8-epi-prostaglandin-f2alpha and Pulmonary-Disease--Chronic-Obstructive

Exhaled breath condensate (EBC) is a non-invasive method for studying the composition of airway lining fluid. EBC is mainly formed by water vapor but also contains aerosol particles in which several biomolecules including hydrogen peroxide, leukotrienes, prostaglandins, isoprostanes, nitric oxide-derived products, and hydrogen ions have been measured in healthy subjects. Some inflammatory mediators are elevated in patients with chronic obstructive pulmonary disease (COPD). Analysis of EBC has several advantages over other methods for assessing lung inflammation: it is completely non-invasive; this technique is particularly suitable for longitudinal studies; this method is potentially useful for assessing the efficacy of pharmacological therapy. Identification of selective profiles of inflammatory markers in EBC might also be of diagnostic value in patients with COPD. EBC analysis is currently more reliable for relative measures than for determining absolute levels of inflammatory mediators. The lack of standardization of the EBC analysis is currently the primary limitation of this technique making it difficult comparisons of data obtained in different laboratories. Reference analytical techniques are required to provide definitive evidence for the presence of several biomolecules in EBC and an accurate assessment of their concentrations in this biological fluid. Moreover, several methodological issues need to be addressed before this technique can be considered in the clinical management of patients with COPD. Despite important current limitations, further research in this area is warranted due to the lack of non-invasive methods for assessing lung inflammation which has a central role in the pathophysiology of COPD.

Topics: Breath Tests; Dinoprost; Dinoprostone; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Leukotriene B4; Malondialdehyde; Pulmonary Disease, Chronic Obstructive; Smoking

In the middle of the nineties a new, non-invasive method for investigation of the lung aroused the interest of many researchers: the exhaled breath condensate. It shows the extent of the interest that in the last five years more than 80 original articles have been published in this theme. Many substances are found in the expired breath which are detectable in the liquid that we obtain by cooling (= condensing) the exhaled breath. The advantages of this method are that it is non-invasive, convenient, it could be performed with mechanically ventilated patients as well as with children. The most studied substance is the hydrogen-peroxide, which is the marker of oxidative stress, and its level in condensate is elevated in numerous inflammatory diseases. 8-isoprostane was also studied a lot, which is another marker of oxidative stress. Numerous substances could be even measured in condensate, so the decay-product of nitric-oxide (nitrite, nitrate, nitrotyrosine), further nitrosothiol, adenosine, ammonia, different ions, leukotrienes, cytokines; recently even other feature of condensate is examined, such as its pH. The different mediators could help us to know better the diseases, support the diagnosis, follow the treatment or the disease. In this study the authors attempt to present the most important knowledge till now.

Topics: Asthma; Biomarkers; Breath Tests; Bronchiectasis; Cystic Fibrosis; Dinoprost; F2-Isoprostanes; Humans; Hydrogen Peroxide; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory Distress Syndrome; Respiratory Tract Diseases; Smoking

Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD. An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks. 75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p = 0.034) and β-cryptoxanthin (p = 0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C-reactive protein) or airway and systemic oxidative stress (8-isoprostane). This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation.

Topics: Aged; Aged, 80 and over; Anticarcinogenic Agents; Biomarkers; C-Reactive Protein; Cryptoxanthins; Diet; Dinoprost; Feeding Behavior; Female; Fruit; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Oxidative Stress; Patient Compliance; Peroxidase; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Sputum; Vegetables; Xanthophylls; Zeaxanthins

Chronic obstructive pulmonary disease (COPD), a major cause of death and disability, is attributed to an abnormal inflammatory response by the lungs to noxious substances, primarily from cigarette smoke. Although oxidative stress is regarded as central to the pathogenesis of COPD, very few studies have examined the effects of antioxidants in this condition. This was a randomized, double-blind, placebo-controlled study on the effects of melatonin in COPD. Thirty-six consecutive patients with clinically stable moderate to very severe COPD (30 men; mean±S.D.=66.6±7.8yr) were randomized to receive 3mg melatonin (N=18) or placebo for 3 months. Oxidative stress was evaluated by 8-isoprostane levels in exhaled breath condensate at baseline (T0) and after one (T1), two (T2), and three months (T3) of treatment. Additionally, exhaled breath condensate levels of IL-8, dyspnea severity (Medical Research Council scale), lung function (spirometry), and functional exercise capacity (six min walk test) were compared at baseline and after treatment. Patients receiving melatonin showed a decrease in 8-isoprostane (T0: mean±S.E.M.=20.41±2.92pg/mL; T1: 18.56±2.68pg/mL; T2: 12.68±2.04pg/mL; T3: 12.70±2.18pg/mL; P=0.04; repeated measures ANOVA) with significant differences from baseline after 2 (P=0.03) and 3months (P=0.01). Dyspnea was improved by melatonin (P=0.01), despite no significant changes in lung function or exercise capacity. Placebo-treated patients, but not those who were given melatonin, showed an increase in IL-8 (P=0.03). In summary, melatonin administration reduced oxidative stress and improved dyspnea in COPD. Further studies are necessary to determine the potential role for melatonin in the long-term management of these patients.

