obstructive pulmo⁃ nary disease,COPD)是一种常见的、可防可治的慢性呼吸系统疾病,以不可逆性气流受限所致的持续性呼吸道症状为主要特征[1],临床表现为反复咳嗽、咳痰与气喘;但上述并非COPD的唯一症状,也可见于心脏病所致心功能不全、支气管哮喘、支气管扩张等患者。COPD的诊断及个体化治疗均依赖于对其症状、肺功能、胸部CT等检查,但这些评估方法均受到患者主观因素、表达能力或设备场所的显著影响,不同程度影响了COPD患者的健康结局。基于 COPD患者治疗依从性差[2] 的临床问题和医生需要多维度评估治疗的有效性及安全性等需求,医患双方均需要能客观反映患者病情且简便易行的临床检测方法,规范患者治疗,减轻患者症状,延缓疾病进展,改善运动耐力及生活质量,降低病死率。

  • 相比肺功能检查需要医患双方良好的协调配合、胸部CT检查的高成本与辐射影响、心肺运动试验的复杂性与高风险,6 min 步行试验(6⁃minute walk test,6MWT)采用的医疗检测设备便携、操作方法简单安全[3],能较好地反映心肺功能和运动耐力,已逐步广泛应用于心肺疾病的严重程度和疗效的评估。因此,中华医学会分别在2020年和2022年发表了6MWT的专家共识[4-5],以促进6MWT的规范化应用及推广。本研究应用6MWT[包括实时脉搏血氧饱和度(pulse oxygen saturation,SpO2)检测]以探讨 COPD稳定期患者动静状态下SpO2及运动耐力的特点和影响因素,为COPD患者的病情评估与治疗管理提供简便有效的客观指标。

  • 1 对象和方法

  • 1.1 对象

  • 本研究共收集南京医科大学第一附属医院门诊及住院的 COPD 稳定期患者 58 例和同时段的对照组患者21例。研究组入组标准:①符合《2022年慢性阻塞性肺疾病全球防治倡议》(global initiative for COPD,GOLD指南)中的相关标准[1];②年龄40~80岁;③近1~3个月有同步肺功能检查和6MWT(包括实时SpO2检测)。排除标准:①病情不稳定、症状反复加重、功能失代偿或其他呼吸系统疾病,心血管疾病,糖尿病;②行走障碍导致无法完成6MWT; ③休息时SpO2<85%;④严重贫血。

  • 对照组入组标准:①活动自如;②肺功能正常; ③胸部CT基本正常;④无心血管疾病史,无胸痛病史,心电图或二维超声心动图正常的个体。本研究已获得南京医科大学第一附属医院伦理委员会批准(编号:2015⁃SR⁃207,2019⁃SR⁃504),并取得患者的知情同意。

  • 1.2 方法

  • 1.2.1 一般资料收集

  • 收集患者的基本信息,包括年龄、性别、身高、体重、吸烟史、疾病史及药物治疗情况、胸部CT、心电图、二维超声心动图、血常规等。其中将COPD患者的吸入药物情况进行如下分类:Ⅰ表示未应用或未规律应用吸入药物,Ⅱ表示应用 1 种或 2 种吸入型长效支气管扩张剂(长效β2 受体激动剂(long⁃ actingβ2 ⁃agonist,LABA)、长效抗胆碱能药物(long⁃ acting muscarinic antagonist,LAMA)),Ⅲ表示联合应用吸入性糖皮质激素(inhaled corticosteroid,ICS) 和 1~2种吸入型长效支气管扩张剂,Ⅳ表示口服糖皮质激素联合应用 1~2 种吸入型长效支气管扩张剂。二维超声心动图参数包括左心房内径(left atrial diameter,LAD)、左心室舒张末期内径(left ventricular diameter in diastole,LVDd)、室间隔厚度(interven⁃ tricular septal thickness,IVS)、左心室后壁厚度(left ventricular posterior wall thickness,LVPW)、左心室射血分数(left ventricular ejection fraction,LVEF)、舒张早期与晚期流速比值(early to late diastolic trans⁃ mitral flow velocity,E/A)及舒张早期流速与舒张早期二尖瓣流速的比值(early diastolic mitral annular velocity,e′)的比值(E/e′)。

  • 1.2.2 COPD症状评分

  • 采用改良版英国医学研究委员会呼吸困难问卷(modified medical research council dyspnoea scale, mMRC)[6] 评估患者自我呼吸困难程度,分为0~4级,分级越高表示患者自觉呼吸困难症状越重。采用 COPD 自我评估测试(COPD assessment test,CAT)[7] 评估患者症状负担及健康状况,包括咳嗽、咳痰、胸闷、气喘、在家活动能力、外出活动能力、睡眠和精力8项,每项0~5分,分数越高,患者自觉症状越多、健康状态越差。

  • 1.2.3 肺功能检查

  • 由资质合格的肺功能检查技师遵循美国胸科学会与欧洲呼吸学会工作组[8] 的标准化建议完成肺功能检查,收集以下反映通气及弥散功能的指标:第 1 秒用力呼气容积(forced expiratory volume in 1 second,FEV1)及其占预计值百分数(FEV1 percent⁃ age of predicted,FEV1%Pred),用力肺活量(forced vi⁃ tal capacity,FVC)及其占预计值百分数(FVC per⁃ centage of predicted,FVC%Pred),一氧化碳弥散量 (diffusing capacity of the lung for carbon monoxide, DLCO)及其占预计值百分数(DLCO percentage of pre⁃ dicted,DLCO%Pred),每升肺泡容积一氧化碳弥散量 (DLCO by the alveolar volume,DLCO/VA)及其占预计值百分数(DLCO/VA percentage of predicted,DLCO/ VA%Pred)。

