Oxidative Stress In Chronic Obstructive Pulmonary Disease Patients Research Articles

Can Blood Biomarkers Be Used to Assess Oxidative Stress in COPD Patients After Pulmonary Rehabilitation.

To determine the level of oxidative stress in the body due to pulmonary rehabilitation (PR) with thiols and disulfide and to investigate their relationship with indirect markers such as creatine kinase (CK), creatine kinase - MB (CK-MB), and lactate dehydrogenase (LDH), which show cell destruction. Patients with chronic obstructive pulmonary disease (COPD) are included in inpatient and outpatient care. They were evaluated before and after for PR, and an exercise program was prescribed. In addition, native thiol (NT), total thiol (TT), disulfide (DS), LDH, CK, and CK-MB values were tested. The mean age of 21 patients was 63±7.31 years. Eleven of them were outpatients and 10 of them were inpatients. Most of the patients were male (M/F=20/1, 95.2/4.8%). There was a significant difference in pulmonary function tests (PFT), St. George Respiratory Questionnaire (SGRQ), and 1 repetition maximum (1RM) before and after the treatment (p<0.001). There was a correlation between PFT and 1RM upper extremity. While there was no significant difference between thiols and disulfide, according to GOLD scores, there was a significant difference in patients with level 3-MMRC. No correlation was found between LDH, CK, CK-MB, and thiols, DS. ΔCK was found to be associated with ΔDS, and ΔCK-MB with ΔNT, and ΔTT. PR contributes to the antioxidant process by improving respiration and reducing oxidative stress. The decrease in LDH, CK with PR, increase in CK-MB, and correlation of CK with thiols and DS gave a different interpretation. In this case, it should be considered that oxidative stress may also be increased in people with high CK values.

Indoor (residential) and ambient particulate matter associations with urinary oxidative stress biomarkers in a COPD cohort

ObjectivesOxidative stress contributes to chronic obstructive pulmonary disease (COPD) pathophysiology. Associations between indoor (residential) exposure to particulate matter ≤2.5 μm in diameter (PM2.5) and one of its components, black carbon (BC), and oxidative stress are ill-defined. MethodsBetween 2012 and 2017, 140 patients with COPD completed in-home air sampling over one week intervals, followed by collection of urine samples to measure oxidative stress biomarkers, malondialdehyde (MDA), a marker of lipid peroxidation, and 8-hydroxy-2′ -deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Ambient (central site) BC and PM2.5 were measured, and the ratio of indoor/ambient sulfur in PM2.5, a surrogate for residential ventilation and particle infiltration, was used to estimate indoor BC and PM2.5 of outdoor origin. Mixed effects linear regression models with a participant-specific random intercept were used to assess associations with oxidative biomarkers, adjusting for personal characteristics. ResultsThere were positive associations (% increase per IQR; 95 % CI) of directly measured indoor BC with total MDA (6.96; 1.54, 12.69) and 8-OHdG (4.18; −0.67, 9.27), and similar associations with both indoor BC of outdoor origin and ambient BC. There were no associations with directly measured indoor PM2.5, but there were positive associations between indoor PM2.5 of outdoor origin and total MDA (5.40; −0.91, 12.11) and 8-OHdG (8.02; 2.14, 14.25). ConclusionsIn homes with few indoor combustion sources, directly measured indoor BC, estimates of indoor BC and PM2.5 of outdoor origin, and ambient BC, were positively associated with urinary biomarkers of oxidative stress. This suggests that the infiltration of particulate matter from outdoor sources, attributable to traffic and other sources of combustion, promotes oxidative stress in COPD patients.

