慢性阻塞性肺疾病患者的静息肺功能与最大摄氧量之间的关系探讨
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摘要
研究背景:
     慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)是一种以气流受限为特征的疾病。气流受限呈不完全可逆,并呈进行性发展,与肺部对有害气体或有害颗粒的异常炎症反应有关。COPD是呼吸系统疾病中的常见病和多发病,患病率和病死率均高,本病的主要临床特征不仅可表现为肺内部炎症性改变,而且还会影响到肺结构的改变,因肺功能减退,严重影响患者的劳动力、生活质量和运动耐力,世界卫生组织(WHO)资料显示,在北美地区,COPD的死亡率居所有死亡原因的第四位,且有逐年增加之势。以美国为例,到2020年,由COPD引起的死亡将由第四位上升的第三位。
     静息肺功能检查(resting pulmonary function test, PFT)是判断气流受限的主要客观指标,对于COPD的诊断、严重程度评价、疾病进展、预后和治疗反应等有重要意义。常用的主要指标包括第1秒用力呼气容积占有力肺活量百分比(FEV1/FVC)及第一秒用力呼气容积(FEV1), FEV1/FVC是评价气流受限的一项敏感指标,是评估COPD严重程度的良好指。FEV1占预计值的百分比是COPD诊断、疾病分级及评估预后的常用指标,但FEV1主要反映气流阻塞的情况,对COPD评价有一定的局限性,无法反映患者在运动状态下的运动耐量和心肺功能的储备。
     运动心肺功能测试(Cardiopulmonary exercise testing,CPET)是指综合评价运动状态下(包括呼吸系统、心血管系统、血液系统、神经系统、骨骼肌肉系统等在内的)器官系统的整体功能,它是一种相对无创性、评价心肺储备功能和运动耐力的检测方法,综合应用呼吸气体监测技术、电子计算机和活动平板或踏车技术,实时检测在不同负荷条件下,机体氧耗量和二氧化碳排出量的动态变化,从而客观、定量地评价心肺储备功能、运动耐力,为医师诊断提供相应临床资料。CPET是目前普遍使用的衡量人体呼吸和循环机能水平的心肺功能检查方法之一。
     CPET中的最大摄氧量(VO2 max)是指受试者在运动的最后阶段,竭尽全力,循环和呼吸系统发挥最大作用时组织细胞每分钟摄取的氧量,其正常值可以通过性别、年龄、身高、体重等来预计,但实际所测得的值则与肺的呼吸(包括通气与换气功能),心血管的循环,肌肉组织的摄氧这三大系统能力的高低及偶联活动有关,主要反映了患者运动耐力的情况,与PFT或单一心功能检测相比,在预测手术并发症和疾病死亡率方面更有优势。
     但由于一些原因使得CPET未能广泛应用,一些研究COPD患者静息肺功能与运动心肺功能关系的研究中发现相比较于静息肺功能,运动心肺试验更能预测COPD患者的生存率及运动耐量,另外研究还发现静息肺功能检查中的—些指标与CPET中VO2max有一定的相关性,其中比较常见的指标为FEVI、MVV、PEF等。另外国外有学者通过研究静息肺功能与VO2max之间关系,推出计算VO2max的计算公式。
     研究目的:
     验证国外VO2vmax公式的准确定及适用性,通过国内静息肺功能检查结果总结出其与最大摄氧量的关系的计算公式并验证公式的准确性。
     研究对象:
     2009年1月-2010年2月就诊于广东省人民医院内科门诊,行静息肺功能检查的慢性阻塞性肺疾病患者129名,以时间段划分,2009年1月-2009年10月间,共104名患者纳入前期研究,其中男性74例,女性30例,为试验组。2009年11月-2010年2月共25名患者纳入后期研究,其中男性18例,女性7例,为验证组。
     1、入选标准:慢性阻塞性肺病稳定期,避免急性加重至少3个月以上,并且停用吸入性短效β2受体兴奋剂或抗胆碱能要4-6小时,停用口服短效β2受体兴奋剂或茶碱8小时,长效或缓释型停用24小时以上,抗组胺药物停用48小时,糖皮质激素口服停24小时,吸入停12小时。
     2、排除标准:
     (1)哮喘患者或既往患有支气管哮喘病史患者或行支气管舒张试验阳性患者。
     (2)吸入室内空气情况下严重低氧血症(PaO2<45mmHg)或高碳酸血症(PaCO2>70mmHg);
     (3)FEV1<20%;
     (4)重身体畸形未纠正者及身高<155cm者;外周血管疾病或神经系统疾病所致的运动受限;贫血;
     (5)严重肺动脉高压;
     (6)糖尿病者;
     (7)高血压者;
     (8)心脏疾病患者(如冠状动脉粥样硬化性心脏病;近期心肌梗塞;不稳定心绞痛;急性肺栓塞或肺栓塞;Ⅱ-Ⅲ度心脏房室传导阻滞;快速室性/房型心律失常;严重的主动脉狭窄者;充血性心力衰竭;室壁动脉瘤;心脏瓣膜疾病等):
     (9)拒绝行纳入本研究或行运动心肺功能检查者。
     研究方法:
     1.静息肺功能测定及动脉血气分析
