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ABSTRACT |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Ethane is a product of lipid peroxidation and can be measured in
the exhaled air as an index of oxidative stress. Oxidant/antioxidant imbalance is important in the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, we measured exhaled ethane in 22 patients with COPD (mean age ± SEM, 59 ± 8 yr;
19 male) and compared it with other noninvasive markers of oxidative stress and inflammation such as carbon monoxide (CO),
measured electrochemically, and nitric oxide (NO), measured by
chemiluminescence. Exhaled ethane was collected during a flow
and pressure-controlled exhalation into a reservoir, discarding dead
space air contaminated with ambient air. A sample of the collected
expired air was analyzed by chromatography. Compared with normal subjects (n = 14; eight men; age, 33 ± 2.8 yr), patients with
COPD not on steroid treatment (n = 12; FEV1, 58 ± 6%) had elevated levels of exhaled ethane (2.77 ± 0.25 and 0.88 ± 0.09 ppb,
respectively, p < 0.05), CO (5.96 ± 0.50 and 2.8 ± 0.25 ppm, p < 0.05) and NO (11.86 ± 0.53 and 6.77 ± 0.50 ppb, p < 0.05) levels.
Ethane was correlated to FEV1 (r = 
0.67, p < 0.05). Patients receiving steroid treatment (n = 10; FEV1, 56 ± 2%) had lower levels
of ethane (0.48 ± 0.05 ppb) than did steroid-treated patients,
whereas CO (5.99 ± 0.63 ppm) and NO (9.11 ± 0.53 ppb) levels
were similar in the two treatment groups. Exhaled ethane is elevated, correlates with FEV1, and is significantly lower in patients
treated with steroids, so it may be complementary to the use of
NO and CO in assessing and monitoring oxidative stress in COPD.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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There is evidence for a role of oxidative stress in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD) (1, 2). Reactive oxygen species (ROS) are unstable compounds with unpaired electrons, capable of initiating oxidation. Several of the inflammatory cells that participate in the
inflammatory response such as neutrophils and eosinophils and
macrophages release ROS in amounts that exceed the capacity
of tissue antioxidant defenses (1, 3). Furthermore, cigarette smoke
generates ROS such as peroxynitrates and oxygen free radicals.
Smokers have increased numbers of macrophages and neutrophils in their bronchoalveolar lavage. In addition, alveolar
macrophages and blood neutrophils of smokers release more
superoxide anions (O2
) than do those from nonsmoking control
subjects (4). A correlation has been demonstrated between O2
release by neutrophils and bronchial hyperactivity in patients with COPD, and O2 release is increased during acute exacerbations (2). The final result of cigarette smoking and chronic
neutrophil inflammation is an oxidant antioxidant imbalance.
One mechanism by which oxidants can cause lung injury is
through lipid peroxidation. ROS such as O2 and hydrogen
peroxide (H2O2) released by activated immune and inflammatory cells can induce (5) the lipid peroxidation of polyunsaturated membrane fatty acids, impair membrane function and
inactivate membrane-bound receptors and enzymes, increase tissue permeability (6), and therefore promote airflow limitation.
The determination of hydrocarbons in the exhaled air has been proposed as a means to assess lipid peroxidation in vivo (7) and ethane received particular attention because of its easier and faster chromatographic measurement compared with other hydrocarbons (10). The first analyses of the organic compounds present in the exhaled air from human subjects were performed in the 1960s (11). Since then, the research in this area has progressed slowly because of technical and practical problems such as the influence of ambient hydrocarbons on exhaled breath levels of these gases. We modified a previously developed technique for single-breath analysis of exhaled hydrocarbons (10) by allowing airway dead space washout during exhalation eliminating ambient contamination of the exhaled breath. We applied this simplified technique to the measurement of exhaled ethane in patients with COPD.