Low 15d-PGJ2 status is associated with oxidative stress in chronic obstructive pulmonary disease patients.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent nuclear receptor and highly expressed in human and rodent lungs. 15-Deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), known for cyclopentenone prostaglandin, is the endogenous ligand of PPARγ. However, the associations among PPARγ, 15d-PGJ2 and chronic obstructive pulmonary disease (COPD) were unclear. All 130 fasting blood samples and 40 lung specimens were obtained from COPD patients and control subjects. Serum 15d-PGJ2 was detected by ELISA. The expressions of oxidative stress indicators were measured using western blotting and PPARγ nuclei were evaluated with immunohistochemistry in lungs. The associations among serum 15d-PGJ2, pulmonary PPARγ and oxidative stress indicators, and COPD were estimated. Serum 15d-PGJ2 was reduced in COPD patients compared with healthy volunteers. Linear and logistic regression analysis indicated that serum 15d-PGJ2 was positively associated with pulmonary function in COPD patients. In addition, PPARγ-positive nuclei were reduced and oxidative stress indicators, included HO-1 and NOX-4, were increased in lungs of COPD patients. Further correlative analysis suggested that pulmonary function parameters was positively correlated with serum 15d-PGJ2 and pulmonary PPARγ-positive nuclei, inversely related to oxidative stress indicators in lungs of COPD patients. Pretreatment with 15d-PGJ2 obviously attenuated TNFα-induced oxidative stress in BEAS-2B cells. Serum 15d-PGJ2 and pulmonary PPARγ are reduced, and oxidative stress is elevated in COPD patients. Serum 15d-PGJ2 is inversely associated with oxidative stress in COPD patients.

Polycyclic Aromatic Hydrocarbons Induced by Smoking and Air Pollution: Correlation with Oxidative Stress in Chronic Obstructive Pulmonary Disease Patients.

Oxidative stress is induced by tobacco smoking and is also associated with exposure to air pollution, which are two of the most important risk factors for chronic obstructive pulmonary disease (COPD). The aim of this study was to correlate tobacco use and exposure to air pollution with oxidative stress markers useful in clinical practice in patients with COPD. A total of 102 patients were included and the levels of polycyclic aromatic hydrocarbons (PAHs), malondialdehyde, uric acid and number of packs-years (PY) were determined. Also, six different ratios were used to assess the source of exposure. The results obtained in this study show an admission of pollutants according to smoking status (former smokers/smoker/non-smokers) quantified in average total concentrations for the group of patients with COPD of 4.12 ng/mL, 6.76 ng/mL, 6.04 ng/mL. The six ratios used show that in COPD, the content of PAHs in the blood could be a result of diesel emissions and fuel combustion. Uric acid levels were lower in the smoker group of COPD patients (mean = 5.21 mg/dL), which indicates that oxidative stress is intensified with each cigarette smoked. Additionally, high concentrations of malondialdehyde were quantified for smoking patients diagnosed with COPD (mean = 2.72 µmol/L) compared to former smokers (mean = 2.43 µmol/L) and non-smoking (mean = 2.32 µmol/L) patients, which is another indicator of the implication of smoking in oxidative stress in COPD patients.

Lnc-IL7R alleviates PM2.5-mediated cellular senescence and apoptosis through EZH2 recruitment in chronic obstructive pulmonary disease.

Long-term exposure to PM2.5 (particulate matter with an aerodynamic diameter of ≤ 2.5μm) is associated with pulmonary injury and emphysema in patients with chronic obstructive pulmonary disease (COPD). We investigated mechanisms through which the long noncoding RNA lnc-IL7R contributes to cellular damage by inducing oxidative stress in COPD patients exposed to PM2.5. Associations of serum lnc-IL7R levels with lung function, emphysema, and previous PM2.5 exposure in COPD patients were analyzed. Reactive oxygen species and lnc-IL7R levels were measured in PM2.5-treated cells. The levels of lnc-IL7R and cellular senescence-associated genes, namely p16INK4a and p21CIP1/WAF1, were determined through lung tissue section staining. The effects of p16INK4a or p21CIP1/WAF1 regulation were examined by performing lnc-IL7R overexpression and knockdown assays. The functions of lnc-IL7R-mediated cell proliferation, cell cycle, senescence, colony formation, and apoptosis were examined in cells treated with PM2.5. Chromatin immunoprecipitation assays were conducted to investigate the epigenetic regulation of p21CIP1/WAF1. Lnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PM2.5 exposure. Lnc-IL7R levels were upregulated in normal lung epithelial cells but not in COPD cells exposed to PM2.5. Lower lnc-IL7R expression in PM2.5-treated cells induced p16INK4a and p21CIP1/WAF1 expression by increasing oxidative stress. Higher lnc-IL7R expression protected against cellular senescence and apoptosis, whereas lower lnc-IL7R expression augmented injury in PM2.5-treated cells. Lnc-IL7R and the enhancer of zeste homolog 2 (EZH2) synergistically suppressed p21CIP1/WAF1 expression through epigenetic modulation. Lnc-IL7R attenuates PM2.5-mediated p21CIP1/WAF1 expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD.

