leptin and Pulmonary-Disease--Chronic-Obstructive

Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs).. To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations. We also describe the commonalities of the defective immune pathways across these susceptible populations that may represent possible targets for future therapeutic or preventative approaches.. We conducted free searches in Medline, Scopus, and Google Scholar for studies focusing on potential mechanisms of immune dysfunction that may be associated with severe viral RTIs in susceptible populations with conditions including pregnancy, obesity, diabetes mellitus, hypertension, cardiovascular disease, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and extremes of age. We considered preclinical/animal data, original human studies, and reviews.. Innate and adaptive immune responses become quantitatively and qualitatively compromised in aging, obesity, and diabetes mellitus, with the most pronounced changes affecting T cells. Moreover, immune dysregulation by the so-called inflamm-aging results in chronic low-grade inflammation in such conditions. Increased leptin levels affect the immune system particularly in obesity, while leptin dysregulation plays a role in asthma and COPD pathogenesis. Deficient production of interferon (IFN) type I and III in response to rhinovirus contributes to asthma exacerbations. Similar attenuation of IFN production in response to influenza and rhinovirus has been documented in pregnancy. Dampened type I IFN responses have also been found in diet-induced obese mice and in obese individuals.. Immunosenescence and chronic low-grade inflammation accompanying aging and a variety of chronic conditions, such as diabetes, obesity, asthma, COPD, chronic renal disease, and hypertension, contribute to the poor outcomes observed following viral respiratory infections. Commonly affected pathways may represent potential future therapeutic targets.

Topics: Animals; Asthma; Disease Susceptibility; Enterovirus Infections; Humans; Hypertension; Immunity; Inflammation; Interferons; Leptin; Mice; Obesity; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus

Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity. The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases. The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia.

Topics: Adaptive Immunity; Animals; Asthma; Humans; Immunity, Innate; Inflammation; Leptin; Lung; Pneumonia; Pulmonary Disease, Chronic Obstructive

Leptin is a product of the obese (ob) gene and acts through its receptor Ob-R. Leptin is primarily known for its role as a hypothalamic modulator of food, especially in intake, energy balance, fat stores and body weight. Recent studies have shown that leptin may be involved in the development of respiratory diseases such as pulmonary artery hypertension, chronic obstructive pulmonary disease, lung neoplasms and asthma. Therefore, further studies are needed to elucidate the mechanisms accounting for the association between leptin and respiratory diseases, which may lead to the development of novel approaches to the prevention and treatment of these diseases. Here we give an overview of the distribution and physiological function of leptin and ob-R, and summarize the recent progress in the relationship between leptin and respiratory diseases.

Topics: Animals; Asthma; Humans; Leptin; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; Respiratory Tract Diseases

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.. To conduct a meta-analysis to determine whether the level of leptin is related to the disease status of COPD.. 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.. 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.. 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.

Topics: Body Fat Distribution; Body Mass Index; C-Reactive Protein; Humans; Interleukin-6; Leptin; Pulmonary Disease, Chronic Obstructive; Sex Factors; Tumor Necrosis Factor-alpha

The overlap syndrome of obstructive sleep apnoea (OSA) and chronic obstructive pulmonary disease (COPD), in addition to obesity hypoventilation syndrome, represents growing health concerns, owing to the worldwide COPD and obesity epidemics and related co-morbidities. These disorders constitute the end points of a spectrum with distinct yet interrelated mechanisms that lead to a considerable health burden. The coexistence OSA and COPD seems to occur by chance, but the combination can contribute to worsened symptoms and oxygen desaturation at night, leading to disrupted sleep architecture and decreased sleep quality. Alveolar hypoventilation, ventilation-perfusion mismatch and intermittent hypercapnic events resulting from apneas and hypopneas contribute to the final clinical picture, which is quite different from the "usual" COPD. Obesity hypoventilation has emerged as a relatively common cause of chronic hypercapnic respiratory failure. Its pathophysiology results from complex interactions, among which are respiratory mechanics, ventilatory control, sleep-disordered breathing and neurohormonal disturbances, such as leptin resistance, each of which contributes to varying degrees in individual patients to the development of obesity hypoventilation. This respiratory embarrassment takes place when compensatory mechanisms like increased drive cannot be maintained or become overwhelmed. Although a unifying concept for the pathogenesis of both disorders is lacking, it seems that these patients are in a vicious cycle. This review outlines the major pathophysiological mechanisms believed to contribute to the development of these specific clinical entities. Knowledge of shared mechanisms in the overlap syndrome and obesity hypoventilation may help to identify these patients and guide therapy.

Topics: Body Mass Index; Cardiovascular System; Comorbidity; Humans; Leptin; Obesity Hypoventilation Syndrome; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Mechanics; Sleep; Sleep Apnea, Obstructive; Smoking

In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation.

Topics: Anorexia; Appetite; Cachexia; Cytokines; Energy Intake; Energy Metabolism; Exercise; Ghrelin; Human Growth Hormone; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Leptin; Malnutrition; Muscular Atrophy; Nutritional Status; Oxygen; Pulmonary Disease, Chronic Obstructive

The systemic manifestations of chronic obstructive pulmonary disease (COPD) exacerbations are recognized, but our understanding of their etiology and importance is lacking largely due to the small number of systematic and longitudinal studies. Most of the systemic manifestations are likely the result of inflammatory processes. Serum biomarkers, such as various cytokines, adipokines, C-reactive protein, and coagulation factors, are elevated during exacerbations. Our understanding of the systemic manifestations can be greatly enhanced if we integrate what is known about the basic science of systemic mediators with the translational science of their role in COPD exacerbations. Many overlapping connections and promising avenues of future research come to light with such a viewpoint.

Topics: Adiponectin; C-Reactive Protein; Endothelium, Vascular; Hemostasis; Humans; Immunity, Innate; Inflammation; Leptin; Pulmonary Disease, Chronic Obstructive

COPD is a major cause of death and disability worldwide. Treatment of COPD improves lung function but is unlikely to slow the steady downhill course of the disease or reduce mortality. In COPD, numerous abnormalities can be found outside the lung. These include systemic inflammation, cachexia, and skeletal muscle dysfunction. Thus, COPD has been called a systemic disease. Convincing data demonstrate that COPD causes neurohumoral activation. By precedents derived from chronic heart failure and other diseases characterized by neurohumoral activation, we propose that the negative consequences of neurohumoral activation, namely inflammation, cachexia, effects on ventilation, and skeletal muscle dysfunction, give rise to a self-perpetuating cycle that contributes to the pathogenesis of COPD, and which may involve respiratory muscle dysfunction as well as systemic inflammation. This concept may further help explain the increased cardiovascular morbidity and mortality in COPD patients. Currently, little is known about the effect of treatments directed at neurohumoral activation and COPD. As this aspect of COPD becomes better understood, new insights may direct novel therapeutic approaches.

Topics: Aldosterone; Animals; Bronchoconstriction; Cachexia; Cardiovascular Diseases; Comorbidity; Heart Rate; Humans; Leptin; Nordefrin; Pulmonary Disease, Chronic Obstructive; Renin; Respiratory Muscles; Risk Factors; Sympathetic Nervous System

Weight loss is a characteristic for advanced chronic obstructive pulmonary disease (COPD), but its mechanism remains unexplained. The decrease of lean body mass is due to a negative energy balance with a noncatabolic hypermetabolic state. Pulmonary inflammation or tissue hypoxia might contribute to it, the decrease in protein content is accompanied by an increase in reactive oxygen forms. Tumor necrosis factor (TNF) has been implicated, other candidates are cytokines IL-1B and IL-6. Activation of apoptosis may be noticed. Pulmonary inflammation and changes in serum leptin may be interrelated. Other hormonal disturbances involve serum IGF-1 level decrease, increase of insulin resistance, raised catecholamine and cortisol levels and other mechanisms which need further investigations. Up to now the attempts undertaken to counteract the observed hormonal changes failed to success.

Topics: Apoptosis; Cachexia; Humans; Leptin; Pulmonary Disease, Chronic Obstructive

The rate of annual change in FEV1 is highly variable among patients with chronic obstructive pulmonary disease (COPD). Reliable blood biomarkers are needed to predict prognosis.. To explore plasma biomarkers associated with an annual change in FEV1 in patients with COPD.. Plasma samples of 261 subjects, all Japanese, with COPD from the 5-year Hokkaido COPD cohort study were analyzed as a hypothesis-generating cohort, and the results were validated using data of 226 subjects with and 268 subjects without airflow limitation, mainly white, from the 4-year COPD Quantification by Computed Tomography, Biomarkers, and Quality of Life (CBQ) study conducted in Denmark. The plasma samples were measured using Human CardiovascularMAP (Myriad RBM, Austin, TX), which could analyze 50 biomarkers potentially linked with inflammatory, metabolic, and tissue remodeling pathways, and single ELISAs were used to confirm the results.. Higher plasma adiponectin levels and a lower leptin/adiponectin ratio at enrollment were significantly associated with an annual decline in FEV1 even after controlling for age, sex, height, and body mass index in the Hokkaido COPD cohort study (P = 0.003, P = 0.004, respectively). A lower plasma leptin/adiponectin ratio was also significantly associated with an annual decline in FEV1 in subjects with airflow limitation in the CBQ study (P = 0.014), the patients of which had largely different clinical characteristics compared with the Hokkaido COPD cohort study. There were no significant associations between lung function decline and adipokine levels in subjects without airflow limitation.. A lower leptin/adiponectin ratio was associated with lung function decline in patients with COPD in two independent Japanese and Western cohort studies of populations of different ethnicity. Measure of systemic adipokines may provide utility in predicting patients with COPD at higher risk of lung function decline.

Topics: Adiponectin; Aged; Biomarkers; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Leptin; Male; Pulmonary Disease, Chronic Obstructive; Risk Factors; Severity of Illness Index; Tomography, X-Ray Computed

Weight loss in patients with severe chronic obstructive pulmonary disease (COPD) is a prognostic bad factor. The objective of this study is to analyze the effectively of megestrol acetate (MA) to increase appetite of these patients.. Randomized double blind placebo controlled trial to study the effect of 160 mg/bid of MA, for 8 weeks, on nutritional, functional, analytical and quality of life parameters, in 38 patients with severe COPD and body mass index (BMI) < 21 kg/m(2), or between 21-25 with involuntary weight loss of 5% in the last 3 months.. At 8 weeks, in the MA group the body weight increased (2.3 kg) with respect to the control group (0.1 kg) (p<0.04). MA improved significantly the triceps skin-fold thickness (p < 0.04), prealbumin (p<0.004), lymphocytes (p<0.0006), C3 (p<0.04), PCO(2) (p<0.007) and bicarbonate levels (p<0.008). MA did not increase the MRC and SGRQ scales, the distance of 6 MWT nor BODE index. The IL-6 and TNF alpha levels were not modified in the MA group, but leptin did increase (p<0.043). MA improved the sense of wellbeing (p<0.02) and the appetite (p<0.008), compared to the control group. Adverse effects were similar in both groups.. MA safely increases the body weight and the appetite in severe COPD patients with weight loss. MA improves blood gases and nutritional parameters and the sense of wellbeing, but it does not improve the respiratory muscular function or exercise tolerance.