Noninvasive markers of inflammation and oxidative stress would be of great benefit in disease management and monitoring and in the assessment of drugs efficacy. In this respect other exhaled gases have already been investigated. In COPD high levels of exhaled nitric oxide (NO) (12) and carbon monoxide (CO) (13) may reflect the release of several mediators, including cytokines and ROS that can induce heme oxygenase-1 (HO-1) and inducible NO synthase (iNOS), the enzymes that catalyze the production of CO and NO respectively.
In view of the role of oxidative stress in the pathogenesis and progression of COPD, we measured exhaled ethane as a marker of lipid peroxidation, and compared it with two other noninvasive volatile markers of oxidative stress and inflammation, NO and CO.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Patients
All the patients enrolled met the American Thoracic Society criteria for the diagnosis of COPD (14): a history of productive cough for 3 mo in each of two successive years and FEV1/VC ratio of less than 60%, the TLC being more than 80% of the predicted value. Furthermore, all the patients were ex-smokers with a history of smoking equivalent to at least 20 pack-years. None of the subjects included in the study had a previous medical history of allergic disease or a significant reversibility of airflow obstruction (> 15% or > 200 ml) after inhalation of 400 µg salbutamol via a metered-dose inhaler. The patients were in a stable state, symptoms of COPD, especially the grade of dyspnea, were unchanged, and the gasometric values had not worsened compared with the best previous values.
Twenty-two patients with COPD (mean age ± SEM, 59 ± 8 yr; 19 male) all of whom were confirmed ex-smokers, were studied (10 had received steroid treatment for at least 3 mo) (Table 1). All the steroid-treated patients were receiving inhaled steroids (n = 3 fluticasone propionate, 500 µg/d; n = 7 beclomethasone, 500 µg/d), and seven of them were receiving oral steroids (prednisolone, 25 ± 5 mg/d). None of 14 nonsmoking control subjects (eight men; age, 33 ± 3 yr) had a history of respiratory or cardiovascular disease. There was no history of upper respiratory tract infection for at least 4 wk before the study in all studied subjects. Considering that cigarette smoke can affect the level of exhaled NO, CO and hydrocarbons, current smokers were excluded from this study. The smoking status of all the subjects was confirmed by nicCheck I (DynaGen, Inc., Cambridge, MA), which detects nicotine and its metabolites in the urine. Active and passive smokers (smoke exposure for more than 30 min/d) were excluded from the study. All patients had at least 1 h of rest before gas measurement, in order to eliminate the effect of any possible exposure to high ethane concentrations (7) during their journey to the hospital.
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Exhaled Ethane
Exhaled air was collected during a flow and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air, as previously described (15). A sample (2 ml) of the collected expired air was analyzed for ethane content using gas chromatography (Chromatograph model PU 4500; Philips, Eindhoven, The Netherlands); column Poropak Q 1-3-m × 4 mm; column temperature, 60° C; injector temperature, 140° C; detector temperature, 160° C; signal output to a CR6A integrator (Shimadzu, Kyoto, Japan). The sensitivity of exhaled ethane measurement was 0.4 ppb.
In a preliminary study the reproducibility of this method was proved by the Bland and Altman test (16). The reproducibility of a method reflects the extent to which a result varies when it is repeated. This variability can be assessed plotting the mean of two measurements against their difference, and the method is considered reproducible if the values are within ± 2 standard deviations of the mean. The reproducibility of ethane measurement was also determined as a coefficient of variation (standard deviation/mean value × 100%). The coefficient of variation of exhaled ethane measured during two successive collections at 5-min intervals (single session variability) was 5.4% (n = 22), whereas between-sessions variability (n = 6, 1-d interval) was 6.2%. The levels of exhaled ethane were strictly exhalation flow-dependent. Six normal subjects and five patients with COPD were instructed to perform a complete exhalation from TLC maintaining two different expiratory flows. Exhaled ethane levels were significantly higher at the lower (5 to 6 L/min) than at the higher exhalation rate (10 to 11 L/min) both in normal subjects (60 ± 8%) and in patients with COPD (65 ± 5%). To reduce the effect of the flow dependency on exhaled ethane levels, all the sample were collected at 10 to 11 L/min. Ethane concentration was equally stable in five polyethylene and five Tedlar reservoirs for 48 h after collection (% increase: 3 ± 1% and 5 ± 2% for the polyethylene and Tedlar reservoirs, respectively).
