The Impact Of Respiratory Training On Exercise Capacity In Patients With COPD

BackgroundChronic obstructive pulmonary disease is a preventable and treatable common disease characterized by persistent airflow limitation,progressive airflow limitation was progress,and accompanied by airways and lungs to noxious particles or gases caused by chronic inflammation the reaction increases,exacerbations and complications affect the overall severity of the patient’s disease.Numerous studies have shown,COPD had an outer extensive lung injury(and systemic effects)systemic disease in addition to a persistent airflow limitation characterized by chronic airway disease,such as skeletal muscle(SMW)and dysfunction(SMD),weight loss,cardiovascular complications,malnutrition and physical constitution changes,among skeletal muscle dysfunction is systemic effects of COPD(ie,extrapulmonary one of the functions)of the outstanding performance,but also an important factor in the decline in the quality of life in patients with COPD.How to improve dyspnea,and quality of life is important and difficult COPD treatment.Recently pulmonary rehabilitation(PR)was considered as one of important non-drug treatments for COPD.Aerobic exercise has been proved its value in PR by based medicine.Breathing training is an important part of PR program for individuals with COPD.Its main objective is releasing dyspnea,enhancing exercise capacity by rectifying breathing pattern and improving respiratory muscle function.Several breathing training manoeuvers have been reported in the literature,which include diaphragmatic breathing,respiratory muscle training and pursed lips breathing.However,diaphragmatic breathing may be difficult for patients to perform.Because it takes therapists a lot of time to teach and supervise.Inspiratory muscle training can enhance inspiratory muscle strength via increasing the inspiratory impedance.It must increase the respiratory drive and exacerbate dyspnea feeling.Pursed lips breathing can release dyspnea for a short time,but it cannot improve breathing pattern and respiratory strength.It’s controversial for breathing retraining because:Firstly,it’s difficult to perform quantification and quality control.Secondly,it’s difficult to prove the efficiency because of the absence of large sample and multicenter clinical trial.Finally,breathing retraining program for now cannot either improve breathing pattern or enhance respiratory muscle strength.Therefore,it is necessary to develop a new breathing training method which can improve breathing pattern and respiratory muscle function on the base of perform quantification and quality control.We develop a new breathing training method based on the principle of respiratory feedback and neuromuscular electrical stimulation which aims at improving breathing pattern and respiratory muscle function.Respiratory Electrical Stimulation Training(REST)includes respiratory control system and electrical stimulation of respiratory muscle.It’s effectiveness has been proved in patients with COPD and patients following lung lobectomy.However,the efficacy of different frequency of phrenic nerve electrical stimulation and respiratory period has not been studied yet.In addition,the effect of REST on diaphragmatic contractility and exercise capacity of patients with COPD is also need to study.The study was divided into two parts:the first part:to assess the difference of biceps and quadriceps dysfunction in COPD patients by population survey,to analyze factors affecting the biceps and quadriceps muscle strength,and to assess lung before rehabilitation exercise capacity and quality of life of patients score;the second part:on the basis of the first part,through the analysis of respiratory electrical stimulation to explore role in improving COPD patients with dyspnea and exercise tolerance in the impact.Part I:Assessment of the lower limb skeletal muscle strength andexercise capacity of COPD patientsObjectives:To assess differences in COPD patients quadriceps and biceps function impairment through population-based surveys and analysis of relevant factors biceps and quadriceps muscle strength and pre-assessment of pulmonary rehabilitation in patients with exercise capacity and life quality score.Methods:1.Normal control group:from Guangdong general hospital(China,Guangzhou)health examination center,a total of 52 healthy volunteers as a control group,the study group.Inclusion criteria for the control group include:1)age,sex matched patients with COPD;2)normal lung function;3)patients without cardiopulmonary disease affect skeletal muscle function and other systemic diseases.2.COPD Group:110 COPD patients with mild to severe reduced lung function were enrolled from Guangzhou Sun Yat-sen Memorial Hospital.According GOLD2013 guidelines,after