     记录所有受试者的身高、体重、性别、根据公式计算BSA及BMI并记录。参照ATS/ERS(美国胸科协会/欧洲呼吸协会)肺功能仪器指控标准,对所有受试者进行静息肺功能检测,测试参数:(1)用力肺通气功能:用力肺活量(FVC)、第一秒用力肺活量(FEV1)、第一秒用力呼吸容积与用量肺活量的比值(FEV1/FVC)、第三秒用力肺活量(FEV3)、用力呼气中期平均流速(FEF25%-75%)、最大呼气流量(PEF);(2)最大自主通气功能:MVV;(3)肺容积检查:肺活量(VC)、深吸气量(IC)、肺总量(TLC)、残气量(RV);(4)气道阻力测定;Raw;(5)弥散功能测定:DLCO;动脉血气分析:PH、PO2、PCO2
     2.运动心肺功能测定
     运动仪器采用功率自行车(踏车)测试。
     3.运动试验方法
     采用1分钟斜坡式递增功率自行车(踏车)方案,运动试验开始,最初3分钟热身为无负荷踏车运动(0W),3分钟后递增运动开始,保持每分钟增加同一功率,直至患者受症状限制或不能继续安全运动为止,并记录最大摄氧量数值(VO2max),整个运动过程车速保持在60 rpm。
     4.用于估计最大摄氧量Efremidis等人的的计算公式:
     VO2max(L/min)=(FEF25.75%×0.47)+(BAS×0.988)+(MVV×0.024)-0.913 (r2=0.81)
     5、统计学方法
     采用SPSS13.0统计软件包对数据进行统计学分析,计量资料采用均数±标准差(x±s)描述,两样本均数比较采用两独立样本t检验,静息肺功能、动脉血气分析各指标与运功心肺功能测定的VO2max相关关系采用多元线性回归方法中逐步回归方法对数据进行回归分析,得出回归方程。P<0.05,表明差异具有统计学意义。
     研究结果:
     1.试验组共纳入104名COPD患者,其中其中男性74例,女性30例,其中属于慢性阻塞性肺疾病Ⅰ级12人,Ⅱ级81人,Ⅲ级11人,Ⅳ级0人,验证组共纳入25名COPD患者,其中男性18例,女性7例,属于慢性阻塞性肺疾病Ⅰ级1人,Ⅱ级24人,Ⅲ和Ⅳ级0人,一般资料为平均年龄(65.57±6.71与64.56±7.56,t=0.657;P=0.512),身高(1.64±0.07与1.66±0.08;t=-1.131;P=0.260),体重(58.48±9.63与59.36±8.32;t=-0.420,P=0.675),BSA(1.60±0.14与1.62±0.12;t=-0.724;P=0.470),BMI(21.66±3.69与21.63±3.65;t=0.045;P=0.965),两组静息肺功能FVC实测值为(2.95±0.55与3.12±0.65;t=-1.380;P=0.170),FVC占预计值百分比分别为(87.05±12.88与89.84±9.34),FEV1实测分别为(1.72±0.42与1.80±0.38;-0.840;P=0.402),FEV1占预计值百分比分别为(65.31±12.57与66.84±9.86),FEV1/FVC%分别为(58.14±8.30与57.80±8.82),FEV3实测值分别为(2.39±0.62与2.60±0.63;t=-1.484;P=0.140),FEV3占预计值百分比分别为(75.10±15.50与80.44±11.95),FEF25-75%实测值分别为(1.03±0.49与1.04±0.37;t=-0.101;P=0.920), FEF25-75%占预计值百分比分别为(44.43±17.40与43.92±15.00),FEF50%实测值分别为(1.11±0.49与1.18±0.45,t=-0.582;P=0.562),FEF50%占预计值百分比分别为(34.13±13.54与35.88±12.88),FEF75%实测值分别为(0.36±0.15与0.35±0.18;t=0.343;P=0.732),FEF75%占预计值百分比分别为(42.57±20.13与47.00±32.51),PEF实测值分别为(3.83±1.22与4.23±1.27;t=-1.433;P=0.154),PEF占预计值百分比分别为(47.72±13.35与51.44±13.44),MVV实测值分别为(60.00±18.43与62.12±15.79;t=-0.530;P=0.597),MVV占预计值百分比分别为(56.31±14.59与59.36±13.63),VC实测值分别为(3.12±0.55与3.20±0.56;t=-0.640;P=0.523),VC占预计值百分比分别为(89.90±11.62与91.56±9.94),IC实测值分别为(1.60±0.54与1.66±0.42;t=-0.512;P=0.609),IC占预计值百分比分别为(62.72±19.79与65.84±16.83),TLC实测值分别为(6.73±0.73与6.78±0.87;t=-0.291;P=0.772),TLC占预计值百分比分别为(117.62±9.91与120.12±11.92),RV实测值分别为(3.48±0.49与3.53±0.66;t=-0.514;P=0.608),RV占预计值百分比分别为(149.93±28.93与149.16±28.10),RV/TLC百分比分别为(52.71±6.42与52.28±5.96),DLCO占实测值百分比分别为(80.87±19.74与83.32±14.70;t=-0.583;P=0.561),Raw实测值分别为(3.18±0.47与2.95±0.40;t=2.295;P=0.023),PH分别为(7.42±0.04与7.42±0.04;t=0.223;P=0.824),PO2分别为(11.52±0.84与10.80±0.85;t=3.845;P=0.000),PCO2分别为(4.31±0.57与4.37±0.27,t=-0.752;P=0.454)
