Exercise-induced Bronchoconstriction In Chinese Elite Athletes Of Summer Olympic Events:Epidemiological Investigation & Research Of Tangeretin Intervention Effect

Objectives:Exercise-induced Bronchoconstriction（EIB）has seriously affected the physical and mental health,as well as sports performance of athletes,which has arouse wide public concern in the world.However,little attention has been paid to the problem of EIB in Chinese athletes.As a traditional EIB treatment,drug treatment not only harms the physical and mental health of athletes,but also could increase the risk of anti-doping rule violation.Therefore,seeking a safer and healthier EIB treatment to replace drug treatment and reduce drug dependence has become the focus of sports science recently.Objective 1:To investigate the status quo of EIB among elite athletes of Summer Olympic events in China.To preliminarily understand the incidence of EIB,compare the differences of EIB among different sport events,different sports type categorized by environments or characteristics and different populations with or without EIB.To analyze the characteristics of respiratory tract inflammation and lung ventilation function of athletes suffering from EIB.Objective 2:To investigate the effects of tangeretin on the key clinical indicators of EIB（respiratory inflammation,pulmonary ventilation function,etc.）and related auxiliary indicators（uric acid,oxidative stress,etc.）,so as to evaluate the therapeutic effect of targeretin on EIB.Objective 3:To investigate the effects of targeretin on explosive force,maximum oxygen uptake and related physiological and biochemical indexes of athletes with EIB,so as to evaluate the potential impact of targeretin on athletic ability of athletes with EIB.Methods:This study included a cross-sectional pilot study（Part I）and a longitudinal intervention study（Part II and Part III）.Part I:Five hundred and two athletes（female 264,male 238;237 elite athletes,265national-level athletes）,divided into indoor（swimming pool,land）and outdoor（road,track）events according to the characteristics of sports environment;also they can be divided into endurance events,skill events,speed-strength events and team events according to the special characteristics of sports.The anthropometric information,disease history,respiratory symptoms and EIB diagnosis of athletes were obtained by questionnaire.Pulmonary ventilation function parameters（FEV₁,FVC,FEV₁decline rate,etc.）were obtained by bronchial stimulation test,and EIB diagnosis was performed by FEV₁decline rate.Fasting venous blood was collected and analyzed to evaluate the respiratory tract inflammation of athletes（blood routine:neutrophil count,eosinophil count,etc.;Serum:IL-5,IL-8,CC16,Ig E,etc.）.Chi-square test,independent sample T test or repeated measure ANOVA were used for statistical analysis for results.Part II:Based on the results of EIB diagnosis,30 athletes（15 male,15 female）with EIB was selected as subjects,and then they were matched and randomly divided into targeretin group（n=15）and placebo group（n=15）.With random,double-blind,placebo-controlled nutrition intervention,questionnaire,bronchial stimulation tests,blood sample collection and other methods,the study aimed to investigate the effects on key clinical indicators（neutrophil count,basophil count,IL-5,IL-8,CC16,Ig E;FEV₁,FVC,FEV₁decline rate,etc.）and related auxiliary indicators of EIB（UA,MDA,SOD,LDH,DA,MT,etc.）after 30 days of targeretin supplementation（200 mg/d）.Meanwhile,the symptom of breathing discomfort of all athletes were recorded during the intervention.Chi-square test,independent sample T test or repeated measure ANOVA were used for statistical analysis for results.Part III:Subject information was consistent with Part II.Adopting the methods of blood sample collection and analysis,body composition test,explosive force test,maximal oxygen uptake（VO₂max）test,the effects of targeretin on explosive force（explosive medicine ball throws,vertical jump,time of the deeper squat jump,etc.）and the related physiological and biochemical indexes:hormone secretion（testosterone,cortisol,etc.）,body composition（muscle mass,body fat rate,etc.）in athletes with EIB were investigated.In addition,the effects of targeretin on VO₂max and its derived indexes（VO₂max velocity,MVV,TLim,etc.）,as well as the related biochemical indexes,such as anemia（Hb,RBC,FT,etc.）,glucolipid metabolism（LDL-C,HDL-C,FFA,GLU,etc.）were also investigated simultaneously.Furthermore,the effects of targeretin and incremental exhaustive exercise on cortisol stress response and muscle oxidative stress injury in EIB athletes were also investigated.Chi-square test,independent sample T test or repeated measure ANOVA were used for statistical analysis for results.Results:Part I:results of questionnaire showed that 3 athletes had been diagnosed with EIB,accounting for 0.6%;The results of bronchial stimulation test showed that 138 athletes（82females and 56 males）were diagnosed with EIB,accounting for 27.5%.Swimming（51.5%）,road cycling（40.9%）,hockey（40.7%）,synchronised swimming（40.0%）and rugby（38.5%）ranked the top 5,followed by rhythmic gymnastics（10.5%）,badminton（9.5%）,table tennis（9.5%）,weightlifting（9.5%）and wrestling（6.5%）.Prevalence was significantly higher in women than in men（31.1%vs 23.7%,P=0.069）;significantly higher in endurance events than in speed-strength events（P<0.001）;significantly higher in outdoor events than indoor events（34.9%vs 22.4%,P=0.002）,and significantly higher in indoor swimming pool than onshore sports.