Topics: Aged; Aged, 80 and over; Antioxidants; Dinoprost; Double-Blind Method; Dyspnea; Female; Humans; Lung; Male; Melatonin; Middle Aged; Oxidative Stress; Placebos; Pulmonary Disease, Chronic Obstructive; Spirometry

Anti-oxidant interventions consist in reduction of direct oxidant damage by removing oxidant agents and/or by supplementing reducing agents with anti-oxidant effects.. Aim of the present study was to investigate the anti-oxidant effects of erdosteine, a recent drug currently used in chronic obstructive pulmonary disease (COPD) for its rheological activity. At present, no data are available on current smokers with COPD to our knowledge.. Two groups of 10 persons matched for sex; age (65.0 yr+/-8.4 S.D. and 65.3 yr+/-6.5 S.D.); basal FEV1 (88.7% pred +/-6.8 S.D. and 85.2% pred +/-5.8 S.D.); and cigarette consumption (25.4 pack/yr+/-3.5 S.D. and 28.1 pack/yr+/-2.3 S.D.) entered a controlled, double blind, parallel groups study. They were randomized to receive erdosteine 600 mg daily or placebo for 10 days. IL-6; IL-8; TNFalpha were measured in bronchial secretions in bsln, after 4, 7, and 10 days of Erdosteine or placebo; e-NO and both ROS and 8-Isoprostane in blood were also measured at the same experimental times.. ANOVA: a t-test with Bonferroni correction; p<0.05 was accepted.. Blood ROS and IL-8 in bronchial secretions dropped significantly following erdosteine starting from day 4 (both p<0.01), while 8-isoprostane drop was significant only after day 10 (p<0.02), and the e-NO decrease proved evident but not significant. No significant changes were observed in the placebo group.. Erdosteine affects substantially some pro-inflammatory cytokines specifically involved in oxidative stress in current smokers with mild COPD. Effects appeared differently time-dependent. Further long-term studies are needed to confirm these pilot data and to assess their long-term clinical relevance.

Topics: Aged; Analysis of Variance; Antioxidants; Breath Tests; Bronchi; Cytokines; Dinoprost; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; Smoking; Thioglycolates; Thiophenes; Time Factors; Tumor Necrosis Factor-alpha

Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug.

Topics: Adult; Carbocysteine; Dinoprost; Exhalation; Female; Humans; Interleukin-6; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Time Factors; Treatment Outcome

An oxidant/antioxidant imbalance in favour of oxidants has been identified as playing a decisive role in the pathogenesis of chronic inflammatory airway diseases. Nutritional antioxidant supplementation might reduce oxidative damage by enhancement of the antioxidant defence, thereby modulating inflammatory processes. In a placebo-controlled, blind study, it was tested whether a dietary antioxidant supplement administered for 4 weeks would improve lung function and reduce airway inflammation in heaves-affected horses. Eight horses in clinical remission of heaves were investigated at rest and after a standardised exercise test before and after treatment with an antioxidant supplement (consisting of a mixture of natural antioxidants including vitamins E and C and selenium from a variety of sources) or placebo (oatfeed pellets without additive). Pulmonary function and exercise tolerance were monitored; systemic and pulmonary lining fluid uric acid, glutathione and 8-epi-PGF(2alpha) were analysed, and bronchoalveolar lavage (BAL) cytology and inflammatory scoring of the airways were performed. The antioxidant treatment significantly improved exercise tolerance and significantly reduced endoscopic inflammatory score. Plasma uric acid concentrations were significantly reduced, suggesting downregulation of the xanthine-dehydrogenase and xanthine-oxydase pathway. Haemolysate glutathione showed a nonsignificant trend to increase, while plasma 8-epi-PGF(2alpha) remained unchanged. Pulmonary markers and BAL cytology were not significantly affected by antioxidant supplementation. The present study suggests that the antioxidant supplement tested modulated oxidant/antioxidant balance and airway inflammation of heaves-affected horses.

Topics: Animals; Antioxidants; Bronchoalveolar Lavage Fluid; Dietary Supplements; Dinoprost; Exercise Test; F2-Isoprostanes; Female; Glutathione; Horse Diseases; Horses; Inflammation; Male; Oxidation-Reduction; Oxidative Stress; Physical Conditioning, Animal; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Uric Acid

Chronic obstructive pulmonary disease (COPD) augments the likelihood of having left ventricular diastolic dysfunction (LVDD)-precursor of heart failure with preserved ejection fraction (HFpEF). LVDD shares overlapping symptomatology (cough and dyspnea) with COPD. Stress induced LVDD is indicative of masked HFpEF. Our aim was to evaluate the predictive value of inflammatory, oxidative stress, cardio-pulmonary and echocardiographic parameters at rest for the diagnosis of stress LVDD in non-severe COPD patients, who complain of exertional dyspnea and are free of overt cardiovascular diseases. A total of 104 COPD patients (26 patients with mild and 78 with moderate COPD) underwent echocardiography before cardio-pulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. Patients were divided into two groups based on peak average E/e': patients with stress induced left ventricular diastolic dysfunction (LVDD)-E/e' > 15 masked HFpEF and patients without LVDD-without masked HFpEF. CPET and echocardiographic parameters at rest were measured and their predictive value for stress E/e' was analysed. Markers for inflammation (resistin, prostaglandine E2) and oxidative stress (8-isoprostanes) were also determined. Stress induced LVDD occurred in 67/104 patients (64%). Those patients showed higher VE/VCO2 slope. None of the CPET parameters was an independent predictor for stress LVDD.Except for prostglandine E2, none of the inflammatory or oxidative stress markers correlated to stress E/e'. The best independent predictors for stress LVDD (masked HFpEF) were RAVI, right ventricular parasternal diameter and RV E/A >0.75. Their combination predicted stress LVDD with the accuracy of 91.2%. There is a high prevalence of masked HFpEF in non-severe COPD with exertional dyspnea, free of overt cardiovascular disease. RAVI, right ventricular parasternal diameter and RV E/A >0.75 were the only independent clinical predictors of masked HFpEF. 288.

