Qin Yin-Yin, Li Rui-Fa, Wu Guo-Feng, Zhu Zheng, Liu Jie, Zhou Cheng-Zhi, Guan Wei-Jie, Luo Jia-Ying, Yu Xin-Xin, Ou Yang-Ming, Jiang Mei, Zhong Nan-Shan, Luo Yuan-Ming
State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory, Guangzhou Institute of Respiratory Disease, 151 Yanjiang Road, Guangzhou, Guangdong, 510120, China.
ShenZhen Nanshan People's Hospital, Shenzhen, Guangdong, 518052, China.
Pulm Pharmacol Ther. 2015 Feb;30:51-6. doi: 10.1016/j.pupt.2014.11.003. Epub 2014 Nov 28.
Studies have shown that tiotropium once daily reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. Mechanisms underlying the effects of the muscarinic receptor antagonist tiotropium on COPD have not been fully understood.
In this study, we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD.
Twenty subjects with severe COPD were randomized into two groups: no treatment (Control, n = 10, 63.6 ± 4.6 years, FEV1 29.6 ± 13.3%pred) or inhaled tiotropium 18 μg once daily for 1 month (n = 10, 66.5 ± 5.4 years, FEV1 33.0 ± 11.1%pred). All subjects were allowed to continue their daily medications other than anti-cholinergics during the study. Constant cycle exercise with 75% of maximal workload and spirometry were performed before and 1 month after treatment. Diaphragmatic EMG (EMGdi) and respiratory pressures were recorded with multifunctional esophageal catheter. Efficiency of neural respiratory drive, defined as the ratio of minute ventilation (VE) and diaphragmatic EMG (VE/EMGdi%max), was calculated. Modified British Medical Research Council Dyspnea Scale (mMRC) was used for the evaluation of dyspnea before and after treatment.
There was no significant difference in spirometry before and after treatment in both groups. Diaphragmatic EMG decreased significantly at rest (28.1 ± 10.9% vs. 22.6 ± 10.7%, P < 0.05) and mean efficiency of neural respiratory drive at the later stage of exercise increased (39.8 ± 2.9 vs. 45.2 ± 3.9, P < 0.01) after 1-month treatment with tiotropium. There were no remarkable changes in resting EMGdi and mean efficiency of neural respiratory drive post-treatment in control group. The score of mMRC decreased significantly (2.5 ± 0.5 vs. 1.9 ± 0.7, P < 0.05) after 1-month treatment with tiotropium, but without significantly difference in control group.
Tiotropium significantly reduces neural respiratory drive at rest and improves the efficiency of neural respiratory drive during exercise, which might account for the improvement in exercise tolerance in COPD.
研究表明，噻托溴铵每日一次可减轻慢性阻塞性肺疾病（COPD）患者运动期间的肺过度充气和呼吸困难，并提高运动耐力。毒蕈碱受体拮抗剂噻托溴铵对COPD作用的潜在机制尚未完全明确。
在本研究中，我们调查了呼吸神经驱动的改善是否是减轻COPD患者运动期间呼吸困难和提高运动耐力的原因。
20例重度COPD患者被随机分为两组：未治疗组（对照组，n = 10，63.6 ± 4.6岁，第1秒用力呼气容积（FEV1）为预计值的29.6 ± 13.3%）或每日吸入18 μg噻托溴铵1个月（n = 10，66.5 ± 5.4岁，FEV1为预计值的33.0 ± 11.1%）。在研究期间，所有受试者除抗胆碱能药物外可继续服用其日常药物。在治疗前和治疗1个月后进行75%最大工作量的恒定周期运动和肺活量测定。使用多功能食管导管记录膈肌肌电图（EMGdi）和呼吸压力。计算呼吸神经驱动效率，定义为分钟通气量（VE）与膈肌肌电图的比值（VE/EMGdi%max）。采用改良英国医学研究委员会呼吸困难量表（mMRC）评估治疗前后的呼吸困难情况。
两组治疗前后肺活量测定结果无显著差异。噻托溴铵治疗1个月后，静息时膈肌肌电图显著降低（28.1 ± 10.9% 对 22.6 ± 10.7%，P < 0.05），运动后期呼吸神经驱动的平均效率增加（39.8 ± 2.9 对 45.2 ± 3.9，P < 0.01）。对照组治疗后静息EMGdi和呼吸神经驱动的平均效率无明显变化。噻托溴铵治疗1个月后，mMRC评分显著降低（2.5 ± 0.5 对 1.9 ± 0.7，P < 0.05），但对照组无显著差异。
噻托溴铵可显著降低静息时的呼吸神经驱动，并提高运动期间呼吸神经驱动的效率，这可能是COPD患者运动耐力提高的原因。
