NOVEL antioxidant and oxidant biomarkers related to sarcopenia in COPD

BackgroundThe relation between oxidative stress (OS) and sarcopenia in COPD remains unknown.ObjectiveTo analyze OS levels and its association with sarcopenia in COPD.MethodsThirty-nine individuals with COPD (69±7years; 41%female) and thirty-five for the control group (69±7years; 43%female) were included. Advanced oxidation protein products (AOPP), paraoxonase-1 (PON1), superoxide dismutase activity (SOD), catalase dismutase activity (CAT), sulfhydryl group (SH), nitric oxide metabolites (NOX), total radical trapping antioxidant parameter (TRAP) were analysed. OS markers were correlated with handgrip and quadriceps strength, gait speed, skeletal muscle mass index, fat-free mass index, maximum inspiratory and expiratory pressure. European criteria were used to identify sarcopenia.ResultsIn COPD, antioxidant capacity was correlated with muscle mass and strength (r from 0.5 to 0.64) P<0.05 for all. TRAP≤ 850 μM/trolox and AOPP≤65 μM/l were associated with sarcopenia (OR:8.3; 95% CI: 1.4–49.6 and OR:14; 95%CI: 2.2–87.1, respectively; P<0.05 for both).ConclusionOS is associated with sarcopenia in COPD.     

Comparison of oxidant/antioxidant balance in COPD and non-COPD smokers

Background/aimOxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Smoking is the leading source of oxidants in lungs. However, it is currently unknown why some individuals are more resistant to the detrimental effects of smoking and do not develop COPD. The aim in this study is to measure and compare the oxidant/antioxidant balance between in non-COPD individuals who smoke and COPD patients who smoke.Materials and methodsIncluded in the study were 137 patients with COPD and 102 healthy individuals. Participants were divided into groups as COPD patients (former and current smokers), non-COPD individuals who smoke and non-smokers healthy persons. In the following stage, the total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) levels were measured in serum for all participants.ResultsIn the current-smoker COPD group, the level of oxidant status were significantly higher than the former-smoker COPD group (p < 0.001). Similarly, oxidant levels were significantly high in current-smoker healthy group than never smoker healthy group. According to these results TOS was associated with especially smoking status rather than COPD. Antioxidant status were similar between former-smoker COPD group and current-smoker COPD group. The antioxidant levels were found significantly low in current-smoker COPD patients, compared to the current-smoker non-COPD individuals (p = 0.007). Nevertheless, no significant difference was found in OSI levels between two groups. Briefly, high TOS and OSI values were correlated with only smoking, independently from COPD.ConclusionIt was concluded that there are complex pathogenetic mechanisms, including genetic and individual variations other than oxidant/antioxidant balance, involved in the development of smoking-related COPD. TOS and OSI values are not predictive parameters for the development of COPD, but high level of TAS in non-COPD smokers is promising for future studies.     

Total oxidant/antioxidant status in sera of patients with thyroid cancers

Oxidative stress is considered to be involved in the pathophysiology of all cancers. In order to evaluate the total oxidant/antioxidant status in patients with thyroid cancer and to investigate the relationship between oxidative stress parameters and serum thyroid profiles among thyroid cancer patients and various controls, we determined oxidative status including total antioxidant status (TAS) and total oxidant status (TOS) and calculation of oxidative stress index (OSI) in sera in 82 thyroid cancer patients, 56 benign thyroid disease patients, and 50 healthy controls. It was found that serum TAS levels were significantly lower in patients with thyroid cancer than in controls (P<0.001), while serum TOS levels and OSI values were significantly higher (both P<0.001) in the cancer patients. No significant correlations were observed between various oxidative stress markers and thyroid profiles in either the thyroid cancer patients or the controls. Receiver operating characteristic curve analysis demonstrated that OSI was the best indicator for distinguishing cancer patients from benign thyroid diseased or healthy controls, followed by TOS and TAS. Risk estimate statistics also indicated that TOS and/or OSI were good risk factors to discriminate patients with thyroid cancer from two controls. These findings suggested that oxidants are increased and antioxidants are decreased in patients with thyroid cancer. OSI may be a more useful oxidative stress biomarker than TAS and TOS for monitoring the clinical status of thyroid cancer patients.     

