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ABSTRACT |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Oxidative stress contributes to airway inflammation and exhaled hydrogen peroxide (H2O2) and nitric oxide (NO) are elevated in asthmatic patients. We determined the concentrations of expired H2O2 and NO in 116 asthmatic (72 stable steroid-naive, 30 stable steroid-treated, and 14 severe steroid-treated unstable patients) and in 35 healthy subjects, and studied the relation between exhaled H2O2, NO, FEV1, airway responsiveness, and eosinophils in induced sputum. Both exhaled H2O2 and NO levels were elevated in steroid-naive asthmatic patients compared with normal subjects (0.72 ± 0.06 versus 0.27 ± 0.04 µM and 29 ± 1.9 versus 6.5 ± 0.32 ppb, respectively; p < 0.001) and were reduced in stable steroid-treated patients (0.43 ± 0.08 µM, p < 0.05, and 9.9 ± 0.97 ppb, p < 0.001). In unstable steroid-treated asthmatics, however, H2O2 levels were increased, but exhaled NO levels were low (0.78 ± 0.16 µM and 6.7 ± 1.0 ppb, respectively). There was a correlation between expired H2O2, sputum eosinophils and airway hyperresponsiveness (methacholine PC20). Exhaled NO also correlated with sputum eosinophils, but not with airway hyperresponsiveness. Our findings indicate that measurement of expired H2O2 and NO in asthmatic patients provides complementary data for monitoring of disease activity.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Oxidative stress, defined as an increased exposure to oxidants
and/or decreased antioxidant capacities, is implicated in airway inflammatory airway diseases, such as chronic obstructive
pulmonary disease (COPD) and asthma (1- 4). Inflammatory
cells, especially eosinophils which produce more superoxide
anions (O2·) than neutrophils or macrophages, release several
reactive oxygen- and nitrogen-derived species such as nitric
oxide (NO). O2· and NO combine to form peroxynitrite (ONOO
),
which is highly reactive and may damage airway epithelium (5). NO has several biological activities in the airways and rapidly reacts to generate peroxynitrite anions (9, 10). O2 is rapidly metabolized to form hydrogen peroxide (H2O2), which diffuses into the
airway lining fluid and may evaporate into exhaled air.
H2O2 in exhaled breath condensate is increased in COPD, adult respiratory distress syndrome, cigarette smokers, and asthma (11), and may be used as a noninvasive marker of oxidative stress. However, the effect of corticosteroids on production of reactive oxygen species (ROS) or H2O2 is not certain. Exhaled NO is another noninvasive marker of airway inflammation, but could be dose-dependently reduced following corticosteroid treatment (17), and may be of limited value in assessment of asthmatic inflammation in patients with asthma treated with steroids. Therefore, we have evaluated the utility these two noninvasive markers of oxidative stress and airway inflammation in asthma of different severity and have compared them with the eosinophils in induced sputum and airway hyperresponsiveness.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects
Four groups of nonsmoking subjects were studied (Table 1). None of
the 35 nonsmoking nonatopic normal subjects had a history of respiratory or cardiovascular disease or was receiving any long-term medication; 72 steroid-naive atopic asthmatic patients were receiving 
2-agonists only as required; 30 stable steroid-treated atopic asthmatic
patients (without asthma symptoms for > 4 wk prior to study with no
history of upper respiratory infection in the last month) were treated
with inhaled corticosteroids; 14 steroid-treated patients (3 nonatopic)
were unstable (peak flow variability > 20%, nocturnal wheezing and
daily asthma symptoms) despite treatment with inhaled and oral steroids. Atopic status was assessed by positive skin prick tests (> 3 mm).
The protocol was approved by the ethics committee of the Royal
Brompton Hospital, and informed consent from each subject was obtained.
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Study Design
Subjects' details were obtained and then baseline spirometry and exhaled NO were measured, followed by collection of expired breath condensate. In some patients, this was followed by methacholine challenge and/or sputum induction.
