目的:肌肉功能和质量的性别差异,呼吸困难,在慢性阻塞性肺疾病(COPD)患者中,尽管气流阻塞程度相似,但仍观察到临床结局。COPD患者的蛋白质和氨基酸代谢发生改变,然而,目前尚不清楚男性和女性COPD患者的代谢特征是否存在差异,这可以解释观察到的肌肉健康和临床结局的差异.
方法:在234名中度至重度COPD患者(男性/女性:113/121)和182名健康对照(男性/女性:77/105)中,我们评估,除了合并症和临床特征的存在,通过手握和腿部测力计的肌肉功能,通过双能X射线吸收法和身体成分。在吸收后状态,通过脉冲给药18种稳定同位素氨基酸的混合物,并对动脉化血液取样2小时。通过LC-MS/MS分析氨基酸浓度和富集,以计算在肌肉健康中起已知作用的氨基酸的全身(净)蛋白质分解(WBnetPB)和全身产生(WBP)速率(μmol/小时)。ANCOVA进行了统计,以检查性别的影响,COPD,以及COPD性别与年龄和瘦体重的协变量相互作用。显著性设定为p<0.05。
结果:男性和女性COPD患者的肺功能相当。作为女性和COPD的存在与阑尾下瘦体重独立相关,肌肉力量,和WBnetPB(p<0.05)。男性与较高的内脏脂肪组织有关,C反应蛋白(CRP)(p<0.05),心力衰竭和阻塞性睡眠呼吸暂停的患病率较高。发现性别与COPD的相互作用表明较低的脂肪量(p=0.0005)和苯丙氨酸的WBP(测量全身蛋白质更新)和必需氨基酸(p<0.05),尤其是COPD女性。较高的内脏脂肪组织(p=0.025),CRP(p<0.0001),在COPD男性中观察到tau-甲基组氨酸的WBP(p=0.010)(反映肌原纤维蛋白分解增强)。
结论:在设计治疗方案以恢复男性和女性COPD患者的肌肉健康时,需要考虑COPD患者存在蛋白质和氨基酸代谢和心脏代谢健康的性别特异性变化。
背景:www.
结果:政府,NCT01787682、NCT01624792、NCT02157844、NCT02065141、NCT02770092、NCT02780219、NCT03327181、NCT03796455、NCT01173354、NCT01154400。
Sex differences in muscle function and mass, dyspnea, and clinical outcomes have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD) despite a similar level of airflow obstruction. Protein and amino acid metabolism is altered in COPD, however, it remains unclear whether a difference in metabolic signature exists between males and females with COPD that may explain the observed differences in muscle health and clinical outcomes.
In 234 moderate to severe COPD patients (males/females: 113/121) and 182 healthy controls (males/females: 77/105), we assessed, besides presence of comorbidities and clinical features, muscle function by handgrip and leg dynamometry, and body composition by dual-energy x-ray absorptiometry. In the postabsorptive state, a mixture of 18 stable isotopes of amino acids was administered by pulse and arterialized blood was sampled for 2 h. Amino acid concentrations and enrichments were analyzed by LC-MS/MS to calculate whole body (net) protein breakdown (WBnetPB) and whole body production (WBP) rates (μmol/hour) of the amino acids playing a known role in muscle health. Statistics was done by ANCOVA to examine the effects of sex, COPD, and sex-by-COPD interaction with as covariates age and lean mass. Significance was set as p < 0.05.
Lung function was comparable between males and females with COPD. Being a female and presence of COPD were independently associated with lower appendicular lean mass, muscle strength, and WBnetPB (p < 0.05). Being a male was associated with higher visceral adipose tissue, C-reactive protein (CRP) (p < 0.05), and higher prevalence of heart failure and obstructive sleep apnea. Sex-by-COPD interactions were found indicating lower fat mass (p = 0.0005) and WBPs of phenylalanine (measure of whole body protein turnover) and essential amino acids (p < 0.05), particularly in COPD females. Higher visceral adipose tissue (p = 0.025), CRP (p < 0.0001), and WBP of tau-methylhistidine (p = 0.010) (reflecting enhanced myofibrillar protein breakdown) were observed in COPD males.
Presence of sex specific changes in protein and amino acid metabolism and cardiometabolic health in COPD need to be considered when designing treatment regimens to restore muscle health in males and females with COPD.
www.
gov, NCT01787682, NCT01624792, NCT02157844, NCT02065141, NCT02770092, NCT02780219, NCT03327181, NCT03796455, NCT01173354, NCT01154400.