（P<0.001）.But there was no significant difference between outdoor track event and road events.In addition,the pulmonary ventilation function indexes of EIB athletes decreased significantly and were lower than those of healthy athletes.Some inflammatory indexes,such as eosinophil count,neutrophil count,IL-5,IL-8,CC16,Ig E,were also significantly higher than those of healthy athletes.Part II:Eosinophil count（P=0.049）,neutrophil count（P=0.039）,IL-5（P=0.037）,IL-8（P=0.003）,Ig E（P=0.011）levels in targeretin group after the intervention.Compared with the initial value（T1）,IL-5（P=0.022）and IL-8（P=0.012）at T5 were significantly lower than those in placebo group.The values of FEV₁（P<0.01）,FVC（P<0.01）,PEF（P=0.047）and MMF（P=0.039）in the targeretin group were significantly higher than those in the first bronchial stimulation test（E1）.Six athletes with EIB became EIB negative at the second bronchial stimulation test（E3）,and the overall EIB negative rate was 40.00%.In addition,the uric acid（UA）metabolism,muscle oxidative stress and neuromodulation indexes were significantly improved in the targeretin group,and the symptoms of breathing discomfort were significantly relieved.UA decreased from 6.01±0.75 mg/d L to 5.22±0.76mg/d L（P<0.01）.MDA decreased from 4.92±0.71 mmol/L to 4.43±0.71 mmol/L（P=0.019）,MT increased from 51.07±15.36μg/L to 79.27±11.26μg/L（P<0.001）.In addition,CK and LDH levels also significantly decreased.Part III:During the intervention,cortisol（P=0.049）and ACTH（P=0.011）in targeretin group decreased significantly,testosterone level remained stable,T/C ratio increased significantly,and muscle mass increased from 61.2±6.3 kg to 63.1±6.3 kg（P=0.032）.The body fat rate decreased from 14.1±3.8%to 12.7±3.9%（P=0.033）,and the explosive force of upper and lower limbs increased to different degrees.Explosive medicine ball throwing increased from 5.59±1.82 m/s to 6.86±1.59 m/s（P=0.015）.Vertical jump with and without arms-swinging increased from 45.81±8.31 cm and 42.62±7.59 cm to 47.13±6.75 cm and44.99±6.09 cm,respectively,and the time of the deeper squat jump decreased from 198.27±51.81 ms to 161.2±22.42 ms.Additionally,Hb in targeretin group was significantly increased（P<0.01）,RBC and FT levels were increased steadily,HDL-C（P=0.019）and MT（P=0.018）were significantly increased.VO₂max and TLim increased significantly from52.77±6.82 ml·kg^-1·min^-1and 12.27±1.79 min before intervention to 54.54±5.18ml·kg^-1·min^-1and 13.03±1.35 min（P=0.042,P=0.050）after intervention,respectively.VO₂/HR and VO₂max speed also increased to different degrees.Conclusions:Conclusion 1:EIB is a serious problem for elite athletes in Summer Olympic events in China,and the incidence of EIB shows four main characteristics:incidence of female is higher than male,incidence of elite athletes are higher than national-level athletes,incidence of outdoor events are higher than indoor events,and incidence of pool events are higher than other events.Sports authority of China should attach great importance to EIB（especially women or pool athletes）,arrange and carry out the diagnosis,treatment and prevention of EIB for elite athletes as soon as possible.In addition,the level of respiratory tract inflammation in EIB athletes is significantly higher than that in healthy athletes,while the lung ventilation function is significantly lower than that in the latter.Therefore,inhibition of respiratory tract inflammation and improvement of lung ventilation function are the key to EIB treatment.Conclusion 2:Targeretin can effectively inhibit the inflammation of the respiratory tract,significantly reduce the blood level of uric acid,defense muscle oxidative stress damage,strengthened the neural regulation,ease the movement of respiratory symptoms,significantly improve the key index of pulmonary ventilation function FEV₁and FVC in athletes with EIB.Simultaneously,targeretin made it possible for some athletes with EIB became EIB negative,which showed a good therapeutic effect for EIB.Conclusion 3:Targeretin can regulate hormone secretion,improve body composition,promote muscle synthesis and increase explosive force.At the same time,targeretin also improve some anemia indicators,optimized the glucolipid metabolism,significantly increased VO₂max,effectively restrain the strenuous exercise induced cortisol stress response and muscle oxidative stress damage,and delay the exercise fatigue in athletes with EIB,which might have a positive impact on the improvement of athletic ability and the increase of sport competitiveness.