Topics: Aged; Biomarkers; Dinoprost; Dinoprostone; Female; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Resistin; Severity of Illness Index; Ventricular Dysfunction, Left

Chronic obstructive pulmonary disease (COPD) is caused by chronic inflammation. Many inflammatory mediators induce the low grade systemic inflammation of COPD. Haptoglobin (Hp) is synthesized in the liver and by lung epithelial and alveolar macrophage cells. However, associations of the serum concentration and phenotype of Hp with COPD are unclear. Therefore, we explored the association of the Hp concentration and Hp phenotype with the inflammatory response and COPD disease severity. We included healthy subjects and COPD patients. The Hp phenotype was categorized by SDS native-PAGE, and concentrations were determined by ELISA. In this trial Hp concentrations in COPD groups were significantly higher than those in healthy controls. There was a significant negative correlation between the Hp concentration and FEV

Topics: Aged; Biomarkers; Case-Control Studies; Dinoprost; DNA-Binding Proteins; Female; Haptoglobins; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Phenotype; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Transcription Factors

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P  <  0.02; healthy subjects: P  <  0.03), whereas EBC PGE2 was elevated in current (P  =  0.0065) and ex-smokers with COPD (P  =  0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P  <  0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P  <  0.01; healthy subjects: P  <  0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P  =  0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

Topics: Aged; Biomarkers; Breath Tests; Cross-Sectional Studies; Dinoprost; Dinoprostone; Exhalation; Female; Humans; Inflammation; Isoprostanes; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Smoking; Sputum

To investigate the effects of short-term exposure to traffic-related air pollution on airway oxidative stress and inflammation in chronic obstructive pulmonary diseases (COPD) patients.. A panel of forty-five diagnosed COPD patients were recruited and followed with repeated measurements of biomarkers reflecting airway oxidative stress and inflammation in exhaled breath condensate (EBC), including nitrate and nitrite, 8-isoprostane, interleukin-8 and acidity of EBC (pH), between 5(th) September in 2014 and 26(th) May in 2015. The associations between air pollution and biomarkers were analyzed with mixed-effects models, controlling for confounding covariates.. The concentration of PM2.5, black carbon, NO2 and number concentration of particles with diameter less than 100 nm (PNC100), and particles in size ranges between 100 nm to 200 nm (PNC100-200) during the first follow-up were (156.5±117.7), (10.7±0.7), (165.9±66.0)μg/m(3) and 397 521±96 712, 79 421±44 090 per cubic meter, respectively; the concentration were (67.9±29.6), (3.4±1.3), (126.1±10.9) μg/m(3) and (295 682±39 430), (24 693±12 369) per cubic meter, respectively during the second follow-up. The differences were of significance, with t value being 3.10, 4.42, 2.61, 4.02, 5.12, respectively and P value being 0.005,<0.001, 0.016, <0.001 and <0.001, respectively. In our COPD-patient panel, per interquartile range (IQR) increase in PNC100-200, we observed an increase of 65% (95% CI: 8%-152%) in nitrate and nitrite in EBC reflecting airway oxidative stress. For an IQR increase in PM2.5, black carbon and PNC100-200, respective increases of 0.17 ng/ml (95% CI: 0.02-0.33), 0.12 ng/ml (95% CI: 0.01-0.24) and 0.13 ng/ml (95% CI:0.02-0.24) in interleukin-8 in EBC reflecting airway inflammation were also observed. An IQR increase in ozone was also associated with a 0.24 (95%CI: 0.05-0.42) decrease in pH of EBC reflecting increased airway inflammation. No significant association observed between air pollution and 8-isoprostane in EBC in COPD patients.. Our results suggested that short-term exposure to traffic-related air pollution was responsible for exacerbation of airway oxidative stress and inflammation in COPD patients.

Topics: Air Pollutants; Air Pollution; Biomarkers; Dinoprost; Environmental Exposure; Female; Humans; Inflammation; Interleukin-8; Longitudinal Studies; Male; Motor Vehicles; Oxidative Stress; Particulate Matter; Pulmonary Disease, Chronic Obstructive; Respiratory System; Soot; Urban Population; Vehicle Emissions; Young Adult

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.

Topics: Aged; Biomarkers; Breath Tests; Cardiovascular Diseases; Comorbidity; Dinoprost; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that is correlated with environmental stress. Particulate matter ≤10 μm (PM10) is considered to be a risk factor for COPD development; however, the effects of PM10 on the protein levels in COPD remain unclear. Fifty subjects with COPD and 15 healthy controls were recruited. Gene ontology analysis of differentially expressed proteins identified immune system process and binding as the most important biological process and molecular function, respectively, in the responses of PM10-exposed patients with COPD. Biomarkers for PM10 in COPD were identified and compared with the same in healthy controls and included proteoglycan 4 (PRG4), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), and apolipoprotein F (APOF). PRG4 and ITIH4 were associated with a past 3-year PM10 exposure level. The receiver operating characteristic curve analysis showed that ITIH4 is a sensitive and specific biomarker for PM10 exposure (area under the curve [AUC] =0.690, P=0.015) compared with PRG4 (AUC =0.636, P=0.083), APOF (AUC =0.523, P=0.766), 8-isoprostane (AUC =0.563, P=0.405), and C-reactive protein (CRP; AUC =0.634, P=0.086). ITIH4 levels were correlated with CRP (r=0.353, P=0.005), suggesting that ITIH4 may be involved in an inflammatory mechanism. In summary, serum ITIH4 may be a PM10-specific biomarker in COPD and may be related to inflammation.

Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Apolipoproteins; Area Under Curve; Biomarkers; Blood Proteins; C-Reactive Protein; Case-Control Studies; Dinoprost; Female; Forced Expiratory Volume; Glycoproteins; Humans; Inflammation Mediators; Inhalation Exposure; Lung; Male; Middle Aged; Particle Size; Particulate Matter; Predictive Value of Tests; Proteinase Inhibitory Proteins, Secretory; Proteoglycans; Pulmonary Disease, Chronic Obstructive; ROC Curve; Taiwan

Eicosanoids are small lipid molecules with diverse biological functions in the airways.. The aim of this study was to investigate changes in leukotriene B4 (LTB4), 8-isoprostane, prostaglandin E2 (PGE2) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery.. Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay.. Sputum PGE2 [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p < 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p < 0.01] and LTB4 [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p < 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE2 levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p < 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE2 and sputum neutrophil and lymphocyte cell counts in patients with exacerbation.. Our results suggest that 8-isoprostane, LTB4 and PGE2 but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE2 for use as a biomarker of recovery from an exacerbation requires further studies.

