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Open Access Highly Accessed Research article

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

Keisuke Miki1*, Ryoji Maekura1, Noritoshi Nagaya2, Seigo Kitada1, Mari Miki1, Kenji Yoshimura1, Yoshitaka Tateishi1, Masaharu Motone1, Toru Hiraga1, Masahide Mori1 and Kenji Kangawa3

Author Affiliations

1 Department of Internal medicine, National Hospital Organization Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka, Osaka, 560-8552, Japan

2 Department of Regenerative Medicine, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan

3 Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan

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BMC Pulmonary Medicine 2013, 13:37  doi:10.1186/1471-2466-13-37

Published: 10 June 2013

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 <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M1','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M1">View MathML</a>. Secondary outcomes included changes in exertional cardio-respiratory functions: O2-pulse, physiologic dead space/tidal volume-ratio (VD/VT), ventilatory equivalent for oxygen <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M2','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M2">View MathML</a>, and ventilatory equivalent for carbon dioxide <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M3','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M3">View MathML</a>.

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 <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M4','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M4">View MathML</a> (1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii) <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M5','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M5">View MathML</a> (-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii) <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M6','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M6">View MathML</a> (-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 <a onClick="popup('http://www.biomedcentral.com/1471-2466/13/37/mathml/M7','MathML',630,470);return false;" target="_blank" href="http://www.biomedcentral.com/1471-2466/13/37/mathml/M7">View MathML</a> (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) C000000061

Keywords:
Dyspnea; Exercise; Pulmonary rehabilitation; Sympathetic nerve activity; Underweight