     2.通过Efremid is等人推算VO2max计算公式与试验组实测值之间的比较(x±s)。可见试验组实测值为1.06±0.30,由于Efremidis等人推算出的VO2max为2.59±0.71,t=20.267,P<0.001。
     3.以年龄、身高、体重、BMI、BAS、FVC、FEV1、FEF3、FEF25-75%、FEF50%、FEF75%、PEF、MVV、VC、IC、TLC、RV、DLCO、Raw为自变量、最大摄氧量为因变量,进行多元线性回归,采用逐步回归分析得出预测最大摄氧量的公式:VO2max(L/min)=(FEF25-75%×0.133)+(BAS×0.603)+(MVV×0.003)+(DLCO×0.005)-0.646 (R2=0.716)
     4.验证组中通过上述公式算出的VO2max(1.07±0.17)与验证组实测值(1.08±0.24)相比较,t=0.150,P=0.881,表明验证组实测VO2max和经公式推算出的VO2max差异不具有统计学意义。
     研究结论:
     1、通过与Efremidis等人推算出最大摄氧量的计算公式,(即VO2max(L/min) =(FEF25-75%×0.47)+(BAS×0.988)+(MVV×0.024)-0.913)相比,实际测出的VO2max明显低于通过公式推算数值,表明不适用于国内COPD患者。
     2、通过对于国内慢性阻塞性肺疾病患者的静息肺功能及运动心肺功能检查结果,首次总结出运动心肺功能中最大摄氧量(VO2max)与静息肺功能指标的关系,通过多元线性回归分析得出计算公式:VO2max(L/min)=(FEF25-75%x 0.133)+(BAS×0.603)+(MVV×0.003)+(DLCO×0.005)-0.646(R2=0.716),考虑最大摄氧量与FEF25-75%、BAS、MVV及DLCO相关。
     3、经过验证组验证公式:VO2max(L/min)=(FEF25-75%×0.133)+(BAS×0.603)+(MVV×0.003)+(DLCO×0.005).0.646(R2=0.716)初步考虑可用于推算VO2max。
Background:
     Chronic obstructive pulmonary disease (COPD) is characterized by slowly progressive development of airflowlimitation that is not fully reversible and it will be exacerbation. The cause of disease have relation with abnormal Inflammation cause by harmful gas or grains. It is very common,and the prevalence and mortality is higher than others.The clinical feature is not only in Inflammation in lung but also affect the structure of the lung,due to the decrease of pulmonary function, It is the fourth leading cause of death in the United States but is expected to be the thirdby the year 2020.
     Resting pulmonary function test(PFT), is a major marker to certificat flow limitation which is ues the dignosis of COPD,and the degree of the disease,also affect the treatment and Prognosis.the most common index are FEV1/FVC and FEV1,FEV1/FVC is a sensitive indsx to evaluate the flow limitation,and it is a better index to evaluate the degree of COPD.FEV1 prediction is a uesfull index in dignosis of COPD and to classification also to prognosis.but FEV1 is reflected the degree of flow limitation, localized in evaluating COPD.because it can't reflected exercise tolerance and cardiac pulmonary reserve under exercise.