Topics: Aged; Biomarkers; Case-Control Studies; Cysteine; Dinoprost; Dinoprostone; Disease Progression; Eicosanoids; Female; Humans; Immunoenzyme Techniques; Leukotriene B4; Leukotrienes; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sputum

 Inflammation and oxidative stress play an essential role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD)..  The aim of the study was to evaluate the echocardiographic parameters of the left and right ventricular functions in patients with COPD with or without CVD and in healthy controls, and to establish their relationships with biomarkers of inflammation and oxidative stress..  The study included 24 patients with COPD and CVD, 20 patients with COPD, and 16 healthy controls. Physical examination, spirometry, and echocardiography were performed in all participants, and blood samples were collected. The levels of 8‑isoprostane, leukotriene B4, and interleukin 8 were determined in the blood and exhaled breath condensate (EBC)..  In patients with COPD, the left ventricular ejection fraction was lower than in healthy controls (58.84% ±9.57% vs. 65.50% ±3.35%, P <0.01); moreover, it was lower in patients with COPD and CVD than in those without comorbidities (54.29% ±10.58% vs. 64.30% ±3.74%, P <0.01). The systolic and diastolic functions of the right ventricle were lower in patients with COPD than in the control group, while systolic pulmonary arterial pressure was significantly higher in patients with COPD than in the control group (37.04 ±7.6 mmHg vs. 28.12 ±4.44 mmHg, P = 0.01). Some echocardiographic parameters of the left and right ventricular functions correlated with the concentrations of inflammatory markers both in serum and EBC..  The echocardiographic parameters of cardiac function correlate with the markers of inflammation in patients with COPD, which emphasizes the inflammatory background of CVD.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diastole; Dinoprost; Echocardiography; Female; Heart Ventricles; Humans; Inflammation; Interleukin-8; Leukotriene B4; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Systole; Ventricular Function, Left; Ventricular Function, Right

Exacerbations in chronic obstructive pulmonary disease (COPD) reduce quality of life and are associated with a more rapid deterioration of the disease. It is desirable to predict an oncoming exacerbation before it occurs. The aim of the present study was to identify biomarkers that may predict a forthcoming exacerbation.. Forty-three patients with COPD in their stable state were included and followed up monthly until exacerbation, or for a maximum of 6 months. The patients come for an extra visit (prior to a scheduled visit) when exacerbated. The patients completed the questionnaires CCQ and MRC. Exhaled breath condensate (EBC) was collected followed by spirometry, impulse oscillometry, and sputum induction.. Twenty-five patients had an exacerbation within the 6-month period. Leukotriene B4 in sputum was the only biomarker that was increased at the visit prior to exacerbation compared to at the stable phase (p = 0.05). There also was a tendency for a similar but not significant increase in the sputum levels of 8-isoprostane, myeloperoxidase activity, and interleukin-8, as well as additional increases during exacerbation. Sputum purulence was not increased until exacerbation (p = 0.02). In contrast, none of the inflammatory biomarkers in EBC, the quality-of-life questionnaire score, CRP, spirometric parameters, or impulse oscillometry parameters were increased at the visit prior to exacerbation compared to the values at the stable phase.. Sputum biomarkers, especially leukotriene B4, could be used as predictors of a forthcoming exacerbation and worsening of COPD. This would be of great value for the patient, who may be a subject for early treatment and thereby avoid a progression of the disease.

Topics: Aged; Biomarkers; Dinoprost; Disease Progression; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Lung; Male; Middle Aged; Oscillometry; Peroxidase; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Quality of Life; Spirometry; Sputum; Surveys and Questionnaires; Time Factors

It has recently been suggested that regular exercise reduces lung function decline and risk of chronic obstructive pulmonary disease (COPD) among active smokers; however, the mechanisms involved in this effect remain poorly understood. The present study evaluated the effects of regular exercise training in an experimental mouse model of chronic cigarette smoke exposure. Male C57BL/6 mice were divided into four groups (control, exercise, smoke and smoke+exercise). For 24 weeks, we measured respiratory mechanics, mean linear intercept, inflammatory cells and reactive oxygen species (ROS) in bronchoalveolar lavage (BAL) fluid, collagen deposition in alveolar walls, and the expression of antioxidant enzymes, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase (TIMP)1, interleukin (IL)-10 and 8-isoprostane in alveolar walls. Exercise attenuated the decrease in pulmonary elastance (p<0.01) and the increase in mean linear intercept (p=0.003) induced by cigarette smoke exposure. Exercise substantially inhibited the increase in ROS in BAL fluid and 8-isoprostane expression in lung tissue induced by cigarette smoke. In addition, exercise significantly inhibited the decreases in IL-10, TIMP1 and CuZn superoxide dismutase induced by exposure to cigarette smoke. Exercise also increased the number of cells expressing glutathione peroxidase. Our results suggest that regular aerobic physical training of moderate intensity attenuates the development of pulmonary disease induced by cigarette smoke exposure.

Topics: Animals; Antioxidants; Bronchoalveolar Lavage Fluid; Dinoprost; Emphysema; Interleukin-10; Macrophages, Alveolar; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Oxidative Stress; Physical Conditioning, Animal; Pulmonary Alveoli; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; Respiratory Mechanics; Tissue Inhibitor of Metalloproteinase-1; Tobacco Smoke Pollution