Blood oxidant/antioxidant status of atherosclerotic patients

In the present study, it is aimed to investigate oxidant/antioxidant status of plasma and erythrocytes from atherosclerotic patients and to establish the possible role of oxidant stress in the formation and progression of atherosclerosis. Antioxidant potential (AOP) values and malondialdehyde (MDA) levels were studied in erythrocyte and plasma samples from 40 atherosclerotic patients and 38 healthy controls. A total of 13 subjects in each group were smokers. AOP was found unchanged in erythrocytes but lower in plasma samples (P<0.0005) from atherosclerotic patients as compared with those of the controls. MDA levels were however higher in erythrocyte hemolysate (P<0.025), erythrocyte membrane (P<0.0005) and blood plasma samples (P<0.0005) from atherosclerotic patients than those of the controls. Moreover, AOP was found to be lower in plasma samples of smoker patients than that of non-smoker patients (P<0.05). In the control group, erythrocyte MDA level was higher in smoker group than that of non-smoker group (P<0.05). Results reveal the presence of oxidant stress in the blood samples from patients with atherosclerosis. It seems antioxidant therapy might give beneficial results for atherosclerotic patients.     

Erythrocyte oxidant/antioxidant status of diabetic patients

Present study aims to establish erythrocyte oxidant/antioxidant status in diabetic patients with and without atherosclerotic complications. Fasting blood samples were obtained from 23 diabetic and 12 control subjects. Thirteen patients had no disease other than diabetes mellitus and 10 patients had also atherosclerosis in addition to diabetes mellitus. Erythrocyte antioxidant potential (AOP) and thiobarbituric acid reagent substances (TBARS) levels were measured in these patients and results were compared with those of controls, who were chosen among healthy subjects. Results suggest that although there is an oxidant stress in the erythrocytes of diabetics, this is not due to reduced erythrocyte antioxidant defence potential but, rather, increased free radical production possibly due to hyperglycemia.     

Altered antioxidant status in peripheral skeletal muscle of patients with COPD

Despite the growing field of interest in the role of pulmonary oxidative stress in chronic obstructive pulmonary disease (COPD), barely any data are available with respect to antioxidant capacity in the peripheral musculature of these patients. The main objective of this study was to assess in detail the antioxidant status in skeletal muscle of patients with COPD. Biopsies from the vastus lateralis of 21 patients with COPD and 12 healthy age-matched controls were analysed. Total antioxidant capacity, vitamin E, glutathione, and uric acid levels were determined and the enzyme activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase were measured. Malondialdehyde was measured as an index of lipid peroxidation. The total antioxidant capacity and the uric acid levels were markedly higher in COPD patients than in healthy controls (25%, P = 0.006 and 24%, P = 0.029, respectively). Glutathione-S-transferase activity was also increased (35%; P = 0.044) in patients compared to healthy subjects. Vitamin E level was lower in patients than in controls (P < 0.05). The malondialdehyde level was not different between the two groups. It can be concluded that the muscle total antioxidant capacity is increased in patients with COPD. Together with the reduced vitamin E levels, the increased glutathione-S-transferase activity and normal levels of lipid peroxidation products, these findings suggest that the antioxidant system may be exposed to and subsequently triggered by elevated levels of reactive oxygen species.     

The changes in beta-adrenergic receptors and cyclic AMP levels of lymphocytes in patients with COPD

The maximal binding capacity (Bmax) of beta-adrenergic receptors and the production of intracellular cAMP in response to isoproterenol in peripheral blood lymphocytes were measured by radioligand binding assay and competitive protein-binding method respectively. Two groups of COPD patients (19 cases was at the onset of disease, 17 cases was stable) were investigated and 20 normal subjects as control. The amount of Bmax at the onset of COPD (208.55 +/- 14.14fmol/10(8)cells) and during the stable stage (299.25 +/- 13.90fmol/10(6)cells) was significantly lower than that in normal subjects (338.35 +/- 12.22fmol/10(8)cells) (P less than 0.01). There were also obvious differences in amounts of Bmax between two groups of COPD (P less than 0.01). The changes of intracellular cAMP were similar to the results of Bmax. This study indicated that beta-adrenergic receptor function is attenuated in COPD patients especially at the onset of the disease. The possible mechanism of the reduction of beta-adrenergic receptor and the clinical significance in the use of beta-adrenoceptor agonist were discussed.     