     Cardiopulmonary exercise testing(CPET)provides a global assessment of the integrative exercise responses involving pulmonary,cardiovascular,blood, neuropsycho logical, and skeletal muscle systems. CPET is an important element of physique study and healthy physical ability evaluation in various countries. It is arelatively noninvasive method, evaluating reserve function of the lungs and the heart,and exercise intolerance.It synthesizes the application breath gas monitor technology,the computer and the treadmill or the cycle technology,real-time examination under different load condition,organism oxygen consumption quantity and carbon dioxide displacement dynamic change, so that it objectively and quantitatively evaluates the reserve function of the lungs and heart and exercise intolerance, providing the physician with relevant information for clinical decision-making. CPET is one of the universal cardiopulmonary functional check methods in evaluating human respiration and cireulationmction levels
     The peak oxygen uptake (VO2 max) is that respiratory system and circulatory system intake the oxygen per min when people exhausted.using VO2 max/kg, eliminated the impact of weight, which could ues gender,age,hight,,weght,and exercise to predict.,but the real value is related with respiration, circulation of cadiovascular,and intake the oxygen of muscles.it is reflecting the exercise tolerance. compare with PFT or single heart function test,which is better in predicting complication and mortality after surgery but it is not appling generally,because some reason, some studies conclude compare with PFT,CPET is better in predicting survival rate and exercise tolerancein COPD,and the VO2max in CPET is related with PFT.also,in research the relationship between PFT and CPET.other stadies discovery some indexs are related with VO2max,for FEV1,MVV,PEF.some reaserch concluded the formula to account VO2max on abroad.
     Summary Purpose:
     The purpose of this study was to test the accuracy and practicality of formula,and examine exercise tolerance in patients with COPD from measurements of resting pulmonary function parameters,and to test the accuracy and practicality of formula which conclude from this reaserch.