  • 1.2.4 6MWT和实时SpO2检测

  • 遵循 6MWT 操作指南[9] 进行试验,患者佩戴血氧仪腕表(型号:CMS60D,天津橙意科技有限公司) 沿着长度30 m走廊尽全力来回走6 min。收集患者试验前的静息SpO2( SpO2rest)、静息脉率(resting pulse rate,Prest)、静息收缩压(resting systolic blood pressure, SBPrest)和静息舒张压(resting diastolic blood pressure, DBPrest,试验过程中最低 SpO2 (minimal SpO2, SpO2min)、最快脉率(maximal pulse rate,Pmax)和 6 min 步行距离(6⁃minute walk distance,6MWD),6MWD 预计值公式[10]:男性6MWD(m)=1 140 m-5.61×BMI (kg/m2)-6.94×年龄(岁);女性6MWD(m)=1 017 m6.24×BMI(kg/m2)-5.83×年龄(岁)。除了6MWD,另外采用 6MWT 代谢当量(metabolic equivalence of task,METs)[11]、6 min步行做功(6⁃minute walk work, 6MWW)[12]、低氧距离比(desaturation distance ratio, DDR)来评估患者运动耐力和心肺功能,METs=[0.1×速度(m/min)+ 3.5 mL O2(kg/min)]÷ 3.5 mL O2(kg/min),6MWW=6MWD(m)×体重(kg)。低氧面积(desaturation area,DA)为单位时间内6MWT每秒记录的 SpO2距 100% SpO2差值的总和,DDR 为 DA 与单位时间内6MWD的比值。运动性低氧(exercise ⁃ induced desaturation,EID)定义为 SpO2min≤90% 且 SpO2rest-SpO2min≥4%,通过软件分析获得试验6 min内的平均SpO2( mean SpO2,SpO2mean)和SpO2分别≤88%、 90%、92%和94%占6 min的时间百分数(percentage of time with SpO2 below 88%,90%,92% and 94%,T88、 T90、T92、T94)。

  • 1.3 统计学方法

  • 应用SPSS25.0统计软件进行数据分析;正态分布的计量资料以均数±标准差(x-±s)表示,非正态分布的计量资料则以中位数(四分位数)[MP25P75)] 表示,分类资料和等级资料以频数(率)表示。采用方差分析、秩和检验、卡方检验、LSD 法比较组间差异。相关性分析采用 Pearson 相关、Spearman 相关和多因素线性回归分析。P <0.05 为差异有统计学意义。

  • 2 结果

  • 2.1 一般临床资料

  • 本研究共纳入符合标准的对照组21例和COPD 组58例,年龄、BMI 组间差异无统计学意义,性别、吸烟指数和mMRC评分组间差异有统计学意义(表1)。将COPD组分为3个亚组,分别为单纯COPD组 (COPD⁃A 组)23 例、联合肺部疾病组(COPD⁃B 组) 17 例和联合心血管疾病和/或糖尿病组(COPD ⁃C 组)18 例;CAT 评分、肺通气及弥散功能指标 (FEV1% Pred、FVC% Pred、DLCO% Pred、DLCO/VA% Pred)和吸入药物情况在COPD组间差异无统计学意义(表2);同时,COPD⁃A组和COPD⁃C组的二维超声心动图参数LAD、LVDd、IVS、LVPW、EF、E/A、E/e′在组间不存在统计学差异(表3)。

  • 2.2 COPD患者运动SpO2特点和运动耐力

  • 在对照组和COPD⁃A 组、B组、C组之间进行运动SpO2比较,SpO2rest、Pmax、SBPrest和DBPrest在组间差异无统计学意义,但 SpO2min、SpO2mean、DA、T88、T90、T92和 Prest在组间差异有统计学意义;COPD 稳定期患者 EID的发生率为34.48%(20例);COPD⁃B组的Prest明显快于其他 3 组(表4)。同时,6MWD%Pred、DDR 在组间存在统计学差异,6MWD、METs、6MWW在组间差异无统计学意义(表5)。

  • 表1 对照组和COPD组的一般资料的组间差异分析

  • Table1 the comparison of background data betweenthe control and the COPD

  • without#:F value in analysis of variance(ANOVA);#:Z value in Mann⁃Whitney U test;##:χ2 value in Chi⁃square test by Yates’correction for continuity. BMI:body mass index;smoking index:product of cigarettes smoked per day and years of smoking.

  • 表2 COPD临床资料的组间差异分析

  • Table2 The comparison of clinical data among COPD subgroups

  • COPD⁃A group:only COPD;COPD⁃B group:COPD with other chronic respiratory diseases(such as asthma,bronchiectasis or pulmonary tuberculo⁃ sis);COPD⁃C group:COPD with hypertension,diabetes or cardiovascular disease;without#:F value in ANOVA;#:H value in Kruskal⁃Wallis H test;b: compared with COPD⁃A group,P <0.05(by used least significant difference for pair⁃wise multiple comparisons).

  • 表3 COPD⁃A组和COPD⁃C组二维超声心动图参数的组间差异

  • Table3 The comparison of echocardiography parameters between COPD⁃A group and COPD⁃C group

  • 2.3 COPD患者运动SpO2和运动耐力的相关性分析

  • 对总样本进行运动耐力、SpO2与 COPD 其他常用评估指标的相关性分析显示,SpO2min、SpO2mean、 DA、DDR、6MWD% Pred 均与 FEV1% Pred、FVC% Pred 相关;其中,SpO2min、DDR、6MWD%Pred 还与 DLCO%Pred、DLCO/VA%Pred相关,SpO2mean、DA、DDR、 6MWD%Pred还与mMRC评分相关,DDR、6MWD% Pred 与 CAT 评分相关;而仅 6MWD%Pred 与 SpO2rest 无相关(表6)。纳入mMRC评分、CAT评分、FEV1% Pred、FVC% Pred、DLCO% Pred、DLCO/VA% Pred 构建 DDR+的逐步多因素线性回归分析,结果显示mMRC 评分、DLCO%Pred 和 SpO2rest对 DDR的影响差异有统计学意义,这3个变量对DDR贡献58.3%的变异 (表7)。

  • 表4 COPD患者动静状态下SpO2特点

  • Table4 The characteristics of SpO2 in COPD

  • without#:F value in ANOVA;#:H value in Kruskal⁃Wallis H test;##:statistic in Fisher’s exact test by used least significant difference for pair⁃ wise multiple comparisons;a:compared with the control group,P <0.05,b:compared with COPD⁃A group,P <0.05.