Exhaled CO and NO Measurements
Exhaled CO was measured by a modified electrochemical sensor with sensitivity from 1 part per million (ppm) to 500 ppm of CO, simultaneously with NO measurement by LR2000 chemiluminescence analyzer (Logan Research Ltd, Rochester, Kent, UK) in order to control exhalation parameters (mouth pressure, 3 ± 0.4 mm Hg; exhalation flow 5 to 6 L/min). The subjects exhaled slowly from TLC over 10 to 15 s trying to keep a constant flow. The mean of two reproducible measurements with less than 5% variation was recorded. Ambient CO was recorded before each measurement and subtracted to the mean value obtained during the maneuvers, as stated by other investigators (17). NO was measured as described previously (18). The response time was 500 ms for NO measurements and the lag time was 1.4 s; therefore, the total response time (lag time + response time) was 1.9 s. This is in compliance with the American Thoracic Society guidelines and European guidelines for exhaled NO measurement, which require a total response time of less than 7 s (18). The response time for CO measurement is < 5 s and the lag time is 200 ms. The accuracy was ± 0.3 ppb for NO and ± 0.2 ppm for CO measurements, this was also in accordance with the European guidelines for exhaled NO measurement (18).
Statistics
All the results were expressed as means ± SEM. Comparisons between groups were made by two-way analysis of variance (ANOVA). A p value < 0.05 was considered significant. The reproducibility of ethane measurement was assessed by the Bland and Altman test (16).
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RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Exhaled Ethane
Ethane levels were elevated in steroid-naïve (2.77 ± 0.25 ppb)
compared with steroid-treated (0.48 ± 0.05 ppb) patients (p < 0.01) and with normal control subjects (0.88 ± 0.09 ppb, p < 0.05) (Figure 1, panel A, and Figure 2). There was a correlation between exhaled ethane and FEV1 in patients not receiving
steroid treatment (r = 0.67, p < 0.05) (Figure 1, panel B).
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Exhaled CO
Exhaled CO levels were similar in untreated (5.99 ± 0.50 ppm) and in steroid-treated (5.96 ± 0.63 ppm) patients (p > 0.05) and higher than in normal subjects (2.8 ± 0.2 ppm, p < 0.05) (Figure 3).
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Exhaled NO
NO levels were similar in untreated patients (11.86 ± 1.27 ppb) compared with steroid-treated patients (9.11 ± 0.53 ppb, p > 0.05), and elevated compared with the control group (6.7 ± 0.5 ppb, p < 0.05) (Figure 4).
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DISCUSSION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We have demonstrated that patients with COPD have elevated levels of exhaled NO, CO, and ethane, and that the latter correlates with disease severity as assessed by FEV1. In addition, we found lower exhaled ethane concentrations in steroid-treated patients than in untreated patients. We interpret these findings as confirmation that oxidative stress and lipid peroxidation are increased in the airways of patients with COPD and we suggest that the measurement of exhaled ethane may be complementary in the noninvasive evaluation of inflammation and oxidative stress in the airways.