Efficacy of silymarin in treatment of COPD via P47phox signaling pathway

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. To investigate effect of silymarin on chronic obstructive pulmonary disease (COPD). The serum samples of 20 healthy controls, 20 patients with acute exacerbation of COPD and 20 patients with stable COPD were collected. LPS and smoking were used to induce COPD mouse model. Our results showed that in patients with acute exacerbation of COPD, O2-level release from peripheral blood neutrophils were negatively correlated with forced expiratory volume in the first second (FEV1), FEV1 in predicted value, FEV1/forced vital capacity (FVC), and arterial partial pressure (PaO2). (r=-0.898, -0.878, -874, -0.890, all P<0.01). Compared with that in the control group, the phosphorylation of NADPH oxidase p47phox factor and peripheral blood neutrophil membrane protein in the stable COPD group and the acute exacerbation COPD group were significantly stronger. Silymarin can inhibit the inflammatory response and oxidative stress. In conclusion, silymarin reduces oxidative stress in phagocytic and non-phagocytic cells, thus decreasing the oxidative stress in COPD patients

The Pleoitropic Effects of Atorvastatin in Patients with Chronic Obstructive Pulmonary Disease: the Influence on the Indicators of Oxidative Stress

Objective: to evaluate the dynamics of the markers of oxidative stress in patients with chronic obstructive pulmonary disease (COPD) during the application of atorvastatin. Material and methods. The study included 52 COPD patients with concomitant hyperlipidemia. The main group (n = 30) were given atorvastatin at a dosage of 20 mg per day in addition to the standard COPD treatment. The comparison group (n = 22) only underwent the standard COPD treatment. The patients were monitored for 24 weeks. The levels of superoxide dismutase, catalase and malondialdehyde were evaluated for the assessment of oxidative stress. Results. In the group of the patients taking atorvastatin, the level of superoxide dismutase decreased from 949 [608; 1042] units/ml initially to 406 [319; 478] u/ml after 24 weeks (p = 0.035). The levels of catalase and malondialdehyde did not change significantly both in the experimental and comparison groups. Conclusion. The intake of atorvastatin decreases the level of superoxide dismutase, which may indicate a decrease in the level of oxidative stress in COPD patients.

Association of PM2.5 of Outdoor Origin with Biomarkers of Oxidative Stress in COPD Patients

Introduction: Studies have shown effects of ambient particulate matter &amp;#8804; 2.5 microns in diameter (PM2.5) on oxidative stress biomarkers; however, less is known of these effects indoors in patients with chronic obstructive pulmonary disease (COPD). In this study, we assessed the association between indoor PM2.5 apportioned into indoor and outdoor origin and biomarkers of oxidative stress.Methods: We recruited 82 men with COPD who ran a micro-environmental sampler in their home for 1 week up to 4 times a year (n&amp;#61;225 samples). Teflon filter samples were analyzed gravimetrically for indoor PM2.5, and outdoor PM2.5 was measured at a central site. Daily indoor PM2.5 was calculated and apportioned into indoor (PMin) and outdoor origin (PMout) using the indoor-outdoor sulfur ratio as a surrogate for infiltration. Urine samples were obtained for analysis of 8-OHdG and malondialdehyde (MDA). We fit mixed effects models with a random intercept for each participant and adjusted for age, race, season, time of urine collection, BMI, creatinine, diabetes, heart disease, indoor nitrogen dioxide, ambient temperature, and relative humidity.Results: We observed suggestive effects of total PM2.5 on 8-OHdG, with the strongest effect on the 1 day lag (3.6% increase per IQR, 95% CI: -0.69-8.2). For MDA, there were statistically significant effects of total PM2.5 with longer moving averages (strongest effect on the 1-7 day moving average: 6.5% per IQR, 95% CI: 0.88-12.4). Effects of PMout across time windows displayed similar yet stronger patterns compared to total PM2.5, with the greatest effects on the 1 day lag (16.7% per IQR, 95% CI: 1.8-33.7) for 8-OHdG and the 1-7 day moving average (19.3% per IQR, 95% CI: -0.9-43.6) for MDA. There were no statistically significant effects of PMin.Conclusions: Our results suggest that indoor infiltration of PM2.5 of outdoor origin is positively associated with increased lipid peroxidation (MDA) and DNA oxidation (8-OHdG) in patients with COPD.

