Treatment of cachexia with ghrelin in patients with COPD.
OBJECTIVE
Ghrelin is a novel growth hormone (GH)-releasing peptide that also induces a positive energy balance by decreasing fat utility and stimulating feeding through GH-independent mechanisms. We investigated whether ghrelin improves cachexia and functional capacity in patients with COPD.


METHODS
This is an open-label pilot study. Human ghrelin (2 microg/kg bid) was IV administered to seven cachectic patients with COPD for 3 weeks. Food intake, body composition, muscle strength, exercise capacity, pulmonary function, and sympathetic nerve activity were examined before and after ghrelin therapy.


RESULTS
A single administration of ghrelin markedly increased serum GH (21-fold). Three-week treatment with ghrelin resulted in a significant increase in mean (+/- SEM) body weight (49.3 +/- 3.6 to 50.3 +/- 3.8 kg; p < 0.05). Food intake was significantly increased during ghrelin therapy. Ghrelin increased lean body mass and peripheral and respiratory muscle strength. Ghrelin significantly increased Karnofsky performance status score and the distance walked in 6 min (370 +/- 30 to 432 +/- 35 m; p < 0.05), although it did not significantly alter pulmonary function. Ghrelin attenuated the exaggerated sympathetic nerve activity, as indicated by a marked decrease in plasma norepinephrine level (889 +/- 123 to 597 +/- 116 pg/mL; p < 0.05).


CONCLUSIONS
These preliminary results suggest that repeated administration of ghrelin improves body composition, muscle wasting, functional capacity, and sympathetic augmentation in cachectic patients with COPD.
Nagaya
Noritoshi
N
Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. nnagaya@ri.ncvc.go.jp
Itoh
Takefumi
T
Murakami
Shinsuke
S
Oya
Hideo
H
Uematsu
Masaaki
M
Miyatake
Kunio
K
Kangawa
Kenji
K
D000368:Aged; D000369:Aged, 80 and over; D001823:Body Composition / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000188:drug therapy; D009133:Muscular Atrophy / Q000188:drug therapy; D036361:Peptide Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D020127:Recovery of Function / Q000187:drug effects; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects
D054439:Ghrelin; D036361:Peptide Hormones; D013007:Growth Hormone-Releasing Hormone