BackgroundPulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.Methodology/Principal FindingsIn a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated.Conclusions/SignificanceIn cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.Trial RegistrationUMIN Clinical Trial Registry C000000061

Objective There is clinical and pathological evidence of thrombosis in pulmonary vessels of patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the presence of hypercoagulability and determine the extent of this abnormality in COPDpatients.Patients and Methods Wemeasured plasma levels of thrombin antithrombin III complex (TAT), fibrinopeptide A (FPA), tissue plasminogen activator-plasminogen activator inhibitor (tPA-PAI) : markers of coagulation-fibrinolysis-systeni, and also (3-thromboglobulin (p-TG): a marker of platelet activation, in 40 COPDpatients and in 20 control subjects. Measurementswere also repeated 12 months after entry in all patients. Results TAT, FPA, tPA-PAI, and p-TG concentrations were significantly higher in COPDthan in control subjects. At 12 months follow-up, AA-aDO2and A^jFEVj were significantly higher in patients with high TATor tPA-PAI levels than in patients with low levels and TAT, FPAand tPA-PAI levels remained elevated, although p-TG levels decreased after domiciliary O2 therapy.Conclusion Our results showed an enhanced prothrombotic process in COPDpatients, which could potentially account for the increased thrombosis in pulmonary vessels in these patients.

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Improvements in the oxygen uptake capacity were greater in patients receiving 2 μg/kg ghrelin twice daily for 3 weeks than in those receiving 1 μg/kg, although exercise tolerance was similar between groups at the end of the 3-week treatment period. Thus, a twice daily dose of 2 μg/kg ghrelin is recommended over 1 μg/kg ghrelin for patients with chronic respiratory failure and weight loss.

Our findings suggest that the expression level of Gal-9 in the lung is increased in patients with CVD-IP and that Gal-9 may have a protective role against pulmonary fibrosis of these patients.