Topics: Adult; Aged; Aged, 80 and over; Appetite; Appetite Stimulants; Bicarbonates; Body Weight; Cachexia; Double-Blind Method; Female; Humans; Hydrocortisone; Interleukin-6; Leptin; Male; Megestrol Acetate; Middle Aged; Nutritional Status; Prealbumin; Pulmonary Disease, Chronic Obstructive; Quality of Life; Skinfold Thickness; Testosterone; Tumor Necrosis Factor-alpha

Natural progesterone, a potent respiratory stimulant, stimulates leptin production in premenopausal females. Leptin and its counterpart neuropeptide Y (NPY) have recently been linked with respiration. The effect of medroxyprogesterone acetate (MPA) on arterial blood gases, serum leptin and NPY was evaluated in this study. Fourteen postmenopausal females with respiratory impairment, due mostly to chronic obstructive pulmonary disease, were recruited for a randomised, double-blind, placebo-controlled crossover trial. Arterial blood gases, serum leptin and NPY concentrations were measured at baseline and after 14 days of treatment with placebo and MPA, separated by a 6-week washout period. Thirteen patients completed the trial. The mean+/-SD carbon dioxide tension in arterial blood (Pa,CO2) was 5.4+/-0.6 kPa at baseline, and decreased by 0.8+/-0.3 kPa during treatment with MPA. The oxygen tension in arterial blood (Pa,O2) and pH did not change. At baseline, the mean base excess was 0.6+/-1.9 mmol x L(-1) and the mean bicarbonate (HCO3-) concentration was 25.1+/-1.6 mmol x L(-1). With MPA, base excess decreased by 2.2+/-1.2 mmol x L(-1) and HCO3- by 1.9+/-1.0 mmol x L(-1) from baseline. The mean concentrations of serum leptin (19.8+/-9.9 microg x L(-1) at baseline, 19.7+/-9.8 microg x L(-1) with MPA) or NPY (94.0+/-18.3 pmol x L(-1) at baseline, 85.1+/-41.2 pmol x L(-1) with MPA) did not change. However, the reduction in Pa,CO2 correlated with the reduction of serum leptin concentration. Medroxyprogesterone acetate effectively decreased the carbon dioxide tension in postmenopausal females with chronic respiratory impairment. The results suggest that a decrease in the carbon dioxide tension of > or = 0.9 kPa is necessary for a reduction in serum leptin concentration.

Topics: Aged; Carbon Dioxide; Cross-Over Studies; Double-Blind Method; Female; Humans; Leptin; Medroxyprogesterone; Neuropeptide Y; Oxygen; Postmenopause; Progesterone Congeners; Pulmonary Disease, Chronic Obstructive

Adipokines, which have pleiotropic activities, are known to be involved in inflammation as adipocytokines. The aim of the current study was to investigate selected adipocytokine levels in the serum of stable chronic obstructive pulmonary disease COPD patients and healthy controls, to assess a potential association between the investigated biomarkers and selected parameters and to conduct receiving operating curve (ROC) analysis. Twenty-five COPD patients and 30 healthy controls were enrolled in the current study. Serum levels of adiponectin, leptin, resistin, chemerin and fetuin A were measured using an enzyme-linked immunosorbent assay (ELISA) method. Both leptin and resistin concentrations were significantly elevated in COPD patients and differentiated them from control subjects. Fetuin A levels were lower in COPD patients and may be related to the disease. Further studies in larger cohorts are needed to confirm the findings of this exploratory study.

Topics: Adipokines; Adiponectin; alpha-2-HS-Glycoprotein; Biomarkers; Humans; Leptin; Pulmonary Disease, Chronic Obstructive; Resistin

As a key adipokine, leptin has been extensively investigated for its potential role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, concordant conclusions have not been attained. In this study, we investigated the relationship between leptin and COPD using an integrative analysis that combined a Mendelian randomization (MR) study with transcriptomic data analysis. Here, the MR analysis was performed on the online platform MR-Base, and the bioinformatics analyses were performed with the aid of R Bioconductor packages. No evidence was found by the integrative analysis to support the association of the two attributes. All methods detected a null causal effect of leptin on COPD in the MR analysis. In particular, when the genetically predicted leptin level increased one unit, the risk of developing COPD was estimated as 0.999 (

Topics: Gene Expression Profiling; Genome-Wide Association Study; Humans; Leptin; Mendelian Randomization Analysis; Pulmonary Disease, Chronic Obstructive; Transcriptome

Asthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.. Five-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6-9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson's trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.. Leptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.. In HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.

Topics: Allergens; Animals; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Fibrosis; Humans; Hypersensitivity; Leptin; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Obesity; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Pyroglyphidae; RNA, Messenger

Adipose tissue is an endocrine organ that interferes with the severity of chronic obstructive pulmonary disease (COPD). Although inflammatory markers, body composition, and nutritional status have a significant impact on pulmonary function, the real contribution of adipocytokines and myokines in COPD is still controversial. We aimed to evaluate the role played by the body composition, leptin, adiponectin, haptoglobin, and irisin on the functional exercise capacity, respiratory function, and quality of life (QoL) in COPD. In 25 COPD (20% GOLD-1; 60% GOLD-2; 20% GOLD-3) patients and 26 matched control subjects, we find that leptin, total adiponectin and haptoglobin are significantly increased whereas the 6 min walk test (6MWT) and physical functioning scores are significantly decreased in COPD versus controls. A significant positive relationship is found between leptin and fat mass and between 6MWT and the good health indicators of nutritional status. A significant inverse relationship is found between 6MWT and leptin and fat mass, FEV

Topics: Adipokines; Adiponectin; Body Composition; Exercise Tolerance; Fibronectins; Haptoglobins; Humans; Leptin; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Quality of Life

Exacerbations are critical events in the course of asthma and chronic obstructive pulmonary disease (COPD). These events are potentially life-threatening, and the studies have shown that they have tremendous implications on long-term disease control and the overall prognosis of the patients. The aim of this study was to examine adipokines, cytokines and C-reactive protein (CRP) as potential biomarkers in asthma and COPD.. Prospective cohort study of COPD and asthma patients treated for acute exacerbations. Thirty-nine COPD patients and 15 asthmatic patients were included in the study. Leptin, adiponectin, resistin, interleukin (Il)-6, 8, 18, tumor necrosis factor-a (TNF-a), and CRP were measured at three time points: on admission, at resolution and at the stable phase. Pre- and post-bronchodilation spirometry was additionally performed at resolution and at the stable phase.. In COPD patients, leptin, leptin/adiponectin (L/A) ratio and resistin were elevated on admission compared to the stable phase. In asthmatic patients, leptin levels were raised on admission compared to the stable phase, and adiponectin was elevated at resolution compared to admission. In both diseases, CRP was significantly increased on admission compared to both resolution and stable disease. Finally, TNF-a could distinguish between asthma and COPD stable phase.. Leptin and CRP levels may be useful biomarkers in monitoring COPD and asthma response to treatment during an exacerbation episode. Hypoadiponectinemia was detected in asthma and COPD during all stages of the diseases. TNF-a could distinguish between asthma and COPD stable phase.

Topics: Adiponectin; Asthma; Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tumor Necrosis Factor-alpha

Topics: Adult; Aged; Biomarkers; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Forced Expiratory Volume; Humans; Leptin; Male; Middle Aged; Prognosis; Pulmonary Disease, Chronic Obstructive; Sex Factors; Spirometry

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition associated with abnormal immune responses, leading to airflow obstruction. Lungs of COPD subjects show accumulation of proinflammatory T helper (Th) 1 and Th17 cells resembling that of autoreactive immune responses. As regulatory T (T

Topics: Alternative Splicing; Female; Forkhead Transcription Factors; Humans; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells

Nonalcoholic fatty liver disease (NAFLD) is independently linked to cardiometabolic morbidity and mortality. Low-grade inflammation, oxidative stress and ectopic fat, common features of chronic obstructive pulmonary disease (COPD), might contribute to the development of NAFLD.We aimed to investigate the prevalence of NAFLD and to evaluate the relationship between various types of liver damage and COPD severity, comorbidities and circulating inflammatory cytokines. Validated noninvasive tests (FibroMax: SteatoTest, NashTest and FibroTest) were used to assess steatosis, nonalcoholic steatohepatitis (NASH) and liver fibrosis. Patients underwent an objective assessment of COPD comorbidities, including sleep studies. Biological parameters included a complete lipid profile and inflammatory markers.In COPD patients the prevalence of steatosis, NASH and fibrosis were 41.4%, 36.9% and 61.3%, respectively. In multivariate analysis, SteatoTest and FibroTest were significantly associated with sex, body mass index (BMI), untreated sleep apnoea and insulin resistance, and, in addition, COPD Global Initiative for Chronic Obstructive Lung Disease stage for SteatoTest. Patients with steatosis had higher tumour necrosis factor-α levels and those with NASH or a combination of liver damage types had raised leptin levels after adjustment for age, sex and BMI.We concluded that NAFLD is highly prevalent in COPD and might contribute to cardiometabolic comorbidities.

Topics: Adiponectin; Aged; Body Mass Index; C-Reactive Protein; Cohort Studies; Comorbidity; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Resistin; Tumor Necrosis Factor-alpha

To investigate the correlation of serum leptin and to energy consumption and metabolization in the patients with chronic obstructive pulmonary disease (COPD).. We included 92 outpatients with stable COPD in West China Hospital of Sichuan University as trail group (COPD group) and 80 healthy elderly people in community as control group. All patients and healthy control received the measurements of body mass index (BMI), fat mass, resting energy expenditure (REE), lung function, serum leptin and tumor necrosis factor-α (TNF-α).. The concentrations of serum leptin, BMI and lung function were lower in COPD group than those in control group (P < 0.01). The concentrations of serum leptin between two groups were not difference after the adjusted results of BMI and fat mass.. There was no difference of REE and TNF-α concentrations in these two groups. The serum leptin had positive correlation with BMI and fat mass, but there were no correlation between of TNF-α and serum leptin.. In elderly people with stable COPD, the decline on the serum leptin is related to the decrease of BMI and fat mass, but barely related to the level of TNF-α.