Expired Breath Condensate and H2O2 Measurement
Expired breath condensate was collected by using a glass condensing device, with an inner glass chamber which contained ice and was suspended
in a larger chamber (Figure 1). Condensate was formed on the outside
surface of the inside glass that was separated from ambient air. After rinsing their mouth, subjects breathed tidally through a mouthpiece connected to the inlet for 15 min while wearing a nose-clip. The mouthpiece
was also used as a saliva trap. Approximately 1 ml of breath condensate
was collected and stored at 
70° C. H2O2 was measured using a colorimetric assay as described previously (20). Briefly, 100 µl of condensate was mixed with 100 µl of 420 µM 3'3'5'5'-tetramethylbenzidine in 0.42 M
citrate buffer pH 3.8 and 10 µl of horseradish peroxidase (52.5 U/ml).
The samples were incubated at room temperature for 20 min and the reaction stopped by the addition of 10 µl of 2 N sulfuric acid. The product
was measured spectrophotometrically (Model AR 8003; Labtech Int.
Ltd., Uckfield, UK) at 450 nm. A standard curve of H2O2 was performed
for each assay with a detection limit of 0.1 µM. In 21 normal subjects the
variation between the H2O2 values on separate days was minor (7.6%).
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Exhaled NO Measurements
Exhaled NO was measured by a chemiluminescence analyzer (Model LR2000; Logan Research, Rochester, UK) as previously described (21, 22). The analyzer is sensitive to NO from 1 (ppb, by volume) to 5,000 ppb, and with a resolution of 0.3 ppb. In addition to NO, the analyzer also measures CO2 (resolution 0.1% CO2; response time, 200 ms) and sample pressure and volume in real time. The analyzer was calibrated using certified NO mixtures (90 ppb and 436 ppb) in nitrogen (BOC Special Gases, Guildford, UK). Measurements of exhaled NO were made by slow exhalation (5-6 L/min) from total lung capacity for 15 to 20 s against a mild resistance to exclude nasal contamination. The value corresponding to the plateau of the end- exhaled CO2 reading (5% CO2) was taken as representative of an alveolar sample. In these measurements the pressure during expiration was kept constant (3 ± 0.4 mm Hg) by using a visual display of expiratory flow measured by pressure and volume sensors in the analyzer.
Sputum Induction
Subjects (n = 32) were instructed to wash their mouth thoroughly with water and then to inhale 3.5% saline nebulized via an ultrasonic nebulizer (De Vilbiss 99; De Vilbiss, Heston, UK). The sputum samples were kept at 4° C for no longer than 2 h prior to processing. The volume of the sample was recorded and the sample was diluted with 2 ml of Hanks' balanced salt solution containing 1% dithiothreitol (Sigma Chemicals, Poole, UK). Total cell counts were done on a hemocytometer using Kimura stain, and slides were made with a cytospin (Shandon, Runcorn, UK) and stained with May-Grunwald-Giemsa stain for differential cell counts.
Pulmonary Function and Methacholine Provocation Test
Forced expiratory volume (FEV1) was measured by a dry spirometer (Vitalograph, Buckingham, UK). Airway responsiveness was assessed by methacholine challenge. After an initial 0.9% NaCl inhalation patients were exposed to doubling concentrations of methacholine delivered as five breaths from a dosimeter (Dosimeter MB3; Mefar, Bovezzo, Italy) at 3-min intervals until FEV1 fell by > 20% from the postsaline value. FEV1 was measured 2 min after each inhalation. The concentration of histamine giving a 20% fall in FEV1 (PC20) was determined by linear interpolation from the log10 concentration-response curve.
Statistical Analysis
Data are given as means ± SEM. Comparisons of H2O2 and NO concentrations between groups were made by Kruskal-Wallis test and subsequent Dunn's multiple comparison test. A two tailed p < 0.05 was considered significant. Spearman correlation tests were performed to detect a correlation between variables.