DNA damage protection by bulk and nano forms of quercetin in lymphocytes of patients with chronic obstructive pulmonary disease exposed to the food mutagen 2-amino-3-methylimidazo [4,5-f]quinolone (IQ)

Chronic obstructive pulmonary disease (COPD) in humans, describes a group of lung conditions characterised by airflow limitation that is poorly reversible. The airflow limitation usually progresses slowly and is related to an abnormal inflammatory response of the lung to toxic particles. COPD is characterised by oxidative stress and an increased risk of lung carcinoma. The 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) is one of a number of mutagenic/carcinogenic heterocyclic amines found mainly in well-cooked meats which are thus part of the regular diet. Antioxidants are very important in order to protect the cells against oxidative damage. The aim of the present study was to assess the effects of IQ on the level of DNA damage and susceptibility to a potent mutagen in peripheral blood cells of COPD patients. DNA damage and the frequency of micronuclei (MNi) were evaluated using the Comet and micronucleus assays, respectively. Differential expressions of both mRNA and protein of the endogenous antioxidant enzyme catalase were evaluated with quantitative polymerase chain reaction (qPCR) and Western blot analysis, respectively. Furthermore, the effect of bulk and nano forms of quercetin and their combination with IQ were examined. Results of the present study clearly demonstrated that MNi frequency in the peripheral blood lymphocytes exhibited a positive correlation with the DNA damage as evident from the different Comet assay parameters. Increase of the endogenous antioxidant catalase also showed there was a stimulation of this enzyme system by IQ. Whereas, the endogenous antioxidant quercetin significantly reduced oxidative stress in COPD patients and healthy individuals.

Oxidant status, iron homeostasis, and carotenoid levels of COPD patients with advanced disease and LTOT

ABSTRACTBackground: The pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with oxidative stress. Both iron (Fe) and oxygen are involved in the chemical reactions that lead to increased formation of reactive oxygen species. Oxidative reactions are prevented by antioxidants such as carotenoids.Objective: To study the differences in Fe status, carotenoid levels, healthy eating habits, and markers of inflammation and oxidative damage on proteins in subjects with severe COPD ± long-term oxygen therapy (LTOT) and lung-healthy control subjects.Methods: Sixty-six Caucasians with advanced COPD (28 with LTOT) and 47 control subjects were included. Questionnaires about general health, lifestyle, and dietary habits were answered. Lung function tests and blood sampling were performed.Results: COPD subjects (±LTOT) did not demonstrate increased oxidative damage, assessed by protein carbonylation (PC), while levels of soluble transferrin receptors (sTfRs) were slightly elevated. Soluble TfRs, which is inversely related to Fe status, was negatively associated with PC. Levels of carotenoids, total and β-cryptoxanthin, α- and β-carotenes, were significantly lower in COPD subjects, and their diet contained significantly less fruits and vegetables. Lutein correlated inversely with IL-6, lycopene correlated inversely with SAT, while β-carotene was positively associated with a Mediterranean-like diet.Conclusions: Fe could favor oxidative stress in COPD patients, suggesting a cautious use of Fe prescription to these patients. COPD subjects ate a less healthy diet than control subjects did and would, therefore, benefit by dietary counseling. COPD patients with hypoxemia are probably in particular need of a lycopene-enriched diet.

Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?