lung function as the gold standard,inhaled bronchodilators,FEV1/FVC<70%into the screening criteria.In addition,patients should also meet the following criteria:Age>40 years;bronchodilator test was negative;stable before enrollment eight weeks without acute episode patients;before enrollment eight weeks have not used oral or intravenous corticosteroids,but allowed inhaled corticosteroids;prior to enrollment or enrolled at the time have not received any functional rehabilitation;pre-selected or elected did not receive any nutritional support.Exclusion criteria:not willing to participate in this study;acute respiratory failure with severe COPD patients can not tolerate the muscle strength test;with severe cardiovascular disease,such as arrhythmia,heart failure and other complications associated with rheumatic disease or immune associated with neuromuscular diseases;with cerebrovascular sequelae;poor compliance,can not be required linkage;severe hypoxic respiratory failure patients;patients with mental illness disorders.All patients routine measurement of lung function,and are in the REST began to calm breathing before,and breathing exercise first 15min after the end of the first REST 5min detecting comprises tidal volume(VT),minute ventilation(VE),inspiratory time(Ti)expiratory time(Te),respiratory cycle(Ttot),respiratory rate(RR),etc.),ventilation index(including oxygen uptake(VO2),carbon dioxide ventilation(VCO2),etc.diaphragm activity,respiratory muscle surface EMG(including muscle,second intercostal muscles,diaphragm,rectus abdominis)the whole process of breathing exercise to assess a 5min dyspnea(Borg scale)intervals.Results1.Baseline informationA total of 110 cases of patients with stable chronic obstructive pulmonary disease and 52 controls were enrolled study.Baseline characteristics of the study are shown in Table 1.In gender,age,height,weight and body mass index,there was no statistical difference between the two groups.In which patients diagnosed with COPD GOLD A,B,C and D groups of patients were 16 cases(14.5%),50 cases(45.5%),36 patients(32.7%)and 8(7.3%).2.Compare skeletal muscle function between COPD patients and healthy controlsCOPD group with respect to the healthy control group,quadriceps and biceps muscle strength are reduced,especially quadriceps reduce statistically different(1.44±0.43 vs 0.93±0.24,P=0.013).3.Compare quadriceps and biceps muscle strength between different genderAfter stratification by gender found that women with COPD with respect to women’s health group quadriceps and biceps muscle strength showed no significant difference;male COPD patients and healthy control group compared to men quadriceps muscle strength were significantly lower(1.57±0.49 vs 0.9510.35,P<0.001),a statistically significant difference.4.Compare quadriceps and biceps muscle strength among different groups GOLDPress GOLD guidelines stable COPD patients were divided into A,B,C,D group,there are significant differences between the biceps and quadriceps muscle,D group were decreased significantly between the four groups most(four shares muscle:A:1.51± 0.45 B:1.07 ± 0.37 C:1.18 ± 0.55 D:0.85 ± 0.37;P = 0.007 biceps:A:0.57±0.11 B:0.32 ± 0.12 C:0.38 ± 0.12 D:0.26.± 0.10;P = 0.047).5.To assess relevant factor for QuadricepsThe results showed that quadriceps strength with age,smoking index and SGRQ activity score was negatively correlated;and FEV1,and score in the 6-minute walk distance was significantly correlated;male COPD patients with quadriceps decreased more significantly,with statistical significance.6.To assess decrease associated factor for Biceps muscle strengthBiceps muscle with age,smoking index and SGRQ activity score was negatively correlated;and FEV1,score in the 6-minute walk distance was positively correlated with statistical significance.Biceps muscle but no significant correlation with gender.7.Multivariate analysis for Quadriceps,biceps muscleMultiple linear regression analysis showed that age,BMI and smoking muscle strength index are four significant predictors,together comprising 23.9%of the four muscle strength;the age,FEVi and smoking index biceps PT predictor comprising 20.6 percent of the biceps muscle.Conclusions:1.COPD patients quadriceps and biceps muscle strength decreased,especially in male patients with COPD decreased more significantly.2.The degree of airflow limitation in patients with COPD and its upper and lower limb muscle strength was positively correlated with the extent of damage.3.Age and smoking indexx was significant predictors for biceps and quadriceps muscle damage of COPD patients.Part II:The effect of NMES on dynamic hyperinflation during the 6-minute walk test in patientswith COPDObjectives:(1)To evaluate the efficacy and safty of NMES technique in Chinese COPD patients;(2)To investigate