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RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Normal subjects had the lowest H2O2 levels and it was below the limit of detection in 10 healthy subjects (Table 1). In steroid-naive asthmatic patients, concentrations of exhaled H2O2 and NO were significantly elevated, whereas those well-controlled on inhaled steroid treatment exhibited significantly lower levels of H2O2 and NO in their exhaled air, which were similar to normal values. Unstable asthmatic patients had elevated H2O2 levels in expired condensate, whereas their exhaled NO was similar to levels in normal subjects (Figure 2). There was a negative correlation between H2O2 and PC20 methacholine (Figure 3A), and positive correlation between eosinophil count in induced sputum and H2O2 (Figure 3B) and NO levels (Figure 3C). However, there was no correlation between the concentrations of exhaled NO and PC20 values in these patients. The relationship between H2O2, NO, and FEV1 was assessed in all asthmatic subjects and no correlation was found.
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DISCUSSION |
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INTRODUCTION
METHODS
RESULTS
DISCUSSION
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We have found that levels of exhaled H2O2 and NO were elevated in mild asthmatic patients compared with normal control subjects and were related to the eosinophil differential counts in induced sputum. Exhaled H2O2 levels were also related to airway responsiveness. Expired H2O2 and NO levels were normal in well-controlled asthma patients treated with inhaled corticosteroids, suggesting that these exhaled markers reflect airway inflammation in asthma. However, in unstable severe patients, the levels of exhaled H2O2 were elevated, while exhaled NO levels were normal.
The concentrations of exhaled H2O2 measured in normal subjects were similar to those reported in previous studies (11, 13). In asthmatic patients, the mean level of exhaled H2O2 (0.72 µM) is also comparable to levels obtained previously from stable asthmatic children (0.8 µM) (14). However, higher levels have been reported in patients with an exacerbation of asthma (1.5 µM) (15).
Increased oxidative stress is implicated in asthma (7) and this may be reflected by expired H2O2. An increased concentration of exhaled H2O2 may represent an increased production of oxidants and/or a reduced free radical scavenging capacity in asthmatic airways. Oxygen radicals may contribute to epithelial shedding, release of inflammatory mediators, and development of airway hyperresponsiveness. Thus, a close relationship between O2· produced by circulating neutrophils and the degree of airway hyperresponsiveness has been shown in asthmatic patients (23). Furthermore, peroxynitrite formed by a reaction between O2· and NO causes airway hyperresponsiveness in animals (24). Indeed, we found a significant correlation between exhaled H2O2 concentrations and the degree of airway hyperresponsiveness to methacholine in our patients.
Activation of inflammatory cells, and particularly eosinophils, is a key feature of asthmatic inflammation (4, 7), and may be reflected by eosinophils in induced sputum (18, 25). In the present study, we found a significant correlation between exhaled H2O2 and NO and eosinophil counts in induced sputum. Because eosinophil differential counts in sputum have been shown to relate to the intensity of airway inflammation in asthma measured in bronchial biopsies and to the severity of the disease (25, 26), this relationship supports the use of expired H2O2 and NO in assessing airway inflammation in asthmatic patients.
However, measurement of exhaled H2O2 and NO may give different information about the inflammatory process. Although almost all of the steroid-naive asthmatic patients had elevated levels of exhaled NO, only approximately 70% of them had increased levels of exhaled H2O2, suggesting that in some patients there is no overproduction of oxidants. This finding implies that measurement of exhaled NO is a more sensitive technique in diagnosing asthma, but that not all of these patients have enhanced oxidative stress. Some of these patients did not need to use a bronchodilator for several months before the study, although they were diagnosed as asthmatic and had airway hyperresponsiveness. In patients well-controlled with inhaled steroids, both exhaled NO and H2O2 showed a similar pattern. Corticosteroids inhibit the oxidative burst of leukocytes and also inhibit expression of inducible nitric oxide synthase resulting in a reduction of exhaled H2O2 and NO. Steroid treatment also inhibits eosinophil recruitment to the airways, therefore it may influence exhaled mediator levels by preventing the influx of H2O2 and NO producing cells. The differences in exhaled H2O2 levels between the inhaled steroid-naive and the steroid-treated patients imply differences in oxidative stress between these two groups. However, in severe unstable asthmatics, exhaled H2O2 levels were elevated, despite the use of high doses of inhaled and of oral steroids, whereas concentrations of exhaled NO were almost normal. Thus, the patients with severe asthma who are still symptomatic presumably have ongoing inflammation as reflected by sputum eosinophil despite steroid therapy, whereas exhaled NO is normalized since iNOS induction sensitive to steroids, while oxidative stress is still present because of the residual inflammation.
