| Objective1.To study the changes of respiratory function,exercise endurance and quality of life in subjects of two groups with chronic obstructive pulmonary disease(chronic obstructive pulmonary disease,COPD),and to evaluate the effect of acupuncture on the pulmonary rehabilitation of chronic obstructive pulmonary disease in stable period.2.To study the situation of reaching standard of target heart rates during aerobic exercise training in two groups of COPD subjects,and to evaluate the optimization effect of acupuncture on pulmonary rehabilitation in two groups of COPD in stable period.3.To study changes of body mass index(BMI),serum inflammatory factors,insulin growth factor and skeletal muscle(quadriceps)myoprotein expression and interaction mechanism of two groups of COPD subjects before and after treatment,to explore mechanism of acupuncture on pulmonary rehabilitation and skeletal muscle atrophy of two groups of subjects with stable COPD.Methods1.Study 1:Effect of electroacupuncture with aerobic exercise on respiratory function and exercise tolerance of stable COPD patientsRecruit 85 stable COPD subjects aged 40-75 years old,set a randomized controlled trial according to the random number table generated by SPSS software and divide them into true needle+aerobic exercise group(hereinafter referred to as "true needle group")and placebo needle+aerobic exercise group(hereinafter referred to as "placebo needle group").Single-blind method was adopted in the efficacy evaluation of indexes of lung function,exercise cardiopulmonary tests,6-minute walking distance and scales.(1)GroupingTrue needle+aerobic exercise group(true needle group)Mainacupoints:CV17/Danzhong,ST18/Rugen(bilateral),CV4/Guanyuan,CV12/Zhongwan,ST25/Tianshu(bilateraI),ST 1 6/Yingchuang(bilateral).Alternative acupoits:LI4/Hegu(unilateral)or ST40/Fenglong(unilateral).Operation:Subjects took the supine position,acupoints were disinfected with iodine,fixed the tube and base after disinfection on the corresponding acupoints,needles(0.30 in lengeh and 25mm in diameter)were inserted beneath the skin through the tubes with the depth of 3 mm without manipulation.Attach the electrodes of the low-frequency electronic pulse therapy equipment to 10 acupoints with continuous wave,frequency of 2 Hz,needle would be withdrawn after retention for 30 min.Aerobic exercise trainingIt began 5 min after each acupuncture,using ergometry.Heart rate,blood pressure,and oxygen saturation values in the resting state were measured before and after training.According to the Karvonen’s formula,the heart rate of the each subject was calculated as the exercise intensity,resistance was controlled between 0.5-2.0kp,duration of exercise was 40 min.For those who could not tolerate high intensity,duration should not be less than 10 min.Fluctuation range of heart rate and blood oxygen and total miles were recorded at time zones of 0-5min,5-10min,10-20min,20-35min and 35-40min,the purpose was to observe and compare whether the actual heart rate fluctuation range of the subject matched the target heart rate,so as to judge whether the actual heart rate of the exercise reached the standard and record the standard duration.Among them,0-5min and 35-40min were warm-up and cool down stages with the resistance of zero.Adjust the resistance according to heart rate change from the second time zone(i.e.5min).Termination criteria:the international Borg scale and rate of perceived exertion scale(RPE),the training was terminated when the point>7 or RPE>14.Placebo needle+aerobic training group(placebo needle group)Acupoint selection:the same with that of true needle group.Operation:appearance of the placebo needles(0.30 in lengeh and 25mm in diameter)is the same as the true needle,but the tip is blunt and flat without being stabbed under the skin,also attached with plastic tube and silicone base,the operation,electrodes connection mode and parameters of the equipment were no different from true needle group.Aerobic training method was undergone in the same way as the true needle group.(2)Treatment course:treatment frequency were the same for two groups,subjects were treated once the other day after inclusion of the trial,3 times in 1 week,totally 24 treatments in 2 months.(3)Indexes for evaluation:Primary outcome measures:① pulmonary function test indexes ② cardiopulmonary exercise test indexes ③ 6 minutes walking distance(6MWD).Secondary outcome measures:① Scores of COPD Assessment Test(CAT)② scores of modified British Society for Medical Research dyspnea(mMRC)③ COPD comprehensive grade④safety outcomes:adverse events/adverse reactions occurring during the intervention.