COPD is characterized by chronic air-flow limitation. Smoking is the most important factor in the pathogenesis of COPD. Smoking is associated with increased oxidative stress in the lungs. In this study our aim was to evaluate the differences in the burden of oxidative stress in patients with COPD, smokers, and non-smokers by measuring hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA), and 8-isoprostane levels in the exhaled breath condensate (EBC) samples.. Eighty subjects were included in the study. Group I (no. = 25) had COPD, Group II (no. = 26) was smokers, and Group III (no. = 29) was nonsmokers. The severity of the COPD and dyspnea was assessed according to the results of pulmonary function tests (PFTs) and Medical Research Council (MRC) scale.. The mean age of the subjects was 58 ± 8.9 years. While 8-isoprostane and H(2)O(2) levels were significantly higher in subjects with COPD (44.8 ± 40.2 pg/mL and 1.9 ± 0.8 μmol/L) and smokers (41.3 ± 26 pg/mL and 1.7 ± 0.7 μmol/L) than non-smokers (15.8 ± 6.9 pg/mL and 0.8 ± 0.4 μmol/L), levels were similar between smokers and COPD subjects. MDA levels were similar between the 3 groups (P = .31). There was no correlation between 8-isoprostane and H(2)O(2) levels and PFT parameters. There was a significant positive correlation between dyspnea grade on the MRC scale and 8-isoprostane levels (r = 0.805, P < .001).. Even if respiratory function tests are within normal limits, oxidant burden in lungs of smokers is equivalent to that in COPD patients. 8-isoprostane could be useful in assessing symptom severity and health status of COPD patients.

Topics: Aged; Breath Tests; Dinoprost; Humans; Hydrogen Peroxide; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Smoking

Inflammation and oxidative stress are linked to the deleterious effects of cigarette smoke in producing chronic obstructive pulmonary disease (COPD). Myeloperoxidase (MPO), a neutrophil and macrophage product, is important in bacterial killing, but also drives inflammatory reactions and tissue oxidation.. To determine the role of MPO in COPD.. We treated guinea pigs with a 2-thioxanthine MPO inhibitor, AZ1, in a 6-month cigarette smoke exposure model, with one group receiving compound from Smoking Day 1 and another group treated after 3 months of smoke exposure.. At 6 months both treatments abolished smoke-induced increases in lavage inflammatory cells, largely ameliorated physiological changes, and prevented or stopped progression of morphologic emphysema and small airway remodeling. Cigarette smoke caused a marked increase in immunohistochemical staining for the myeloperoxidase-generated protein oxidation marker dityrosine, and this effect was considerably decreased with both treatment arms. Serum 8-isoprostane, another marker of oxidative stress, showed similar trends. Both treatments also prevented muscularization of the small intrapulmonary arteries, but only partially ameliorated smoke-induced pulmonary hypertension. Acutely, AZ1 prevented smoke-induced increases in expression of cytokine mediators and nuclear factor-κB binding.. We conclude that an MPO inhibitor is able to stop progression of emphysema and small airway remodeling and to partially protect against pulmonary hypertension, even when treatment starts relatively late in the course of long-term smoke exposure, suggesting that inhibition of MPO may be a novel and useful therapeutic treatment for COPD. Protection appears to relate to inhibition of oxidative damage and down-regulation of the smoke-induced inflammatory response.

Topics: Airway Remodeling; Animals; Dinoprost; Disease Models, Animal; Disease Progression; Enzyme Inhibitors; Female; Guinea Pigs; Hypertension, Pulmonary; Inflammation; Lung; Oxidative Stress; Peroxidase; Pulmonary Disease, Chronic Obstructive; Purines; Smoking; Thiones; Thioxanthenes; Tyrosine

There is considerable evidence that oxidative stress is increased in patients with COPD, although little information is available about its relationship with the structural and functional alterations produced by COPD. In this study, we evaluated the relationship between 8-isoprostane in exhaled breath condensate (EBC) of stable patients with COPD and the main parameters of the disease (such as dyspnea), stages of severity, lung parenchyma densities, lung function impairment, and exercise tolerance in order to identify the predictors of airway oxidative stress.. In a cross-sectional study, we included 76 men with moderate to very severe COPD. 8-Isoprostane levels in EBC were measured by enzyme immunoassay. Regional lung densities were measured by lung densitometry with high-resolution CT scanning. Arterial blood gas levels, lung volumes, and diffusing capacity were determined. Patients performed a 6-min walk test and an incremental exercise test with measurement of breathing pattern and operating lung volumes.. Significant severity-related differences in 8-isoprostane were identified according to the BMI, obstruction, dyspnea, and exercise (BODE) index. 8-Isoprostane levels were related to smoking intensity, lung densities in expiration, static lung volumes, PaO(2), diffusion capacity, distance walked in 6 min, peak oxygen uptake, and anaerobic threshold. Concentration of 8-isoprostane was higher in the 60 patients (79%) who developed dynamic hyperinflation than in the remaining 16 (21%) who did not. In a multivariate linear regression analysis using 8-isoprostane as a dependent variable, end-expiratory lung volume change and PaO(2) were retained in the prediction model (r(2) = 0.734, P < .001).. In stable patients with COPD, oxygen level and dynamic hyperinflation are related to airway oxidative stress.

Topics: Adult; Aged; Cross-Sectional Studies; Dinoprost; Dyspnea; Exercise Tolerance; Exhalation; Female; Humans; Inhalation; Linear Models; Lung; Male; Middle Aged; Oxidative Stress; Oxygen; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tomography, X-Ray Computed

It has been reported that small airway inflammation is closely associated with the severity of airflow limitation in COPD (chronic obstructive pulmonary disease). We tested a new method of measurement of biochemical constituents in ELF (epithelial lining fluid) obtained separately from the central or peripheral airways using a bronchoscopic microsampling technique. The present study was designed to determine the validity of measuring CML [N(epsilon)-(carboxymethyl)lysine] levels in ELF for the assessment of small airway inflammation in COPD. Ten non-smokers, ten current smokers and 16 COPD patients were included in the present study. Concentrations of CML, 8-isoprostane and IL-8 (interleukin-8) were measured in ELF separately from the central or peripheral airways. CML levels in central airways did not differ significantly, but were markedly higher in peripheral than in central airways in the three groups. However, CML levels in peripheral airways of COPD patients were significantly higher than those in non-smokers and current smokers. In COPD patients, the CML level in peripheral airways was significantly correlated with FEV1 (forced expiratory volume in 1 s) (r=-0.82, P=0.002) and FEV1/FVC (forced vital capacity) (r=-0.57, P=0.03). Moreover, CML levels in peripheral airways were significantly correlated with levels of both 8-isoprostane (r=0.76, P=0.003) and IL-8 (r=0.67, P=0.01). In conclusion, these findings suggest that elevated levels of CML in ELF from peripheral airways were observed in COPD patients, and this parameter was correlated with the severity of airflow limitation.