  • 表5 COPD患者运动耐力特点

  • Table5 The characteristics of exercise tolerance in COPD

  • 表6 总样本运动耐力、SpO2的相关性分析

  • Table6 The correlation analysis of SpO2 and exercise tolerance with other general COPD parameters in the total samples

  • DDR= DDR to follow a normal distribution. without*:Pearson correlation coefficient. *:Spearman correlation coefficient.

  • 另外,对 COPD 组内进行运动耐力、SpO2 与 COPD 其他常用评估指标的相关性分析显示,SpO2min、SpO2mean、DA、DDR、6MWD% Pred 均与 FEV1%Pred、FVC%Pred相关;其中,DDR、6MWD% Pred 还与 mMRC 评分相关,而 6MWD%Pred 与 CAT 评分相关,但 6MWD%Pred 与 SpO2rest无相关(表8)。纳入mMRC评分、FEV1%Pred、FVC%Pred构建DDR 的逐步多因素线性回归分析,结果显示mMRC评分和SpO2rest对DDR的影响差异有统计学意义,这2个变量对DDR贡献44.4%的变异(表9)。

  • 此外,COPD 患者的 6MWD 与年龄则呈负相关 (r=-0.225,P=0.046),然而6MWD%Pred与年龄呈正相关(r=0.332,P=0.003);COPD 患者中肥胖组的 SpO2mean较正常体重组显著降低,DA、DDR指标显著增高(表10)。

  • 3 讨论

  • 目前全球成人 COPD 患病率为 10.3%,其中男性患病率高于女性,且COPD患病率随着年龄增加而增加[13]。同时,COPD 全因病死率目前位于我国第3位,仅次于中风、缺血性心脏病[14],其直接和间接的经济负担逐年加重。因此,对COPD患者而言,尽早明确诊断、规范化药物治疗和联合肺康复锻炼等综合治疗尤其重要[15-16]

  • 研究表明,伴有EID的COPD患者的急性加重及住院风险增加、肺功能损害加重、生存期缩短、死亡风险增加[17],其中 COPD 患者的 EID 如发生在 6MMWT 的第 1 分钟内(即早期 EID)提示其住院风险比非早期EID者高[18-19],而且Garcia⁃Talavera等[19] 对 319 例 COPD 患者进行随访(平均随访时间为 5.6 年),发现早期 EID 患者死亡率高于非早期 EID 的患者,属于更需要关注和干预的COPD人群。鉴于 EID 的预后价值,临床上需要确定 EID 发生人群。虽然既往研究表明 COPD 患者的年龄、性别、 BMI、症状评分、肺气肿严重程度、肺通气及弥散功能受损程度、6MWD、静息SpO2及共病等因素均与EID 相关[20-24],但一直缺乏准确有效的EID预测模型。综上所述,对COPD患者开展6MWT(包含SpO2监测)是必要的。因此,本研究采用6MWT联合动态SpO2监测仪,分析COPD患者动静状态下SpO2及运动耐力情况及相关因素,多维度评估COPD患者的病情。

  • 表7 DDR的多因素线性回归分析

  • Table7 Multiple linear regression of DDR in the total sample

  • DDR= DDR to follow a normal distribution. ***P <0.001. B:partial regression coefficient. β:standardized regression coefficient.

  • 表8 COPD样本运动耐力、SpO2的相关性分析

  • Table8 The correlation analysis of SpO2 and exercise tolerance with other general COPD parameters in COPD

  • DDR= DDR to follow a normal distribution. without *:Pearson correlation coefficient. *:Spearman correlation coefficient.

  • 表9 COPD样本DDR的多因素线性回归分析

  • Table9 Multiple linear regression of DDR in COPD

  • ***P <0.001. B:partial regression coefficient. β:standardized regression coefficient.

  • 表10 COPD样本SpO2的BMI分级的组间差异分析

  • Table10 The comparison of SpO2 among BMI subgroups

  • According to the Chinese BMI classification,underweight was defined as <18.5 kg/m2,normal weight as 18.5 to <24 kg/m2,overweight as 24 to <28 kg/m2 and obesity as ≥28 kg/m2;by used least significant difference for pair⁃wise multiple comparisons:compared with normal weight group,P <0.05.

  • 虽然既往研究中对EID的定义标准各不相同,但最近研究表明,COPD患者EID的发生率在21%~39%之间[21]。本研究发现 COPD 稳定期患者中, 53.4%的患者肺功能为 GOLD Ⅱ级,34.48%(20 例) 的患者出现 EID,这与既往研究一致,可见 EID 是 COPD 患者常见的临床特征。同时,本研究发现 SpO2rest正常的COPD稳定期患者运动SpO2下降可表现为SpO2min、SpO2mean下降,T88、T90、T92、DA增加,运动 SpO2下降与mMRC评分、肺通气及弥散功能、SpO2min 有关。但在COPD组内分析发现部分运动SpO2指标与 mMRC 评分、肺弥散功能无显著相关,这与本研究纳入了弥散功能损害程度较轻[(DLCO/VA%Pred 均值为(62.71±23.64)%]的COPD稳定期患者,其损害程度未明显影响氧气交换有关。

