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Vol. 69, No. 3, 2002
Issue release date: May–June 2002
Respiration 2002;69:211–216
(DOI:10.1159/000063622)

Variability of Exhaled Hydrogen Peroxide in Stable COPD Patients and Matched Healthy Controls

van Beurden W.J.C.a · Dekhuijzen P.N.R.c · Harff G.A.b · Smeenk F.W.J.M.a
aDepartment of Pulmonology, and bDepartment of Clinical Chemistry, Catharina Hospital Eindhoven, and cDepartment of Pulmonology, University Medical Center Nijmegen, The Netherlands
email Corresponding Author

Abstract

Background: Because inflammation induces oxidative stress, exhaled hydrogen peroxide (H2O2), which is a marker of oxidative stress, may be used as a non-invasive marker of airway inflammation in chronic obstructive pulmonary disease (COPD). There are no data on the circadian variability of exhaled H2O2 in COPD patients. Objective: The aim of this study was to investigate the variability of the H2O2 concentration in breath condensate of stable COPD patients and of matched healthy control subjects. Methods: We included 20 patients with stable mild COPD (forced expiratory volume in 1 s ∼70% of predicted) and 20 healthy subjects, matched for age, sex and pack-years, all smokers or ex-smokers. Breath condensate was collected and its H2O2 concentration determined fluorometrically three times on day 0 (9 and 12 a.m., and 3 p.m.) and once on days 1, 2, 3, 8 and 21. Results: The mean H2O2 concentration increased significantly during the day in both the patient and control groups (p = 0.02 and p < 0.01, respectively). Over a longer period up to 21 days, the mean concentration did not change in both groups. There was no significant difference between patients and controls. The mean coefficient of variation over 21 days was 45% in the patient group and 43% in the control group (p = 0.8). Conclusions: The exhaled H2O2 concentration increased significantly during the day in both stable COPD patients and controls. Over a period of 3 weeks, the mean H2O2 concentration did not change and the variability within the subjects was similar in both groups.


 Outline


 goto top of outline Key Words

  • Chronic obstructive pulmonary disease
  • Hydrogen peroxide
  • Oxidative stress
  • Variability

 goto top of outline Abstract

Background: Because inflammation induces oxidative stress, exhaled hydrogen peroxide (H2O2), which is a marker of oxidative stress, may be used as a non-invasive marker of airway inflammation in chronic obstructive pulmonary disease (COPD). There are no data on the circadian variability of exhaled H2O2 in COPD patients. Objective: The aim of this study was to investigate the variability of the H2O2 concentration in breath condensate of stable COPD patients and of matched healthy control subjects. Methods: We included 20 patients with stable mild COPD (forced expiratory volume in 1 s ∼70% of predicted) and 20 healthy subjects, matched for age, sex and pack-years, all smokers or ex-smokers. Breath condensate was collected and its H2O2 concentration determined fluorometrically three times on day 0 (9 and 12 a.m., and 3 p.m.) and once on days 1, 2, 3, 8 and 21. Results: The mean H2O2 concentration increased significantly during the day in both the patient and control groups (p = 0.02 and p < 0.01, respectively). Over a longer period up to 21 days, the mean concentration did not change in both groups. There was no significant difference between patients and controls. The mean coefficient of variation over 21 days was 45% in the patient group and 43% in the control group (p = 0.8). Conclusions: The exhaled H2O2 concentration increased significantly during the day in both stable COPD patients and controls. Over a period of 3 weeks, the mean H2O2 concentration did not change and the variability within the subjects was similar in both groups.

Copyright © 2002 S. Karger AG, Basel


goto top of outline introduction

Airway inflammation and oxidative stress have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) [1, 2, 3]. The presence of inflammation in the (peripheral) airways of COPD patients has been demonstrated by analyses of sputum induction, transbronchial biopsies and bronchoalveolar lavage. Biopsies from the lungs of COPD patients and smokers contained an increased number of neutrophils [4, 5]. These investigations provide direct information about the level of airway inflammation, but are invasive for patients and thus not very suitable for determining the severity of COPD or for evaluating the effect of therapy in clinical practice.