Topics: Aged; Body Mass Index; Case-Control Studies; China; Energy Metabolism; Humans; Leptin; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Hokkaido COPD cohort study is a carefully-designed, well-conducted, prospective observational 10 year-long study, which ended early in 2015. We have obtained a number of clinically-relevant novel findings, some of which are as follows. Severity of emphysema was highly varied even in those individuals whose airflow limitation is comparable. The annual change in forced expiratory volume in 1 second (FEV1) over 5 years was also widely varied with normal distribution among the subjects under appropriate treatment. Some patients maintained their pulmonary function for a long time, and others showed a rapid decline. Emphysema severity, but not pulmonary function, was independently associated with such an inter-subject variation in the annual decline in FEV1. When we explored any biomarkers for predicting the FEV1 decline, a lower leptin/adiponectin ratio alone emerged as an explanatory parameter for the rapid decline, and this was also confirmed in an independent Danish cohort study of different ethnicity. Monitoring of quality of life (QOL), using SGRQ scores, also provided interesting observations. The annual change in total score reflected that of FEV1 decline during the follow-up period. However, activity component in QOL deteriorated in almost all the subjects, while symptom component rather improved in many of the patients under appropriate treatment.

Topics: Adiponectin; Biomarkers; Cause of Death; Cohort Studies; Humans; Japan; Leptin; Maximal Expiratory Flow Rate; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Quality of Life; Respiratory Function Tests; Severity of Illness Index; Time Factors

Cigarette smoking, which is a well-known major risk factor for chronic obstructive pulmonary disease (COPD), causes both pulmonary and extrapulmonary abnormalities. Ghrelin is a gastric peptide that regulates energy homeostasis. In the present study, we investigated the effects of ghrelin on the catabolic changes, respiratory function and emphysema in an animal model of COPD induced by chronic exposure to cigarette smoke. Rats were exposed to cigarette smoke, and they were administered human ghrelin (0.1 or 1 mg/kg, subcutaneous, twice daily) for 12 weeks. Compared with air-exposed rats, body weight gain, food intake, food efficiency, tidal volume, peak expiratory flow rate, and forced expiratory volume at 100 ms were significantly lower, while functional residual capacity, lung capacity, and neutrophils in bronchoalveolar lavage fluid were significantly higher in cigarette smoke-exposed rats. These indicated that the systemic abnormalities associated with COPD developed after the exposure to cigarette smoke. Ghrelin significantly and dose-dependently increased the body weight gain and food efficiency in cigarette smoke-exposed rats. In ghrelin-treated rats, skeletal muscle strength, which tended to be lowered by cigarette smoke exposure, was improved. Ghrelin ameliorated respiratory function and emphysema in a dose-dependent manner, but did not inhibit the increase in neutrophils in the bronchoalveolar lavage fluid. The respiratory functional parameters and lung capacity were significantly correlated with body weight gain. These results suggest that ghrelin inhibited the development of the catabolic changes, respiratory dysfunction, and emphysema that were induced by cigarette smoke exposure in rats, at least in part, through the amelioration of nutritional status.

Topics: Animals; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Cell Count; Disease Models, Animal; Forced Expiratory Volume; Forelimb; Ghrelin; Hand Strength; Leptin; Lung; Male; Nicotiana; Peak Expiratory Flow Rate; Pulmonary Disease, Chronic Obstructive; Rats, Wistar; Smoke; Tidal Volume

Two adipokines, leptin and adiponectin, regulate metabolic and inflammatory systems reciprocally. The role of adiponectin in chronic obstructive pulmonary disease (COPD) has been studied. However, there are few data evaluating the relationship of plasma leptin with COPD severity or progression.. The objective of this study was to evaluate the relationship of leptin, adiponectin, and the leptin/adiponectin ratio with COPD severity and progression according to COPD phenotypes.. Plasma leptin and adiponectin levels were measured in 196 subjects with COPD selected from the Korean Obstructive Lung Disease cohort. Using a linear regression model and mixed linear regression, we determined the relationship of plasma leptin and adiponectin levels and the leptin/adiponectin ratio to COPD severity and progression over 3 years.. The concentration of adiponectin in plasma positively correlated with percent emphysema on initial computed tomography (CT) (adjusted P = 0.022), whereas plasma leptin concentrations and the leptin/adiponectin ratio exhibited a significant inverse correlation with initial FEV1 (adjusted P = 0.013 for leptin and adjusted P = 0.041 for leptin/adiponectin ratio). Increased plasma leptin and leptin/adiponectin ratio were significantly associated with change in percent emphysema over 3 years (adjusted P = 0.037 for leptin and adjusted P = 0.029 for leptin/adiponectin ratio), whereas none of the adipokines demonstrated an association with FEV1 decline over the 3-year period.. Plasma adiponectin and leptin vary according to COPD phenotypes. Plasma leptin and the leptin/adiponectin ratio, but not adiponectin, were significantly associated with changes in CT-assessed emphysema, suggesting a potential role as a biomarker in emphysema progression in patients with COPD.

Topics: Adiponectin; Aged; Biomarkers; Cohort Studies; Disease Progression; Emphysema; Female; Humans; Leptin; Linear Models; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Republic of Korea; Respiratory Function Tests; Severity of Illness Index

Topics: Adiponectin; Emphysema; Female; Humans; Leptin; Male; Pulmonary Disease, Chronic Obstructive

Morbid obesity, the most significant risk factor for development of sev- eral respiratory diseases, is linked to decreased pulmonary function. The aim of this study was to determine the relationships between pulmonary function and plasma levels of homeostasis model assessment-insulin resistance (HOMA-IR), insulin, leptin, hs-CRP and fasting glucose. Values were measured in 39 Thai children and adolescents, divided into three groups according to lung function (forced expiratory volume in one second, FEV1); normal (Group A) FEV1 ≥ 80% (n = 19), obese normal (Group B) FEV1 ≥ 80% (n = 14) and obese (Group C) FEV1 < 80% (n = 6). Body mass index was highest in group C. Groups A and B were comparable for FEV1, forced vital capacity (FVC), maximal voluntary ventilation (MVV) and FEV1/FVC, whereas Group C exhibited significantly reduced FEV1, FVC and MVV but a normal FEV1/FVC ratio. All values except the FEV1/FVC ratio were significantly lower than in groups A and B. Group C had significantly higher levels of leptin, insulin, FG and HOMA-IR than Groups A and B (p < 0.001). There was a significant negative correlation between FEV1 and MVV with leptin, insulin and HOMA-IR, but not with high-sensitivity C-reactive protein (hs-CRP). We conclude that FEV1 is reduced in obese children and adolescents and inversely correlates with plasma leptin, insulin and HOMA-IR levels. We have shown that the most important factor in inducing a restrictive lung in these patients may be related to leptin status.

Topics: Adolescent; Body Mass Index; C-Reactive Protein; Child; Female; Forced Expiratory Volume; Humans; Insulin; Insulin Resistance; Leptin; Male; Pediatric Obesity; Pulmonary Disease, Chronic Obstructive; Risk Factors; Vital Capacity

Weight loss and muscle wasting are common features reported in COPD patients and they are all related with systemic inflammation. In this study, the relationship between pulmonary functions and inflammatory and metabolic parameters in low weight COPD patients were investigated.. Fifty male COPD patients were grouped according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Group 1: Mild-moderate COPD patients (n=18; with a mean age of 66.4 ± 9.2 yrs; body mass index (BMI):19.7 ± 1.5 kg/m(2)), group 2: Severe-very severe COPD patients (n=32; with a mean age of 65.9 ± 10.0 yrs; BMI:19.3 ± 1.6 kg/m(2)), group 3: Control group composed of healthy nonsmoking males (n=17; with a mean age of 50.2 ± 8.4 yrs; BMI:21.85 ± 1.5 kg/m(2)). Anthropometric parameters, serum levels of adiponectin (ApN), ghrelin, leptin, hsCRP, IL-6, IL-1β, IL-8, TNF-α and pulmonary functions were compared.. Adiponectin concentration was higher in group 1 (43.3 ± 28.6 ng/mL; p<0.05) and group 2 (59.9 ± 31.8 ng/mL; p<0.001) when compared with the control group (23.5 ± 13.6 ng/mL). Ghrelin concentrations were higher in COPD groups (1281.0 ± 1173.7 and 1840.0 ± 403.6 pg/mL; p<0.05) compared to the control subjects (554.0 ± 281.9 pg/mL). When the groups were compared, no significant difference was found for leptin, IL-1β, TNF-α, and IL-8. Interleukin-6 and hsCRP levels were higher in group 1 than in the control group. ApN was negatively correlated with BMI and FEV1. In all groups, FEV1 showed positive correlation with BMI, skinfold thicknesses, insulin and triglyceride; negative correlation with age, pack/years, HDL-Chol and ApN. Increased SHBG with decreased insulin level and HOMA-IR may indicate increased insulin sensitivity in COPD groups.. The anti-inflammatory effect of ApN and ghrelin is more evident in severe-very severe COPD patients.

Topics: Adiponectin; Aged; Body Mass Index; Case-Control Studies; Ghrelin; Humans; Interleukin-1beta; Interleukin-6; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Thinness; Tumor Necrosis Factor-alpha

Topics: Animals; Asthma; Humans; Leptin; Pneumonia; Pulmonary Disease, Chronic Obstructive

Chronic obstructive pulmonary disease (COPD) due to sulfur mustard (SM), known as mustard lung, is an important late pulmonary complication of SM poisoning. Due to the possible role of systemic inflammation in mustard lung, we evaluated the serum levels of adiponectin and leptin in these patients.. Thirty nonsmoker mustard lung patients in stable phase were enrolled into this study. Also, 30 COPD and 21 healthy participants were entered as control groups. Complete lung function tests were performed in the participants. The serum levels of adiponectin and leptin were measured in all groups.. There were no statistically significant differences in mean adiponectin and leptin levels among the groups (p = 0.38 and p = 0.35, respectively). There was a downward trend in leptin to adiponectin ratio from lower to higher stages of global initiative for chronic obstructive lung disease guidelines in mustard lung patients, which was not statistically significant (p = 0.8).. Our results showed that there is no difference in mean adipokine levels in stable mustard lung patients compared with control groups. There was a foot-point in the alterations of serum adipokines regarding the severity of COPD, which needs to be documented by larger sample group.