In summary, our study shows that the levels of exhaled H2O2 and NO are elevated in asthmatic patients and this is related to other indices of airway inflammation. The fact that expired H2O2 is elevated in patients with severe asthma not well controlled on high doses of inhaled steroids, whereas exhaled NO is normal, indicates that this measurement may be more useful in monitoring control of asthmatic inflammation.
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Footnotes |
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Correspondence and requests for reprints should be addressed to Professor P. J. Barnes, M.A., D.M., D.Sc., F.R.C.P., Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK.
(Received in original form October 28, 1997 and in revised form May 6, 1998).
Dr. Horváth was supported by the European Respiratory Society and the Hungarian National Scientific Research Foundation (OTKA-F017050), Dr. Donnelly by the National Asthma Campaign (UK), and Dr. Kharitonov by the British Lung Foundation.Acknowledgments: The authors thank Julaiha Mohamed and Susan Woollett for their excellent technical help.
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References |
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INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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1. Rahman, I., D. Morrison, K. Donaldson, and W. MacNee. 1996. Systemic oxidative stress in asthma, COPD and smokers. Am. J. Respir. Crit. Care Med. 154: 1055-1060 [Abstract].
2.
Repine, J. E.,
A. Bast,
I. Lankhorst, and
the Oxidative Stress Study
Group.
1997.
Oxidative stress in chronic obstructive pulmonary disease. State of art.
Am. J. Respir. Crit. Care Med.
156:
341-357
3. Halliwell, B., J. M. C. Gutteridge, and C. E. Cross. 1992. Free radicals, antioxidants and human disease: where are we now? J. Lab. Clin. Med. 119: 598-620 [Medline].
4. Djukanovic, F., W. R. Roche, J. W. Wilson, C. R. W. Beasley, O. P. Twentyman, P. H. Howarth, and S. T. Holgate. 1990. Mucosal inflammation in asthma. Am. Rev. Respir. Dis. 142: 434-457 [Medline].
5. Kallenbach, J., R. Baynes, B. Fine, D. Dajee, and W. Bezwoda. 1992. Persistent neutrophil activation in mild asthma. J. Allergy Clin. Immunol. 90: 272-274 [Medline].
6. Royal, I. J. A., N. W. Kooy, and J. S. Beckman. 1996. Peroxynitrite and other nitric oxide-derived oxidants. In W. M. Zapol and K. D. Bloch, editors. Nitric Oxide and the Lung. Marcel Dekker, New York. 223-246.
7. Barnes, P. J.. 1990. Reactive oxygen species and airway inflammation. Free Rad. Biol. Med. 9: 235-243 [Medline].
8.
Beckman, J. S., and
W. H. Koppenol.
1996.
Nitric oxide, superoxide, and
peroxynitrite: the good, the bad, and ugly.
Am. J. Physiol.
271:
C1424-C1437
9. Moncada, S., R. J. M. Palmer, and E. A. Higgs. 1991. Nitric oxide: physiology and pharmacology. Pharmacol. Rev. 43: 109-142 [Medline].
10. Darley-Usmar, V., H. Wiseman, and B. Halliwell. 1995. Nitric oxide and oxygen radicals: a question of balance. FEBS Lett. 369: 131-135 [Medline].
11. Baldwin, S. R., C. M. Grum, L. A. Boxer, R. H. Simon, L. H. Ketai, and L. J. Devall. 1986. Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet 1: 11-14 [Medline].
12.