Besides airway inflammation, oxidative stress plays an important role in the pathogenesis of COPD. Oxidative stress is caused by an imbalance between the production of oxidants and the presence of antioxidants. Oxidants are produced in the lungs by inflammatory cells, especially neutrophils and macrophages [6]. An important exogenous source of oxidants in COPD patients is cigarette smoke. Oxidants deactivate antiproteases that protect the lungs against proteases like elastase. Elastase can damage alveoli, stimulate inflammation, impair healing and produce surfactant abnormalities. Oxidants also increase mucus production by epithelial cells and impair cilia function [2].

The level of pulmonary oxidative stress may be used as an indirect marker of airway inflammation. It can be determined by measuring the hydrogen peroxide concentration in exhaled breath condensate [7, 8, 9, 10, 11, 12]. This is a rather simple and non-invasive procedure. Several investigators found that the H2O2 concentration was significantly elevated in patients with mild stable COPD compared to healthy non-smoking control persons and that it was further increased in COPD patients during acute exacerbation [7, 12, 13].

Although H2O2 exhalation has been studied by several investigators, there are few data on variability within 1 day and over a longer period of time. To investigate if the H2O2 concentration may be a suitable measurement for the follow-up of COPD patients, it is necessary to elucidate the variability of the H2O2 concentration in exhaled breath condensate over time. This study was therefore performed to determine the variability in the H2O2 concentration in exhaled air in stable COPD patients and in matched healthy controls.

 

goto top of outline patients and methods

goto top of outline patients

We recruited stable COPD patients from the outclinic with no increase in symptoms over the last 3 months. Inclusion criteria were: age between 45 and 85 years, a diagnosis of COPD according to the European Respiratory Society criteria [14] and current smokers or ex-smokers with at least 10 pack-years.

Patients were excluded if they had signs of upper respiratory tract infections, another pulmonary disease at present or in the past possibly contributing to chronic airflow obstruction, or any other significant medical disease that could influence the study results. They were not allowed to use vitamin C, E, acetylcystein, inhaled or systemic corticosteroids and theophylline for at least 1 month before the study.

The study was approved by the local Ethics Committee of the hospital, and all subjects gave informed consent.

goto top of outline control group

The inclusion criteria for the control group were: healthy males and females between 45 and 85 years of age, normal lung function tests [forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) within 1.64 × standard deviation], current smokers or ex-smokers with at least 10 pack-years. The controls were not allowed to have any pulmonary or non-pulmonary disease that could influence the study, or complaints of chronic cough and/or dyspnea, or atopic complaints.

Each patient was matched with a healthy control person regarding sex, age (± 5 years) and pack-years (± 5 pack-years).

goto top of outline study design

The H2O2 concentration in breath condensates was measured several times in all patients and controls. The concentration was measured three times on day 0 with an interval of 3 h (9 and 12 a.m. and 3 p.m.). In addition, the H2O2 concentration was measured once on days 1, 2, 3, 8 and 21 at the same time each day for each subject (some in the morning, some in the afternoon). Patients were withdrawn from the study if they developed an exacerbation.

To confirm the current smoking status, cotinine concentration in the urine was measured. In both groups flow-volume curves were measured. In the patient group we also measured postbronchodilator FEV1 (after inhalation of 400 μg salbutamol by pressurized metered dose inhaler). The measurements of exhaled H2O2 were performed 30 min after the lung function tests.

goto top of outline measurement of exhaled h2o2

All subjects were asked not to drink coffee or tea during visit days, since these beverages have been shown to contain oxidants. Otherwise they were allowed to drink and eat normally before and during visit days. The current smokers were told to refrain from smoking during visit days, starting at midnight before each visit day. Before each measurement the subjects rinsed their mouth with water.