Circulating levels of soluble Fas ligand in cachexic patients with COPD are higher than those in non-cachexic patients with COPD

OBJECTIVE: Apoptosis may be involved in the pathophysiology of cachexia in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the potential role of the Fas-Fas ligand (FasL) system in cachexic patients with COPD. PATIENTS AND METHODS: We measured the circulating levels of soluble FasL (sFasL), with a newly developed, highly sensitive enzyme-linked immunosorbent assay system in seventy patients with COPD and forty-seven control subjects. RESULTS: The levels of sFasL in the COPD patients were significantly lower than those in the control subjects (46+/-29 vs. 55+/-28 pg/ml; p<0.05), whereas the levels of soluble Fas (sFas) remained unchanged between the two groups. The significant correlation between the levels of sFasL and sFas, observed in the control subjects (r=0.304; p<0.05), was absent in the COPD patients. Cachexic COPD patients with a relatively lower BMI (BMI <20 kg/m(2), n=45) and %fat (%fat <20%, n=34), showed significantly increased levels of sFasL compared to non-cachexic COPD patients with a relatively higher BMI (BMI > or =20 kg/m(2), n=25) and %fat (%fat > or =20%, n=36) (BMI; 51+/-33 vs. 36+/-15 pg/ml; p<0.05. %fat; 55+/-33 vs. 37+/-21 pg/ml; p<0.01), due to the inverse relationships between the body composition measurements and the levels of sFasL observed exclusively in the patients (BMI; r=-0.307; p<0.05. %fat; r=-0.283; p<0.05). CONCLUSION: These results may suggest that the Fas-FasL system does not play a significant role in the potential triggers of enhanced apoptosis leading to skeletal muscle wasting and adipose tissue depletion in cachexic patients with COPD.     

血清瘦素与COPD男性患者 FEV1水平相关性的研究

目的 观察COPD患者血清中瘦素水平变化与FEV1% pred相互关系.方法 设立COPD稳定期组和正常对照组.测定血清瘦素、TNF-α与FEV1% pred进行相关性分析.结果瘦素、TNF-α与COPD患者FEV1% pred值呈负相关关系,两组比较差异具有显著意义;COPD患者血清瘦素与TNF-α呈正相关关系;COPD稳定期组中血清瘦素明显高于正常对照组.结论 瘦素是COPD重要的炎症指标,血清瘦素浓度高低反映病情的严重程度.     

C-reactive protein levels and survival in patients with moderate to very severe COPD

BACKGROUND: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease. OBJECTIVE: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease. METHODS: In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality. RESULTS: During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival. CONCLUSIONS: In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV(1), IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.     

Hepatic oxidant and antioxidant systems in portacaval-shunted rats.

The purpose of the present study was to determine the effects of chronic portal diversion on antioxidant levels in the rat liver. Male Sprague-Dawley rats (n = 32) were used for these studies. An end-to-side portacaval anastomosis was constructed in 17 of the rats. Sham-operated rats (n = 15) served as controls. Two weeks later, hepatic blood flow was measured by the radioactive microsphere technique and the liver was harvested for biochemical measurement of catalase, manganese superoxide dismutase, copper-zinc superoxide dismutase, selenium glutathione peroxidase, xanthine oxidase, xanthine dehydrogenase and reduced glutathione (acid soluble sulfhydryls). Total hepatic blood flow was approx. 40% lower in portacaval-shunted rats when compared to sham-operated control rats. Total superoxide dismutase (SOD) and xanthine dehydrogenase (XD) levels were significantly reduced in the liver of shunted rats when compared to controls. Xanthine oxidase activity was unaltered. The decreased superoxide dismutase levels were exclusively due to reductions in the cytosolic Ca/Zn SOD; Mn SOD levels were unaltered. These data are consistent with oxidant stress and suggest that the liver of subjects with conditions characterized by decreased portal blood flow may be more susceptible to oxidant-induced liver injury.     