Topics: Adiponectin; Adult; Case-Control Studies; Chemical Warfare Agents; Enzyme-Linked Immunosorbent Assay; Humans; Leptin; Middle Aged; Mustard Gas; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Severity of Illness Index

Adipokines are protein mediators first described as products of adipose tissue regulating energy metabolism and appetite. Recently, adipokines have also been found to modulate inflammation and smooth muscle cell responses. Therefore we investigated the association of two adipokines, adiponectin and leptin, with the degree of emphysema, pulmonary function, symptoms and glucocorticoid responsiveness in patients with COPD.. Plasma adiponectin and leptin levels, spirometry, body plethysmography and symptoms were measured in 43 male COPD patients with smoking history ≥ 20 pack-years, post bronchodilator FEV1/FVC < 0.7 and pulmonary emphysema on HRCT. The measurements were repeated in a subgroup of patients after 4 weeks' treatment with inhaled fluticasone.. In patients with COPD, plasma adiponectin levels correlated positively with airway resistance (Raw) (r = 0.362, p = 0.019) and functional residual capacity (FRC) (r = 0.355, p = 0.046). Furthermore, the baseline adiponectin concentration correlated negatively with the fluticasone induced changes in St George's Respiratory questionnaire (SGRQ) symptom score (r = -0.413, p = 0.040) and in FRC % pred (r = -0.428, p = 0.003), i.e. a higher baseline plasma adiponectin level was associated with more pronounced alleviation of symptoms and dynamic hyperinflation. Plasma leptin levels were not related to the measures of lung function, symptoms or glucocorticoid responsiveness.. Plasma adiponectin levels were associated with peripheral airway obstruction and dynamic hyperinflation in patients with COPD. A higher adiponectin level predicted more favourable relief of symptoms and hyperinflation during glucocorticoid treatment. Adiponectin may have a role in the COPD pathogenesis; it may also be a biomarker of disease severity and treatment responses in this disease.

Topics: Adiponectin; Adipose Tissue; Administration, Inhalation; Androstadienes; Biomarkers; Bronchodilator Agents; Fluticasone; Glucocorticoids; Humans; Leptin; Male; Plethysmography, Whole Body; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Risk Factors; Sensitivity and Specificity; Smoking; Spirometry; Surveys and Questionnaires; Treatment Outcome

Recent studies suggest an important role for leptin in respiratory immune responses and pathogenesis of inflammatory respiratory diseases. There has been an interest to explore whether leptin plays any role in the pathogenesis of chronic obstructive pulmonary disease (COPD).. We conducted a population-based study to evaluate the relationship between serum leptin and COPD in the third US National Health and Nutrition Examination Survey participants.. Our study group was constituted by 6415 adults who had fasting serum leptin and underwent spirometry measurement.. Serum leptin levels were compared (1) between subjects with normal lung function and those with COPD and (2) among COPD subjects with different severities.. Among male participants, 2257 were controls, and 680 had COPD. Compared with controls, COPD subjects were older (62 vs 43 years) and had higher prevalence of smokers (78% vs 58%), lower body mass index (BMI) (26.3 vs 26.9), and higher serum leptin levels (6.6 vs 5.9). For female participants, 2918 were controls, and 560 had COPD. Those with COPD were older (60 vs 43 years) and had lower BMI (26.9 vs 27.7). No differences in serum leptin levels were observed. The independent predictors of COPD in both sexes were age, BMI, and smoking, but not serum leptin. There were no differences in serum leptin among COPD subjects with different severities.. We did not find any significant difference in the levels of serum leptin in subjects with COPD. Our data provide indirect evidence against a major role for serum leptin in the pathogenesis of COPD in humans.

Topics: Adult; Case-Control Studies; Demography; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nutrition Surveys; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Sex Characteristics; United States

Chronic obstructive pulmonary disease (COPD) affects body composition, adipokine secretion, and skeletal integrity. The aim was to determine the association between leptin, body mass (BM) and body composition parameters - fat mass (FM) and fat mass index (FMI), lean tissue mass (LTM), lean tissue mass index (LTMI) and bone mineral density (BMD) in 67 male COPD patients.. BM, body composition and biochemical indicators were measured or calculated using standard methods. Data were analyzed according to groups: non-obese (N = 48, BMI 21.0-29.9 kg/m(2)) and obese (N = 19, BMI ≥ 30.0 kg/m(2)).. In the non-obese group statistically significant correlations were observed: negative ones of age with most BMD T scores, positive ones of BMI with all T scores, FM, FMI, LTMI and leptin, of FMI with leptin and all T scores, and of LTMI with most T scores. In the obese group also statistically significant correlations were found: positive ones of BMI with FMI, LTM, leptin and T scores (trochanter, total hip); of FMI with leptin; and of leptin with total hip T score.. A positive relationship between FMI and BMD was found only in non-obese but not in obese COPD patients. Leptin concentration was associated positively with the total hip T score only in obese COPD patients, suggesting its protective role on the skeleton of obese COPD patients.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Body Composition; Bone and Bones; Bone Density; Female; Humans; Leptin; Male; Middle Aged; Obesity; Pulmonary Disease, Chronic Obstructive

Topics: Adiponectin; Female; Humans; Leptin; Male; Pulmonary Disease, Chronic Obstructive

The aim of the present study was to compare leptin and interleukin (IL)-6 expression in patients and rat models with chronic obstructive pulmonary disease (COPD). Leptin and IL-6 levels were determined in patients with an acute exacerbation of COPD (AECOPD), stable COPD and in healthy controls. Rat models of COPD were developed, histological and immunohistochemical analyses were performed and leptin and IL-6 levels were determined. Leptin and IL-6 levels in the serum and sputum were higher in patients with AECOPD compared with stable COPD and control patients. In rats, leptin and IL-6 were expressed in bronchial epithelial and inflammatory cells, while leptin expression was observed in alveolar cells and IL-6 expression in blood vessel cells only. Serum levels of leptin and IL-6 were significantly higher in COPD1 and COPD2 rats compared with the control rats, and were even higher in COPD1 rats than COPD2 rats. In conclusion, leptin and IL-6 levels were demonstrated to be associated with the severity of COPD.

Topics: Adult; Animals; Body Weight; Disease Models, Animal; Humans; Immunohistochemistry; Interleukin-6; Leptin; Lung; Male; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Sputum

Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world. The increasing severity of inflammatory processes in the respiratory tract leads to exacerbation of COPD. This process may be associated with changes in the synthesis of adipokines, the peptides that participate in immune processes.. The aim of this study was to identify more sensitive and specific laboratory markers useful in diagnosing inflammatory processes in patients with COPD.. The study involved 33 patients with COPD without exacerbation. During the previous year, 1 episode of exacerbation was reported in 15 patients and no exacerbations were reported in the remaining 18 patients. Serum concentrations of adipokines were measured using an enzyme-linked immunosorbent assay (ELISA).. In patients with COPD, we observed a 2-fold increase in leptin levels compared with healthy controls (18.8 ±10.2 ng/ml vs. 9.06 ±4.33 ng/ml; P = 0.042). Mean resistin levels in these patients were also 2-fold higher than those in controls (8.24 ±4.18 ng/ml vs. 3.58 ±1.51 ng/ml, respectively; P = 0.027). Significant positive correlations between C-reactive protein (CRP) and leptin as well as CRP and resistin levels were observed in patients with COPD (r = 0.75 and r = 0.83, respectively; P <0.05). Moreover, a statistically significant negative correlation between the forced expiratory volume in 1 second (FEV1) and resistin was noted in this group (r = 0.62; P <0.05). There was no correlation between FEV1 and leptin levels either in patients with COPD or in healthy controls.. A significant increase in leptin and resistin levels in patients with COPD may suggest that these adipokines are involved in the inflammatory process underlying the disease.

Topics: Adult; Aged; C-Reactive Protein; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Forced Expiratory Volume; Humans; Leptin; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Resistin; Respiratory Function Tests

To detect nutrition disorders (underweight and obesity) in patients with chronic obstructive disease (COPD) and presence of systemic inflammation by determination of inflammatory mediators serum values C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α) and leptin.. The examination involved 85 patients with COPD. Nutrition categories were defined by body mass index (BMI). Fat free mass (FFM) was evaluated by mid upper-arm circumference (MUAC) and fat mass (FM) by tricipital skin-fold thickness (TFS). Values of TNF-α and leptin were measured by standardized ELISA kits and, CRP by latex turbidimetry.. There were 14 (16.5%) underweight patients, 28 (32.9%) normal, 28 (32.9%) pre-obese and 15 (17.6%) obese. Values of MUAC and TSF were significantly different among the nutrition categories (p=0.000). The lowest MUAC and TSF values were in the underweight, and the highest in the obese. There was no significant difference of CRP and TNF-α among nutrition categories. Leptin of the underweight and normal nutrition was significantly different from leptin of the pre-obese and obese (p=0.000). The highest CRP and the lowest TNF-α and leptin were in the underweight patients. The obese had the lowest CRP (although increased as compared to normal values) and the highest leptin, while the pre-obese had the highest TNF-α.. Two basic nutrition disorders (underweight and obesity) were manifested in COPD patients. The inflammatory profile differs between underweight COPD patients and obese. Probably that happens due to systemic inflammation, and in part due to dysfunction of adipose tissue.

Topics: Body Mass Index; C-Reactive Protein; Humans; Inflammation; Leptin; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

To estimate the heritabilities of maximally attained lung function in young adult twins, and to examine whether circulating leptin, leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with maximally attained lung function.. Measures on forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were available of 578 twins recruited from the East Flanders Prospective Twin Survey (165 monozygotic (MZ) and 73 dizygotic (DZ) complete pairs and 102 single twins). Twin model fitting and (genetic) association analyses were performed.. Intra-pair correlations of FEV(1) and FVC did not differ significantly between MZ monochorionic and MZ dichorionic pairs. Heritability estimates of FEV(1) and FVC were 69% and 63%, respectively. The A allele of the LEP 19G>A SNP was significantly associated with a lower FEV(1) (p(Additive) = 0.01) and FVC (p(Dominant) = 0.047), while the LEPR K109R and Q223R SNPs showed no associations. Accounting for body mass index, serum leptin was negatively associated with FVC (p = 0.02) in men, but not in women.. More than 60% of variation in maximally attained FEV(1) and FVC is explained by genetic factors. Moreover, these results suggest that leptin may be important in the determination of maximally attainable lung function.