Sznajder, J. I.,
A. Fraiman,
J. B. Hall,
W. Sanders,
G. Schmidt,
G. Crawford,
A. Nahum,
P. Factor, and
L. D. H. Wood.
1989.
Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic
respiratory failure.
Chest
96:
606-612
13. Dekhuijzen, P. N., K. K. H. Aben, I. Dekker, L. P. H. J. Aarts, P. L. M. L. Wielders, C. L. A. Van Herwaarden, and A. Bast. 1996. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary diseases. Am. J. Respir. Crit. Care Med. 154: 813-816 [Abstract].
14. Jöbsis, Q., H. C. Raatgeep, P. W. M. Hermans, and J. C. de Jongste. 1997. Hydrogen peroxide in exhaled air is increased in stable asthmatic children. Eur. Respir. J. 10: 519-521 [Abstract].
15. Dohlman, A. W., H. R. Black, and J. A. Royall. 1993. Expired breath hydrogen peroxide is a marker of acute airway inflammation in pediatric patients with asthma. Am. Rev. Respir. Dis. 148: 955-960 [Medline].
16. Horvath, I., L. E. Donnelly, S. A. Kharitonov, S. Lim, K. F. Chung, and P. J. Barnes. 1997. Non-invasive markers of airway inflammation in asthmatic patients. Int. Rev. Allergol. Clin. Immunol. 3(Suppl. 1):17.
17. Alving, K., E. Witzberg, and J. M. Lundberg. 1993. Increased amount of nitric oxide in exhaled air of asthmatics. Eur. Respir. J. 6: 1268-1270 .
18. Kharitonov, S. A., D. Yates, R. A. Robbins, R. Logan-Sinclair, E. Shineboume, and P. J. Barnes. 1994. Increased nitric oxide in exhaled air of asthmatic patients. Lancet 343: 133-135 [Medline].
19. Kharitonov, S. A., D. Yates, and P. J. Barnes. 1996. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am. J. Respir. Crit. Care Med. 153: 454-457 [Abstract].
20. Gallati, H., and I. Pracht. 1985. Horseradish peroxidase: kinetic studies and optimization of peroxidase activity determination using the substrates H2O2 and 3,3',5,5'-tetramethylbenzidine. J. Clin. Chem. Clin. Biochem. 23: 453-460 [Medline].
21. Kharitonov, S. A., K. F. Chung, D. Evans, B. J. O'Connor, and P. J. Barnes. 1996. Increased exhaled nitric oxide in asthma is mainly derived from the lower respiratory tract. Am. Rev. Respir. Dis. 153: 1773-1780 .
22. Kharitonov, S. A., K. Alving, and P. J. Barnes. 1997. Exhaled and nasal nitric oxide measurements: recommendations. Eur. Respir. J. 10: 1683-1693 [Medline].
23. Joseph, B. Z., J. M. Routes, and L. Borish. 1993. Activities of superoxide dismutase and NADPH oxidase in neutrophils obtained from asthmatics and normal donors. Inflammation 17: 361-370 [Medline].
24. Sadeghi-Hashjin, G., G. Folkerts, P. A. J. Henricks, A. K. C. P. Verheyen, H. J. van der Linde, I. Van Ark, A. Coene, and F. P. Nijkamp. 1996. Peroxynitrite induces airway hyperresponsiveness in guinea pigs in vitro. Am. J. Respir. Crit. Care Med. 153: 1697-1701 [Abstract].
25. Fahy, J. V., J. Liu, H. Wong, and H. A. Boushey. 1993. Cellular and biochemical analysis of induced sputum from asthmatics and from healthy subjects. Am. Rev. Respir. Dis. 147: 1126-1131 [Medline].
26. Ronchi, M. C., C. Piragino, E. Rosi, L. Stendardi, A. Taninti, G. Galli, R. Duranti, and G. Scano. 1997. Do sputum eosinophils and ECP relate to the severity of asthma? Eur. Respir. J. 10: 1809-1813 [Abstract].