Oxidative stress has been implicated in the pathogenesis of
COPD (1, 2). Smoking increases the oxidant-antioxidant imbalance, in part because cigarette smoke itself contains a great
number of ROS such as peroxynitrates and in part because it
increases the number of inflammatory cells in alveoli, which
release ROS such as O2 and hydrogen peroxide (H2O2) (3,
19), causing oxidation of nucleic acids, proteins, and membrane lipids (19). There is evidence for an increased lipid peroxidation in COPD (20, 21) and breath hydrocarbons have
been studied as a measure of its activity (7). Polyunsaturated fatty acids are found in the cellular and subcellular membranes and are prone to lipid peroxidation as a result of the
extremely weak binding of the hydrogen atoms to the carbon
chain. Ethane and pentane are hydrocarbons released during
lipid peroxidation in biological tissues. Ethane specifically results from the effects of free radicals on the omega-3 fatty acids such as 9,12,15-linolenic acid, whereas pentane derives
from the peroxidation of n-6 polyunsaturated acids such as
9,12,15-linoleic and arachidonic acid. Ethane has been used as
a noninvasive marker of lipid peroxidation since the 1960s (11) and has been confirmed as a potential marker of lipid peroxidation in vivo (9). We favor ethane over pentane as a measure of lipid peroxidation because of the more rapid metabolism of pentane and of its difficult chromatographic separation
from isoprene, another product of lipid peroxidation.
We found elevated levels of exhaled ethane in patients with COPD when compared with normal subjects. These results indicate that there is increased lipid peroxidation in COPD, confirming previous studies showing elevated levels of other markers of lipid peroxidation such as urinary and plasma concentrations of 8-isoprostane (20, 21). Furthermore, in keeping with the results of Habib and coworkers (22), who showed that exhaled ethane is correlated with airway obstruction, we found a negative correlation between exhaled ethane and disease severity as assessed by FEV1. This indicates that in patients with more severe COPD lipid peroxidation is more active and may play a major role in the progression of the disease. Spirometric measurements and arterial blood gas determinations are the best predictor of mortality; however, they provide an incomplete picture of the other elements that are important to define the severity and progression of COPD such as inflammation and oxidative stress (1). Therefore, even if the rate of decline of lung function may return to normal in patients with COPD who are ex-smokers, the measurement of exhaled gases may complement the clinical assessment, being a reflection of the underlying activity of the inflammatory process and oxidative stress. Pathologic studies are necessary to confirm this hypothesis.
Age does not influence the levels of ethane in the exhaled breath (9); therefore, the older age of the patients with COPD compared with the control group does not explain the difference in exhaled ethane levels in these two groups. However, exhaled ethane may not be solely of lung origin but may be transported to the lung for elimination. Ethane is in fact produced in other organs such as the intestine, brain, kidney, liver, heart, diaphragm, and testis (23), therefore, the systemic oxidative stress that characterizes COPD (2) may contribute to the final concentration of ethane in the exhaled breath.
The use of steroid treatment in patients with stable COPD is controversial, even though some patients can benefit from it (24). High bronchoalveolar and sputum (25) eosinophils counts have been suggested as predictors of the efficacy of steroid treatment. In the present study, of the 10 patients receiving steroid treatment, seven were receiving oral as well as inhaled steroids and had lower levels of exhaled ethane than the untreated patients. This indicates that steroid treatment reduces lipid peroxidation. Steroids, in fact, by reducing inflammation, attenuating the release of oxidants by inflammatory cells (26), and suppressing proinflammatory cytokines production (27) may reduce lipid peroxidation, and therefore the synthesis of ethane. It is noteworthy that the levels of exhaled NO and CO were not different in the two treatment groups. This may be due to the lack of a suppressive effect of inhaled steroids on the neutrophilic inflammation that characterizes COPD (28), reflected in the constant activation of iNOS and HO-1 and therefore in the high production of NO and CO also in steroid-treated patients. Exhaled ethane is a marker of lipid peroxidation and therefore it reflects the damage of cell membranes caused by reactive oxygen species. On the other hand, exhaled CO and NO are an indirect measurement of oxidative stress mediated by HO and iNOS activity. The different effect of steroid treatment on the level of exhaled gases may be the result of a complex interaction with enzymes and release of ROS by inflammatory cells. The measurement of exhaled ethane, CO, and NO may be complementary, providing an estimate of the intensity of the oxidative stress and the actual cell damage. The combined use of exhaled gases as noninvasive markers of oxidative stress is particularly appealing if one considers that decreasing the inflammatory response may prevent structural damage to the airways.