The extent of emphysema in patients with COPD

Background and Aims: The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction. Materials and Methods: We included 209 patients with COPD. COPD was defined as FEV₁/FVC < 0.70 and no reversibility to β₂‐agonists. All patients were current smokers with a smoking history of ≥20 pack‐years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below ?910 Hounsfield units (RA‐910) was extracted. Results: Mean RA‐910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA‐910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema. Conclusion: The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD. Please cite this paper as: Shaker SB, Stavngaard T, Hestad M, Bach KS, Tonnesen P and Dirksen A. The extent of emphysema in patients with COPD. The Clinical Respiratory Journal 2009; 3: 15–21.     

The pharmokinetic limitations of antioxidant treatment for COPD

COPD is one of the leading causes of death worldwide and the age-adjusted mortality for this disease has risen significantly over the past 30 years. Current pharmacological treatments do not effectively address the inflammatory and apoptotic mechanisms that are critical in the development of this disease. Thus, despite therapy, patients typically experience a continued deterioration of their clinical status. Markers of oxidative stress are increased in the lungs of COPD patients and epidemiologic and animal studies indicate that antioxidants can protect the lungs from the damaging effects of cigarette smoke. To date, however, clinical trials of antioxidants for COPD have yielded disappointing results. This review discusses the pharmokinetic factors that limit the use of exogenous antioxidants as a treatment for this disease. In addition, it addresses strategies to overcome these limitations so that the beneficial properties of antioxidants can be translated into effective therapies for COPD patients.     

急性肺损伤的氧化作用与抗氧化研究进展

急性肺损伤(ALI)是临床常见的呼吸系统急症,发病率高,确切发病机制不甚明确,临床治疗效果欠佳。本文对近几年ALI的氧化作用研究和抗氧化对ALI的治疗作用和相关研究进展,以及抗氧化作用对ALI的治疗前景作一综述。     

The cost of treating patients with COPD in Denmark--a population study of COPD patients compared with non-COPD controls

This paper describes a population-based study of health care resource use of patients with chronic obstructive pulmonary disease (COPD) compared to non-COPD controls. Through a screening of the Danish Patient Registry for patients admitted with COPD diagnoses for a 5-year period, 1998-2002, 66,000 individuals with COPD still alive at the beginning of 2002 were identified. Their use of health care resources in 2002 were compared with equivalent data, stratified for age, sex and mortality rates, for a control population without COPD based on data for the 300,000 remaining patients on the Danish Patient Registry in 2002. Results indicated that the gross cost of treating patients with COPD in the Danish somatic hospital and primary health care sector corresponded to 10% of the total cost of treating patients of 40 years or more. The net cost for COPD patients was 1.9 billion DKK (256 million euro), 6% of the total annual costs of treating the population of 40 years or more. The gross cost related to any disease and the net cost reflected the resource use which could be attributed to COPD and its related diagnoses. The incidence of inpatient hospital admissions was almost four times higher in the COPD population than in the control group. COPD patients contacted their general practitioner 12 times more per year than non-COPD controls, but for specialist and paramedic treatment in the primary care sector there was no significant difference between COPD patients and non-COPD controls. Only one third of the COPD costs were due to treatment of COPD as the primary diagnosis. The remaining two-thirds of the COPD-related costs were mainly due to admissions for other diseases such as cardio-vascular diseases, other respiratory diseases, and cancer.     