     Objective:
     Subjects:During January 2009 and February 2010,129 out-patient of COPD in Gangdong provincial people's hospital needing PET.According to the date,from January 2009 to October 2009,104 out-patient as test groupmarriage, male 74,female 30.From november 2009 to February 2010,25 out-patient as a proog group,male member 8,female 7.
     1.Select normal people standard:stable COPD, avoid AECOPD at last 3months,and stop using Short-acting inhaledβ2-agonists or Anticholinergics at lest 4-6 hours,stop using Short-acting oralβ2-agonist or Theophylline at lest 8 hours,and the long-acting at lest 24 hours.stop using antihistaminc at lest 48 hrous, and avoid oral Corticosteroids at lest 24 hours and inhaled at lest 12 hours.
     2. Eliminated standard:
     (1)asthma or history of asthma or bronchodilatation is positive
     (2)severe of hypoxemia(PaO2<45mmHg) or hypercapnemia(PaCO2>70mmHg);
     (3)FEV1<20%;
     (4)abnormalities or heghts<155cm, periphery vessels disease or nervous system diseases which lead to limitated exercise; anemia
     (5)severe pulmonary hypertension.
     (6)diabetes mellitus
     (7)hypertension
     (8)heart disease(coronary heart disease; myocardial infarction; angina pectoris, acute pulmonary embolism or pulmonary embolism;Ⅱ-Ⅲdegree atrioventricular block; severe arrhythmia; severe aortic stenosis; congestive heart failure; heart valve diseases);
     (9)rejection participate our research.
     Methods
     1. Resting pulmonary function check and arterial blood gas analysis:Before the test, accurately record height, weight, age, sex,BSA,BMI.The pulmonary function test using ATS/ERS control standard. Spirometry(FVC, FEV1, FEV1/FVC, FEF3, FEF25%-75%, PEF), MVV, VC, IC, TLC, RV, Raw,, DLCO, and the value of the prediction were performed and arterial blood gas analysis.
     2. CPET check:The exercise instrument uses ergometry cycling.
     3. Exercise testing method:
     Data were subsequently collected during a 1-min rest period followed by a 3-min period of unloaded cycling. The patient then continued to exercise on a ramp-patterned incremental exercise test until exhaustion occurred. The work rate was increased at a same rate, depending on the formula. A visual pedal rate indicator maintained a pedalling frequency of 60 revolutions/min. throughout each test.
     4. Assessment VO2max
     VO2max (L/min)= (FEF25-75%×0.47)+(BAS×0.988)+(MVV×0.024)-0.913 (r2=0.81)
     5. Statistical method:
     Carried on the data processing using the SPSS 13.0 statistics soft-ware. The measurement material expressed with the mean value±standard deviation. Beteen the VO2max of Formula to calculate and VO2max from CPET ues independentt-test.P<0.05(two-tailed test) was considered statistically significant. Stepwise multiple regression was performed on the test group to determine the best predictors of VO2max from independent variables.