The patients and control persons breathed tidally during 10 min into a mouthpiece connected to a valve system. The expiration valve was connected to a bulb, which was constantly cooled by flowing ice water. At the end of the bulb cooler, the condensate was collected into a glass container, with an air volume meter attached to a side opening at the bottom of the cooler. The valve system was heated to >37°C with a stream of hot air to avoid condensation on the valves and to make sure that all of the condensate formed could be collected (the influence of heating of the system on the stability of exhaled H2O2 was not tested). The device was cleaned with distilled water each time before and after the measurement (without drying the collecting system).

The condensate was immediately transported to the laboratory in a sealed glass container. First of all, the volume of the condensate was measured and subsequently the reagents were added (within 30 min). To 250 μl condensate, 10 μl p-hydroxyphenylacetic acid and 10 μl horseradish peroxidase (15 U/l) were added (modified according to Hyslop and Sklar [15]). The reaction product (dimer 2,2′-dihydroxybiphenyl-5,5′diacetate) was frozen at –70°C.

Every 2 weeks the reaction products were measured fluorometrically. The fluorescence of the reaction product was measured with an automated sampler, flow injection and scanning fluorescence detector from Waters, Millipore (Milford, Mass., USA), with an excitation wavelength of 295 nm and an emission wavelength of 405 nm. The reaction product was injected into the fluorometer which produced a curve and the fluorescence was presented by the area under the curve. The detection limit was 0.02 μmol/l H2O2.

In a previous study, we showed that this procedure was reproducible, that the sensitivity of the method of analysis was good and that there was no effect of storage on the H2O2 concentration up to 40 days [16]. In addition, we compared the total volume of exhaled air and the number of breaths with the exhaled H2O2 concentration and found no correlation. Therefore, we did not control the expiratory flow in the present study.

goto top of outline cotinine measurement

To establish the actual smoking status of all patients and controls, we measured the cotinine concentration in morning urine. The concentration in non-smokers is below 1 mg/l; in current smokers it is >3 mg/l. The cotinine concentration was measured colorimetrically [17, 18]. In short, 1 ml centrifuged urine was mixed with acetate buffer, potassium cyanide, chloramine T and diethylthiobarbituric acid. The extinction of the specimen was measured at 532 nm. The subjects were categorized as current or ex-smokers according to their cotinine concentration, because this is an objective measurement (the results from the cotinine measurements were only known at the end of the study).

goto top of outline statistical analysis

Data are expressed as means ± SEM. To investigate the variability in the H2O2 concentration in exhaled breath condensate during the day, we compared the mean H2O2 concentration at 9 a.m. with the mean concentration at 12 a.m. and 3 p.m. using the paired Student’s t test. To investigate the variability over a longer time period, we compared the mean H2O2 concentration measured on day 1 with that of days 2, 3, 8 and 21 using the paired Student’s t test, for both groups. We determined the intra-individual variability by calculating the coefficient of variation (CV) over the study period: SD/mean × 100. We used the unpaired Student’s t test to compare the mean H2O2 concentrations and mean differences between the patient group and the control group. A p value of 0.05 was considered to be statistically significant.

We performed these tests for the whole patient and control groups, respectively, and for subgroups according to the smoking status.

 

goto top of outline results

goto top of outline study population

Twenty patients and 20 healthy controls were studied. Characteristics of the study population are shown in table 1. One patient was withdrawn from the study after day 0 because of an exacerbation. The matching control person was also excluded from the analysis after day 0.

TAB01

Table 1. Characteristics of the patients and controls

goto top of outline cotinine measurement

All patients and control persons were asked if they were current smokers or ex-smokers. We checked this by determining the cotinine concentration in the urine. All but 2 outcomes were compatible, these 2 were left out of the subanalysis according to the smoking status.

goto top of outline variability in the h2o2 exhalation

Patient Group. The mean H2O2 concentrations were 0.22 ± 0.02 μmol/l at 9 a.m., 0.30 ± 0.03 μmol/l at 12 a.m. and 0.36 ± 0.06 μmol/l at 3 p.m. The differences compared to the value at 9 a.m. were significant (p = 0.02 and p = 0.02, respectively; fig. 1). The SEM appeared to be smallest at 9 a.m. The mean H2O2 concentration increased during the day in both the current smokers and the ex-smokers, though not significantly.