Chronic obstructive pulmonary disease (COPD) patients are at increased risk of developing nonsmall cell lung carcinoma, irrespective of their smoking history. Although the mechanisms behind this observation are not clear, established drivers of carcinogenesis in COPD include oxidative stress and sustained chronic inflammation. Mitochondria are critical in these two processes and recent evidence links increased oxidative stress in COPD patients to mitochondrial damage. We therefore postulate that mitochondrial damage in COPD patients leads to increased oxidative stress and chronic inflammation, thereby increasing the risk of carcinogenesis.The functional state of the mitochondrion is dependent on the balance between its biogenesis and degradation (mitophagy). Dysfunctional mitochondria are a source of oxidative stress and inflammasome activation. In COPD, there is impaired translocation of the ubiquitin-related degradation molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in excessive dysfunctional mitochondria. We hypothesise that deranged pathways in mitochondrial biogenesis and mitophagy in COPD can account for the increased risk in carcinogenesis. To test this hypothesis, animal models exposed to cigarette smoke and developing emphysema and lung cancer should be developed. In the future, the use of mitochondria-based antioxidants should be studied as an adjunct with the aim of reducing the risk of COPD-associated cancer.

Lack of association between increased mitochondrial DNA4977 deletion and ATP levels of sputum cells from chronic obstructive pulmonary disease patients versus healthy smokers

In this study we looked at smokers with and without chronic obstructive pulmonary disease (COPD) patients in order to evaluate the incidence of 4977 base pair (bp) mtDNA (mtDNA4977) deletion and mtDNA copy number in sputum cells and in peripheral blood leukocytes (PBLs) in relation to mitochondrial function and oxidative stress status. Twenty-five COPD patients who were current smokers, 22 smokers and 23 healthy nonsmokers (for only PBLs studies) participated in this study. The 4977-bp deletion was detected in all examined samples within 40 cyles of PCR amplification, using a quantitative real time PCR. The frequency of the mtDNA4977 was significantly higher in the sputum cells of patients with COPD compared to smokers without COPD (p < 0.0001). This difference was not observed in PBLs. Levels of cellular oxidative stress were significantly higher in the sputum cells of subjects with COPD than in the smoker group. However, mtDNA copy number, mitochondrial membrane potential (ΔΨm) and cellular ATP levels in PBLs and sputum cells were not significantly different between the studied groups. The Pearson analysis revealed no correlations between the accumulation of mtDNA4977, and intracellular ATP content and ΔΨm values of the sputum cells, although there was a positive correlation between the increase in the percentage of deleted mtDNA4977 and the levels of cellular oxidative stress in COPD patients (r = 0.80, p < 0.0001). Our studies may suggest that the accumulation of mtDNA4977 in the sputum cells of smokers with COPD does not seem to have an important impact on mitochondrial dysfunction in relation to ATP production and ΔΨm when compared to those of healthy smokers.

Evaluation of Markers of Inflammation and Oxidative Stress in COPD Patients with or without Cardiovascular Comorbidities

Although both chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) are characterised by chronic, systemic inflammation, their reciprocal interactions are poorly understood. The purpose of this study was to determine the concentrations of both inflammatory and oxidative stress biomarkers in the serum and exhaled breath condensate (EBC) of COPD patients, either with coexisting CVD or without cardio-vascular comorbidities. Twenty-four COPD patients with CVD were allocated to group A, 20 COPD patients without CVD were assigned to group B and 16 healthy patients were included as a control. A medical history and physical examination were performed, and the following were measured: serum CRP concentration, glucose level, uraemic acid level and lipid profile. In addition 8-isoprostane, LTB4 and IL-8 concentrations were measured both in serum and EBC. Spirometry, six-minute walk test and echocardiography were performed in all subjects. EBC concentrations of 8-isoprostane and LTB4, and serum levels of CRP, 8-soprostane, LTB4, IL-8 were significantly higher in COPD patients than in healthy controls. COPD patients with CVD were not found to have higher concentrations of the assessed markers than those without CVD, neither in the serum nor EBC. CRP, 8-isoprostane and LTB4 levels in serum, and IL-8 concentration in EBC correlated negatively with the value of forced expiratory volume in one second. Although systemic inflammation coexists with COPD, it is not elevated in COPD patients with CVD. Since this phenomenon may result from treatment with statins, future studies should state whether COPD patients could benefit from the additional statin therapy.

