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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 uptakeV  •    o  2. Secondary outcomes included changes in exertional cardio-respiratory functions: O 2 -pulse, physiologic dead space/tidal volume-ratio (V D /V T ), ventilatory equivalent for oxygenV  •   E   /   V  •    o  2, and ventilatory equivalent for carbon dioxideV  •   E  /   V  •   c   o  2.    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) peakV  •    o  2(1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii)V  •   E  /   V  •    o  2(-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii)V  •   E    /  V   •   c   o  2(-4.1, 95% CI: -8.2 to -0.1, between-group p = 0.045); iv) V D /V T  (-0.04, 95% CI: -0.08 to -0.00, between-group p = 0.041); and v) O 2 -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 peakV  •    o  2(p = 0.025).    Conclusion  Ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters.    Trial registration  UMIN (University Hospital Medical Information Network in Japan)  C61

bmc pulmonary medicine

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