title: Effects of ghrelin treatment on exercise capacity in underweight COPD patients: a substudy of a multicenter, randomized, double-blind, placebo-controlled trial of ghrelin treatment.
abstract: BACKGROUND
  The aim of this substudy of the ghrelin treatment, multicenter, randomized, double-blind, placebo-controlled trial was to investigate the effects of ghrelin administration on exercise capacity and the underlying mechanisms in underweight patients with chronic obstructive pulmonary disease (COPD) using cardiopulmonary exercise testing.
  
  
  METHODS
  Twenty underweight COPD patients were randomized to pulmonary rehabilitation with intravenous ghrelin (2 μg/kg, n = 10) or placebo (n = 10) twice daily for 3 weeks in a double-blind fashion. The primary outcome was changes in peak oxygen uptake V•o2. Secondary outcomes included changes in exertional cardio-respiratory functions: O2-pulse, physiologic dead space/tidal volume-ratio (VD/VT), ventilatory equivalent for oxygen V•E/V•o2, and ventilatory equivalent for carbon dioxide V•E/V•co2.
  
  
  RESULTS
  With incremental exercise, at peak exercise, there was a significant difference in the mean difference (ghrelin minus placebo), i.e., treatment effect in: i) peak V•o2 (1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii) V•E/V•o2 (-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii) V•E/V•co2 (-4.1, 95% CI: -8.2 to -0.1, between-group p = 0.045); iv) VD/VT (-0.04, 95% CI: -0.08 to -0.00, between-group p = 0.041); and v) O2-pulse (0.7 mL/beat, 95% CI: 0.3 to 1.2 mL/beat, between-group p = 0.003). Additionally, repeated-measures analysis of variance (ANOVA) indicated a significant time-course effect of ghrelin versus placebo in the peak V•o2 (p = 0.025).
  
  
  CONCLUSIONS
  Ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters.
  
  
  BACKGROUND
  UMIN (University Hospital Medical Information Network in Japan) C000000061.
authors.affiliation: Department of Internal medicine, National Hospital Organization Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka, Osaka, Japan. mikisuke@toneyama.go.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Maekura
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
authors.forename: Seigo
authors.initials: S
authors.lastname: Kitada
authors.forename: Mari
authors.initials: M
authors.lastname: Miki
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tateishi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Motone
authors.forename: Toru
authors.initials: T
authors.lastname: Hiraga
authors.forename: Masahide
authors.initials: M
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects* / Q000502:physiology; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology* / Q000534:rehabilitation; D012129:Respiratory Function Tests; D013851:Thinness / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D054439:Ghrelin