Topics: Adult; Age Distribution; Belgium; Body Mass Index; Female; Forced Expiratory Volume; Genetic Association Studies; Humans; Leptin; Male; Polymorphism, Genetic; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; Respiratory Function Tests; Sex Distribution; Twins, Dizygotic; Twins, Monozygotic; Vital Capacity; Young Adult

Increases in resting energy expenditure (REE) likely contribute to weight loss in various chronic diseases. In chronic obstructive pulmonary disease (COPD), relationships between the ventilatory impairment and increased REE, and between disturbances in adipokines and weight loss were previously described. Therefore, we investigated serum levels and adipose tissue expression of leptin and adiponectin, and their relationships to REE in patients with COPD. In 44 patients with stable COPD (38 male; age 62.3+/-7.2 years), REE was assessed using indirect calorimetry. Subcutaneous adipose tissue samples were analyzed using real-time PCR. From underweight [n=9; body mass index (BMI) <20.0 kg.m(-2)], to normal weight-overweight (n=24, BMI=20.0-29.9 kg.m(-2)) and obese patients (n=11; BMI>/=30 kg.m(-2)), REE adjusted for body weight decreased (32.9+/-6.1 vs. 26.2+/-5.8 vs. 23.9+/-6.6 kcal.kg(-1).24 h(-1), p=0.006), serum levels and adipose tissue expression of leptin increased (p<0.001 for both), and serum and adipose tissue adiponectin decreased (p<0.001; p=0.004, respectively). REE was inversely related to serum and adipose tissue leptin (R=-0.547, p<0.001; R=-0.458, p=0.002), and directly to serum adiponectin (R=0.316, p=0.039). Underweight patients had increased REE compared to normal weight-overweight patients, in association with reductions in serum and adipose tissue leptin, and increased serum adiponectin, suggesting a role of adipokines in energy imbalance in COPD-related cachexia.

Topics: Adiponectin; Adipose Tissue; Energy Metabolism; Female; Humans; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Rest

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway obstruction that is not fully reversible, and there is evidence of a hereditary component in COPD. We aimed to determine whether the polymorphisms -2548G/A of leptin (LEP) gene were associated with COPD and its severity in Chinese. A total of 456 subjects with COPD and 422 healthy controls from West China Hospital were enrolled in this study. COPD patients had been undergone a spirometry and a physical examination to refer the GOLD I-IV stages. The polymorphisms in the leptin promoter region at position -2548G/A were detected by Polymerase chain reaction-restriction fragment length polymorphism analysis. The genotypes and alleles were scored, and the frequencies of the alleles and genotypes in patients and controls were compared. A significantly higher risk for COPD was observed for carriers of the LEP -2548AA genotype [odds ratio (OR)=7.87, 95% confidence interval (CI) 4.19-14.77, P<0.001] and carriers of the LEP -2548GA genotype (OR=2.98, 95% CI 1.57-5.66, P=0.001). The LEP -2548A allele: frequency was significantly higher in the patient group compared with the control group (OR=2.75, 95% CI: 2.20-3.44, P<0.001). We also found a significant relationship between leptin gene polymorphism and the severity of COPD. In the present case-control study, we found an association between the -2548G/A variant of the leptin gene and pathogenesis, severity of COPD in the Chinese population. It suggests that leptin -2548G/A should be used as a genetic marker of COPD severity.

Topics: Aged; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Systemic effects of COPD are incompletely reflected by established prognostic assessments. We determined the prognostic value of objectively measured physical activity in comparison with established predictors of mortality and evaluated the prognostic value of noninvasive assessments of cardiovascular status, biomarkers of systemic inflammation, and adipokines.. In a prospective cohort study of 170 outpatients with stable COPD (mean FEV(1), 56% predicted), we assessed lung function by spirometry and body plethysmography; physical activity level (PAL) by a multisensory armband; exercise capacity by 6-min walk distance test; cardiovascular status by echocardiography, vascular Doppler sonography (ankle-brachial index [ABI]), and N-terminal pro-B-type natriuretic peptide level; nutritional and muscular status by BMI and fat-free mass index; biomarkers by levels of high-sensitivity C-reactive protein, IL-6, fibrinogen, adiponectin, and leptin; and health status, dyspnea, and depressive symptoms by questionnaire. Established prognostic indices were calculated. The median follow-up was 48 months (range, 10-53 months).. All-cause mortality was 15.4%. After adjustments, each 0.14 increase in PAL was associated with a lower risk of death (hazard ratio [HR], 0.46; 95% CI, 0.33-0.64; P < .001). Compared with established predictors, PAL showed the best discriminative properties for 4-year survival (C statistic, 0.81) and was associated with the highest relative risk of death per standardized decrease. Novel predictors of mortality were adiponectin level (HR, 1.34; 95% CI, 1.06-1.71; P = .017), leptin level (HR, 0.81; 95% CI, 0.65-0.99; P = .042), right ventricular function (Tei-index) (HR, 1.26; 95% CI, 1.04-1.54; P = .020), and ABI < 1.00 (HR, 3.87; 95% CI, 1.44-10.40; P = .007). A stepwise Cox regression revealed that the best model of independent predictors was PAL, adiponectin level, and ABI. The composite of these factors further improved the discriminative properties (C statistic, 0.85).. We found that objectively measured physical activity is the strongest predictor of all-cause mortality in patients with COPD. In addition, adiponectin level and vascular status provide independent prognostic information in our cohort.

Topics: Adipokines; Aged; Cohort Studies; Echocardiography; Energy Metabolism; Exercise Tolerance; Female; Humans; Leptin; Male; Middle Aged; Motor Activity; Nutritional Status; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry; Survival Analysis; Survival Rate

COPD is characterized by a multi-component character involving a state of low-grade systemic inflammation and an increased prevalence of cardiovascular co-morbidity. The role of circulating leptin and other adipokines in the involvement of the systemic inflammation in COPD is only studied scarcely.. To investigate gender related differences in the adipokine metabolism in relation to systemic inflammatory biomarkers in clinically stable subjects with COPD.. In total, 91 clinically stable COPD patients and 35 healthy control subjects, matched for body mass index (BMI) with the COPD subjects, were included. Lung function measurement and body composition were performed in patients with COPD. In the total group, plasma concentration of the adipokines (leptin, adiponectin and resistin) and systemic inflammatory biomarkers C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNFα), and its soluble receptors 55 and 75 (sTNFα-R55, R75) were analyzed.. The COPD group was characterized by increased levels of CRP, IL-6 and leptin. Plasma adiponectin and resistin concentrations were not different between the COPD and the control group. Within the COPD group, there was a significant interaction between gender and BMI on the leptin/fat mass ratio. In COPD women, a significant correlation between leptin and CRP was present.. In men with clinically stable COPD, leptin, adiponectin and resistin appear to be physiologically regulated, while in women, leptin metabolism is altered. Leptin secretion is increased in COPD women when compared to healthy women and compared to COPD men, and to a greater extent in overweight women with COPD.

Topics: Adipokines; Adipose Tissue; Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sex Factors; Tumor Necrosis Factor-alpha

The role of fat-bone interactions in the pathogenesis of osteoporosis in chronic obstructive pulmonary disease (COPD) is poorly understood. Our aim was to investigate expressions of leptin and osteoprotegerin (OPG) in the adipose tissue, and their relationships to osteoporosis in patients with COPD.. In 39 patients with stable COPD, bone mineral density (BMD) and body composition was assessed by Dual Energy X-Ray Absorptiometry. Serum leptin was determined by the enzyme-linked immunosorbent assay, and bone turnover markers osteocalcin and β-crosslaps by the electrochemiluminiscence immunoassays. Subcutaneous adipose tissue samples were analyzed using real-time PCR.. Twenty-one patients without, and 18 with osteoporosis were enrolled (35 men; age 62.2 ± 7.3years). Compared to patients without osteoporosis, those with the disease had significantly lower serum levels and adipose tissue expressions of leptin, in association with increased serum β-crosslaps (p=0.028, p=0.034, p=0.022, respectively). Log adipose tissue leptin was inversely related to serum β-crosslaps (p=0.015), and directly to serum leptin (p<0.001) and to the total, femoral, and lumbar BMD and T-score (p<0.02 for all relationships). Adipose tissue OPG expression was related to all variables of bone density except for lumbar BMD and T-score (p<0.05 for all relationships). Log adipose tissue leptin and OPG expressions predicted femoral T-score independently of age, gender and pulmonary function (p<0.001, adjusted R(2)=0.383; p=0.008, adjusted R(2)=0.301, respectively). Introducing body mass (or fat mass) index into these models eliminated independent predictive value of leptin and OPG expressions.. Our results suggest that adipose tissue leptin and OPG expressions are related to osteoporosis in patients with COPD, and appear to act as mediators between fat mass and BMD.

Topics: Adipose Tissue; Biomarkers; Bone Density; Bone Remodeling; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Osteoporosis; Osteoprotegerin; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

To study effects of leptin regulation of energy and activity of TNF-alpha on the trophologic status and digestion of main nutrients in patients with stable chronic obstructive pulmonary disease (COPD).. Somatometric methods were used to examine trophologic status in 93 patients with stable COPD. Of them, 22 had stage I, 36 - stage II, 35 patients - stage III. Serum leptin was measured with enzyme immunoassay (EIA) using DSL kit (USA), TNF-alpha and receptors sTNF-R55 and -R75 with EIA (kits BioSource, Belgium). The absorption was assessed biochemically and with radionuclide investigation. Body fat was estimated by bioelectric impedance (OmRon BF-302, Japan).. The level of circulating leptin decreased with progression of COPD and correlated with body fat depletion (r = 0.88 +/- 0.12). Activation of the TNF-alpha system was detected in the presence and progression of trophologic insufficiency (TI) in patients with COPD stage II and III. A correlation was found between an elevated level of circulating TNF-alpha and enhanced fat and 131-I-albumin excretion, subnormal excretion of D-xylose.. Low blood serum leptin concentration in patients with moderate and severe stable COPD correlates with fat tissue depletion reflecting reduced energetic potential of adipocytes. High TNF-alpha concentration in the serum was seen only in TI and its progression. This evidences for cytokine involvement in induction of metabolic disorders in COPD patients. Elevated concentration of circulating TNF-alpha closely correlated with excretion of higher quantities of fats, protein, low excretion of D-xylose and proves its involvement in TI development in COPD patients. Activation of TNF-alpha system in COPD does not influence leptin concentration in blood serum as it functions as an independent physiological system.