  • 既往研究表明,联合SpO2rest<95%、DLCO%Pred<50%、FEV1%Pred<45%、PaO2<10 kPa 和女性的多因素模型对 EID 具有较高的预测价值,SpO2rest的独立预测价值不足[25]。而 Andrianopoulos 等[20]在 ECLIPSE 研究中调查了 2 050 例 COPD 患者,发现 SpO2rest下降(≤93%)与 EID 独立相关。本研究发现 SpO2rest是运动SpO2下降最重要的影响因素,这提示SpO2rest除了与 COPD 导致的呼吸功能障碍有关以外,可能也与COPD患者存在的全身炎症等病理表现有关;但目前研究只证实了COPD患者肺功能及预后与患者出现的全身炎症、氧化应激等相关生物标志物有关[26],而生物标志物与COPD患者的静息及运动脉氧的相关性和可能机制则有待进一步探讨。

  • 肥胖与EID的相关性存在争议,Perez等[21] 未发现两者的相关性;但是,另一研究表明肥胖与EID呈正相关,同时发现肥胖与低 SpO2rest有关[20],考虑低 SpO2rest是肥胖与EID存在相关性的主要决定因素之一。重度肥胖及腹型肥胖患者静息状态下咽喉部脂肪堆积致上气道阻力增加,而腹部脂肪增多致膈肌运动功能受限,最终降低肺有效通气并导致低 SpO2rest的发生[27]。本研究纳入的COPD稳定期肥胖患者的SpO2rest较低,运动SpO2下降更严重;虽然由于本研究COPD 稳定期肥胖组样本量少,参考BMI 分级标准分为 4 组,SpO2rest在组间尚未达到统计学差异,但相比体重正常组,COPD肥胖组的SpO2rest显著降低,提示COPD患者的肥胖与运动SpO2存在相关性,但这仍需进一步分析COPD患者中肥胖严重程度和脂肪分布情况对运动SpO2下降的影响。

  • 考虑到COPD 患者多为老人,且常合并其他慢性疾病,其年龄、吸烟暴露量和合并症如高血压、缺血性心脏病、糖尿病也可能对COPD患者运动SpO2 和运动耐力有影响,本研究进行了相应的观察研究。Perez等[21] 通过多因素分析发现,在COPD患者中高血压与EID相关,其相关性可能与高血压导致的亚临床左心舒张功能障碍有关。另外,有研究发现以左室舒张功能受损为主要特征的射血分数保留型心力衰竭患者在心肺运动试验时出现运动性低氧(SpO2<94%)的概率为 25%,随访 2.8 年后发现运动性低氧与死亡风险增加相关[28]。Fermoyle等[29] 发现运动时肺泡毛细血管功能障碍引起的肺弥散功能下降是射血分数保留型心力衰竭患者出现运动性低氧的原因。而本研究发现,心血管疾病及糖尿病合并症并未对COPD患者的动静状态下SpO2和运动耐力情况产生影响,这与本研究入组的COPD⁃ A 组和 COPD⁃C 组患者的射血分数在正常范围,且相关二维超声心动图参数不存在差异有关。

  • Prest或静息心率主要与心肺功能、缺氧等生理及应激反应等相关,也与过敏状态有关。一项针对过敏性鼻炎的日常动态心率监测的研究发现,患者的静息心率与过敏症状呈正相关,静息心率的增快可能是心脏对过敏负担的增加导致的交感神经和副交感神经功能失衡的适应性反应的早期临床表现[30]。同时,有研究发现高基础心率(>72次/min)的COPD患者全因死亡风险增高,高基础心率与低FEV1、低TLCO、糖尿病病史和短效β受体激动剂药物治疗独立相关[31]。本研究发现COPD⁃B组患者(合并支气管哮喘者占 70.59%)的Prest较高,而其SpO2rest、肺功能指标、吸入药物治疗情况均与其他COPD组无差异,因此考虑高 Prest可能与哮喘存在的过敏效应有关。

  • 运动耐力是全民健康的重要评估方法,当然也适用于COPD患者的全身评估。临床上6MWD是最常用的运动耐力评估指标。6MWD 下降可预测 COPD 患者的急性加重风险和死亡风险[32]。但是, 6MWD受多因素影响,除了生理性因素如年龄、身高外,还包括慢性呼吸道疾病、慢性血管疾病、慢性肌肉骨骼疾病等[533]。Spruit等[34] 在ECLIPSE研究中调查了2 747例COPD患者,发现有41%患者运动耐力下降(6MWD<350 米),运动耐力与 mMRC 评分、 GOLD分级、肺气肿严重程度、6MWT期间氧疗需求相关。其次,SpO2rest也是运动耐力下降的预测指标, Perez 等[21] 对稳定期 COPD 患者的队列研究结果提示,仅通过临床表现和肺功能无法可靠地评估患者的运动耐力情况;运动功能也受COPD合并的心血管疾病等肺外因素影响,相关研究发现心脏的收缩功能、舒张功能障碍及心室扩大也与COPD 患者的运动耐力有关[35-37],另有研究发现25%的糖尿病患者会出现运动耐量下降,其原因与糖尿病致靶器官心肺损害导致的功能障碍有关[38-39]。这也说明 6MWT在COPD患者管理中的价值及检查评估的必要性。本研究步行试验中发现6MWD%Pred具有较好的临床价值,其与mMRC评分、CAT评分、肺通气功能、肺弥散功能相关,这与既往研究发现的6MWD 相关因素一致[40-41]。既往研究将6MWD低于350 m 定义为运动耐力下降,而本研究 6MWD 均在 350 m 以上,这可能与本研究纳入的患者平均年龄在 65岁,症状少、GOLD Ⅳ级占比少(5例)、无并发肺源性心脏病或其他功能失代偿的心脑血管疾病有关。但既往也有研究发现 6MWD 存在局限性,其预测 COPD患者急性加重或病死率的最佳阈值并不一致,而年龄才是影响最佳阈值取值的重要因素[3242]。而本研究发现,相比6MWD,6MWD%Pred和DDR能更敏感地识别运动耐力轻度降低的 COPD 人群。 6MWD%Pred 排除了年龄、体重、身高的影响,DDR 可以同时反映 6MWD 和运动 SpO2情况的运动功能指标。因此,COPD患者运动耐力参数6MWD%pred 较6MWD绝对值更具临床指导价值。