FIG01

Fig. 1. The H2O2 concentration in the group of stable COPD patients and in the group of matched healthy controls at three time points of a day. Error bars represent means ± SEM. n = Number of subjects. * p < 0.05.

The mean H2O2 concentrations on days 1, 2, 3, 8 and 21 were 0.28 ± 0.04, 0.30 ± 0.03, 0.30 ± 0.03, 0.30 ± 0.05 and 0.26 ± 0.04 μmol/l, respectively. These concentrations were not significantly different (p = 0.69, 0.63, 0.75 and 0.67, respectively; fig. 2). The mean CV over the study period was 45%.

FIG02

Fig. 2. The H2O2 concentration in the group of stable COPD patients and in the group of matched healthy controls measured on days 1–21 (differences were not significant). Error bars represent means ± SEM. n = Number of subjects.

Control Group. The mean H2O2 concentrations were 0.23 ± 0.02 μmol/l at 9 a.m., 0.30 ± 0.04 μmol/l at 12 a.m. and 0.35 ± 0.04 μmol/l at 3 p.m.

The differences in concentration compared to 9 a.m. were significant (p = 0.04 and p < 0.01, respectively; fig. 1). The SEM appeared to be smallest at 9 a.m. The mean H2O2 concentration increased during the day in both the current and the ex-smokers, though not significantly.

The H2O2 concentrations on days 1, 2 ,3, 8 and 21 were 0.28 ± 0.04, 0.23 ± 0.03, 0.27 ± 0.04, 0.28 ± 0.05 and 0.27 ± 0.03 μmol/l, respectively. These concentrations were not significantly different (p = 0.10, 0.79, 0.97 and 0.82, respectively; fig. 2). The mean CV over the study period was 43%.

goto top of outline differences between patients and controls

The mean H2O2 concentration on day 0 (mean of measurements at 9 and 12 a.m., and 3 p.m.) in the patient group (0.28 μmol/l) did not significantly differ from the mean H2O2 concentration on day 0 in the control group (0.29 μmol/l: p = 0.8). There was also no significant difference between the patient and control groups in the mean H2O2 concentrations measured at 9 a.m. This was also the case for all other days.

 

goto top of outline discussion

The H2O2 concentration in exhaled breath condensate increased significantly over the day in both patients and healthy controls (in both current smokers and ex-smokers). The variability within both groups appeared to be the smallest at 9 a.m. Over a period of several days and weeks, the mean H2O2 concentration did not change significantly, but the intra-individual variability was high (> 40%). There was no significant difference in H2O2 concentration between the stable COPD patients and matched healthy controls.

The method applied to measure the exhaled H2O2 concentration was valid and reproducible [16]. Therefore, the variability in H2O2 concentration we observed in this study had to originate from biological mechanisms. There are several factors that could play a role.

First, there is some evidence that the H2O2 concentration in breath condensate is influenced by the intake of food and drinks or by exercise. Substantial amounts of H2O2 can be present in several beverages like instant coffee [19]. Also exercise may play a role. An increased production of oxidants in the serum of COPD patients has been demonstrated during exercise [20]. Exhaled NO, which is another marker of inflammation [C1], is increased during exercise in patients with stable COPD as well as in healthy persons [21].

Another explanation for the high daily variability may be the presence of a circadian rhythm in the activity of the inflammatory cells. Recently, Nowak et al. [22] have shown a circadian rhythm of exhaled H2O2 in healthy subjects. They postulated that several mechanisms might be involved in this circadian rhythm, including possible fluctuations in the number and activity of phagocytes and epithelial cells to produce H2O2, diurnal changes in leukocyte receptors [23] and in circulating levels of adhesion molecules [24] and circadian rhythms in antioxidant capacities [25].