(4)Time points for evaluation are the same for two groups.Indexes of pulmonary function test and cardiopulmonary exercise test were evaluated at baseline and after the 24th treatment.The remaining outcome measures were evaluated at baseline,after the 14th treatment and after the 24th treatment.2.Study 2:The optimal effect of acupuncture for aerobic exercise in pulmonary rehabilitation for stable COPD patientsSource of subjects and intervention were totally the same as in study l,the situation of reaching standard of target heart rates during the whole exercise,during 4 different time zones of 5-10min,10-20min,20-35min and 35-40min,kilometers were recorded after each training.3.Study 3:Study on the effect and regulation mechanism of electroacupuncture and aerobic exercise on skeletal muscle atrophy in stable COPD patientsSource of subjects and intervention were totally the same as in study 1.LBMI,concentration of IGF-1 and serum inflammatory factors TNF-α,IL-1β,IL-10,gene expression of MyoD,Atrogin-1,MURF-1,AKT,mTOR,and IGF-1 were assessed before and after intervention of the two groups.BMI was assessed at baseline,after 14th,and 24th treatment.Serum inflammatory factors and muscle gene expression were assessed at baseline and after the 24th treatment.The data were statistically analyzed by SPSS22.0 software.The measurement data that meet the normal distribution and equal variance were expressed as the mean ± standard deviation(x±s),and those which did not meet the normal distribution and have different variance were expressed as the median(lower quartile to upper quartile).Count data,grade data were expressed as cases and composition ratio(%).The comparison of continuous numerical variables between two groups was conducted using two independent sample t-test(Mann-Whitney U test was used when data did not meet the normal distribution),and paired-sample t-test was used for intra-group comparison(Wilcoxon paired signed rank sum test was used when data did not meet the normal distribution).Group comparisons of composition ratios were performed using chi-square test or Fisher exact probability method,and paired chi-square test was used for within-group comparisons.Comparison of ordered variables between groups was conducted using Mann-Whitney U test and intra-group comparison was conducted using Wilcoxon paired-signed rank sum.The comparison of the same variable at different time points was analyzed by repeated measures,general linear model was used for continuous numerical variables(non-parametric Scheirer-Ray-Hare test was used if data did not meet the normal distribution),and generalized estimating equation was used for ordered variables and dichotomous variables.All the levels tested were two-sided,the significance level of difference was α=0.05,and P<0.05 was considered as statistically significant.ResultsStudy 1A total of 85 stable COPD subjects,43 in true needle group and 42 in placebo group were included.71 participants underwent the whole process and 14 dropped,including 6 in the true needle group and 8 in the placebo needle group.(1)Two independent samples t test,chi-square test and Mann-Whitney U test were used to compare the baseline results,such as age,medical history,height,weight,gender,pulmonary function grade between two groups(P>0.05).The overall homogeneity of baseline data of the two groups was good.(2)Pulmonary function test①Comparison between groups:there was no statistical difference in all indexes before the treatment.There was no statistical difference in FVC%,FEV1%,FEV1/FVC after the treatment(P>0.05),there was statistical difference in MVV%and MEF50%after the treatment(P<0.05),the values of true needle group were higher than the placebo group,suggesting that there was no difference in improving lung function time,but the true needle group was better than the placebo group in improving the expiratory flow of lung function.②Within-group comparison:FEV1/FVC in the placebo needle group decreased compared with those before treatment and was statistically different(P<0.05).There were no statistical differences in FVC%,FEV1%,FEV1/FVC,and FVC%and FEV1%in the placebo needle group(P>0.05).It indicated that all the time spirometric measures in the true needle group and FVC%and FEV1%in the placebo needle group did not improve after treatment,while FEV1/FVC treatment in the placebo needle group decreased instead.MVV%,ME75%，MEF50%,and MEF25%increased in the true needle group and were statistically different(P<0.05);MEF50%increased and MEF25%decreased after treatment for the placebo needle group(P<0.05).It indicated that MVV%,MEF75%,MEF50%,MEF25%and MEF50%in the true needle group improved after treatment,but MEF 5%decreased in the placebo needle group.