A Novel Pathophysiologic Phenomenon in Cachexic Patients with Chronic Obstructive Pulmonary Disease

Takabatake, Noriaki; Nakamura, Hidenori; Minamihaba, Osamu; Inage, Minoru; Inoue, Sumito; Kagaya, Shigeru; Yamaki, Michiyasu; Tomoike, Hitonobu

doi:10.1164/ajrccm.163.6.2004175

Cited by 88 publications

(18 citation statements)

References 40 publications

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“…Likewise, in our meta-analysis, circulating leptin levels were correlated with nutritional parameters in COPD patients. Four articles [17,30,35,44] reported that circulating leptin levels decreased in COPD patients with lower BMI compared to healthy controls, which was not consistent with the small study of Takabatake et al [31], who reported that no difference was found between stable COPD patients and healthy controls. In addition, there was no difference in either circulating leptin levels or BMI between noncachexic COPD patients and healthy controls.…”

Section: Discussionmentioning

confidence: 88%

“…Eker et al [19] found that in stable COPD patients leptin levels were low and the frequency of insulin resistance was high compared with the controls, although no difference in body FM was determined between the study populations. In other studies where COPD patients and controls were well matched for age, gender and BMI, the circulating leptin levels were not significantly different between stable COPD patients and healthy controls [17,24,25,30,31,32]. However, Gaki et al [33] demonstrated that leptin levels were higher in COPD patients who used inhaled corticosteroids.…”

Section: Resultsmentioning

confidence: 95%

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Circulating Leptin Concentrations in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Zhou

Yuan

Zhang³

et al. 2013

Respiration

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Background: Weight loss is a clinically important risk factor indicating a poor prognosis in chronic obstructive pulmonary disease (COPD). Leptin is an important regulator of food intake and energy expenditure. Objectives: To conduct a meta-analysis to determine whether the level of leptin is related to the disease status of COPD. Methods: Studies published before December 2012 were identified by searching PubMed, Embase and the Cochrane Database. Observational studies comparing circulating leptin levels between COPD patients and healthy controls were included. Data were independently extracted by two investigators and analyzed using Stata 12.0 software. Results: Ten articles were included in the meta-analysis. Circulating leptin levels were correlated with the body mass index (BMI) as well as percent fat mass in stable COPD patients. The correlation coefficient tended to be weaker during exacerbation. A positive correlation between leptin and tumor necrosis factor (TNF)-α levels was found in COPD exacerbations, while it disappeared in patients with stable disease. Most studies indicated that circulating leptin levels in stable COPD patients were not significantly different from those in healthy controls when adjusted for gender and BMI, whilst leptin levels tended to elevate in exacerbation groups. Conclusions: The normal regulatory mechanism of leptin is maintained in stable COPD patients despite weight loss. The additional correlation between leptin and TNF-α during exacerbations may support the closer association of leptin with changes in nutritional parameters and suggests its valuable role in the evaluation of systemic inflammatory responses in COPD patients during exacerbation, which merits further study.

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Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 95%

Circulating Leptin Concentrations in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Zhou

Yuan

Zhang³

et al. 2013

Respiration

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“…By contrast, we opted to study 3 clearly defined groups of COPD patients with a mixed male-female population. The latter point is particularly relevant when studying leptin, for instance, where normal females have been shown to have an approximately 3-fold higher leptin level than males [33], while investigation of leptin levels in COPD were principally determined in males [24, 32, 34]. Indeed, development of cachexia in COPD was previously suggested to be attributed to a cytokine-leptin link when the plasma levels of TNF-α and leptin were correlated [32].…”

Section: Discussionmentioning

confidence: 99%

Increased Serum Inflammatory Markers in the Absence of Clinical and Skeletal Muscle Inflammation in Patients with Chronic Obstructive Pulmonary Disease

Piehl-Aulin

Jones²,

Lindvall³

et al. 2009

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Background: Muscle wasting and cachexia are common occurrences in patients with chronic obstructive pulmonary disease (COPD). Objectives: The current study aimed to investigate markers of inflammation in the circulation and skeletal muscle that might be associated with development of muscle wasting. Methods: Three groups of patients with mild, moderate and severe COPD and matched healthy controls were recruited. Serum levels of C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), IL-6, IL-8, TNF-α, cortisol, insulin-like growth factor 1 (IGF-1), leptin and ghrelin were analysed. Skeletal muscle inflammation was investigated microscopically using a panel of antibodies and standard staining for inflammatory cell infiltration. Results: All COPD patients were clinically stable, with no sign of inflammation and normal CRP values. Compared to controls, significantly increased hs-CRP levels were observed in all COPD patient groups. Significant rises in IL-6 levels were first observed in moderate COPD, while IL-8 levels were significantly elevated at the late severe stage. Circulating levels of TNF-α, cortisol, IGF-1, leptin and ghrelin were similar to control levels. No microscopic signs of skeletal muscle inflammation were observed. Conclusion: Our results identify hs-CRP as an early marker of inflammation that is significantly increased in the circulation even in mild COPD. Serum interleukin levels appear to be increased with disease progress. These changes were manifested in the absence of any clinical signs of disease exacerbation, evidence of skeletal muscle inflammation or hormonal changes.

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“…The molecules receiving the greatest amount of attention are TNF-a, IL-1b, IL-6, C-reactive protein, and ROS and reactive nitrogen species (RNS). There may also be a link between inflammation and low leptin levels [34,35].…”

Section: Energy Imbalancementioning

confidence: 99%

Possible mechanisms underlying the development of cachexia in COPD

Pd¹

2008

European Respiratory Journal

228

173

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About 25% of patients with chronic obstructive pulmonary disease (COPD) will develop cachexia (fat-free body mass index ,17 kg?m -2 (males) or ,14 kg?m -2 (females)). This is associated with ,50% reduction in median survival. The pathogenetic mechanism has been variously suggested to result from the following: 1) energy imbalance; 2) disuse atrophy; 3) tissue hypoxia from arterial hypoxaemia; 4) systemic inflammation; and 5) anabolic hormonal insufficiency. Genetic polymorphisms implicate inflammatory cytokines, especially interleukin (IL)-1b, but IL-6 and tumour necrosis factor (TNF)-a do not show polymorphisms in these patients. Early reports of elevated TNF-a levels suggested a role for inflammation, but recent studies have not shown elevated levels of either IL-6 or TNF-a. Therapeutic trials of nutritional support, hormonal supplementation, anti-TNF-a immunotherapy, ghrelin and antioxidants have been conducted, but only a few have shown any benefits in muscle structure and function.Considerably more mechanistic knowledge is needed before therapeutic recommendations can be made. At this time, it is not possible to attribute cachexia in COPD unequivocally to inflammation or any other cause, and much more research is needed.To date, studies have been predominantly cross-sectional, with measurements made only after cachexia has developed. Future research should target prospective observation, studying patients as cachexia progresses, since once cachexia is established, inflammatory cytokine levels may not be abnormal.

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A Novel Pathophysiologic Phenomenon in Cachexic Patients with Chronic Obstructive Pulmonary Disease

Cited by 88 publications

References 40 publications

Circulating Leptin Concentrations in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Circulating Leptin Concentrations in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Increased Serum Inflammatory Markers in the Absence of Clinical and Skeletal Muscle Inflammation in Patients with Chronic Obstructive Pulmonary Disease

Possible mechanisms underlying the development of cachexia in COPD

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