Some indirect information that may point into this direction is a study performed by Wojnarowski et al. [26]. They found a relatively high intra-individual variability in the concentrations of eosinophil cationic protein in nasal lavages, but not a clear circadian rhythm.

In this study, we found a mean CV of 45 and 43% for the patient and control groups, respectively, representing the intra-individual variability. Few studies have investigated the variability in exhaled biomarkers. One study investigating the variability in exhaled NO showed a CV of 16.8% over a period of 23 days in healthy non-smoking subjects [27]. In another study, the intra-individual variability in exhaled H2O2 was tested at three expiratory flow rates over a period ranging from 1 to 40 days. The CV was 68, 62 and 82%, respectively [28]. The variability appears to be higher for exhaled H2O2 than for exhaled NO. Our data show that the variability may be smaller when samples are obtained early in the morning.

Although not the aim of the present study, we found, in contrast to other investigators, no significant difference in H2O2 concentrations between stable COPD patients and healthy controls. Previous investigators showed that the exhaled H2O2 concentration in stable COPD patients was significantly higher than the concentration in healthy controls [7, 12, 13]. The difference between those studies and the present study is that in previous studies the controls were (young) healthy never-smokers, while we compared stable COPD patients with current or ex-smokers of the same age. This may indicate that the H2O2 concentration is influenced not only by chronic airway inflammation, but also by age and/or smoking history. Indeed, Nowak et al. [22] found a positive correlation between age and exhaled H2O2 in healthy controls. If we want to use exhaled H2O2 as a diagnostic marker for COPD in clinical practice, we will need comparisons between COPD patients and healthy controls of comparable age and smoking habits.

In conclusion, the H2O2 concentration increased significantly during the day in stable COPD patients as well as in healthy controls. The high variation indicates that the H2O2 concentration is not only determined by the pulmonary oxidative status, but also by other factors, which are still unclear. The present data suggest that the influence of these factors may be smaller early in the morning, which is of importance when using H2O2 as an effective parameter in intervention studies.

 

goto top of outline acknowledgments

The authors would like to thank Maria van den Bosch for her effort.


 goto top of outline References
  1. Barnes PJ: Chronic obstructive pulmonary disease. N Engl J Med 2000;343:269–280.
  2. Repine E, Bast A, Lankhorst I: Oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:341–357.
  3. Kerstjens HAM: Stable chronic obstructive pulmonary disease. BMJ 1999;319:495–499.
  4. O’Byrne PM, Postma DS: Airway inflammation in asthma and COPD. Am J Respir Crit Care Med 1999;159:S50–S51.
  5. Rutgers SR, Timens W, Kaufmann HF: Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. Eur Respir J 2000;15:109–115.
  6. Hangen TS, Skjonsberg OH, Kahler H, Lyberg T: Production of oxidants in alveolar macrophages and leukocytes. Eur Respir J 1999;14:1100–1105.
  7. Nowak D, Kasielski M, Antczak A, Pietras T, Bialasiewicz P: Increased content of thiobarbituric acid-reactive substances and hydrogen peroxide in the expired breath condensate of patients with stable chronic obstructive pulmonary disease: No significant effect of cigarette smoking. Respir Med 1999;93:389–396.
  8. Sznajder JI, Fraiman A, Hall JB, Sanders W, Schmidt G: Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure. Chest 1989;96:606–612.
  9. Jobsis Q, Raatgeep HC, Hermans PWM, de Jongste WM: Hydrogen peroxide in exhaled air is increased in stable asthmatic children. Eur Respir J 1997;10:519–521.
  10. Loukides S, Horvath I, Wodehouse T, Cole PJ, Barnes PJ: Elevated levels of expired breath hydrogen peroxide in bronchiectasis. Am J Respir Crit Care Med 1998;158:991–994.
  11. Kietzmann D, Kahl R, Muller M, Burchardi R, Kettler D: Hydrogen peroxide in expired breath condensate of patients with acute respiratory failure and with ARDS. Intensive Care Med 1993;19:78–81.
  12. Dekhuijzen PNR, Aben KKH, Dekker I, Aarts PHJ, Wielders PML, van Herwaarden CLA, Bast A: Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;145:813–816.
  13. De Benedetto F, Aceto A, Dragani B, Spacone A, Formisano S, Cocco R, Sanguinetti CM: Validation of a new technique to assess exhaled hydrogen peroxide: Results from normals and COPD patients. Monaldi Arch Chest Dis 2000;55:185–188.