Topics: Aged; Bronchioles; Bronchoscopy; Dinoprost; Forced Expiratory Volume; Humans; Interleukin-8; Lysine; Middle Aged; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Smoking; Specimen Handling; Vital Capacity

Markers of airway inflammation and oxidative stress have been mainly investigated in moderate/severe chronic obstructive pulmonary disease (COPD) or during its exacerbation. They have not been compared in noninvasive specimens such as exhaled breath condensate (EBC) and induced sputum in healthy nonsymptomatic smokers or in those who have symptoms and are at risk for COPD development.. To compare the relative proportions of 2 potential COPD biomarkers, 8-isoprostane and interleukin- 8 (IL-8) in the induced sputum and EBC sampled from the same subjects: nonsmokers (n = 14), healthy smokers (n = 17) and symptomatic smokers (n = 9) who are considered to be at risk for COPD. COPD patients with acute exacerbation (n = 10) were employed as positive controls.. The levels of the aforementioned biomarkers in induced sputum and EBC were investigated using commercial biochemical techniques.. In induced sputum, the levels of 8-isoprostane and IL-8 were at least 10-fold higher compared to EBC levels in all groups. Healthy nonsmokers had the lowest levels, and patients with exacerbation of COPD the highest levels of 8-isoprostane in induced sputum and EBC. The same observation held true for IL-8 in induced sputum. Inverse correlations with lung function parameters were observed for both mediators.. The levels of both potential markers were clearly higher in the induced sputum than in EBC. The results point to an advantage of induced sputum over EBC for assessing the degree of airway oxidative stress and inflammation in smokers with a potential risk for COPD development.

Topics: Adult; Aged; Biomarkers; Breath Tests; Dinoprost; Female; Humans; Interleukin-8; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Smoking; Sputum

We assessed the effect of therapy on nuclear signaling related to inflammatory processes in sputum cells of patients with chronic obstructive pulmonary disease (COPD). Patients were treated with formoterol (F) or formoterol plus budesonide (F/ICS) b.i.d. for 4 weeks, their sputum cells were isolated and subjected to RNA extraction or lysis, followed by differential centrifugation. Signaling protein levels were assessed by Western blots, their specific mRNAs were quantified using qRTPCR, while 8-isoprostane levels were examined using enzyme immunoassay kit. Cytosolic 8-isoprostane levels and nuclear glucocorticoid receptor expression (protein and mRNA) were not significantly different in both groups, while nuclear cAMP response element binding protein (CREB; protein and mRNA) and peroxisome proliferator-activated receptor gamma (PPARgamma protein and mRNA) were significantly higher in cells from F/ICS-treated patients. CREB-binding protein (CBP; protein and mRNA) levels were significantly lower in F/ICS patients. These changes indicate increased anti-inflammatory signaling in F/ICS-treated patients and seem to be beneficial.

Topics: Blotting, Western; Bronchodilator Agents; CREB-Binding Protein; Dinoprost; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Oxidative Stress; PPAR gamma; Pulmonary Disease, Chronic Obstructive; Receptors, Glucocorticoid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sputum

8-Isoprostane is a potential in vivo marker for oxidant burden, but its usefulness in induced sputum of smokers and chronic obstructive pulmonary disease (COPD) has not been investigated. The current study investigated 58 subjects comprising 11 never-smokers, 11 ex-smokers, 13 healthy current smokers and 23 COPD with stage 0-III disease (according to the Global Initiative for Chronic Obstructive Lung Disease criteria). 8-Isoprostane was determined from induced sputum by enzyme immunoassay. Sputum 8-isoprostane levels were similar in the never-smokers and ex-smokers, but were elevated in the healthy smokers compared with nonsmokers, and in those with stage I-III COPD. Sputum 8-isoprostane levels could not differentiate nonsymptomatic smokers from those with Stage 0 COPD. There was a correlation between sputum 8-isoprostane level and lung function parameters (forced expiratory volume in one second/forced vital capacity and sputum neutrophils. In conclusion, sputum 8-isoprostane levels correlate with the severity of chronic obstructive pulmonary disease. However, they do not appear to differentiate healthy smokers from those who are at risk of developing chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease stage 0).

Topics: Biomarkers; Case-Control Studies; Dinoprost; Female; Humans; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Smoking; Sputum

Topics: Biomarkers; Breath Tests; Dinoprost; Humans; Leukotriene B4; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results

The reproducibility of exhaled breath condensate (EBC) mediators is not well documented in chronic obstructive pulmonary disease (COPD). This study assessed within assay (WA), within (WD) and between day (BD) reproducibility of EBC leukotriene B4 (LTB4) and 8-isoprostane. Three EBC samples were collected from 24 COPD patients separated by 1 h and 1 wk, to assess WD and BD reproducibility. WA reproducibility was assessed by sample analysis by enzyme immunoassay in triplicate. WA coefficient of variation for LTB4 and 8-isoprostane (18.2% and 29.2%, respectively) was lower than corresponding values for WD (47.7% and 65.3%, respectively) and BD (75.7% and 79.1%, respectively). Repeatability coefficient for 8-isoprostane and LTB4 assays were 18.6 pg/ml and 13.2 pg/ml, respectively. Group mean differences for WD and BD were small and statistically nonsignificant. Using the Bland Altman method, there were wide limits of agreement for WD (-51.6 to 47.2 for 8-isoprostane and -31.8 to 31.4 for LTB4) and BD reproducibility (-61.4 to 75.7 for 8-isoprostane and -29.3 to 38.6 for LTB4). This is the first study to fully report the variability of EBC 8-isoprostane and LTB4 in COPD. WA variability and group mean changes were small. However, we observed considerable WD and BD variability for these biomarkers.