the effect of short-term,high-frequency NMES on DH during the 6MWT in patients with COPD.Methods:The present study is a prospective double blinded randomized trial.The ethic committee of Guangzhou Sun Yat-sen Memorial Hospital approved the study.All patients signed the consent.The research was registered at clinical website(No.ChiCTR-TNRC-15006234;Website:http://www.chictr.org/en/).The investigators examined all the subjects at the beginning(baseline)and the end of the 12-week study.Each session of the examination successively included anthropometric measurements,pulmonary function tests,IC maneuvours,6MWT,assessment of quality of life and dyspnea,measurements of quadriceps function.Results:There were no significant differences between two groups in any of the baseline characteristics.No significant changes were observed in VO2(t=1.045,P=0.331),heart rate(t=-1.387,P=0.208),VE(t=-0.614,P=0.559),respiratory rate(t=-1.905,P=0.098),SPO2(t=-0.935,P=0.381)and Borg dyspnea scale(t=-1.520,P=0.170)between the final NMES training session and the sham training session.After the training period,isokinetic quadriceps peak torque and isokinetic total work showed no significant change both in NMES training group and in sham group.At the end of training,no significant change of 6MWD was observed both in NMES training group(t=-0.498,P=0.625)and in sham group(t=1.012,P=0.338).In NMES training group,NMES training increased IC(t=-4.472,P<0.001)significantly at the end of 6MWT,but without changes in IC(t=0.655,P=0.521)or other variables of pulmonary function at rest.No changes of IC and other variables of pulmonary function at rest were observed in sham group.In the NMES training group,NMES training decreased significantly the SGRQ total score(t=3.710,P=0.002),activity domain score(t=2.432,P=0.026)and impactdomain score(t=3.463,P=0.003),no statistically significantimprovementsin symptom domain score(t=2.041,P=0.056)were observed.No significant changes of SGRQ total scoreand each domain score were observed in controls.MMRC dyspnea scaledecreased from 1.37 ±0.50 to 0.89 ±0.94(P=0.025)afterNMES training.No significant change was observed in sham group(1.40 ±0.52 to1.20±0.63,P=0.443).Muscle stimulation was well tolerated by thepatients with no dropouts and had95%compliance with theprotocol.Conclusions:1.NMES can be a safe and effective strategy for rehabilitating patients with moderate to severe COPD.2.NMES may improve the exercise tolerance in COPD patients,these benefits may be associated with reduction in dynamic hyperinflation.Part III:Effect of Respiratory Training on COPD patients with dyspnea,exercise toleranceObjectives:To observe breathing electrical stimulation training on dyspnea,exercise tolerance,quality of life in patients with COPD,and correlation analysis with respiratory musclesquadriceps was done to explore the breathing electrical stimulation changes dyspnea,exercise tolerance underlying mechanisms.Methods:Stable moderate to severe COPD patients were enrolled in the out-patient clinics of Guangdong general hospital from July 2013 to December 2014.The COPD diagnosis was confirmed with clinical presentation and spirometric testing.All the patients were randomized to receive REST or control.Control group received usual care and respiratory physiology education.Train group received usual care and respiratory physiology education the same as control group.Besides,they took a 30 min long respiratory period and high frequency of phrenic stimulation of REST for 12 weeks,two sessions per week.Measurements at baseline and post-training are as following:pulmonary function,diaphragmatic contractility(include diaphragmatic motion,thickening ratio and maximal contractive velocity),respiratory strength(maximal inspiratory pressure,MIP and maximal expiratory pressure,MEP),ventilation,MRC scale of dyspnea and 6 minutes walking distance.(1)phrenic nerve and muscle stimulation:There are two alternating current output channels,A bi-directional symmetrical square wave channel output,the output frequency is 30Hz,pulse width of 0.5ms,stimulating electrodes placed on both sides of the sternocleidomastoid 1/3 foreign aid to stimulate the phrenic nerve;B-channel low-frequency modulation frequency sine wave output,the carrier frequency of 4kHz,frequency modulation wave 50Hz,stimulate the rectus abdominis.(2)respiratory Feedback:patient comfort sitting in the level of the umbilicus tie cummerbund,cummerbund by a simple baroreceptor connected to the computer,you can visually see the abdominal contraction and relaxation cycle,set the respiratory cycle time based on the patient’s condition,combined with the sound of the instrument instructions issued suction start time "suck" instruction,issued a "call" instruction exhalation start time,according to the patient to adjust sound and light tips respiratory muscle rhythm.