    External Resources

  14. Siakakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, Yernault JC, Decramer M, Higenbottam T, Postma DS, et al: Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995;8:1398–1420.
  15. Hyslop PA, Sklar LA: A quantitative fluorimetric assay for the determination of oxidant production by polymorphonuclear leukocytes: Its use in the simultaneous fluorimetric assay of cellular activation processes. Anal Biochem 1984;141:280–286.
  16. van Beurden WJC, Harff GA, Dekhuijzen PNR, van den Bosch MJA, Creemers JPHM, Smeenk FWJM: An efficient and reproducible method for measuring exhaled hydrogen peroxide in exhaled breath condensate. Respir Med, accepted.
  17. Peach H, Ellard GA, Jenner PJ, Morris RW: A simple, inexpensive urine test of smoking. Thorax 1985;40:351–357.
  18. Barlow RD, Stone RB, Wald NJ, Puhakainen EVJ: The direct barbituric acid assay for nicotine metabolites in urine: A simple colorimetric test for the routine assessment of smoking status and cigarette smoke intake. Clin Chim Acta 1987;165:45–52.
  19. Halliwell B, Clement MV, Long LH: Hydrogen peroxide in the human body. FEBS Lett 2000;486:10–13.
  20. Heunks MA, Vina J, van Herwaarden CLA, Folgering HTM, Gimeno A, Dekhuijzen PNR: Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Physiol 1999;277:R1697-R1704.

    External Resources

  21. Clini E, Bianchi L, Vitacca M, Porta R, Foglio K, Ambrosino N: Exhaled nitric oxide and exercise in stable COPD patients. Chest 2000;117:702–707.
  22. Nowak D, Kalucka S, Bialasiewicz P, Krol M: Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARS) by healthy subjects. Free Radic Biol Med 2001;30:178–186.

    External Resources

  23. Xu R, Liu Z, Zhao Y: A study on the circadian rhythm of glucocorticoid receptor. Neuroendocrinology 1991;53:31–36.

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  24. Maple C, Kirk G, McLaren M, Veale D, Belch JJ: A circadian variation exists for soluble levels of intracellular adhesion molecules-1 and E-selectin in healthy volunteers 1998;94:537–540.
  25. Doroshow JH, Locker GY, Baldinger J, Myers CE: The effect of doxorubicin on hepatic and cardiac glutathione. Res Commun Chem Pathol Pharmacol 1979;26:285–295.

    External Resources

  26. Wojnarowski C, Studnicka M, Kuhr J, Koller DY, Haschke N, Gartner C, Renz S, Frischer T: Determinants of eosinophil cationic protein in nasal lavages in children. Clin Exp Allergy 1998;28:300–305.

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  27. Ekroos H, Tuominen J, Sovijarvi AR: Exhaled nitric oxide and its long-term variation in healthy non-smoking subjects. Clin Physiol 2000;20:434–439.