Nitric oxide (NO) is a gas produced by several types of pulmonary cells, including inflammatory, endothelial, and airway epithelial cells. Elevated levels of exhaled NO in asthma (29) are likely to be due to the activation of the inducible form of NO synthase (iNOS) (30) and therefore may reflect airway inflammation. In COPD the measurement of exhaled NO as a noninvasive marker of inflammation has already been investigated (12, 31). The finding by some investigators of high levels of exhaled NO (12, 31) in patients with stable COPD was not confirmed by others who showed either normal exhaled NO concentrations (32) or even low levels of this gas (33). These disparities may be due to a diversity of methods used for NO measurements such as excretion rate (32) versus single breath (12), or in patient selection with mild (31) versus severe (33) disease. In the present study NO levels were elevated in COPD and were not influenced by steroid treatment in accordance with our previous data (12). The measurement of exhaled NO may provide a noninvasive method to assess airway inflammation also in COPD. Furthermore, because NO levels are correlated with sputum eosinophil counts (25) and that the latter are a predictor of steroid efficacy, NO measurement may be of assistance in the selection of patients who may benefit from steroid treatment.
CO is a product of heme degradation by HO. The inducible form of HO (HO-1) is activated in the alveolar macrophages of asthmatic patients compared with normal subjects (34) as a result of increased oxidative stress. Elevated levels of CO in exhaled air may reflect the degree of HO-1 induction as confirmed by higher levels of CO during allergen challenge (35).
We found high levels of exhaled CO in patients with COPD who were ex-smokers, as previously shown (13). Heme oxygenase is present in the pulmonary vascular endothelium and alveolar macrophages and can be upregulated by oxidative stress and proinflammatory cytokines (5), thus increasing the production of CO. We presume that the high levels of exhaled CO found in patients with COPD are due to inflammatory cytokines or ROS induced HO-1 expression and therefore that the measurement of exhaled CO may reflect inflammation, oxidative stress, or both.
Measurement of exhaled ethane may be another means of detecting and monitoring cytokine and oxidant-mediated inflammation and of assessing anti-inflammatory treatments. In addition to its potential as a marker of oxidative stress, it is possible that the increase in exhaled ethane may be of pathophysiologic significance. Further studies are necessary to investigate the correlation of exhaled ethane with other markers of lipid peroxidation and the clinical utility of exhaled ethane measurement in the follow-up of patients with COPD.
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Footnotes |
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Correspondence and requests for reprints should be addressed to Professor P. J. Barnes, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK. E-mail: p.j.barnes{at}ic.ac.uk
(Received in original form September 7, 1999 and in revised form January 14, 2000).
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References |
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INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers Eur. Respir. J., February 1, 2008; 31(2): 416 - 469. [Abstract] [Full Text] [PDF]
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E. Bathoorn, D-J. Slebos, D. S. Postma, G. H. Koeter, A. J. M. van Oosterhout, M. van der Toorn, H. M. Boezen, and H. A. M. Kerstjens Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study Eur. Respir. J., December 1, 2007; 30(6): 1131 - 1137. [Abstract] [Full Text] [PDF]
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 P. Paredi, S. Ward, D. Cramer, P. J. Barnes, and S. A. Kharitonov Normal Bronchial Blood Flow in COPD Is Unaffected by Inhaled Corticosteroids and Correlates With Exhaled Nitric Oxide Chest, April 1, 2007; 131(4): 1075 - 1081. [Abstract] [Full Text] [PDF]
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P. J. Barnes, B. Chowdhury, S. A. Kharitonov, H. Magnussen, C. P. Page, D. Postma, and M. Saetta Pulmonary Biomarkers in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 6 - 14. [Abstract] [Full Text] [PDF]
