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

The aim of the present study was to evaluate exercise limiting factors using cardiopulmonary exercise testing (CPET) in patients with idiopathic pulmonary fibrosis (IPF), and to investigate whether these parameters are related to survival after CPET. We evaluated 41 patients with IPF (mean 68.2 years, 27 male) who performed CPET. The exercise capacity in patients with IPF was limited more strongly by gas exchange and/or ventilatory impairments, compared with cardiac impairment. Using univariate analysis, the severity of exercise-induced hypoxemia (EIH) evaluated by deltaPaO2/deltaVO2 (PaO2-slope), oxygen uptake at maximum exercise, oxygen pulse at maximum exercise, ventilatory equivalent for carbon dioxide at maximum exercise and age were significantly related to the survival rate. Interestingly, the PaO2-slope was most closely correlated with the survival rate using multiple analysis with a stepwise evaluation. Nevertheless, PaO2 at rest and at maximum exercise were not factors influencing survival. In patients with IPF, CPET can simultaneously evaluate the ability of both the cardiovascular and respiratory systems, and should be available so that parameters can be derived to make the necessary prognostic estimations, with the most useful parameter being the degree of EIH as represented by the PaO2-slope.

NBE MAC-PD is a slowly but substantially progressive long-term infection (5-10 years). Our data suggest that patients with lower BMI, cavitary disease and resistance to a macrolide at initial visit are more likely to progress to deteriorating disease.

In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.