Topics: Biomarkers; Breath Tests; Data Interpretation, Statistical; Dinoprost; Female; Humans; Leukotriene B4; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results

The aim of this study was to test the hypothesis that pulmonary inflammation and emphysema induced by cadmium (Cd) inhalation are associated with pulmonary oxidative stress. Two groups of Sprague Dawley rats were used: one vehicle-exposed group undergoing inhalation of NaCl (0.9%, n = 24) and one Cd-exposed group undergoing inhalation of CdCl(2) (0.1%, n = 24). The animals in the vehicle-and Cd-exposed groups were divided into 4 subgroups (n = 6 per group), which underwent either a single exposure (D2) of 1H or repeated exposures 3 times/week for 1H for a period of 3 weeks (3W), 5 weeks (5W) or 5 weeks followed by 2 weeks without exposure (5W + 2). At sacrifice, the left lung was fixed for histomorphometric analysis (median inter-wall distance, MIWD), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. Cytological analysis of BALF was performed and BALF was analysed for oxidant markers 8-iso-PGF(2a), uric acid (UA), reduced (AA) and oxidised ascorbic acid (DHA) and reduced (GSH) and oxidised glutathione (GSSG). Cd-exposure induced a significant increase of BALF macrophages and neutrophils. 8-iso-PGF(2a), UA, GSH and GSSG were significantly increased at D2. At 5W and 5W + 2, AA and GSH were significantly lower in Cd-exposed rats, indicating antioxidant depletion. MIWD significantly increased in all repeatedly Cd-exposed groups, suggesting development of pulmonary emphysema. 8-iso-PGF(2a) and UA were positively correlated with macrophage and neutrophil counts. GSH, GSSG and 8-iso-PGF(2a) were negatively correlated with MIWD, indicating that Cd-induced emphysema could be associated with pulmonary oxidative stress.

Topics: Animals; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Cadmium; Dinoprost; Glutathione; Inflammation; Lung; Macrophages; Male; Neutrophils; Oxidation-Reduction; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Sprague-Dawley; Uric Acid

Chronic obstructive pulmonary disease (COPD) is believed to result from an abnormal inflammatory response in the lungs to noxious particles and gases usually found in cigarette smoke.. In this study, the molecular mechanisms for the enhanced proinflammatory cytokine gene transcription in COPD were investigated.. Lung tissue was examined from 56 subjects undergoing resection for peripheral lung tumors as follows: current smokers with (n = 14) and without COPD (n = 17), ex-smokers with COPD (n = 13), and nonsmokers (n = 12). The levels of inhibitor kappaB-alpha (IkappaB-alpha), histone deacetylase 2 (HDAC2), acetylated (ac-) histone H3 and H4, the transcription factor nuclear factor-kappaB (NF-kappaB), proinflammatory cytokine messenger RNA, and 8-isoprostane were measured.. IkappaB-alpha levels were significantly decreased in healthy smokers and current and ex-smoking patients with COPD when compared with nonsmokers (p < 0.001), with an associated increase in NF-kappaB DNA binding in current smokers (p < 0.05). An increase in acetylated histone 4 (ac-H4; p < 0.01) was found in current smokers. Conversely, ex-smokers with COPD showed an increase in ac-H3 (p < 0.05). Decreased levels of cytoplasmic, but not nuclear, HDAC2 protein levels were detected. From the cytokine profiles, no significant differences were detected; however, interleukin-12p40 expression correlated with ac-H4 in current smokers with COPD (p < 0.01).. These data propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking. The imbalance between histone deacetylation and acetylation in favor of acetylation may contribute to the enhanced inflammation in smokers susceptible to the development of COPD.

Topics: Aged; Case-Control Studies; Cytokines; Dinoprost; Female; Histone Deacetylase 2; Histone Deacetylases; Histones; Humans; I-kappa B Proteins; Male; Middle Aged; NF-kappa B; NF-KappaB Inhibitor alpha; Pulmonary Disease, Chronic Obstructive; Repressor Proteins; RNA, Messenger; Smoking

To study whether patients with chronic obstructive pulmonary disease (COPD) at the same level of flow limitation but with different clinical phenotypes present different degrees of systemic and/or pulmonary inflammation.. We studied 15 male smokers without COPD (control group) and 39 males with COPD in stable clinical condition. The COPD patients were assigned to 2 groups based on the ratio of carbon monoxide diffusing capacity (DLCO) to alveolar volume (DLCO/VA) expressed as a percentage as follows: a) mainly emphysema (n = 15) and b) mainly chronic bronchitis (n = 24). Classification was determined by comparing both clinical features and diagnostic images.. Mean (SD) concentrations of interleukin 8 (IL-8) and 8-isoprostane in exhaled breath condensate (EBC) were significantly lower in patients with mainly emphysema (IL-8, 0.34 [0.70] pg/mL; 8-isoprostane, 0.07 [0.26] pg/mL) than in patients with chronic bronchitis (IL-8, 2.32 [3.10] pg/mL; 8-isoprostane, 1.77 [2.98] pg/mL) or in the controls (IL-8, 3.14 [4.59] pg/mL; 8-isoprostane, 1.92 [2.84] pg/mL); P < .05 for IL-8 comparisons and P < .01 for 8-isoprostane. IL-8, leukotriene B4, and 8-isoprostano in EBC correlated significantly with DLCO/VA (% of predicted) (r = 0.30, P < .05; r = 0.29, P < or = .05; and r = 0.46, P < .01, respectively) but not with forced expiratory volume in 1 second. There was a negative correlation between EBC and serum levels of both IL-8 (r = -0.31; P < .05) and 8-isoprostane (r = -0.51; P < .001). The correlation between leukotriene B4 concentrations in EBC and serum was not significant, however. No significant differences were found between smokers' and ex-smokers' serum levels of IL-8, leukotriene B4, 8-isoprostane in serum or EBC.. The results indicate that COPD patients with an emphysematous phenotype have a less intense inflammatory response and less oxidative stress in the lung.