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 K Nagai, T Betsuyaku, T Kondo, Y Nasuhara, and M Nishimura Long term smoking with age builds up excessive oxidative stress in bronchoalveolar lavage fluid Thorax, June 1, 2006; 61(6): 496 - 502. [Abstract] [Full Text] [PDF]
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 W. Cao and Y. Duan Breath Analysis: Potential for Clinical Diagnosis and Exposure Assessment Clin. Chem., May 1, 2006; 52(5): 800 - 811. [Abstract] [Full Text] [PDF]
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 H. M. Ochs-Balcom, B. J. B. Grant, P. Muti, C. T. Sempos, J. L. Freudenheim, R. W. Browne, M. Trevisan, L. Iacoviello, P. A. Cassano, and H. J. Schunemann Oxidative Stress and Pulmonary Function in the General Population Am. J. Epidemiol., December 15, 2005; 162(12): 1137 - 1145. [Abstract] [Full Text] [PDF]
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 I. M. Adcock and K. Ito Glucocorticoid Pathways in Chronic Obstructive Pulmonary Disease Therapy Proceedings of the ATS, November 1, 2005; 2(4): 313 - 319. [Abstract] [Full Text] [PDF]
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S. Kanoh, H. Kobayashi, and K. Motoyoshi Exhaled Ethane: An In Vivo Biomarker of Lipid Peroxidation in Interstitial Lung Diseases Chest, October 1, 2005; 128(4): 2387 - 2392. [Abstract] [Full Text] [PDF]
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 P. J. Barnes New approaches to COPD Eur. Respir. Rev., September 1, 2005; 14(94): 2 - 11. [Abstract] [Full Text] [PDF]
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W. MacNee Treatment of stable COPD: antioxidants Eur. Respir. Rev., September 1, 2005; 14(94): 12 - 22. [Abstract] [Full Text] [PDF]
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P. J. Barnes and R. A. Stockley COPD: current therapeutic interventions and future approaches Eur. Respir. J., June 1, 2005; 25(6): 1084 - 1106. [Abstract] [Full Text] [PDF]
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H. Yasuda, M. Yamaya, K. Nakayama, S. Ebihara, T. Sasaki, S. Okinaga, D. Inoue, M. Asada, M. Nemoto, and H. Sasaki Increased Arterial Carboxyhemoglobin Concentrations in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1246 - 1251. [Abstract] [Full Text] [PDF]
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P. Santus, A. Sola, P. Carlucci, F. Fumagalli, A. Di Gennaro, M. Mondoni, C. Carnini, S. Centanni, and A. Sala Lipid Peroxidation and 5-Lipoxygenase Activity in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 838 - 843. [Abstract] [Full Text] [PDF]
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W. MacNee Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 50 - 60. [Abstract] [Full Text] [PDF]
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S. F. P. Man and D. D. Sin Effects of Corticosteroids on Systemic Inflammation in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 78 - 82. [Abstract] [Full Text] [PDF]
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E M Drost, K M Skwarski, J Sauleda, N Soler, J Roca, A Agusti, and W MacNee Oxidative stress and airway inflammation in severe exacerbations of COPD Thorax, April 1, 2005; 60(4): 293 - 300. [Abstract] [Full Text] [PDF]
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P. J. Barnes, I. M. Adcock, and K. Ito Histone acetylation and deacetylation: importance in inflammatory lung diseases Eur. Respir. J., March 1, 2005; 25(3): 552 - 563. [Abstract] [Full Text] [PDF]
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 C M Harrison and C C Andersen Exhaled breath measures of inflammation: are they useful in neonatal chronic lung disease? Arch. Dis. Child. Fetal Neonatal Ed., January 1, 2005; 90(1): F6 - F10. [Abstract] [Full Text] [PDF]
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M. Corradi, P. Pignatti, P. Manini, R. Andreoli, M. Goldoni, M. Poppa, G. Moscato, B. Balbi, and A. Mutti Comparison between exhaled and sputum oxidative stress biomarkers in chronic airway inflammation Eur. Respir. J., December 1, 2004; 24(6): 1011 - 1017. [Abstract] [Full Text] [PDF]