The relation between oxidant and antioxidant parameters and severity of acute coronary syndromes

OBJECTIVE: Acute coronary syndromes (ACS) encompass a continuum of cardiac ischaemic events, ranging from unstable angina pectoris (UA) to ST-segment elevation myocardial infarction (STEMI). Oxidative stress may play an important role in the pathogenesis of acute coronary diseases. In the present study, we examined the associations between lipid and protein susceptibility to oxidation and total sialic acid (SA) and antioxidant status and the severity of ACS as determined by having UA, non-STEMI or STEMI. METHODS AND RESULTS: The study sample consisted of 102 patients with ACS and 45 controls. Malondialdehyde (MDA) as a marker of lipid peroxidation and protein carbonyls as a marker of protein oxidation were measured to show the susceptibility to oxidation.Antioxidant status was determined by measuring the carotenoids, vitamin C and vitamin E levels and paraoxonase and arylesterase activities. In addition to conventional lipid and lipoprotein analysis, MDA and vitamin E were quantitated by high-performance liquid chromatography. Total SA and other oxidant and antioxidant parameters were studied spectrophotometrically.As expected, patients had significantly higher total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, lipoprotein (a), apolipoprotein (apo) B values and lower high-density lipoprotein cholesterol and apoAl values than controls. Our results demonstrated significant increases both in total SA levels and in indicators of oxidative stress in patients with ACS compared with the controls. However, antioxidant parameters were decreased in patients with ACS. When the patients were divided into groups with UA, non-STEMI and STEMI, respectively, total SA and oxidant parameters were significantly increased and antioxidant parameters were significantly decreased in going from UA to STEMI. CONCLUSIONS: Our study shows gradually increased lipid and protein oxidation and total SA and gradually decreased antioxidant status when the conditions advance from UA to STEMI. These results indicate that these markers may be useful both in understanding plaque destabilization and in determination of risk stratification of patients. Also, measurement of these markers may provide a noninvasive window to study atherosclerotic lesions.     

The efficacy of incentive spirometry in patients with COPD

OBJECTIVE: Although incentive spirometry (IS) is frequently used to prevent postoperative pulmonary complications, its efficacy in patients with COPD has not been documented. The aim of this study was to evaluate the effects of IS on pulmonary function tests, arterial blood gases, dyspnoea and health-related quality of life in patients hospitalized for COPD. METHODOLOGY: A total of 27 consecutive patients (mean age, 68.4 +/- 7.9 years; 26 males) admitted for COPD exacerbations were recruited for the study. In total, 15 (IS treatment group) used IS for 2 months, together with medical treatment. The remaining 12 (medical treatment group) were given only medical treatment. Pulmonary function and blood gases were measured. Assessment of dyspnoea by visual analogue scale (VAS) and quality of life using the St. George's Respiratory Questionnaire (SGRQ) were performed at admission and after 2 months of treatment. RESULTS: The activity, impact and total scores for the SGRQ improved (all P < or = 0.0001), PaCO2 values decreased (P = 0.02), PaO2 and PAO2 values increased (P = 0.02 and P = 0.01, respectively) in the IS treatment group. However, there were no significant differences between the measurements made pretreatment and after 2 months of medical therapy in the medical treatment group, with regards to pulmonary function, blood gases, SGRQ scores and VAS. CONCLUSION: The use of IS appears to improve arterial blood gases and health-related quality of life in patients with COPD exacerbations, although it does not alter pulmonary function parameters.     

High levels of interleukin-6 in the exhaled breath condensate of patients with COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the respiratory tract. METHODS: We investigated the presence of interleukin-6 (IL-6: a cytokine secreted by monocytes/macrophages, T cells, B cells, fibroblasts, bone marrow stromal cells, keratinocytes and endothelial cells) in the exhaled breath condensate of 16 exsmokers with moderate COPD, 12 healthy non-smokers. IL-6 was measured by means of a specific enzyme immunoassay. RESULTS: IL-6 levels were detectable in all of the subjects, but were higher in the COPD patients (8.0 +/- 0.1 pg/ml; P < 0.0001) than in the healthy non-smokers (4.9 +/- 0.2 pg/ml) with a correlation in this group between age and IL-6 levels (r = 0.597; P < 0.05). CONCLUSIONS: The increased IL-6 levels in exhaled breath condensate may reflect airway inflammation in patients with COPD.