Topics: Carbon Monoxide; Diffusion; Dinoprost; Emphysema; Humans; Hydrogen-Ion Concentration; Interleukin-8; Leukotriene B4; Male; Middle Aged; Oxidative Stress; Phenotype; Pneumonia; Pulmonary Disease, Chronic Obstructive; Smoking

Exacerbations are an important feature of chronic obstructive pulmonary disease (COPD), accounting for a large proportion of health care costs. They are associated with increased airway inflammation and oxidative stress.. Concentrations of leukotriene B4 (LTB4), a marker of inflammation, and 8-isoprostane, a marker of oxidative stress, were measured in the exhaled breath condensate of 21 patients (11 M) with COPD during an exacerbation and 2 weeks after treatment with antibiotics. In 12 patients who had no further exacerbations these markers were also measured after 2 months.. LTB4 concentrations were raised during the COPD exacerbation (mean (SE) 15.8 (1.1) pg/ml and fell after treatment with antibiotics to 9.9 (0.9) pg/ml (p<0.0001). In 12 patients the level of LTB4 fell further from 10.6 (1.1) pg/ml to 8.5 (0.8) pg/ml (p<0.005) after 2 months. In 12 normal age matched subjects the LTB4 levels were 7.7 (0.5) pg/ml. Concentrations of 8-isoprostane were also increased during the exacerbation (13.0 (0.9) pg/ml) and fell after antibiotic treatment to 9.0 (0.6) pg/ml (p<0.0001). In 12 patients there was a further fall from 9.3 (0.7) pg/ml to 6.0 (0.7) pg/ml (p<0.001) after 2 months compared with normal subjects (6.2 (0.4) pg/ml).. Non-invasive markers of inflammation and oxidative stress are increased during an infective exacerbation of COPD and only slowly recover after treatment with antibiotics.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Antagonists; Adrenergic beta-Agonists; Aged; Anti-Bacterial Agents; Biomarkers; Breath Tests; Dinoprost; F2-Isoprostanes; Female; Forced Expiratory Volume; Humans; Leukotriene B4; Male; Oxidative Stress; Pneumonia; Pulmonary Disease, Chronic Obstructive; Vital Capacity

In heaves-affected horses the relation between oxidant status, airway inflammation (AI) and pulmonary function (PF) is unknown. The oxidant status of blood and pulmonary epithelial lining fluid (PELF) of healthy (H, n = 6) and heaves-affected horses in clinical remission (REM, n = 6) and in crisis (CR, n = 7) was assessed at rest, during and after standardised exercise test by measurement of reduced and oxidised glutathione, glutathione redox ratio [GRR%]; uric acid and 8-epi-PGF2alpha. Oxidant status was related to PF parameters (mechanics of breathing and arterial blood gas tension) and Al parameters (bronchoalveolar lavage [BAL] neutrophil % and AI score). Haemolysate glutathione was significantly different between groups and was correlated with PF and AI parameters; GRR in PELF was increased during CR and was correlated with PF and AI parameters. Exercise induced an increase of plasma uric acid that was significantly higher both in REM and CR. PELF 8-epi-PGF2alpha was significantly increased in CR and correlated with PF and AI parameters. These results suggest that oxidative stress occurring in heaves is correlated with PF and AI and may be locally assessed by PELF glutathione status, uric acid and 8-epi-PGF2alpha. Systemic repercussions are reflected by assay of GSH in resting horses and by uric acid in exercising horses.

Topics: Animals; Bronchoalveolar Lavage Fluid; Chronic Disease; Dinoprost; F2-Isoprostanes; Glutathione; Glutathione Disulfide; Horse Diseases; Horses; Inflammation; Lung; Neutrophils; Oxidation-Reduction; Physical Conditioning, Animal; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Uric Acid

Exercise-induced oxidative stress is investigated as a potential performance-limiting factor in human sports medicine. Therefore, the present study aimed to assess whether physiological variables that change with exercise intensity were correlated with blood oxidant markers in healthy and heaves-affected horses. Seven healthy horses, 8 heaves-affected in remission and 7 heaves-affected in crisis performed a standardised exercise test (SET) of stepwise increasing intensity. Variables monitored during exercise were heart rate (HR), venous plasma lactate (LA), packed cell volume (PCV) and arterial oxygen tension (PaO2). Oxidant markers (uric acid [UA], 8-iso-PGF2alpha and reduced [GSH] and oxidised glutathione [GSSG]) were analysed in venous peripheral blood sampled at rest (R), at peak-exercise intensity (Emax), 15 (E15) and 60 (E60) min after SET. There was a significant effect of heaves on oxidant markers and, therefore, correlation analyses between physiological variables and oxidant markers were performed separately per horse group. In healthy horses, UA analysed at Emax was positively correlated with LA. Furthermore, GSH analysed at Emax and E15 was positively correlated with PaO2. In healthy and heaves-affected horses in remission, GSH and GSSG determined at Emax were negatively correlated with HR. There was no significant correlation between 8-iso-PGF2alpha and physiological variables. In conclusion, a correlation between the physiological response to exercise and some oxidant markers exists in healthy horses. However, in heaves-affected horses the blood oxidant status is probably more dependant on airway disease than on exercise. Future studies should be undertaken to assess whether antioxidant supplementation might positively influence the oxidant-antiodidant balance in exercising horses.

Topics: Animals; Antioxidants; Biomarkers; Blood Gas Analysis; Dinoprost; Exercise Test; F2-Isoprostanes; Glutathione; Heart Rate; Hematocrit; Horse Diseases; Horses; Lactates; Oxidative Stress; Oxygen; Physical Conditioning, Animal; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Uric Acid