title: Effect of tiotropium on neural respiratory drive during exercise in severe COPD.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  In this study, we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Yin-Yin
authors.initials: YY
authors.lastname: Qin
authors.affiliation: ShenZhen Nanshan People's Hospital, Shenzhen, Guangdong, 518052, China.
authors.forename: Rui-Fa
authors.initials: RF
authors.lastname: Li
authors.affiliation: Li-Wan Hospital of Guangzhou Medicine University, Guangzhou, Guangdong, 510170, China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Cheng-Zhi
authors.initials: CZ
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Guan
authors.affiliation: 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.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Yang-Ming
authors.initials: YM
authors.lastname: Ou
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.affiliation: 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. Electronic address: nanshan@vip.163.com.
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Zhong
authors.affiliation: 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. Electronic address: y.m.luo@qq.com.
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Luo
mesh_terms: D000368:Aged; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005541:Forced Expiratory Volume; D006801:Humans; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012602:Scopolamine Derivatives / Q000494:pharmacology*; D012720:Severity of Illness Index; D013147:Spirometry; D000069447:Tiotropium Bromide
chemical_list: D018727:Muscarinic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide
keywords: 20836); 5487426); Albuterol (PubChem CID; Bronchodilator; Diaphragmatic EMG; Dyspnea; Efficiency of neural respiratory drive; Exercise tolerance; Muscarinic receptor antagonist; Tiotropium (PubChem CID