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  28. Schleiss MB, Holz O, Behnke M, Richter K, Magnussen H, Jörres RA: The concentration of hydrogen peroxide in exhaled air depends on expiratory flow rate. Eur Respir J 2000;16:1115–1118.

 goto top of outline Author Contacts

W.J.C. van Beurden
Department of Pulmonology, Catharina Hospital
PO Box 1350
NL–5602 ZA Eindhoven (The Netherlands)
Tel. +31 40 2397280, Fax +31 40 2435149, E-Mail w.beurden@researchlab-long.demon.nl


 goto top of outline Article Information

Received: Received: August 20, 2001
Accepted after revision: February 4, 2002
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 1, Number of References : 28


 goto top of outline Publication Details

Respiration (International Review of Thoracic Diseases)
Founded 1944 as ‘Schweizerische Zeitschrift für Tuberkulose und Pneumonologie’ by E. Bachmann, M. Gilbert, F. Häberlin, W. Löffler, P. Steiner and E. Uehlinger, continued 1962–1967 as ‘Medicina Thoracalis’ as of 1968 as ‘Respiration’, H. Herzog (1962–1997)
Official Journal of the European Association for Bronchology and Interventional Pulmonology

Vol. 69, No. 3, Year 2002 (Cover Date: May-June 2002)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/journals/res


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Because inflammation induces oxidative stress, exhaled hydrogen peroxide (H2O2), which is a marker of oxidative stress, may be used as a non-invasive marker of airway inflammation in chronic obstructive pulmonary disease (COPD). There are no data on the circadian variability of exhaled H2O2 in COPD patients. Objective: The aim of this study was to investigate the variability of the H2O2 concentration in breath condensate of stable COPD patients and of matched healthy control subjects. Methods: We included 20 patients with stable mild COPD (forced expiratory volume in 1 s ∼70% of predicted) and 20 healthy subjects, matched for age, sex and pack-years, all smokers or ex-smokers. Breath condensate was collected and its H2O2 concentration determined fluorometrically three times on day 0 (9 and 12 a.m., and 3 p.m.) and once on days 1, 2, 3, 8 and 21. Results: The mean H2O2 concentration increased significantly during the day in both the patient and control groups (p = 0.02 and p < 0.01, respectively). Over a longer period up to 21 days, the mean concentration did not change in both groups. There was no significant difference between patients and controls. The mean coefficient of variation over 21 days was 45% in the patient group and 43% in the control group (p = 0.8). Conclusions: The exhaled H2O2 concentration increased significantly during the day in both stable COPD patients and controls. Over a period of 3 weeks, the mean H2O2 concentration did not change and the variability within the subjects was similar in both groups.



 goto top of outline Author Contacts

W.J.C. van Beurden
Department of Pulmonology, Catharina Hospital
PO Box 1350
NL–5602 ZA Eindhoven (The Netherlands)
Tel. +31 40 2397280, Fax +31 40 2435149, E-Mail w.beurden@researchlab-long.demon.nl


 goto top of outline Article Information

Received: Received: August 20, 2001
Accepted after revision: February 4, 2002
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 1, Number of References : 28


 goto top of outline Publication Details

Respiration (International Review of Thoracic Diseases)
Founded 1944 as ‘Schweizerische Zeitschrift für Tuberkulose und Pneumonologie’ by E. Bachmann, M. Gilbert, F. Häberlin, W. Löffler, P. Steiner and E. Uehlinger, continued 1962–1967 as ‘Medicina Thoracalis’ as of 1968 as ‘Respiration’, H. Herzog (1962–1997)
Official Journal of the European Association for Bronchology and Interventional Pulmonology

Vol. 69, No. 3, Year 2002 (Cover Date: May-June 2002)

Journal Editor: C.T. Bolliger, Cape Town
ISSN: 0025–7931 (print), 1423–0356 (Online)

For additional information: http://www.karger.com/journals/res


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Barnes PJ: Chronic obstructive pulmonary disease. N Engl J Med 2000;343:269–280.
  2. Repine E, Bast A, Lankhorst I: Oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:341–357.
  3. Kerstjens HAM: Stable chronic obstructive pulmonary disease. BMJ 1999;319:495–499.
  4. O’Byrne PM, Postma DS: Airway inflammation in asthma and COPD. Am J Respir Crit Care Med 1999;159:S50–S51.
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