(3)abdominal breathing:abdominal muster the patient inhales,exhale relax the abdomen,the entire process requires breathing try to relax the neck chest).12 patients completed the training weekend again performed above indicators were detected.Results:1.Baseline demographic and clinical characteristics49 subjects with COPD were enrolled in this study with 65 subjects completed the study.In training group,24(20 males and 4 female,70.45±5.98 years)were enrolled in the study and 3 drop out.In control group,24(22 males and 3 female,68.59±5.395 years)were enrolled in the study and 5 drop out.There was no significant difference in the baseline measurements including average age,BMI,pulmonary function,diaphragmatic contractility,respiratory muscle strength,ventilation,exercise capacity and dyspnea.However,forced expiratory training group than in the control group,large diaphragm thickness(P<0.05).2.Impact on pulmonary functionIn training group,IC and PEF increased significantly after 12 weeks’ REST compared to baseline values(all P<0.05).No significant changes(all P>0.05)were found in other pulmonary function parameters,including FEVi,FEV1%pre,FEVi/FVC and FVC.In control group,no significant changes were observed in all the pulmonary function parameters(all P>0.05)at the end of 12 weeks.IC after intervention training group was significantly greater than in the control group(P<0.01),the other two groups showed no significant difference in lung function(P>0.05).3.Impact on Biceps and quadriceps muscleTraining group and control groups of quadriceps,biceps peak torque and its peak torque kg had no significant effect(P>0.05).4.Impact on Maximum respiratory pressure(1)Comparison of intervention:exercise group after intervention MIP,MEP compared with an increase(P<0.01;in the control group 12 weeks MIP,MEP no significant difference(P>0.05).(2)between the two groups:training group after intervention MIP,MEP were significantly higher than the control group(P<0.01).5.Impact on Diaphragmatic activity(1)Comparison of intervention:exercise group after intervention QDM,FDM was increased compared with 12 weeks ago(P<0.05 or P<0.01);QDM,FDM was no significant difference(P>0.05)before and after 12 weeks in the control group.(2)between the two groups:training group after intervention QDM,FDM were significantly higher than the control group(P<0.05 or P<0.01).6.Impact on 6-MWD6-MWD increased significantly after 12 weeks compared to baseline values in training group(464.83±53.79m vs 521.65±50.12m,P<0.05).At the end of 12 weeks,no significant change was observed in 6-MWD in control group(P>0.05).7.Impact on ventilation during exercise(1)RR,VD/VT and VE/VCO2 at the end of CPET decrease significantly and Ttot increased significantly after 12 weeks compared to baseline values in training group(P<0.05).However,VO2/kg at the end of CPET decrease significantly(16.06±2.4L/kg/min vs15.56±2.07 L/kg/min,P<0.05).At the end of 12 weeks,no significant change was observed in ventilation during exercise in control group(P>0.05).(2)Between the two groups:training group after intervention Borg index,VD/VT were lower than the control group(P<0.05).8.Impact on MRC and SGRQAfter the training group before intervention SGRQ total score,symptom score,activity score,impact score and MRC scores were 12 weeks significantly reduced(P<0.01);in the control group,MRC and SGRQ scores were not significantly different(P>0.05).(2)between the two groups:training group SGRQ total score,symptom score,activity score,impact score and MRC scores were less than the control group(P<0.01)9.Pearson’s correlation analysis was done about training group feedback electrical stimulation before and after training FDM difference between 6-MWD(R=0.304,P<0.05).The results suggest that patients improved 6-minute walk test distance(A6-MWD)and forced expiratory diaphragmatic activity increase(△FDM)linear correlation,but the degree of correlation in general.10.Pearson’s correlation analysis was done about 6-minute walk test distance improved degree(△6-MWD)and maximum inspiratory pressure degree of improvement(△MIP)(R=0.7115 P=0.00),results suggest that 6-MWD degree of improvement and MIP improve degree of linear correlation,and a strong degree of correlation.11.Pearson’s correlation analysis was done about Quality of life symptom score improved degree(△Symp)and quiet breathing diaphragm activity improve the degree(△QBDM)(R=-0.576,P = 0.00),the results suggest that patients with health-related quality of life improved and quiet breathing diaphragm activity negatively correlated increase its relevance as moderate.Conclusions:Respiratory Electrical Stimulation Training could enhance respiratory muscles strength not peripheral skeletal muscle function in COPD patients.