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(Chest. 2005;128:1187-1193.)
© 2005 American College of Chest Physicians

Treatment of Cachexia With Ghrelin in Patients With COPD*

Noritoshi Nagaya, MD; Takefumi Itoh, MD; Shinsuke Murakami, MD; Hideo Oya, MD; Masaaki Uematsu, MD; Kunio Miyatake, MD and Kenji Kangawa, PhD

* From the Department of Internal Medicine (Drs. Nagaya, Itoh, Murakami, Oya, and Miyatake), National Cardiovascular Center, Osaka, Japan; Cardiovascular Division (Dr. Uematsu), Kansai Rosai Hospital, Hyogo, Japan; and Department of Biochemistry (Dr. Kangawa), National Cardiovascular Center Research Institute, Osaka, Japan.

Correspondence to: Noritoshi Nagaya, MD, Department of Internal Medicine, National Cardiovascular Center, 5–7-1 Fujishirodai, Suita, Osaka 565-8565, Japan; e-mail: nnagaya{at}ri.ncvc.go.jp

Study objectives: 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 µg/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.

Key Words: cachexia • chronic obstructive • exercise capacity • ghrelin • nutrition






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