Oxidative stress in expired breath condensate of patients with COPD.

OBJECTIVE: To evaluate the levels of hydrogen peroxide (H(2)O(2)) and 8-isoprostane in the expired breath condensate (EBC) of patients with COPD, and to assess the relationship between the above markers of oxidative stress and parameters expressing inflammatory process and disease severity. SETTING: Inpatient respiratory unit and outpatient clinic in tertiary care hospital. DESIGN: Cross-sectional study. PATIENTS: Thirty stable COPD patients (all smokers) with disease severity ranging from mild to severe. Ten subjects who were smokers with stage 0 disease (ie, at risk for COPD; mean [+/- SD] FEV(1), 88 +/- 5% predicted) were studied as a control group. METHODS: H(2)O(2) and 8-isoprostane levels were measured in EBC, and the values were correlated with variables expressing COPD severity (ie, FEV(1) percent predicted, dyspnea severity score (ie, Medical Research Council scale) and airway inflammation (ie, differential cell counts from induced sputum). RESULTS: The mean concentration of H(2)O(2) was significantly elevated in COPD patients compared to control subjects (mean, 0.66 micromol/L [95% confidence interval (CI), 0.54 to 0.68 micro mol/L) vs 0.31 micro mol/L [95% CI, 0.26 to 0.35 micromol/L], respectively; p < 0.0001). The difference was primarily due to the elevation of H(2)O(2) in patients with severe and moderate COPD, whose expired breath H(2)O(2) levels were significantly higher than those of patients with mild disease (mean, 0.96 micromol/L [95% CI, 0.79 to 1.13 micromol/L], 0.68 micromol/L [95% CI, 0.55 to 0.81 micromol/L], and 0.33 micromol/L [95% CI, 0.24 to 0.43 micromol/L], respectively, p < 0.0001). The mean concentration of 8-isoprostane was significantly elevated in patients with COPD compared to that of the control group (47 pg/mL [95% CI, 41 to 53 pg/mL] vs 29 pg/mL [95% CI, 25 to 33 pg/mL], respectively; p < 0.0001) but did not differ significantly among the different stages of the disease (p = 0.43). Repeatability and stability data within measurements showed that H(2)O(2) has a better repeatability and stability than 8-isoprostane. Furthermore, we observed significant correlations of H(2)O(2) with FEV(1), neutrophil count, and dyspnea score. Those correlations existed only in patients with moderate and severe disease. No correlations were found between levels of 8-isoprostane and the above parameters. CONCLUSIONS: We conclude that levels of H(2)O(2) and 8-isoprostane are elevated in the EBC of patients with COPD, but that H(2)O(2) seems to be a more repeatable and a more sensitive index of the inflammatory process and the severity of the disease.

pH in expired breath condensate of patients with inflammatory airway diseases.

Endogenous airway acidification, as assessed by pH in expired breath condensate, has been implicated in asthma pathophysiology. We measured pH in breath condensate of patients with inflammatory airway diseases in stable condition and examined its relationship with the inflammatory process (as assessed by differential cell counts in induced sputum), oxidative stress (as assessed by H(2)O(2) and 8-isoprostane), and nitric oxide metabolism (as assessed by total nitrate/nitrite). We studied 40 patients with bronchial asthma (20 with moderate disease, forced expiratory volume in 1 second 60 [10]% SD predicted), 20 patients with bronchiectasis, 20 patients with chronic obstructive pulmonary disease (COPD), and 10 normal subjects. Mean (95% confidence intervals) pH values were significantly lower in patients with COPD and bronchiectasis compared with patients with asthma and control subjects (7.16, 7.09-7.23 and 7.11, 7.04-7.19 versus 7.43, 7.35-7.52 and 7.57, 7.51-7.64, respectively, p < 0.0001). Patients with moderate asthma had significantly lower values compared with mild and control subjects. In patients with COPD and bronchiectasis, the values of pH were significantly correlated with both sputum neutrophilia and oxidative stress. Respectively, in patients with moderate asthma, a significant correlation was observed between pH and sputum eosinophilia, total nitrate/nitrite, and oxidative stress. The pH of the expired breath condensate might be a simple, noninvasive, inexpensive, and easily repeatable procedure for the evaluation of the inflammatory process in airway diseases.

The relationships among hydrogen peroxide in expired breath condensate, airway inflammation, and asthma severity.