  • 同时,有研究证明气流受限程度会影响 COPD 患者的运动 SpO2和运动耐力[2334],进而影响 DDR。而且有研究发现 DDR 较 SpO2min能更好地反映气流受限和肺弥散功能受损严重程度,也能间接反映胸部 CT 的肺气肿程度和肺动脉扩张情况[43]。因此, DDR用于综合评估运动功能的临床指导价值优于单纯运动SpO2指标。但本研究发现DDR与mMRC评分、肺通气及弥散功能、SpO2rest相关,而多因素线性回归分析中未能显示FEV1%Pred对DDR的独立影响,这可能与入组受试者肺功能FEV1%Pred差异小和样本量小有关,有待后续更大规模研究进一步验证。

  • 本研究还发现动静状态下的 SpO2 情况均与 6MWD 和 6MWD%Pred 无关,这与先前的研究结果一致[21]。这再次说明6MWT时监测SpO2的重要性。

  • 本研究发现 6MWD 与年龄呈负相关,但 6MWD%Pred 与年龄呈正相关;可见 Enright 等[10] 基于北美人群的 6MWD 预计值公式未能有效调整年龄对6MWD的影响,而本研究采用Zou等[44] 基于中国人群的6MWD预计值公式所得的6MWD%Pred与年龄无相关性(r=-0.145,P=0.202),表明 Enright 等[10] 的6MWD预测公式并不完全适用于我国人群,这可能与不同人群的种族背景差异有关。因此,虽然Enright预测公式常常被研究采纳,但本研究发现使用基于中国人群的预测公式来分析中国人群的运动耐力情况更为准确。

  • 总之,本研究主要分析 COPD 患者 6MWT 动静状态 SpO2、运动耐力的特点及其影响因素,发现运动 SpO2 参数(SpO2min、SpO2mean、DA)、运动耐力参数 (6MWD%Pred、DDR)与 mMRC 评分、肺通气功能、肺弥散功能的相关性,特别是运动耐力参数中 6MWD%Pred和DDR能更敏感地识别运动耐力轻度降低的 COPD 人群。虽然 2024 年 GOLD 指南对 COPD患者的病情评估推荐SpO2rest [45],但不包含运动SpO2参数的运用;而本研究表明,将实时 SpO2检测运用于 6MWT 能获取更有效、综合的病情信息,有助于简化 COPD 患者的评估方法,及时发现运动 SpO2变化和调整药物治疗、氧疗和有氧运动方案,改善患者预后。虽然COPD临床实践已通过肺功能或胸部CT检查发现并及时诊断COPD患者,但本研究采用 6MWT 联合持续 SpO2检测的客观临床方法来评估病情,检查成本低、方法易行、安全,更易被患者接受,便于推广到社区及乡镇卫生院实施应用,提示6MWT联合实时SpO2检测在COPD 管理中的临床应用价值及前景。

  • 参考文献

    • [1] GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE(GOLD).Global Strategy for Prevention,Diagnosis and Management of chronic obstructive pulmonary disease 2022 report[EB/OL][.2021⁃ 11 ⁃ 15].https://goldcopd.org/wp-content/uploads/2021/12/GOLD⁃REPORT⁃2022⁃v1.1⁃22Nov2021_WMV.pdf

    • [2] JANJUA S,PIKE K C,CARR R,et al.Interventions to improve adherence to pharmacological therapy for chronic obstructive pulmonary disease(COPD)[J].Cochrane Database Syst Rev,2021,9(9):CD013381

    • [3] PIRES I M,DENYSYUK H V,VILLASANA M V,et al.Development technologies for the monitoring of six-min⁃ ute walk test:a systematic review[J].Sensors(Basel),2022,22(2):581

    • [4] 中华医学会老年医学分会.老年患者6分钟步行试验临床应用中国专家共识[J].中华老年医学杂志,2020,39(11):1241-1250

    • [5] 中华医学会心血管病学分会,中国康复医学会心肺预防与康复专业委员会,中华心血管病杂志编辑委员会.6分钟步行试验临床规范应用中国专家共识[J].中华心血管病杂志,2022,50(5):432-442

    • [6] SUNJAYA A,POULOS L,REDDEL H,et al.Qualitative validation of the modified Medical Research Council(mMRC)dyspnoea scale as a patient⁃reported measure of breathlessness severity[J].Respir Med,2022,203:106984

    • [7] GIL H I,ZO S,JONES P W,et al.Clinical characteristics of COPD patients according to COPD assessment test(CAT)score level:cross⁃sectional study[J].Int J Chron Obstruct Pulmon Dis,2021,16:1509-1517

    • [8] GRAHAM B L,STEENBRUGGEN I,MILLER M R,et al.Standardization of spirometry 2019 update.An official american thoracic society and european respiratory society technical statement[J].Am J Respir Crit Care Med,2019,200(8):e70-e88

    • [9] HEINICKE G,CLAY R,DECATO T W.Six⁃minute⁃walk testing[J].Am J Respir Crit Care Med,2021,204(3):P5-P6

    • [10] ENRIGHT P L,SHERRILL D L.Reference equations for the six-minute walk in healthy adults[J].Am J Respir Crit Care Med,1998,158(5 Pt 1):1384-1387

    • [11] SANTOS C D,SANTOS A F,DAS N R,et al.Telemonitor-ing of daily activities compared to the six-minute walk test further completes the puzzle of oximetry⁃guided interventions[J].Sci Rep,2021,11(1):16600

    • [12] DELBRESSINE J M,JENSEN D,VAES A W,et al.Reference values for six ⁃minute walk distance and six ⁃minute walk work in Caucasian adults[J].Pulmonology,2023,29(5):399-409