Topics: Adipose Tissue; Adult; Aged; Digestion; Disease Progression; Female; Humans; Immunoenzyme Techniques; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tumor Necrosis Factor-alpha; Xylose

Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation.. To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation.. We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios.. Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30–50%) for each 5 kg/m(2) increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sex-adjusted P = 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass.. Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.

Topics: Adiponectin; Aged; Biomarkers; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Linear Models; Logistic Models; Lung Diseases, Interstitial; Lung Transplantation; Male; Middle Aged; Obesity; Odds Ratio; Overweight; Primary Graft Dysfunction; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Resistin; Risk Factors; Severity of Illness Index; Survival Analysis; Time Factors; United States

Topics: Adiponectin; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Pulmonary Disease, Chronic Obstructive

COPD is a multicomponent disease and systemic inflammation represents one of the possible mechanisms responsible for its systemic manifestations, including skeletal muscle weakness and cachexia. Fat-free mass index (FFMI) that reflects the skeletal muscle mass, has been shown to be associated with both dyspnoea and exercise capacity. We hypothesized that the multidimensional BODE index, that reflects the multicomponent nature of COPD, might be related to biomarkers of systemic inflammation. We further evaluated associations between FFMI and systemic inflammation.. BODE index and FFMI were calculated in 222 stable COPD patients and 132 smokers or ex-smokers with normal lung function. Systemic inflammation was evaluated with the measurement of leptin, adiponectin, CRP, IL-6, and TNF-α in serum samples of COPD patients.. In patients with COPD, both BODE index and FFMI presented significant positive and negative associations respectively with leptin levels (R(2) 0.61 and 0.65, respectively), whereas FFMI presented an additional negative association with the levels of TNF-α (R(2) 0.38). No significant associations were observed in smokers or ex-smokers with normal lung function.. Both BODE index and FFMI, are related to the circulating levels of leptin in patients with COPD, suggesting a possible role for leptin in the systemic component of COPD. The additional association of FFMI with TNF-α may further support a role of systemic inflammation in muscle wasting in COPD.

Topics: Aged; Biomarkers; Body Fat Distribution; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cross-Sectional Studies; Dyspnea; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Interleukin-6; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Severity of Illness Index; Tumor Necrosis Factor-alpha

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome represent common causes of morbidity and mortality in ageing populations. The effect of the co-existence of COPD and metabolic syndrome on adipose tissue hormones and insulin resistance as well as the differences between COPD patients with and without metabolic syndrome have not been adequately studied. The prevalence of metabolic syndrome, based on Adult Treatment Panel III (ATP III) criteria, was evaluated in 114 male patients with COPD without significant co-morbidities. Pulmonary functions tests (PFTs), arterial blood gases, quality of life and BODE index were assessed. Blood samples were obtained for the assessment of adipose tissue hormones and insulin resistance. The overall prevalence of metabolic syndrome was 21%, being more prevalent in earlier stages of COPD. Patients with COPD and metabolic syndrome were younger with higher body-mass index (BMI), had better pulmonary function, less static hyperinflation and air-trapping, better diffusing capacity for carbon monoxide and BODE index. These patients had higher levels of leptin, lower levels of adiponectin and increased insulin resistance, as expressed by HOMA index, compared with patients without metabolic syndrome. Metabolic syndrome was more prevalent in younger patients with less severe COPD. These patients may constitute a specific COPD phenotype with greater leptin to adiponectin imbalance and insulin resistance, despite smaller impairment in PFTs. The prognosis and differences of these patients compared with other COPD phenotypes needs to be determined in prospective studies.

Topics: Adiponectin; Age Factors; Aged; Body Mass Index; Humans; Insulin Resistance; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Severity of Illness Index; Smoking

Various systemic inflammatory markers have been evaluated for their value in acute exacerbations of chronic obstructive pulmonary disease (COPD). Leptin and adiponectin have been linked to acute exacerbations and stable COPD.. To assess plasma leptin, adiponectin and their ratio in acute exacerbations of COPD and to study possible associations with inflammatory biomarkers.. Plasma leptin, adiponectin and their ratio (L/A) and serum biomarkers of systemic inflammation C-reactive protein (CRP), Tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were assessed at three time points (admission, resolution and stable phase - 8 weeks after resolution) in a selected cohort of 63 COPD patients hospitalized for acute exacerbations. Subjects with comorbidities related to adipose tissue hormones were meticulously excluded.. All systemic inflammatory biomarkers, leptin and L/A ratio were elevated during admission compared to resolution and stable phase (mean L/A ratio 2.6 vs. 1.57 vs. 1.22, respectively; p<0.0001), whereas adiponectin was elevated at resolution compared to admission. Log leptin, adiponectin and L/A ratio were significantly associated with variables of systemic inflammation, after proper adjustments, both on admission and in stable condition. In stepwise multiple linear regression models, IL-6 and TNF-alpha present the most significant associations with leptin, adiponectin and their ratio.. Our data suggest that both leptin and adiponectin are associated with the systemic inflammatory process during exacerbations of COPD. The most significant associations seem to be those with IL-6 and TNF-alpha.

Topics: Adiponectin; Aged; Biomarkers; C-Reactive Protein; Disease Progression; Female; Humans; Interleukin-6; Leptin; Male; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tumor Necrosis Factor-alpha

The aim of the study was to compare endocrine parameters such as leptin, visfatin, insulin resistance, exercise capacity and body composition change, the pulmonary functions test (PFT) and arterial blood gases (ABG) parameters of chronic obstructive pulmonary disease (COPD) patients and in healthy controls.. Fifty-five patients with COPD and without malnutrition and 25 healthy controls were included in our study. The serum leptin, visfatin, tumor necrosis factor alpha (TNF-alpha) and insulin resistance, body fat-free mass (FFM) and fat mass (FM) were measured in the groups. Additionally, body mass index (BMI) was calculated and the 6-minute walk test (6MWT), PFT and ABG analyses were performed in all of the cases.. No difference in BMI between the COPD group and controls was determined. Serum leptin and visfatin levels, FFM and 6MWT distance were significantly lower in the patients with COPD (p < 0.001, p = 0.001, p = 0.032, p < 0.001, respectively). A correlation was found between serum leptin levels and BMI (r = 0.333, p = 0.027), and with FM (r = 0.365, p = 0.029). Serum visfatin level was correlated with the percentage of forced expiratory volume in the first second in the patients with COPD (r = 0.371, p = 0.013). HOMA-IR (Homeostasis model assessment of insulin resistance) and serum TNF-alpha levels in the patients with COPD were found to be significantly higher than controls (p = 0.001, p < 0.001).. These results may be earlier signs for further diseases that can emerge in the advanced stages in patients with COPD. Evaluating the patients not only with the pulmonary function and also systemically, contributes to minimizing the mortality and morbidity.

Topics: Adipose Tissue; Aged; Body Composition; Body Mass Index; Exercise; Female; Humans; Insulin Resistance; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Tumor Necrosis Factor-alpha

Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inflammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inflammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue of WT, ob/ob, and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice (p<0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob, and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4+, CD8+, and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice (p<0.05). Exogenous leptin administration completely restored the skewed inflammatory profile in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice.

Topics: Adaptive Immunity; Animals; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Enzyme-Linked Immunosorbent Assay; Immunity, Innate; Immunohistochemistry; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumonia; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction; Tobacco Smoke Pollution

To study the specific features of the nutritional status of patients with persistent chronic obstructive pulmonary disease (COPD) in relation to the hormone-regulating function of energy exchange in terms of leptin and to concurrently evaluate the functional status of fat and protein digestion and absorption and to measure body fat percentage. To assess the influence of these factors on the regulation of the serum concentration of leptin and its potential role in the development of trophological insufficiency in patients.. In 93 patients with COPD (Stages I, II, and III in 22, 36, and 35 patients, respectively, the nutritional status was evaluated by somatometric methods. The concentration of leptin was measured by enzyme immunoassay using a test system (DSL, USA). Absorption was estimated by biochemical studies and by using radionuclides. Body fat content was determined, by measuring bioelectric impedance with an OmRon BF-302 apparatus (Japan).. Protein and fat absorption was decreased in patients with moderate and mainly severe COPD as compared with that in the control group and correlated with body weight deficit and lower body fat percentage. Decreased leptin levels were detected in Stages II-III COPD and correlated with the degree of the disease and reduced protein (r = 0.68 +/- 0.02) and fat (r = 0.64 +/- 0.18) absorption.. Protein and fat absorption impairments correlating with body weight deficit in patients with COPD underline the significant role of this mechanism in the development of trophological insufficiency. In COPD patients with trophological insufficiency, the lower circulating leptin levels that correlate with impaired absorption of fatty acids and protein characterize the pathogenetic role of secondary malabsorption syndrome in leptin-mediated impairments of energy exchange mechanisms. Functional insufficiency of the hormone-regulating mechanism responsible for energy exchange in terms of leptin in patients with Stages II-III COPD gives warning of the insufficient stock of adipose tissue and its reduced energy reserve.

Topics: Absorption; Adipose Tissue; Adult; Aged; Body Weight; Dietary Fats; Dietary Proteins; Energy Metabolism; Female; Humans; Intestine, Small; Leptin; Male; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Severity of Illness Index

Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extrapulmonary manifestations including systemic inflammation and weight loss. Increased levels of interleukin-6 (IL-6) have been demonstrated in sputum and serum of COPD patients. Therefore, the authors investigated the in vivo role of IL-6 in a murine model of COPD. Wild-type (WT) and IL-6 knockout (KO) mice were exposed subacutely (4 weeks) and chronically (24 weeks) to air or cigarette smoke (CS). Subacute and chronic CS exposure significantly increased pulmonary IL-6 mRNA expression in lung tissue and IL-6 protein levels in bronchoalveolar lavage fluid of WT mice. However, CS-induced accumulation of inflammatory cells at both time points and lymphoid aggregate formation upon chronic CS exposure were independent of IL-6. Chonic CS exposure was associated with a significant failure to gain weight in both WT mice and IL-6 KO mice. Remarkably, air-exposed IL-6 KO mice have lower body weight, serum leptin levels, and adipose tissue mass compared to air-exposed WT mice. In conclusion, IL-6 is of minor importance in CS-induced pulmonary and systemic manifestations in mice, but this study confirms the role for IL-6 as regulator of body weight and body composition.