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 P. J. Barnes Mediators of Chronic Obstructive Pulmonary Disease Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548. [Abstract] [Full Text] [PDF]
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S. A. Kharitonov and P. J. Barnes Effects of Corticosteroids on Noninvasive Biomarkers of Inflammation in Asthma and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, November 1, 2004; 1(3): 191 - 199. [Abstract] [Full Text] [PDF]
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G. Beilman Exhaled Nitric Oxide in Pathophysiologic States: The Substance Behind the Gas Chest, January 1, 2004; 125(1): 11 - 13. [Full Text] [PDF]
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 R. Zegdi, O. Fabre, N. Lila, P. Fornes, M. Cambillau, M. Shen, P. Herve, A. Carpentier, and J.-N. Fabiani Exhaled carbon monoxide and inducible heme oxygenase expression in a rat model of postperfusion acute lung injury J. Thorac. Cardiovasc. Surg., December 1, 2003; 126(6): 1867 - 1874. [Abstract] [Full Text] [PDF]
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 G. von Basum, H. Dahnke, D. Halmer, P. Hering, and M. Murtz Online recording of ethane traces in human breath via infrared laser spectroscopy J Appl Physiol, December 1, 2003; 95(6): 2583 - 2590. [Abstract] [Full Text]
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A.W. Boots, G.R.M.M. Haenen, and A. Bast Oxidant metabolism in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 14s - 27s. [Abstract] [Full Text] [PDF]
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P J Barnes Chronic obstructive pulmonary disease * 12: New treatments for COPD Thorax, September 1, 2003; 58(9): 803 - 808. [Full Text] [PDF]
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V. L. Kinnula and J. D. Crapo Superoxide Dismutases in the Lung and Human Lung Diseases Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1600 - 1619. [Abstract] [Full Text] [PDF]
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M. Corradi, I. Rubinstein, R. Andreoli, P. Manini, A. Caglieri, D. Poli, R. Alinovi, and A. Mutti Aldehydes in Exhaled Breath Condensate of Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., May 15, 2003; 167(10): 1380 - 1386. [Abstract] [Full Text] [PDF]
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W A Biernacki, S A Kharitonov, and P J Barnes Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD Thorax, April 1, 2003; 58(4): 294 - 298. [Abstract] [Full Text] [PDF]
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P. Paredi, G. Caramori, D. Cramer, S. Ward, A. Ciaccia, A. Papi, S.A. Kharitonov, and P.J. Barnes Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease Eur. Respir. J., March 1, 2003; 21(3): 439 - 443. [Abstract] [Full Text] [PDF]
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P. Paredi, S. A. Kharitonov, and P. J. Barnes Analysis of Expired Air for Oxidation Products Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S31 - 37. [Abstract] [Full Text] [PDF]
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R. P. Bowler and J. D. Crapo Oxidative Stress in Airways: Is There a Role for Extracellular Superoxide Dismutase? Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S38 - 43. [Abstract] [Full Text] [PDF]
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I. Rahman, A. A. M. van Schadewijk, A. J. L. Crowther, P. S. Hiemstra, J. Stolk, W. MacNee, and W. I. De Boer 4-Hydroxy-2-Nonenal, a Specific Lipid Peroxidation Product, Is Elevated in Lungs of Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., August 15, 2002; 166(4): 490 - 495. [Abstract] [Full Text] [PDF]
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M. J. TOBIN Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2000 Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1789 - 1804. [Full Text] [PDF]
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P. Montuschi, S. A. Kharitonov, and P. J. Barnes Exhaled Carbon Monoxide and Nitric Oxide in COPD Chest, August 1, 2001; 120(2): 496 - 501. [Abstract] [Full Text] [PDF]
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S. A. KHARITONOV and P. J. BARNES Exhaled Markers of Pulmonary Disease Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1693 - 1722. [Full Text] [PDF]
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