Urinary 8-hydroxydeoxyguanosine is a potential indicator for estimating pulmonary rehabilitation-induced oxidative stress in COPD patients.

Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease and is an important cause of morbidity worldwide. The aim of this study was to evaluate whether pulmonary rehabilitation (PR) improves the oxidant/antioxidant imbalance, exercise capacity and health-related quality of life (HRQL) in patients with different stages of COPD. Eighteen stable COPD patients participated in 8-week PR; the exercise intensity was set at 70% of the VO2 peak. Subjects were divided into 2 groups: moderate to severe (stages II/III: n = 12) and very severe COPD with FEV1 < 30% predicted (stage IV: n = 6). In patients at stages II/III, PR improved exercise capacity (6-minute walking test: 431.2 ± 26.6 vs. 489.1 ± 26.5 m, P < 0.01 and shuttle walking test: 329.2 ± 41.4 vs. 378.2 ± 41.5 m, P < 0.01) and HRQL, whereas no significant change was observed in erythrocyte lipid peroxidation and urinary 8-hydroxydeoxyguanosine, a marker for DNA damage. In contrast, PR for stage IV patients did not improve exercise capacity and HRQL, but significantly increased urinary 8-hydroxydeoxyguanosine (14.5 ± 1.7 vs. 24.3 ± 2.6 ng/mg Cr, P < 0.05). In both groups, erythrocyte antioxidants (superoxide dismutase, glutathione peroxidase, and catalase) did not change significantly after PR. Thus, urinary 8-hydroxydeoxyguanosine is a useful indicator for the PR-induced oxidative stress in COPD patients. In conclusion, appropriate exercise program in COPD patients can improve exercise capacity and HRQL without further increase of oxidative stress. However, PR for very severe COPD patients enhanced exercise-induced oxidative stress.

Altered oxidant-antioxidant levels in the disease prognosis of chronic obstructive pulmonary disease

It is well known that oxidant-antioxidant imbalance plays a key role in the pathophysiology of chronic obstructive pulmonary disease (COPD). To examine the role of altered levels of oxidant-antioxidants in disease severity of COPD and correlate it with the degree of airflow obstruction. We assessed malondialdehyde (MDA), total protein carbonyl and sulfhydryl levels in blood plasma and examined the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in erythrocytes. We also evaluated the level of total blood glutathione in whole blood and ferric ion reducing antioxidant power (FRAP) in plasma. Levels of MDA (P < 0.001) and total protein carbonyls (P < 0.01) were significantly increased, while total protein sulfhydryl (P < 0.01) was decreased in COPD patients. We also observed decreased SOD (P < 0.05), GPx (P < 0.01) and catalase (P < 0.05) activity. FRAP (P < 0.001) in plasma was also decreased, whereas total blood glutathione was increased (P < 0.01). Correlations between oxidative stress and antioxidant markers with forced expiratory volume in 1 second (FEV1%) in COPD were negative with plasma TBARS and total blood glutathione, whereas a positive correlation was noticed with erythrocyte GPx and FRAP. These results support the hypothesis that an oxidant-antioxidant imbalance, associated with oxidative stress in COPD patients, plays an important role in the progression of disease severity.

Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: central actor and therapeutic target

Muscle dysfunction is a common complication and an important prognostic factor in chronic obstructive pulmonary disease (COPD). As therapeutic strategies are still needed to treat this complication, gaining more insight into the process that leads to skeletal muscle decline in COPD appears to be an important issue. This review focuses on mitochondrial involvement in limb skeletal muscle alterations (decreased muscle mass, strength, endurance and power and increased fatigue) in COPD. Mitochondria are the main source of energy for the cells; they are involved in production of reactive oxygen species and activate an important pathway that leads to apoptosis. In COPD patients, skeletal muscles are characterized by decreased mitochondrial density and biogenesis, impaired activity and coupling of mitochondrial respiratory chain complexes, increased mitochondrial production of reactive oxygen species and, possibly, increased apoptosis. Of particular interest, a sedentary lifestyle, hypoxia, hypercapnia, tobacco smoking, corticosteroid therapy and, possibly, inflammation participate in this mitochondrial dysfunction, which is accessible to conventional therapies, such as exercise and tobacco cessation, as well as, potentially, to more innovative approaches, such as antioxidant treatment and supplementation with polyunsaturated fatty acids.

Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients

BackgroundPrevious studies have demonstrated the potential beneficial effect of N-acetylcysteine (NAC) in chronic obstructive pulmonary disease (COPD). However, the required dose and responder phenotype remain unclear. The current study investigated the effect of high-dose NAC on airway geometry, inflammation, and oxidative stress in COPD patients. Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy.MethodsTwelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were randomized to receive NAC 1800 mg or placebo daily for 3 months and were then crossed over to the alternative treatment for a further 3 months.ResultsSignificant correlations were found between image-based resistance values and glutathione levels after treatment with NAC (P = 0.011) and glutathione peroxidase at baseline (P = 0.036). Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC (P = 0.02), changes in glutathione peroxidase levels (P = 0.035), and reduction in lobar functional residual capacity levels (P = 0.00084). In the limited set of responders to NAC therapy, the changes in airway resistance were in the same order as changes induced by budesonide/formoterol.ConclusionA combination of glutathione, glutathione peroxidase, and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy. The findings of this small pilot study need to be confirmed in a larger pivotal trial.

Dietary modulation of oxidative stress in chronic obstructive pulmonary disease patients

A total of 267 clinically stable chronic obstructive pulmonary disease (COPD) patients provided complete data about diet and oxidative stress markers in order to assess the relationship between antioxidant rich food groups and nutrients, and serum markers of oxidative stress in COPD. Dietary data of the last 2 years was assessed using a validated food frequency questionnaire (122 items). Levels of carbonyls, nitrotyrosine, malondialdehyde and reduced glutathione (GSH) were measured in serum. Vitamin E intake was inversely associated with levels of carbonyls (p = 0.05) and olive oil was positively associated with GSH levels (p = 0.01), in active smokers. Intake of vegetables was related to a decrease of malondialdehyde levels (p = 0.04) in former smokers. No statistically significant associations were found between remaining dietary antioxidants and serum oxidative stress markers. These results provide new data for a potential dietary modulation of systemic oxidative stress in COPD patients, particularly in those that continue smoking.

Enhanced exercise‐induced plasma cytokine response and oxidative stress in COPD patients depend on blood oxygenation

In healthy subjects, hypoxemia and exercise represent independent stressors promoting the exercise-induced cytokine response and oxidative stress. We hypothesized that hypoxemia in patients with chronic obstructive pulmonary disease (COPD) may affect the cytokine production and/or the changes in oxidant-antioxidant status in response to maximal exercise. Exercise-induced changes in PaO2 allowed to transiently increase or decrease baseline hypoxemia and to point out its specific action on muscle metabolism. COPD patients with severe to moderate hypoxemia (56 < PaO2 < 72 mmHg) performed an incremental cycling exercise until volitional exhaustion. Two cytokines [interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha] and three blood indices of oxidative stress [plasma thiobarbituric acid reactive substances (TBARS) and two antioxidants, reduced erythrocyte glutathione (GSH), and reduced plasma ascorbic acid, RAA] were measured at rest, then during and after exercise. The changes in the cytokine levels and oxidant-antioxidant status were analysed in relation with the baseline PaO2 and its exercise-induced variations. Data were compared with those obtained in an age- and body mass index-matched group of healthy subjects. Compared with healthy subjects, COPD patients presented a marked accentuation of exercise-induced increase in IL-6 level and earlier changes in their oxidant-antioxidant status. Resting levels of IL-6 and TNF-alpha and exercise-induced peak variations of TBARS, IL-6 and TNF-alpha were negatively correlated with the baseline PaO2. In COPD patients, the peak increases in IL-6 and TBARS were attenuated when exercise hyperventilation reduced the baseline hypoxemia. Our study indicates that the PaO2 level affects both the exercise-induced oxidative stress and cytokine response in hypoxemic COPD patients.

Mitochondrial dysfunction in COPD patients with low body mass index

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.