     Result:
     1.104 patients in testing group (male 74,female 30).stage 1 of COPD is 12,stageⅡof COPD is 81,stageⅢof COPD is 24;stegeⅣof COPD is 0,25patient in proof group (male 18,female 7), stage 1 of COPD is 1,stageⅡof COPD is 11,stageⅢandⅣof COPD is 0,the mean value±standard deviation of testing group and proof group,the results are mean age (65.57±6.71 vs 64.56±7.56, t=0.657; P=0.512), hights(1.64±0.07 vs 1.66±0.08;t=-1.131;P=0.260),weight(58.48±9.63 vs 59.36±8.32;t=-0.420,P=0.675),BSA(1.60±0.14 vs 1.62±0.12;t=-0.724;P=0.470), BMI(21.66±3.69 vs 21.63±3.65;t=0.045;P=0.965),FVC(2.95±0.55 vs 3.12±0.65;t=-1.380;P=0.170),FVC% prediction(87.05±12.88 vs 89.84±9.34), FEV1(1.72±0.42 vs 1.80±0.38;t=-0.840;P=0.402),FEV1%prediction(65.31±12.57 vs 66.84±9.86),FEV1/FVC%(58.14±8.30 vs 57.80±8.82),FEV3(2.39±0.62 vs 2.60±0.63;t=-1.484;P=0.140),FEV3% prediction(75.10±15.50 vs 80.44±11.95),FEF25-75%(1.03±0.49 vs 1.04±0.37;t=-0.101;P=0.920), FEF25-75% prediction(44.43±17.40 vs 43.92±15.00),FEF50% (1.11±0.49 vs 1.18±0.45,t=-0.582;P=0.562),FEF50% prediction(34.13±13.54 vs 35.88±12.88)FEF75%(0.36±0.15 vs 0.35±0.18;t=-0.343;P=0.732),FEF75% prediction (42.57±20.13 vs 47.00±32.51),PEF(3.83±1.22 vs 4.23±1.27;t=-1.433;P=0.154),PEF% prediction(47.72±13.35 vs 51.44±13.44),MVV(60.00±18.43 vs 62.12±15.79;t=-0.530:P=0.597),MVV% prediction(56.31±14.59 vs 59.36±13.63),VC(3.12±0.55 vs 3.20±0.56;t=-0.640;P=0.523),VC% prediction (89.90±11.62 vs 91.56±9.94),IC(1.60±0.54 vs 1.66±0.42:t=-0.512;P=0.609) and IC% prediction(62.72±19.79 vs 65.84±16.83),TLC(6.73±0.73 vs 6.78±0.87;t=-0.291;P=0.772)and TLC% prediction(117.62±9.91 vs 120.12±11.92), RV(3.48±0.49与3.53±0.66;t=-0.514;P=0.608)and RV%prediction(149.93±28.93 vs 149.16±28.10),RV/TLC(52.71±6.42 vs 52.28±5.96),DLCO% prediction(80.87±19.74 vs 83.32±14.70;t=-0.583;P=0.561),Raw(3.18±0.47 vs 2.95±0.40:t=2.295;P=0.023),PH(7.42±0.04 vs 7.42±0.04;t=0.223;P=0.824),PO2(11.52±0.84 vs 10.80±0.85;t=3.845;P=0.000),PCO2(4.31±0.57 vs 4.37±0.27,t=-0.752;P=0.454)
     2.The VO2max calculation beteen fOrmula calculate(2.59±0.71)and CPET test(1.06±0.30),t=20.267,P<0.001。
     3.Using age,height,weight,BMI、BAS、FVC、FEV1、FEF3、FEF25-75%、 FEF50%、FEF75%、PEF、MVV、VC、IC、TLC、RV、DLCO、Raw as independent variables and VO2max as dependent variable, Stepwise multiple regressions in variables revealed that peak oxygen consumption (VO2 max) was predicted best by the following equation:VO2max (L/min)=(FEF25-75%×0.133)+(BAS×0.603) +(MVV×0.003)+(DLCO×0.005)-0.646 (R2=0.716)
     4. In the proof group the VO2max calculation beteen Formula calculate(1.07±0.17) and CPET test(1.08±0.24), t=0.150, P=0.881.
     Conclusion:
     1. Compare with formula of Efremidis,VO2max is highter than the real test value, P<0.001 which was considered statistically significant.
     2、Stepwise multiple regressions in variables revealed that peak oxygen consumption (VO2max) was predicted best by the following equation:VO2max (L/min)= (FEF25-75%×0.133)+(BAS×0.603)+(MVV×0.003)+(DLCO×0.005)-0.646 (R2=0.716) for the first time.maximum exercise tolerance is predicted reasonably well from measurements of resting pulmonary function in these COPD patients. The most consistent predictors of VO2 max were measurements of FEF25-75%, MVV, BAS and DLCO.
     3、In the proof group compare with formul:VO2max (L/min)= (FEF25-75%×0.133)+(BAS×0.603)+(MVV×0.003)+(DLCO×0.005)-0.646 (R2=0.716), and the real test value was not considered statistically significant,which can used to calculate VO2max.
引文
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