Peripheral Skeletal Muscle Dysfunction In AECOPD Patients:Preliminary Investigation And Mechanism Study

Background: Chronic obstructive pulmonary disease(COPD) is not only a disease limited to airway and lung, but also a systemic and chronic inflammatory disease with co-participation of various factors and mediation of multiple biological mechanisms. The patients with COPD, especially the severe ones, usually have decline of exercise tolerance, which was explained by progressive degradation of pulmonary function. But recent studies have revealed that COPD patients often develop skeletal muscle dysfunction(SMD), peripheral skeletal muscle dysfunction(PSMD) in particular, which is directly related to the decrease of exercise capacity in COPD patients. As acute exacerbation of COPD results in worsening of PSMD, understanding of the features of PSMD in COPD patients and its relationship with severity of the illness may contribute to correct evaluation of its severity and provide new strategies for its treatment and prevention.Objective: To investigate the function of peripheral skeletal muscles in AECOPD patients and the mechanisms for AECOPD patients developing PSMD and compare the role HGS, QMVC, and serum Myostatin play in assessing the severity of AECOPD.Methods:1. Eighty-two patients who were diagnosed with AECOPD and hospitalized in Headquarter of Suzhou Municipal Hospital from January 2015 to December 2015 were involved according to the inclusion and exclusion criteria and divided into moderate group(group A) and severe group(group B); meanwhile, 78 age-matched healthy persons who underwent physical examination in our physical examination center served as controls. Their body mass index(BMI), forced expiratory volume in 1 second as percentage of normal prediction(FEV1%pred), quadriceps maximum voluntary contraction(QMVC), hand grip strength(HGS), and six-minute walk test(6MWT) were recorded to verify the existence of PSMD in the AECOPD patients and its relationship with severity of the illness.2. Serum Myostatin was determined and a correlation analysis between Myostatin and severity of AECOPD was performed to investigate the clinical values of serum Myostatin in the evaluation and treatment of AECOPD.3. Levels of serum interleukin-6(IL-6)tumor necrosis factor-α(TNF-α), insulin-like growth factor-1(IGF-1), arterial partial pressure of oxygen(PaO2), and arterial partial pressure of carbon dioxide(PaCO2) were measured and the relationship between PSMD and risk factors above in the AECOPD patients was statistically analyzed.Results:1. Comparison of baseline between the AECOPD group and the healthy control group: the AECOPD group had decreased BMI, 6MWT, FEV1%pred, PaO2 and increased PaCO2(all P<0.01), which suggested that, compared with the age-matched healthy controls, AECOPD patients had poor nutrition, skeletal muscle dysfunction, and decreased activities of daily life.2. Function of peripheral skeletal muscles between each group: QMVC and HGS in the AECOPD group were significantly lower than those in the healthy control group(P<0.01); QMVC was significantly lower in the COPD B group than in the COPD A group(P<0.01) and, in spite of the decrease, there was no significant difference in HGS between the COPD A and B groups(P>0.05), which illustrated that QMVC in the AECOPD patients was correlated with the severity of the illness.3. Comparison of serum factors between each group: compared with the controls, the AECOPD patients had significantly higher serum Myostatin, IL-6, and TNF-α levels(all P<0.01) and significantly lower IGF-1 level(P<0.01); the worse the pulmonary function for the AECOPD patients in stable phase was, the higher the Myostatin, IL-6, and TNF-α levels were, and the lower the IGF-1 was.4. A correlation analysis of muscle strength and FEV1%pred in the AECOPD group: separately, the correlation analysis was performed between QMVC and FEV1%pred by gender as there was a great difference in muscle strength between male and female. QMVC and FEV1%pred were significantly correlated both in the female and male groups(Pearson coefficient was 0.836 and 0.715, respectively. Both P<0.01); there were no significant correlation between HGS and FEV1%pred in female and male groups(Pearson coefficient was 0.336 and 0.305, respectively. Both P>0.05).5. Correlation of serum Myostatin level and muscle strength: a correlation analysis was conducted between QMVC and Myostatin, and HGS and Myostatin in the AECOPD patients by gender, respectively. Results showed negative relationships between QMVC and Myostatin, and HGS and Myostatin in the female patients(Pearson coefficient was-0.664 and-0.680, respectively. Both P <0.01) and also negative relationships between QMVC and Myostatin, and HGS and Myostatin in the male patients(Pearson coefficient was-0.653 and-0.512, respectively. Both P<0.01)..6. Relationship between serum Myostatin level and severity of illness in the AECOPD group: serum Myostatin level was negatively correlated with FEV1%pred(Pearson coefficient was-0.581, P <0.01) and positively correlated with hospital stays(Pearson coefficient was 0.595, P <0.01) in the AECOPD group, which indicated that serum Myostatin level was related to the severity of AECOPD.7. Risk factors of 6MWT in the AECOPD patients: results of the regression analysis showed that, the risk factors for QMVC included FEV1%pred,QMVC,BMI and age(R2=0.68,P<0.01),the β coefficient in the regression analysis between 6MWT and risk factors in the AECOPD patients showed that QMVC was second to FEV1%pred as the related factors.8. Risk factors of PSMD in the AECOPD patients: results of the regression analysis showed that, in addition to gender, the risk factors for QMVC included Myostatin,FEV1%pred,serum inflammatory factors, such as IL-6,TNF-α,IGF-1 and BMI,PaO2,PaCO2(R2=0.84, P<0.01),the risk factors for HGS included Myostatin,BMI,serum inflammatory factors, such as IGF-1,TNF-α,IL-6 and PaO2,PaCO2(R2=0.76, P<0.01),the β coefficients in the regression analysis between PSMD and risk factors in the AECOPD patients all showed that Myostatin was second to gender as the related factors,and FEV1%pred was excluded from the regression equation with HGS as the dependent variable.Conclusion:1. Compared with the age-matched healthy controls, the patients with AECOPD have significantly decreased QMVC and HGS, which verifys that PSMD develops; the severity of COPD is correlated with QMVC and there is no evidence for HGS as an assessment index for the severity of AECOPD.2. PSMD in the COPD patients assessed as severe for pulmonary function in stable phase is worse during acute exacerbation than that in the COPD patients assessed as moderate for pulmonary function in stable phase.3. Both pulmonary function in stable phase and QMVC during acute exacerbation greatly affect 6MWT in AECOPD patients, 6MWT can not simply be used as an index to evaluate the degree of PSMD in AECOPD patients.4. Serum Myostatin level in the COPD patients during acute exacerbation can reflect the severity of the illness during their stable phase.