    • [13] ADELOYE D,SONG P,ZHU Y,et al.Global,regional,and national prevalence of,and risk factors for,chronic obstructive pulmonary disease(COPD)in 2019:a systematic review and modelling analysis[J].Lancet Respir Med,2022,10(5):447-458

    • [14] ZHOU M,WANG H,ZENG X,et al.Mortality,morbidity,and risk factors in China and its provinces,1990⁃2017:a systematic analysis for the global burden of disease study 2017[J].Lancet,2019,394(10204):1145-1158

    • [15] KIM T,KIM H,KONG S,et al.Association between regular moderate to vigorous physical activity initiation following COPD diagnosis and mortality:an emulated target trial using nationwide cohort data[J].Chest,2024,165(1):84-94

    • [16] VOGELMEIER C F,FRIEDRICH F W,TIMPEL P,et al.Impact of COPD on mortality:an 8⁃year observational retrospective healthcare claims database cohort study[J].Respir Med,2024,222:107506

    • [17] KIM C,KO Y,LEE J S,et al.Predicting long⁃term mortality with two different criteria of exercise ⁃induced desaturation in COPD[J].Respir Med,2021,182:106393

    • [18] AGARWAL M,ANAND S,PATRO M,et al.Early versus non⁃early desaturation during 6MWT in COPD patients:a follow⁃up study[J].Lung India,2023,40(3):235-241

    • [19] GARCIA⁃TALAVERA I,FIGUEIRA⁃GONCALVES J M,GOLPE R,et al.Early desaturation during 6⁃minute walk test is a predictor of mortality in COPD[J].Lung,2023,201(2):217-224

    • [20] ANDRIANOPOULOS V,CELLI B R,FRANSSEN F M,et al.Determinants of exercise ⁃induced oxygen desaturation including pulmonary emphysema in COPD:results from the ECLIPSE study[J].Respir Med,2016,119:87-95

    • [21] PEREZ T,DESLÉE G,BURGEL P R,et al.Predictors in routine practice of 6⁃min walking distance and oxygen desaturation in patients with COPD:impact of comorbidi-ties[J].Int J Chron Obstruct Pulmon Dis,2019,14:1399-1410

    • [22] GUPTA R,RUPPEL G L,ESPIRITU J.Exercise⁃induced oxygen desaturation during the 6 ⁃ minute walk test[J].Med Sci(Basel),2020,8(1):8

    • [23] CHANG C H,LIN H C,YANG C H,et al.Factors associated with exercise ⁃induced desaturation in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:2643-2652

    • [24] WAATEVIK M,FRISK B,REAL F G,et al.CT ⁃defined emphysema in COPD patients and risk for change in desaturation status in 6 ⁃ min walk test[J].Respir Med,2021,187:106542

    • [25] ANDRIANOPOULOS V,FRANSSEN F M,PEETERS J P,et al.Exercise⁃induced oxygen desaturation in COPD patients without resting hypoxemia[J].Respir Physiol Neu-robiol,2014,190:40-46

    • [26] 肖心儒,施宇佳,张倩.慢性阻塞性肺疾病生物学标志物的研究进展[J].南京医科大学学报(自然科学版),2023,43(7):1011-1016

    • [27] NEDER J A.Exercise ventilation and dyspnea in the obese patient with chronic obstructive pulmonary disease:“how much”versus“how well”[J].Chron Respir Dis,2021,18:241483804

    • [28] OMAR M,OMOTE K,SORIMACHI H,et al.Hypoxaemia in patients with heart failure and preserved ejection fraction[J].Eur J Heart Fail,2023,25(9):1593-1603

    • [29] FERMOYLE C C,STEWART G M,BORLAUG B A,et al.Simultaneous measurement of lung diffusing capacity and pulmonary hemodynamics reveals exertional alveolar⁃capillary dysfunction in heart failure with preserved ejection fraction[J].J Am Heart Assoc,2021,10(16):e019950

    • [30] BUEKERS J,STAS M,AERTS R,et al.Daily allergy burden and heart rate characteristics in adults with allergic rhinitis based on a wearable telemonitoring system[J].Clin Transl Allergy,2023,13(4):e12242

    • [31] OMLOR A J,TRUDZINSKI F C,ALQUDRAH M,et al.Time-updated resting heart rate predicts mortality in patients with COPD[J].Clin Res Cardiol,2020,109(6):776-786

    • [32] FERMONT J M,MASCONI K L,JENSEN M T,et al.Biomarkers and clinical outcomes in COPD:a systematic review and meta⁃analysis[J].Thorax,2019,74(5):439-446

    • [33] LAGE V,DE PAULA F A,LIMA L P,et al.Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia[J].Exp Gerontol,2022,164:111834

    • [34] SPRUIT M A,WATKINS M L,EDWARDS L D,et al.Determinants of poor 6⁃min walking distance in patients with COPD:the ECLIPSE cohort[J].Respir Med,2010,104(6):849-857

    • [35] RA F,CL G,PB S,et al.Association of right ventricle diastolic diameter with pulmonary function,exercise tolerance and exacerbation period in patients with chronic obstructive pulmonary disease:a prospective study[J].Heart Lung,2022,55:11-15

    • [36] WASHKO G R,NARDELLI P,ASH S Y,et al.Smaller left ventricle size at noncontrast CT is associated with lower mortality in COPD gene participants[J].Radiology,2020,296(1):208-215

    • [37] MASSON S J,TANNUS S D,FURTADO R G,et al.Correlation between 2D strain and classic echocardiographic indices in the diagnosis of right ventricular dysfunction in COPD[J].Int J Chron Obstruct Pulmon Dis,2021,16:1967-1976

    • [38] ANTWI⁃BOASIAKO C,KOLLIE M F,KYEREMEH K A,et al.Associations between spirometric measures and exercise capacity in type 2 diabetes[J].Diabetes Metab Syndr,2023,17(8):102831