(3)The cardiopulmonary exercise test indexes①Comparison between groups:there was no statistical difference between the two groups before treatment(P>0.05).After treatment,VO2/kg%、VE%、VEmax、VE/VO2、VE/VCO2 were statistically different between groups(P<0.05),indicating that most of the indexes were different after 2 months after treatment,and VO2/kg%,VE%and VEmax of the true needle group were higher than those in the placebo group,and VF/VO2 and VE/VCO2 were lower than those in the placebo group,indicating that the above indexes in the true needle group were improved compared with those in the placebo group after treatment.②Within-group comparison:All indicators were statistically different compared with those of the true needle group before treatment(P<0.05),where METs%,VO2/kg%,VE%,VO2/HR%and VEmax increased after treatment,VE/NO2,VE/VCO2 decreased after treatment;Statistical differences were found in VO2/kg%,VE%,VO2/HR%,VEmax,VE/VO2,VE/VCO2 after treatment for the placebo needle group(P<0.05),Among which,VO2/kg%,VE%,VO2/HR%,and VEmax decreased while VE/VO2 and VE/VCO2 increased.It suggested that the indexes of VO2/kg%,VE%,VO2/HR%,VEmax and VE/VO2 and VE/VCO2 of the true needle group improved while the same indexes of the placebo needle group tended to deteriorate.(4)6-minute walking distance(6 MWD)①Comparison between groups:there was no statistical difference between groups before treatment(P>0.05).6MWD of the true needle group was higher than that of the placebo needle group after the 14th and 24th treatments,but the difference was not significant(P>0.05),indicating that the true needle group was not superior to the placebo needle group in improving exercise endurance.②Repeated measures analysis:Compared with the baseline,the true needle group showed a significant difference P<0.001,and 6MWD after the 24th treatment showed a statistical difference compared with the baseline(P<0.05),6MWD after the 14th treatment also showed a statistical difference compared with the baseline(P<0.05).There was no statistical difference in any pairwise comparison for the placebo needle group(P>0.05).The results showed that the 6 MWD difference in the true acupuncture group was obvious after the 14th treatment,suggesting that the acupuncture had been effective in improving exercise tolerance after the 14th treatment.(5)Total scores of CAT①Comparison between groups:there was no statistical difference between groups before treatment(P>0.05).After the 14th and 24th treatment,the total CAT scores of the true needle group was lower than placebo needle group,but the difference was not significant(P>0.05).It indicates that the true needle group was not better than the placebo needle group in improving the severity of COPD symptoms.②Repeated measures analysis:the total CAT scores will change with time and grouping,but the change trend is not affected by grouping.The true needle group improves the severity of COPD symptoms and the impact of disease on daily life at the end of treatment.(6)mMRC score①Comparison between groups:there was no statistical difference between groups at baseline and after the 14th treatment(P>0.05),but there was statistical difference between groups after the 24th treatment(P<0.05).It shows that after 2 months of treatment,the true needle group was better than the placebo needle group in improving dyspnea.②Repeated measures analysis:there was no statistical difference in the effect of grouping on scores(P>0.05),and the effect of time point on scores was statistically different(P<0.05).Among them,the mMRC score was significantly different at baseline compared with that of the 24th treatment(P<0.001),and the OR value was 1.76,indicating that the baseline mMRC was 1.76 times the mMRC score after the 24th treatment,indicating a gradual decline in the mMRC score as the treatment progressed.The results suggested that the dyspnea level was improved in both groups at the end of the treatment.(7)COPD comprehensive grade①Comparison between groups:there was no statistical difference between 2 groups at baseline,after the 14th and 24th treatment(P>0.05),indicating that there was no difference between the two groups in improving overall COPD condition after 2 months of treatment.