Topics: Adipose Tissue, White; Animals; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Disease Models, Animal; Gene Expression; Interleukin-6; Leptin; Lung; Lymphocytes; Male; Mice; Mice, Knockout; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; RNA, Messenger; Smoking; Tobacco Smoke Pollution

Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory reaction of the lungs involving activation of epithelial cells. Leptin is a pleiotropic cytokine important in the regulation of immune responses via its functional receptor Ob-Rb. This study was undertaken to test the hypothesis that severe COPD is associated with increased leptin expression in epithelial cells.. Immunohistochemistry for leptin was performed on peripheral lung specimens from 20 patients with COPD (GOLD stage 4), 14 asymptomatic ex-smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression were determined by rtPCR in cultured primary bronchial epithelial cells and primary type II pneumocytes. NCI-H292 and A549 cell lines were used to study functional activation of leptin signalling.. Leptin immunoreactivity in lung tissue was observed in bronchial epithelial cells, type II pneumocytes, macrophages (tissue/alveolar) and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary bronchial epithelial cells and pneumocytes. Leptin-expressing bronchial epithelial cells and alveolar macrophages were markedly higher in patients with severe COPD and ex-smokers than in never smokers (p<0.02). Exposure of cultured primary bronchial epithelial cells to smoke resulted in increased expression of both leptin and Ob-Rb (p<0.05). Leptin induced phosphorylation of STAT3 in both NCI-H292 and A549 cells.. Leptin expression is increased in bronchial epithelial cells and alveolar macrophages of ex-smokers with or without severe COPD compared with never smokers. A functional leptin signalling pathway is present in lung epithelial cells.

Topics: Blotting, Western; Bronchi; Cells, Cultured; Epithelial Cells; Female; Forced Expiratory Volume; Humans; Immunohistochemistry; Leptin; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; RNA, Messenger; Smoking; Vital Capacity

Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-alpha). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.. We measured serum leptin, IGF-I, TNF-alpha, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-alpha, IL-1 beta, IL-6 and IL-8 were measured by ELISA.. Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001). A positive correlation was observed between leptin and TNF-alpha on Day 1 (r = 0.620, p < 0.001). Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).. Inappropriately increased circulating leptin levels along with decreased IGF-I levels occurred during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.

Topics: Aged; Biomarkers; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Humans; Insulin-Like Growth Factor I; Leptin; Male; Prognosis; Pulmonary Disease, Chronic Obstructive; Radioimmunoassay; Recurrence; Severity of Illness Index

Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD). Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking. The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD. This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center. Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry. Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%). On bivariate analysis, there was no association between TNF-alpha and BMD. Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density. However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability. Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis. The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis. We conclude that the effect of adipokines on BMD does not appear to be independent of body mass. However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD.

Topics: Absorptiometry, Photon; Adipokines; Adiponectin; Aged; Biological Factors; Body Composition; Bone Density; Cross-Sectional Studies; Hip Joint; Humans; Leptin; Lumbar Vertebrae; Lung; Male; Middle Aged; Osteoporosis; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Resistin; Severity of Illness Index; Tumor Necrosis Factor-alpha

To study nutritional status in chronic obstructive pulmonary disease (COPD) in relation to the serum content of adipose tissue hormones.. Ninety-four patients with Stages II and III COPD and 20 gender- and age-matched healthy non-smoking volunteers were examined. Interviews, analysis of laboratory data, enzyme immunoassay, and somatometry were made.. The patients with COPD are characterized by the development of malnutrition, even in the absence of body weight loss and in the presence of normal body mass index (BMI) with predominant lean body mass (LBM) loss, normal serum concentrations of adipose tissue hormones. With more advanced COPD and a worse nutritional status, the level of leptin decreases and that of adiponectin increases. The content of adiponectins is closely related to the indicators of nutritional status, mainly to the value of body weight loss, BMI, LBM, absolute blood lymphocyte count, and degree of malnutrition. The COPD patients with emphysema show the most pronounced changes in nutritional status and higher adiponectin levels.. An integrated assessment of the degree of protein-energy malnutrition and measurement of the level of adipose tissue hormones should be made when nutritional status is studied in patients with COPD.

Topics: Adiponectin; Adipose Tissue; Body Weights and Measures; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Nutritional Status; Protein-Energy Malnutrition; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD.. Twenty-eight male patients with COPD were divided into an overweight/obese group [ n = 16, body mass index (BMI) = 33.5 +/- 4.2 kg/m(2)] and normal weight group (n = 12, BMI = 21.1 +/- 2.6 kg/m(2)). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured.. Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume(1): 51 +/- 19% versus 31 +/- 12% predicted, respectively, P < 0.01). The metabolic syndrome was diagnosed in 50% of overweight/obese patients and in none of the normal weight patients. TNF-alpha, IL-6 and leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight.. The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities.

Topics: Adiponectin; Aged; Body Composition; C-Reactive Protein; Comorbidity; Humans; Inspiratory Capacity; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Pulmonary Disease, Chronic Obstructive; Risk Factors; Tumor Necrosis Factor-alpha

To investigate the potential roles of leptin and ghrelin in malnutrition in patients with chronic obstructive pulmonary disease (COPD).. Plasma leptin, total ghrelin and active ghrelin, TNF-alpha and IL-6 levels were determined in 53 patients with COPD and 26 control subjects. Body compositions were assessed by bioelectrical impedance analysis.. Plasma leptin levels were significantly lower in underweight patients than those in normal weight patients and in healthy controls [2.6 (2.0 - 4.4) vs. 6.1 (5.1 - 7.8) vs. 4.8 (3.3 - 6.1) ng/L]. The leptin level was associated positively with fat mass (r = 0.662, P = 0.000) and TNF-alpha (r = 0.431, P = 0.001) in the patients. By a stepwise multiple regression analysis, fat mass, TNF-alpha, presence of COPD, smoking and sex were found to affect leptin level (R(2) = 0.635). Both plasma total ghrelin levels and active ghrelin levels were significantly higher in underweight patients than those in normal weight patients and in healthy controls [total ghrelin: 1090 (860 - 2838) vs. 765 (651 - 941) vs. 844 (676 - 1045) ng/L; active ghrelin: 63 (50 - 97) vs. 47 (41 - 56) vs. 54 (41 - 60) ng/L]. Plasma total ghrelin and active ghrelin were associated negatively with BMI respectively (total ghrelin: r = -0.517, P = 0.000; active ghrelin: r = -0.417, P = 0.002).. Plasma leptin levels were decreased, while plasma total ghrelin and active ghrelin levels were elevated in underweight patients with COPD, and the levels were associated with nutritional parameters. The plasma levels of leptin and ghrelin may be a compensatory mechanism in malnutritional status of COPD. After adjustment for nutritional parameters, leptin levels were elevated in COPD patients and correlated to TNF-alpha. The result suggests that leptin may play a role in systemic inflammation of COPD.

Topics: Aged; Case-Control Studies; Female; Ghrelin; Humans; Interleukin-6; Leptin; Male; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Tumor Necrosis Factor-alpha

To investigate the relationship between Leptin-insulin resistance and pulmonary function in patients with chronic obstructive pulmonary disease (COPD) with acute exacerbation.. Fifty-six patients with COPD with acute exacerbation were divided into two groups according to the fasting plasma glucose level [the hyperglycemia group: fasting blood glucose (FBG)> or =6.2 mmol/L, n=42. the hypoglycemia group: FBG 3.1-6.2 mmol/L, n=14], and 20 normal healthy controls [the control group, FBG (5.49+/-1.06) mmol/L)] were also included in the study. All patients had complete data of FBG, C-reactive protein (CRP), albumin (ALB), Leptin, fasting serum insulin (FISN), counting insulin sensitivity index (ISI), and pulmonary function tests [forced expiratory volume in one second (FEV1), FEV1 in percentage of forced vital capacity (FEV1/FVC), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), total respiratory impedance (Zrs), airway resistance at 5, 20 Hz (R5, R20), airway resistance of capacitance and inertance at 5, 20 Hz (X5, X20), core resistance (Rc), periphery resistance (Rp), frequency resonant (Fres)].. The FBG, FISN, CRP were significantly higher and body mass index (BMI), ALB, ISI were significantly lower in the hyperglycemia group compared with control group (all P<0.01), but there was no difference in Leptin level (P>0.05). However, BMI, ALB, Leptin, ISI were significantly decreased and CRP, FISN were significantly increased in hypoglycemia group compared with the control group (P<0.05 or P<0.01). FBG, FISN, Leptin, CRP were significantly higher and ISI was significantly lower in hyperglycemia group compared with the hypoglycemia group (all P<0.01), but there was no significant difference in BMI and ALB (both P>0.05). The serum levels of Leptin was significantly positively correlated with Zrs, R5, R20, Rc, BMI (all P<0.01), and with significantly negative correlations with FEV1, X20 (P<0.01 and P<0.05), but had no correlation with FEV1/FVC, PEF, MMEF, X5, Rp, Fres (all P>0.05). ISI had significant positive correlations with FEV1/FVC, FEV1, PEF, MMEF (P<0.05 or P<0.01), but it had significant negative correlations with Zrs, R5, R20, X5, Rc, Rp, X20, BMI (P<0.05 or P<0.01), and no correlation with Fres. Multiple organ failure (MOF) was found in 6 cases (14%) in hyperglycemia group, one case (7%) was found in the second group, the incidence of MOF in hyperglycemia group was significantly higher compared with the hypoglycemia group (P<0.01). The length of hospital stay was prolonged in hyperglycemia group, compared with hypoglycemia group [(25.00+/-0.13) days vs. (17.93+/-0.22) days, P<0.01].. High glucose and Leptin-insulin resistance may aggravate the impairment of pulmonary function, prolong the length of hospital stay in the patient with COPD.