    • [39] ZHANG R H,ZHOU J B,CAI Y H,et al.Non⁃linear association between diabetes mellitus and pulmonary function:a population⁃based study[J].Respir Res,2020,21(1):292

    • [40] LIU W,LIU Y,LI X.Impact of exercise capacity upon respiratory functions,perception of dyspnea,and quality of life in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2021,16:1529-1534

    • [41] CAMARGO P F,DITOMASO-LUPORINI L,DE CARV-ALHO L J,et al.Association between the predictors of functional capacity and heart rate off⁃kinetics in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:1977-1986

    • [42] COX N S,DAL CORSO S,HANSEN H,et al.Telerehabil-itation for chronic respiratory disease[J].Cochrane Database Syst Rev,2021,1(1):CD013040

    • [43] FUJIMOTO Y,OKI Y,KANEKO M,et al.Usefulness of the desaturation-distance ratio from the six ⁃minute walk test for patients with COPD[J].Int J Chron Obstruct Pul-mon Dis,2017,12:2669-2675

    • [44] ZOU H,ZHANG J,ZOU Y,et al.Six⁃minute walking distance in healthy Chinese people older than 60 years[J].BMC Pulm Med,2020,20(1):177

    • [45] GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE(GOLD).Global Strategy for Prevention,Diagnosis and Management of chronic obstructive pulmonary disease 2024 report[EB/OL][.2023⁃ 11⁃15].https://goldcopd.org/2024⁃gold⁃report/

  • 参考文献

    • [1] GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE(GOLD).Global Strategy for Prevention,Diagnosis and Management of chronic obstructive pulmonary disease 2022 report[EB/OL][.2021⁃ 11 ⁃ 15].https://goldcopd.org/wp-content/uploads/2021/12/GOLD⁃REPORT⁃2022⁃v1.1⁃22Nov2021_WMV.pdf

    • [2] JANJUA S,PIKE K C,CARR R,et al.Interventions to improve adherence to pharmacological therapy for chronic obstructive pulmonary disease(COPD)[J].Cochrane Database Syst Rev,2021,9(9):CD013381

    • [3] PIRES I M,DENYSYUK H V,VILLASANA M V,et al.Development technologies for the monitoring of six-min⁃ ute walk test:a systematic review[J].Sensors(Basel),2022,22(2):581

    • [4] 中华医学会老年医学分会.老年患者6分钟步行试验临床应用中国专家共识[J].中华老年医学杂志,2020,39(11):1241-1250

    • [5] 中华医学会心血管病学分会,中国康复医学会心肺预防与康复专业委员会,中华心血管病杂志编辑委员会.6分钟步行试验临床规范应用中国专家共识[J].中华心血管病杂志,2022,50(5):432-442

    • [6] SUNJAYA A,POULOS L,REDDEL H,et al.Qualitative validation of the modified Medical Research Council(mMRC)dyspnoea scale as a patient⁃reported measure of breathlessness severity[J].Respir Med,2022,203:106984

    • [7] GIL H I,ZO S,JONES P W,et al.Clinical characteristics of COPD patients according to COPD assessment test(CAT)score level:cross⁃sectional study[J].Int J Chron Obstruct Pulmon Dis,2021,16:1509-1517

    • [8] GRAHAM B L,STEENBRUGGEN I,MILLER M R,et al.Standardization of spirometry 2019 update.An official american thoracic society and european respiratory society technical statement[J].Am J Respir Crit Care Med,2019,200(8):e70-e88

    • [9] HEINICKE G,CLAY R,DECATO T W.Six⁃minute⁃walk testing[J].Am J Respir Crit Care Med,2021,204(3):P5-P6

    • [10] ENRIGHT P L,SHERRILL D L.Reference equations for the six-minute walk in healthy adults[J].Am J Respir Crit Care Med,1998,158(5 Pt 1):1384-1387

    • [11] SANTOS C D,SANTOS A F,DAS N R,et al.Telemonitor-ing of daily activities compared to the six-minute walk test further completes the puzzle of oximetry⁃guided interventions[J].Sci Rep,2021,11(1):16600

    • [12] DELBRESSINE J M,JENSEN D,VAES A W,et al.Reference values for six ⁃minute walk distance and six ⁃minute walk work in Caucasian adults[J].Pulmonology,2023,29(5):399-409

    • [13] ADELOYE D,SONG P,ZHU Y,et al.Global,regional,and national prevalence of,and risk factors for,chronic obstructive pulmonary disease(COPD)in 2019:a systematic review and modelling analysis[J].Lancet Respir Med,2022,10(5):447-458

    • [14] ZHOU M,WANG H,ZENG X,et al.Mortality,morbidity,and risk factors in China and its provinces,1990⁃2017:a systematic analysis for the global burden of disease study 2017[J].Lancet,2019,394(10204):1145-1158

    • [15] KIM T,KIM H,KONG S,et al.Association between regular moderate to vigorous physical activity initiation following COPD diagnosis and mortality:an emulated target trial using nationwide cohort data[J].Chest,2024,165(1):84-94

    • [16] VOGELMEIER C F,FRIEDRICH F W,TIMPEL P,et al.Impact of COPD on mortality:an 8⁃year observational retrospective healthcare claims database cohort study[J].Respir Med,2024,222:107506

    • [17] KIM C,KO Y,LEE J S,et al.Predicting long⁃term mortality with two different criteria of exercise ⁃induced desaturation in COPD[J].Respir Med,2021,182:106393

    • [18] AGARWAL M,ANAND S,PATRO M,et al.Early versus non⁃early desaturation during 6MWT in COPD patients:a follow⁃up study[J].Lung India,2023,40(3):235-241