②Repeated measures analysis:there was no statistical difference in the effect of grouping(P>0.05),and the effect of time point had statistical difference(P<0.05),the comprehensive COPD grade at baseline was statistically different from that after the 24th treatment(P=0.001),and the OR value was 1.4,indicating that the comprehensive grade of COPD at the baseline was 1.4 times of that after the 24th treatment,indicating that it gradually decreased with the progression of treatment.The results suggest that both groups could improve the overall condition of COPD at the end of treatment.Study 2(1)Overall rate of reaching the standard during exercise①Comparison between groups:there was no statistical difference between the two groups during the first exercise(P>0.05).In the 24 exercises,there were only 4 exercises in which the standard rate was not different between groups,there were statistical differences in the remaining 20 exercises(P<0.05),and the rate in the true needle group was higher than that of the placebo needle group in all 24 exercises,indicating that the target heart rates in the 20 times better reached the standard than the placebo needle group.②Repeated measures analysis:There was a significant statistical difference in the overall rate of 24 exercises(P<0.001),and the OR value was 4.12,indicating that the rate of the true needle group was 4.12 times that of the placebo needle group.There was no statistical difference in the effect of the time point(all P>0.05),indicating that the rate of the two groups did not change with the increase of the number of exercises.(2)Rate of reaching the standard during 5-10minComparison between groups:the proportion of reaching standard during 5-10min for both groupswas very low,indicating that the actual heart rate of most subjects during 5-10min failed to reach the standard.(3)Rate of reaching the standard during 10-20min①Comparison between groups:there was no statistical difference between groups in the first exercise(P>0.05).10 in 24 exercises was statistically different(P<0.05),and there was no statistical difference between groups in the remaining exercises(P>0.05),and the rate of the true needle group in all times was higher than that of the placebo needle group,indicating that the target heart rate in the second time interval in the 10 exercises was better than that of the placebo group.②Repeated measures analysis:there were statistical differences in the effect on grouping(P<0.05).The OR value was 4.74,indicating that the rate of true needle group was 4.74 times that of the placebo needle group.There was no statistical difference in the effect of the time point(all P>0.05),indicating that the rate of the two groups during this time interval did not change with the increase of the number of exercise.(4)Rate of reaching the standard during 20-35min①Comparison between groups:there was no statistical difference between groups in the first exercise(P>0.05).There was statistical difference in 14 out of 24 exercises(P<0.05),while there was no statistical difference between groups in the remaining times(P>0.05),and the rate of the true needle group was higher than the placebo needle group,indicating that the target heart rate of the true needle group in the fourth time interval was better than that of the placebo needle group in 14 times.②Repeated measures analysis:there were statistical differences in the effect on grouping(P<0.05),and the OR value was 2.75,indicating that the rate of true needle group was 2.75 times that of the placebo needle group during 20-35min.(5)Rate of reaching the standard during 35-40minThere was no statistical difference between groups during the first exercise(P>0.05).Among the 24 exercises,only the 19th exercise showed a statistical difference(P<0.05),and there was no statistical difference between groups in the remaining exercises(P>0.05),indicating that the target heart rate of the true needle group was not better than that of the placebo needle group during the fifth time interval in the 23 exercises.(6)Comparison of the rate of reaching the standard during 10-20min and 20-35min between groupsRate during 20-35min was higher than that during 10-20min for both groups,and some differences were statistically significant(P<0.05),indicating that the rate of the two groups mainly concentrated in the time interval of20-35min.(7)Duration of reaching target heart rate①Comparison between groups:there was no statistical difference between groups during the first exercise time(P>0.05).There were statistical differences between groups for the 4th-17th and 19th-24th exercises(P<0.05),and the duration of the true needle group was better than that of the placebo needle group.And the duration of the true needle group was mainly 5min,10min,20min and 25min.②Repeated measures analysis:there were statistical differences in the effect on grouping(P<0.05),and the OR value was 3.94,indicating that the duration of the true needle group was 3.94 times that of the placebo needle group.However,there was no statistical difference in the effect on each time point(P>0.05),indicating that the duration did not increase with the number of exercise.