The Efficacy Of Aerobic Training Combined With Functional Exercise In Ankylosing Spondylitis And Anti-inflammatory Mechanism Study

Objective:The aims of this study were to investigate the efficacy of aerobic training combined with functional exercise on patients with Ankylosing spondylitis（AS）,using smartphones and smart wearable devices to supervise the exercise,to provide a safe and effective sports physiotherapy method for patients with AS.To explore the impact of aerobic training combined with functional exercise on inflammatory cytokines,according to the improvement of clinical performance,the key cytokines of anti-inflammatory and therapeutic effects were further analyzed,which can provide a theoretical basis for further exploring the best sports physiotherapy intervention.Part one:The efficacy of aerobic training combined with functional exercise on ankylosing spondylitis-a randomized controlled study.Methods:A total of 54 eligible subjects were randomly assigned to the exercise intervention group（26）and control group（28）.In addition to routine medical treatment,the exercise intenvention group performed aerobic training and functional exercise over 16 weeks.The control group only received routine medical treatment and were instructed to maintain their usual physical activity level.The intensity of aerobic training was 40% to 60% HRR（Heart Rate Reserve,HRR）and the effective time of each session was not less than 30 minutes,5 times per week.The functional exercise consisted of posture training,range of motion exercise,resistance training,stability training and strethching exercise,which was about 60 minutes,3 times per week,using smart wearable devices and mobile phone applications to monitor the completion of exercise intervention.The ankylosing spondylitis disease activity scale(ASDAS_CRPhigher score=worst),bath AS disease activity index（BASDAI）,bath AS functional index（BASFI）,and bath AS mobility index（BASMI）,ASAS health index（ASAS HI）,night pain,wholeday pain and other clinical indicators reflecting the severity of the disease were tested at baseline,8 weeks and 16 weeks,of which ASDAS_CRP was the primary outcome.The estimated maximum oxygen uptake(EVO_2max),cervical spine and hip joint mobility,standing walking function,flexor muscle endurance test（FET）and extension muscle endurance test（EET）were also tested in both groups at each visit time.The body compositions were reflected by skeletal muscle mass,body mass index（BMI）,and visceral fat area in two groups.Results:（1）22 subjects of the exercise intervention group completed the follow-up,of which 16 subjects completed more than 80% of the recommended amount of exercise,and the primary outcome(ASDAS_CRP)of 12 subjects fell to inactive state(ASDAS_CRP<1.3 points),and 4 subjects had no significant changes in ASDAS_CRPbefore and after treatment.24 subjects of the control group completed the follow-up,the primary outcome of 3 subjects fell to inactive state,19 subjects showed no significant improvement in disease activity status,and 2 subjects changed from medium disease activity(1.3≤ASDAS_CRP<2.1)to high disease activity(2.1≤ASDAS_CRP≤3.5).（2）At 8 and 16 weeks,the primary outcome of subjects in the exercise intervention group was significantly improved compared with the baseline（P<0.01）,and the control group was not significantly improved compared with the baseline（P＞0.05）,the changes of exercise intervention group were significantly improved compared with the control group（P=0.011 and P=0.032）.Similarly,the clinical observation indicators such as BASDAI overall score,BASDAI-spine pain,BASDAI-morning stiffness,BASMI,PGA and Ph GA of the exercise intervention group were significantly improved compared with the control group.At 8 weeks,the BASDAI-morning stiffness duration and ASAS HI in the exercise intervention group was significantly improved compared with the control group（P=0.020 and P=0.030）.At 16 weeks,BASDAI-fatigue and BASFI of the exercise intervention group were significantly improved from the baseline（P=0.017 and P<0.001）,while the control group showed no significant improvement from the baseline（P>0.05）.The changes of exercise intervention group were significantly improved compared with the control group（P=0.037 and P=0.035）.The degree of low back pain in the exercise intervention group was significantly improved compared to the control group.（P=0.004）.There were no significant differences in the occurrence of peripheral arthritis pain,finger distance,ESR and CRP between the two groups.（3）At 8 weeks,the changes of estimated maximum oxygen uptake(EVO_2max)were significant different between the two groups（P=0.029）.The hip extension range of motion（ROM）of the exercise intervention group were significantly improved compared with the baseline（P=0.029）,the control group did not significant change（P>0.05）,which the exercise intervention group was significantly improved compared to the control group（P=0.024）.At 16weeks,the changes of estimated maximum oxygen uptake(EVO_2max)were significant different between the two groups（P=0.048）.The changes of EET in the exercise intervention group were significantly higher than that of the control group（P=0.044）.The changes of cervical side flexion ROM in the exercise intervention group were significantly improved compared with the control group（P=0.038）.（4）In terms of body composition,at 8 weeks,the changes of percentage of body fat were asignificant different between the two groups（P=0.048）.Similarly,the changes of visceral fat area were significant different between the two groups（P=0.008）.（5）The incidence of adverse events in the exercise intervention group and the control group were 11.5%（3/26）and 0,respectively.There were no significant differences in the incidence of adverse events between the two groups（P>0.05）,and no serious adverse events occurred in either group.Part two:Study on the anti-inflammatory mechanism of aerobic training combined with functional exercise on patients with AS.Methods:The venous blood of the experimental group at baseline,30 minutes after exercise and 16 weeks were collected,the venous blood of the control group at baseline and 16 weeks were also collected.The cytokines IL-1,IL-4,IL-6,IL-15,IL-17,TNF-α,IL-1ra and IL-10 were analyzed using Luminex 200 multi-function flow matrix and Shanghai Bole Life Science the Bio-Plex Pro Cytokine Assays kit after a bout and long-term aerobic training combined with functional exercise,with reference to clinical improvement,analyzing the key cytokines that exercise exerts in anti-inflammatory and therapeutic effects.Results:（1）After a bout of aerobic training combined with functional exercise,the levels of IL-1ra,IL-6 and TNF-α in the circulating blood of AS patients did not change significantly（P>0.05）.（2）After long-term aerobic training combined with functional exercise,comprehensive exercise rehabilitation program significantly reduced IL-1ra and TNF-α levels in the exercise intervention group（P=0.029 and P=0.018）.The level of IL-1ra,IL-6 and TNF-α in the control group had no significant changes（P>0.05）.（3）There were a positive correlation between the levels of cytokines IL-1ra,IL-6 and TNF-α and the primary outcome(ASDAS_CRP)（r=0.297,r=0.498 and r=0.297）,and ASDAS_CRP changes in the exercise intervention group patients with significant clinical improvement were positively correlated with TNF-α changes（r=0.646）.Conclusions:（1）Moderate-intensity（40%～60%HRR）aerobic training combined with functional exercise intervention program is a comprehensive,safe and effective intervention program for AS patients.This program can not only effectively improve the clinical symptoms of AS patients such as disease activity,pain,and fatigue,but also effectively improve the extension muscle endurance,the ROM of cervical side flexion,the ROM of hip extension and other physical activity capabilities and maintenance body composition indicators such as body fat percentage and visceral fat area of AS patients.Meantime,it does not increase the incidences of adverse events in AS patients.However,there are individual differences in the intervention effect of moderate-intensity aerobic training combined with functional exerciseon AS patients.（2）One single bout of moderate-intensity（40%～60%HRR）aerobic training combined with functional exercise can not significantly ameliorate the inflammation status of AS patients.Long-term moderate-intensity aerobic training combined with functional exercise may play an anti-inflammatory and therapeutic effect by reducing the level of IL-1ra and TNF-α cytokines in AS patients.TNF-α is a sensitive indicator reflecting the effect of exercise intervention,which is better than IL-1ra and IL-6.