STUDY OBJECTIVE: To investigate which cells are the main source of hydrogen peroxide (H(2)O(2)) production in stable patients with asthma and the associations among H(2)O(2) levels, airway inflammation, and disease severity. SETTING: Inpatient respiratory unit and outpatient clinic in tertiary-care hospital. PATIENTS: Fifty stable asthmatic patients with disease severity ranging from mild to moderate. METHODS: H(2)O(2) was measured in expired breath condensate and was correlated with variables expressing both asthma severity (ie, FEV(1) percent predicted, peak expiratory flow rate [PEFR] variability, symptom score, and histamine airways responsiveness) and airway inflammation (ie, differential cell counts from induced sputum and levels of eosinophil cationic protein [ECP]). RESULTS: The mean (95% confidence interval [CI]) concentration of H(2)O(2) was significantly elevated in patients with asthma compared to that in control subjects (mean, 0.67 microM [95% CI, 0.56 to 0.77 microM] vs 0.2 microM [95% CI, 0.16 to 0.24 microM]; p < 0.0001). The difference was primarily due to the elevation of H(2)O(2) in patients with moderate asthma whose expired breath H(2)O(2) level of 0.95 microM (95% CI, 0.76 to 1.12 microM) was significantly higher from that of patients with mild-persistent and mild-intermittent asthma (mean, 0.59 microM [95% CI, 0.47 to 0.7 microM] and 0.27 [95% CI, 0.23 to 0.32 microM], respectively; p < 0.0001). H(2)O(2) concentration was positively related to sputum eosinophilia as well as to ECP concentration. A similar correlation was found between H(2)O(2) and neutrophils in patients with moderate asthma. A positive correlation was observed between H(2)O(2) level, symptom score, and PEFR variability. H(2)O(2) level was negatively related to FEV(1) percent predicted. Further analysis showed that only patients with moderate asthma who were not receiving inhaled steroids were found to have a strong relationship with the variables tested. CONCLUSIONS: Eosinophils are the predominate cells that generate H(2)O(2) in all forms of the disease, while neutrophils might be responsible for the highest levels that are observed in the more severe forms of the disease. The role of H(2)O(2) concentration in predicting the severity of the disease as well as in the inflammatory process is limited and depends on the use of inhaled steroid therapy and the classification of the severity of the disease.

Exhaled H(2)O(2) in steady-state bronchiectasis: relationship with cellular composition in induced sputum, spirometry, and extent and severity of disease.

STUDY OBJECTIVES: To determine the concentration of exhaled H(2)O(2) in patients with bronchiectasis, and to study the relationship between levels of exhaled H(2)O(2), extent of disease, symptoms score, spirometry, and cellular composition obtained from induced sputum; furthermore, to account for possible confounding effects of inhaled corticosteroids (ICS) usage, long-term oral antibiotic treatment, and chronic colonization with Pseudomonas aeruginosa. DESIGN: Cross-sectional study. PATIENTS: Thirty patients with steady-state bronchiectasis. RESULTS: Mean (95% confidence interval [CI]) exhaled H(2)O(2) levels were significantly elevated in patients with bronchiectasis compared to normal subjects: 1.1 (0.87 to 1.29) microM vs 0.3 (0.19 to 0.36) microM, respectively (p < 0.0001). Patients treated with ICS had similar values as steroid-naïve patients. The group of patients with P aeruginosa colonization showed a significantly increased concentration of H(2)O(2) compared to the group without P aeruginosa colonization. Patients receiving long-term oral antibiotic treatment had significantly higher values of H(2)O(2) compared to those not receiving antibiotics. There was a significant positive correlation between H(2)O(2) and either the percentage of neutrophils in induced sputum or the extent of the disease as defined by high-resolution CT. A significant negative correlation was found between H(2)O(2) and FEV(1) percent predicted. Finally, there was a significant positive correlation between H(2)O(2) and the symptoms score. CONCLUSIONS: Patients with bronchiectasis in stable condition showed increased levels of exhaled H(2)O(2). The above-mentioned levels were not decreased either by ICS or long-term oral antibiotic treatment, but were significantly affected by chronic colonization with P aeruginosa. H(2)O(2) levels could be an indirect index of neutrophilic inflammation, impairment of lung function, and extension and severity of the disease.