(8)Kilometers①Comparison between groups:there was no statistical difference between groups in the first exercise(P>0.05).From the second time,the kilometers of each exercise was significantly different(P<0.05),and the true needle group was more than the placebo needle group,indicating that kilometers in the true needle group was higher than that of the placebo needle group.②Repeated measures analysis:time point,grouping and the interaction factors of both all had significant effects on kilometers(P<0.001),indicating that kilometers would change with the time point,and the change trend was obviously affected by grouping.Further analysis found that kilometers in the true needle group showed an overall upward trend,especially from the 4th to 13 times.It decreased from the 14th time,the 15th and 21th were low.It showed that kilometers in the true needle group increased with the progress of the treatment,but fluctuated during the period.Study 3(1)BMI①Comparison between groups:There was no statistical difference between groups before treatment(P>0.05).The BMI of the true needle group after the 14th treatment was higher than that of the placebo needle group,but the difference was not statistically significant(P>0.05),while there was statistical difference between groups after the 24th treatment(P<0.05),indicating that the true needle group was better than the placebo needle group in body weight maintenance after 2 months of treatment.②Repeated measures analysis:there was no statistical difference in the effect on time point and grouping for BMI(P>0.05),but there was a significant statistical difference in the interaction factors between grouping and time point(P<0.001),indicating that the change trend of BMI was affected by the grouping.Further analysis found that the BMI after the 14th treatment showed a significant difference P=0.001,and the other time points showed no statistical difference(P>0.05),indicating that the trend of BMI between the two groups after the 14th treatment was obvious.(2)Concentration changes in serum concentrations of inflammatory cytokines TNF-α,IL-1 β,IL-10 and growth factor IGF-1①Comparison between groups:There was no statistical difference between groups before and after treatment(P>0.05),indicating that there was no difference in the regulation of inflammatory factors and growth factors after 2 months of treatment.②Within-group comparison:TNF-αand IL-10 of the true needle group decreased after treatment,and IGF-1 increased with statistical differences(P<0.05).There was no statistical difference in all the indexes of the placebo needle group and IL-1βin the true needle group(P>0.05).It suggested that the true needle group could downregulate the level of inflammatory factors and upregulate IGF-1 level after 2 months of treatment.(3)Gene expression of MyoD,Atrogin-1,MURF-1,AKT,mTOR,and IGF-1 in vastus lateralis muscle①Comparison between groups:There was no statistical difference between groups before and after the treatment(P>0.05),indicating that there was no difference between groups in the regulation of muscular gene expression after 2 months of treatment.②Within-group comparison:Atrogin-1 was downregulated and statistically different after the treatment for both groups(P<0.05),mTOR was up-regulated in both groups but statistically different after treatment only in placebo needle group(P<0.05),and AKT was downregulated and statistically different after treatment for the placebo needle group(P<0.05).None of the other indicators had statistical difference(P>0.05),including the increasing trend of MyoD,AKT,mTOR and IGF-1,and decreasing trend of MURF-1 of the true needle group,and the opposite trend was shown in the placebo needle group.It indicated that both groups could downregulate Atrogin-1 and upregulate mTOR after 2 months of treatment,and the change trend of other indicators was inconsistent.Conclusion(1)Acupuncture improves dyspnea through improving small airway ventilation and exercise tolerance so as to reduce the symptom limitation of high-intensity exercise training,and improves the compliance and tolerance of aerobic training,so as to easily achieve the target exercise intensity and complete the effective exercise training.(2)Acupuncture may have an inhibitory effect on skeletal muscle atrophy through intervening NF-κB pathway and UPS pathway by downregulating inflammatory factors and Atrogin-1 so as to relieve respiratory muscle fatigue,maintain muscle mass and contraction ability and improve motor function. |
PDF Full Text Request