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

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.

Exhaled breath condensate: methodological recommendations and unresolved questions

“…Furthermore, a circadian rhythm of exhaled H 2 O 2 was shown in healthy subjects with highest levels at 12:00 and 24:00 h and also in patients with COPD [13]. Increase in EBC H 2 O 2 level was found in asthma [22,58,60,[71][72][73], healthy smokers [35,39], COPD [34,44,45,59,65,74,75], bronchiectasis [76,77], CF [78,79] and acute respiratory distress syndrome (ARDS) [5,80,81], acute hypoxaemic respiratory failure [14], reperfusion injury [82], allergic rhinitis [83], common cold [84], post-operative period after lung resection [85], systemic sclerosis [86] and in experimental models of hypoxia/reoxygenation [87,88].…”

“…A circadian rhythm has been demonstrated for EBC H 2 O 2 level both in normal subjects and patients with COPD [13,34]. No circadian rhythm was identified for pH in a study of 152 subjects [12].…”

“…This mediator is not age-dependent in children, but higher levels were found in older than younger adults [13,33,34]. Body weight or height do not affect EBC volume and H 2 O 2 concentration in adults [28]; however no data are available regarding other mediators.…”

“…Values presented both for healthy individuals and patients with different respiratory disorders vary widely, most of them are close to the lower limit of detection and often include zero (see more details below). Data on reproducibility have not been given in many publications and the reported values vary between studies showing quite good agreement of data [62,64,65] or a rather high coefficient of variation within repeated measurements [19,34,63]. The mean coefficient of variation over 21 days was 45% in COPD patients and 43% in healthy subjects [34].…”

“…Data on reproducibility have not been given in many publications and the reported values vary between studies showing quite good agreement of data [62,64,65] or a rather high coefficient of variation within repeated measurements [19,34,63]. The mean coefficient of variation over 21 days was 45% in COPD patients and 43% in healthy subjects [34]. Due to the variability of data, concern has been raised regarding the reproducibility of the colorimetric assay in the range of values found in EBC and the usefulness of this measurement for monitoring oxidative stress in the airways [15,36,63,66].…”