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R. Pawliczak, X.-L. Huang, U. B. Nanavaty, M. Lawrence, P. Madara, and J. H. Shelhamer Oxidative Stress Induces Arachidonate Release from Human Lung Cells through the Epithelial Growth Factor Receptor Pathway Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 722 - 731. [Abstract] [Full Text] [PDF]
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A. Emelyanov, G. Fedoseev, O. Krasnoschekova, A. Abulimity, T. Trendeleva, and P.J. Barnes Treatment of asthma with lipid extract of New Zealand green-lipped mussel: a randomised clinical trial Eur. Respir. J., September 1, 2002; 20(3): 596 - 600. [Abstract] [Full Text] [PDF]
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K. Kostikas, G. Papatheodorou, K. Ganas, K. Psathakis, P. Panagou, and S. Loukides pH in Expired Breath Condensate of Patients with Inflammatory Airway Diseases Am. J. Respir. Crit. Care Med., May 15, 2002; 165(10): 1364 - 1370. [Abstract] [Full Text] [PDF]
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 A. Schwingshackl, R. Moqbel, and M. Duszyk Nitric oxide activates ATP-dependent K+ channels in human eosinophils J. Leukoc. Biol., May 1, 2002; 71(5): 807 - 812. [Abstract] [Full Text] [PDF]
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T J Warke, P S Fitch, V Brown, R Taylor, J D M Lyons, M Ennis, and M D Shields Exhaled nitric oxide correlates with airway eosinophils in childhood asthma Thorax, May 1, 2002; 57(5): 383 - 387. [Abstract] [Full Text] [PDF]
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S. Loukides, D. Bouros, G. Papatheodorou, P. Panagou, and N. M. Siafakas The Relationships Among Hydrogen Peroxide in Expired Breath Condensate, Airway Inflammation, and Asthma Severity Chest, February 1, 2002; 121(2): 338 - 346. [Abstract] [Full Text] [PDF]
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A. Emelyanov, G. Fedoseev, A. Abulimity, K. Rudinski, A. Fedoulov, A. Karabanov, and P. J. Barnes Elevated Concentrations of Exhaled Hydrogen Peroxide in Asthmatic Patients Chest, October 1, 2001; 120(4): 1136 - 1139. [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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S. LIM, D. GRONEBERG, A. FISCHER, T. OATES, G. CARAMORI, W. MATTOS, I. ADCOCK, P. J. BARNES, and K. F. CHUNG Expression of Heme Oxygenase Isoenzymes 1 and 2 in Normal and Asthmatic Airways . Effect of Inhaled Corticosteroids Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1912 - 1918. [Abstract] [Full Text]
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L. M. van den TOORN, J.-B. PRINS, S. E. OVERBEEK, H. C. HOOGSTEDEN, and J. C. de JONGSTE Adolescents in Clinical Remission of Atopic Asthma Have Elevated Exhaled Nitric Oxide Levels and Bronchial Hyperresponsiveness Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 953 - 957. [Abstract] [Full Text]
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G. L. LARSEN and P. G. HOLT The Concept of Airway Inflammation Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): S2 - 6. [Full Text] [PDF]
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J. C. de JONGSTE and K. ALVING Gas Analysis Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): S23 - 27. [Full Text] [PDF]
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M. Silvestri, D. Spallarossa, E. Battistini, V. Brusasco, and G. A Rossi Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma Thorax, June 1, 2000; 55(6): 484 - 488. [Abstract] [Full Text]
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J. A. NIGHTINGALE, D. F. ROGERS, K. FAN CHUNG, and P. J. BARNES No Effect of Inhaled Budesonide on the Response to Inhaled Ozone in Normal Subjects Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 479 - 486. [Abstract] [Full Text]
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J. A Nightingale, D. F Rogers, and P. J Barnes Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects Thorax, December 1, 1999; 54(12): 1061 - 1069. [Abstract] [Full Text]
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B. D. Johnson, K. C. Beck, R. J. Zeballos, and I. M. Weisman Advances in Pulmonary Laboratory Testing Chest, November 1, 1999; 116(5): 1377 - 1387. [Abstract] [Full Text] [PDF]
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