Topics: Blood Glucose; C-Reactive Protein; Female; Humans; Insulin; Insulin Resistance; Leptin; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Serum Albumin

Weight loss is common in patients with chronic obstructive pulmonary disease (COPD). However, the mechanisms of this weight loss are still unclear.. Sixty male patients with stable COPD and 45 healthy male controls participated in this study. The COPD patients were divided into two groups, that is, the emphysema and chronic bronchitis groups, by the transfer coefficient of carbon monoxide. The body composition, resting energy expenditure (REE), plasma leptin levels and serum tumor necrosis factor-alpha (TNF-alpha) were measured in all the study participants. The difference and correlation of these parameters were investigated between the two groups.. Emphysematous patients were characterized by a lower body mass index (BMI) and fat-mass (FM) compared with the chronic bronchitis patients (p < 0.001). The plasma leptin levels, as corrected for the FM, were not different between the COPD patients and healthy controls (78.3 +/- 30.9 pg/mL/kg vs. 70.9 +/- 17.3 pg/mL/kg, respectively), and the plasma leptin levels, as adjusted for the FM, were also not different between the two groups of COPD patients. In the chronic bronchitis patients, the plasma leptin concentration was correlated with the BMI (r = 0.866, p < 0.001) but it was not correlated with the BMI in the emphysema patients. The serum TNF-alpha levels were higher in the stable COPD patients than those in the controls, but there was no statistical difference (10.7 +/- 18.6 pg/mL vs. 7.2 x 3.5 pg/mL, respectively, p0.05). The leptin concentration was well correlated with the BMI and %FM in the patients with chronic bronchitis and the leptin concentration was only correlated with the %FM (r = 0.450, p = 0.027) in emphysema patients. There was no correlation between the plasma leptin concentration, as adjusted for the fat mass, and the activity of the TNF-alpha system.. The interaction of leptin and the activity of the TNF-alpha system in the pathogenesis of tissue depletion may not play an important role in chronic stable COPD patients.

Topics: Aged; Body Composition; Bronchitis, Chronic; Case-Control Studies; Emphysema; Energy Metabolism; Humans; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Tumor Necrosis Factor-alpha; Weight Loss

Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha.. Seventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed.. Serum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group.. Leptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Topics: Adult; Aged; Anorexia; Humans; Leptin; Male; Malnutrition; Middle Aged; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha; Weight Loss

Chronic inflammation of the lung is a characteristic finding in chronic obstructive pulmonary disease (COPD). Leptin is a pleiotropic cytokine thought to play a role in host response to inflammation. As recent studies have shown that leptin receptors are present in the lung, this study aimed to determine if leptin is detectable in induced sputum of COPD patients and if there is a relationship between leptin and other inflammatory markers in sputum.. Sputum was induced in 14 male patients with moderate COPD (FEV1: 56 (15) % pred.). Leptin, total tumour necrosis factor (TNF)-alpha, and C-reactive protein (CRP) were analyzed in induced sputum supernatant by ELISA. Leptin was also determined in EDTA plasma.. Leptin was detectable in induced sputum of 10 COPD patients. A significant relationship was found between sputum leptin and CRP (r = 0.943, P < 0.001) and total TNF-alpha (r = 0.690, P < 0.01). Plasma leptin and sputum leptin were inversely correlated (r = -0.643, P < 0.01).. The present study demonstrated that leptin is detectable in induced sputum of patients with moderate COPD and is related to other inflammatory markers. The observed correlations between leptin and inflammatory markers in sputum may indicate that leptin is involved in the local inflammatory response in COPD.

Topics: Adult; Aged; Anthropometry; Biomarkers; C-Reactive Protein; Forced Expiratory Volume; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sputum; Tumor Necrosis Factor-alpha; Vital Capacity

To investigate the serum resistin and leptin levels, their relationship to nutritional state and the associated factors in patients with chronic obstructive pulmonary disease (COPD).. The serum resistin and leptin levels in 57 stable COPD patients and 31 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA) and radio-immunoassay respectively. Correlated factors of serum resistin and leptin were analyzed.. The serum resistin and leptin levels in COPD patients [(2.1 +/- 1.2), (0.65 +/- 0.41) microg/L] were significantly lower than those in the healthy controls [(3.6 +/- 2.3), (1.03 +/- 0.71) microg/L, all P < 0.01]. The serum resistin and leptin levels in patients with malnutrition [(1.7 +/- 0.7), (0.43 +/- 0.16) microg/L] were significantly lower than those in patients without malnutrition [(2.2 +/- 1.2), (0.73 +/- 0.48) microg/L, all P < 0.05]. The serum resistin level in the patients was correlated with the serum leptin level, forced expiratory volume in one second (FEV(1)), and FEV(1)/forced vital capacity (FVC) (r = 0.426 - 0.531, all P < 0.01). The serum leptin level in the patients was correlated with serum resistin, FEV(1)/FVC, body mass index (BMI), percentage of ideal body weight (IBW%), chest circumference and abdominal circumference (r = 0.371 - 0.580, all P < 0.01).. The serum resistin and leptin levels in stable COPD patients were significantly lower, especially in patients with malnutrition.

Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Resistin

The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast, in the sub-mucosa, leptin was over-expressed in COPD when compared with normal subjects and smokers. Leptin and its receptor were co-localised, mainly with activated T cells (CD45R0) and CD8+ T lymphocytes. In smokers, apoptosis was found in some inflammatory cells, whereas in COPD inflammatory cells, leptin and leptin-receptor positive cells were not apoptotic. Leptin expression was related to COPD severity and assessed using the Global initiative for Chronic Obstructive Lung Disease classification. In conclusion, the present study shows an increased leptin expression in bronchial mucosa of chronic obstructive pulmonary disease patients, associated with airway inflammation and airflow obstruction.

Topics: Adult; Aged; Apoptosis; Bronchi; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptors, Cell Surface; Receptors, Leptin; Respiratory Function Tests; Respiratory Mucosa; Smoking; T-Lymphocytes

Nutritional depletion and weight loss are two features of chronic obstructive pulmonary disease (COPD), and the association between low body mass index (BMI) and poor prognosis in patients with COPD is a common clinical observation. Mechanisms of weight loss are still unclear in COPD. Excessive energy expenditure partly due to increased work of breathing was shown, but other mechanisms have been searched for. Leptin is a hormone secreted by adipocytes that plays an important role in energy homeostasis and regulates body weight through control of appetite and energy expenditure. The aim of this study was to evaluate the association of circulating leptin levels and measures of body composition in COPD patients. Thirty male COPD outpatients (mean age 66.3 +/- 8.4) and 20 controls (mean age 65.9 +/- 10.8) were included in the study. After standard spirometry and body composition measurements, serum leptin concentration was measured by ELISA assay. COPD patients were grouped according to BMI. Mean BMI was 19.01 +/- 2.26 kg/m2 in group 1 (COPD patients with low BMI), 26.85 +/- 4.51 in group 2 COPD (COPD patients with normal/high BMI) and 27.64 +/- 2.75 kg/m2 in healthy controls (group 3). Mean serum leptin concentration was 1.41 +/- 1.86 ng/ml in group 1, 2.60 +/- 1.38 ng/ml in group 2 and 2.82 +/- 1.46 ng/ml in group 3 (p = 0.002). Leptin correlated to not only BMI but also body weight, waist circumference, triceps and biceps skinfold thickness and body fat percent (p < 0.05 for all). Results of this study suggest that the cause of weight loss is not increased circulating leptin in COPD. Instead, leptin remains regulated in COPD and further decreased in patients with low BMI, probably as a compensatory mechanism to preserve body fat content, which should be evaluated in further studies.

Topics: Aged; Anthropometry; Body Composition; Body Mass Index; Humans; Leptin; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response.. We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients.. A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II-IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1beta (IL-1beta -511), IL-6 (IL-6 -174), and the tumor necrosis factor system (TNF-alpha -308 and lymphotoxin-alpha +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured.. Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1beta -511 polymorphism was significantly different between the groups (P < 0.05).. In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.

Topics: Adipose Tissue; Body Composition; Body Mass Index; C-Reactive Protein; Cachexia; Case-Control Studies; Cross-Sectional Studies; Electric Impedance; Energy Metabolism; Female; Genetic Predisposition to Disease; Humans; Interleukin-1; Interleukin-6; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Pseudouridine; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

To explore the function of serum leptin in COPD patients with malnutrition, and to investigate the relationship between leptin and TNF-alpha.. A total of 81 subjects (47 COPD patients and 34 control subjects) participated in this study. The 47 COPD patients were divided into 2 groups: group COPD I (patients without malnutrition during stable disease, n=29), group COPDII (patients with malnutrition during stable disease, n=18). To eliminate the effect of sex differences, all the patients and controls were male. Body mass index (BMI), percent ideal body weight (IBWå), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference(MAMC),serum leptin and tumor necrosis factor-alpha(TNF-alpha) levels, serum prealbumin (PA), serum transferrin (TF), serum albumin(Alb),total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure(MIP)and maximal expiration pressure(MEP)were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analysed.. (1) Serum leptin levels were significantly lower in group COPDII (4.07+/-3.42 microg/L) than in group COPD I (9.72+/-6.67 microg/L) and controls (8.21+/- 5.41 microg/L, P<0.05). (2) There were no statistical differences in serum TNF-alpha levels between group COPDII (8.03+/-3.37 ng/L)and group COPD I (7.25+/- 2.08 ng/L). (3) There was no significant correlation between leptin and TNF-alpha in any group.. Leptin was not involved in anorexia and weight loss of COPD patients. There was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Topics: Aged; Energy Metabolism; Enzyme-Linked Immunosorbent Assay; Humans; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Radioimmunoassay; Respiratory Function Tests; Transferrin; Tumor Necrosis Factor-alpha

To explore the significance of serum leptin and TNF-alpha in malnutrition of COPD.. Serum leptin and TNF-alpha concentrations were measured by radioimmunoassay. Body mass index (BMI), percent normal body weight (NW%), triceps skin-fold thickness (TSF), subscapular skin-fold thickness (SSF), mid-upper arm circumference (MAC), serum albumin (ALB) and total lymphocytes count (LYM) were determined in 31 patients with COPD and in 11 healthy controls. The correlation between leptin and nutritional parameters was analysed.. (1) Serum leptin concentrations (3.0 +/- 2.5) micrograms/L in 42 subjects were significantly correlated with BMI, NW%, TSF, SSF and MAC (P < 0.001). (2) Serum leptin concentrations were significantly correlated with BMI in both malnourished patients with COPD and non-malnourished patients (P < 0.05-0.001). The leptin level was significantly lower in malnourished group (1.3 +/- 1.0) micrograms/L than in non-malnourished group (4.5 +/- 2.6) micrograms/L, (P < 0.05). The differences in serum leptin level and BMI between non-malnourished group and healthy group were not significant. (3) Serum TNF-alpha level was significantly higher in COPD group (1.8 +/- 0.3) micrograms/L than in healthy group (1.0 +/- 0.5) microgram/L (P < 0.05). Serum leptin levels didn't significantly correlate with TNF-alpha levels in COPD patients.. Serum leptin levels correlate with nutritional parameters in COPD patients and leptin may contribute to the malnutrition in COPD patients.

Topics: Aged; Body Mass Index; Female; Humans; Leptin; Lymphocyte Count; Male; Middle Aged; Nutritional Status; Pulmonary Disease, Chronic Obstructive; Serum Albumin; Skinfold Thickness