    • [19] GARCIA⁃TALAVERA I,FIGUEIRA⁃GONCALVES J M,GOLPE R,et al.Early desaturation during 6⁃minute walk test is a predictor of mortality in COPD[J].Lung,2023,201(2):217-224

    • [20] ANDRIANOPOULOS V,CELLI B R,FRANSSEN F M,et al.Determinants of exercise ⁃induced oxygen desaturation including pulmonary emphysema in COPD:results from the ECLIPSE study[J].Respir Med,2016,119:87-95

    • [21] PEREZ T,DESLÉE G,BURGEL P R,et al.Predictors in routine practice of 6⁃min walking distance and oxygen desaturation in patients with COPD:impact of comorbidi-ties[J].Int J Chron Obstruct Pulmon Dis,2019,14:1399-1410

    • [22] GUPTA R,RUPPEL G L,ESPIRITU J.Exercise⁃induced oxygen desaturation during the 6 ⁃ minute walk test[J].Med Sci(Basel),2020,8(1):8

    • [23] CHANG C H,LIN H C,YANG C H,et al.Factors associated with exercise ⁃induced desaturation in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:2643-2652

    • [24] WAATEVIK M,FRISK B,REAL F G,et al.CT ⁃defined emphysema in COPD patients and risk for change in desaturation status in 6 ⁃ min walk test[J].Respir Med,2021,187:106542

    • [25] ANDRIANOPOULOS V,FRANSSEN F M,PEETERS J P,et al.Exercise⁃induced oxygen desaturation in COPD patients without resting hypoxemia[J].Respir Physiol Neu-robiol,2014,190:40-46

    • [26] 肖心儒,施宇佳,张倩.慢性阻塞性肺疾病生物学标志物的研究进展[J].南京医科大学学报(自然科学版),2023,43(7):1011-1016

    • [27] NEDER J A.Exercise ventilation and dyspnea in the obese patient with chronic obstructive pulmonary disease:“how much”versus“how well”[J].Chron Respir Dis,2021,18:241483804

    • [28] OMAR M,OMOTE K,SORIMACHI H,et al.Hypoxaemia in patients with heart failure and preserved ejection fraction[J].Eur J Heart Fail,2023,25(9):1593-1603

    • [29] FERMOYLE C C,STEWART G M,BORLAUG B A,et al.Simultaneous measurement of lung diffusing capacity and pulmonary hemodynamics reveals exertional alveolar⁃capillary dysfunction in heart failure with preserved ejection fraction[J].J Am Heart Assoc,2021,10(16):e019950

    • [30] BUEKERS J,STAS M,AERTS R,et al.Daily allergy burden and heart rate characteristics in adults with allergic rhinitis based on a wearable telemonitoring system[J].Clin Transl Allergy,2023,13(4):e12242

    • [31] OMLOR A J,TRUDZINSKI F C,ALQUDRAH M,et al.Time-updated resting heart rate predicts mortality in patients with COPD[J].Clin Res Cardiol,2020,109(6):776-786

    • [32] FERMONT J M,MASCONI K L,JENSEN M T,et al.Biomarkers and clinical outcomes in COPD:a systematic review and meta⁃analysis[J].Thorax,2019,74(5):439-446

    • [33] LAGE V,DE PAULA F A,LIMA L P,et al.Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia[J].Exp Gerontol,2022,164:111834

    • [34] SPRUIT M A,WATKINS M L,EDWARDS L D,et al.Determinants of poor 6⁃min walking distance in patients with COPD:the ECLIPSE cohort[J].Respir Med,2010,104(6):849-857

    • [35] RA F,CL G,PB S,et al.Association of right ventricle diastolic diameter with pulmonary function,exercise tolerance and exacerbation period in patients with chronic obstructive pulmonary disease:a prospective study[J].Heart Lung,2022,55:11-15

    • [36] WASHKO G R,NARDELLI P,ASH S Y,et al.Smaller left ventricle size at noncontrast CT is associated with lower mortality in COPD gene participants[J].Radiology,2020,296(1):208-215

    • [37] MASSON S J,TANNUS S D,FURTADO R G,et al.Correlation between 2D strain and classic echocardiographic indices in the diagnosis of right ventricular dysfunction in COPD[J].Int J Chron Obstruct Pulmon Dis,2021,16:1967-1976

    • [38] ANTWI⁃BOASIAKO C,KOLLIE M F,KYEREMEH K A,et al.Associations between spirometric measures and exercise capacity in type 2 diabetes[J].Diabetes Metab Syndr,2023,17(8):102831

    • [39] ZHANG R H,ZHOU J B,CAI Y H,et al.Non⁃linear association between diabetes mellitus and pulmonary function:a population⁃based study[J].Respir Res,2020,21(1):292

    • [40] LIU W,LIU Y,LI X.Impact of exercise capacity upon respiratory functions,perception of dyspnea,and quality of life in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2021,16:1529-1534

    • [41] CAMARGO P F,DITOMASO-LUPORINI L,DE CARV-ALHO L J,et al.Association between the predictors of functional capacity and heart rate off⁃kinetics in patients with chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:1977-1986

    • [42] COX N S,DAL CORSO S,HANSEN H,et al.Telerehabil-itation for chronic respiratory disease[J].Cochrane Database Syst Rev,2021,1(1):CD013040

    • [43] FUJIMOTO Y,OKI Y,KANEKO M,et al.Usefulness of the desaturation-distance ratio from the six ⁃minute walk test for patients with COPD[J].Int J Chron Obstruct Pul-mon Dis,2017,12:2669-2675

    • [44] ZOU H,ZHANG J,ZOU Y,et al.Six⁃minute walking distance in healthy Chinese people older than 60 years[J].BMC Pulm Med,2020,20(1):177

    • [45] GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE(GOLD).Global Strategy for Prevention,Diagnosis and Management of chronic obstructive pulmonary disease 2024 report[EB/OL][.2023⁃ 11⁃15].https://goldcopd.org/2024⁃gold⁃report/