Chest
Volume 121, Issue 2, February 2002, Pages 338-346
Journal home page for Chest

Clinical Investigations
Asthma
The Relationships Among Hydrogen Peroxide in Expired Breath Condensate, Airway Inflammation, and Asthma Severity

https://doi.org/10.1378/chest.121.2.338Get rights and content

Study objective

To investigate which cells are the main source of hydrogen peroxide (H2O2) production in stable patients with asthma and the associations among H2O2 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

H2O2 was measured in expired breath condensate and was correlated with variables expressing both asthma severity (ie, FEV1 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 H2O2 was significantly elevated in patients with asthma compared to that in control subjects (mean, 0.67 μM [95% CI, 0.56 to 0.77 μM] vs 0.2 μM [95% CI, 0.16 to 0.24 μM]; p < 0.0001). The difference was primarily due to the elevation of H2O2 in patients with moderate asthma whose expired breath H2O2 level of 0.95 μM (95% CI, 0.76 to 1.12 μM) was significantly higher from that of patients with mild-persistent and mild-intermittent asthma (mean, 0.59 μM [95% CI, 0.47 to 0.7 μM] and 0.27 [95% CI, 0.23 to 0.32 μM], respectively; p < 0.0001). H2O2 concentration was positively related to sputum eosinophilia as well as to ECP concentration. A similar correlation was found between H2O2 and neutrophils in patients with moderate asthma. A positive correlation was observed between H2O2 level, symptom score, and PEFR variability. H2O2 level was negatively related to FEV1 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 H2O2 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 H2O2 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.

Section snippets

Patients

Fifty nonsmoking stable patients with asthma who were attending the asthma outpatient clinic and 15 healthy, nonatopic, nonsmoking control subjects (Table 1) participated in the study. Thirty-two asthma patients were atopic, as judged by positive responses to skin prick tests of six common allergens and the elevated serum level of IgE. A diagnosis of asthma was established according to the National Heart, Lung, and Blood Institute (NHLBI) guidelines for the diagnosis and management of asthma.1

H2O2 Concentration in Expired Breath Condensate, Airway Inflammatory Cells, and ECP in Induced Sputum

Repeated measurements on 2 consecutive days showed a mean within-subject difference of 0.09 μM (SD, 0.03 μM) for patients and 0.07 μM (SD, 0.04 μM) for healthy subjects. The stability of the H2O2 in frozen samples showed no significant differences among the four measurements (after 2 days: mean, 0.54 μM [SD, 0.21 μM]; after 1 week: mean, 0.58 μM[SD, 0.3 μM]; after 2 weeks: mean, 0.6 μM [SD, 0.3 μM]; after 3 weeks: mean, 0.57 μM [SD, 0.4 μM]; p = 0.43).

The mean H2O2 concentration in expired

Discussion

In a cross-sectional study from a wide spectrum of patients with asthma of stable severity, we have demonstrated for the first time that the increased oxidative stress, as assessed by H2O2 levels in expired breath condensate, is related to eosinophilic inflammation, while in more severe forms of the disease neutrophils might participate to a lesser extent. This increase in H2O2 levels is affected by both the severity of the disease and the use of ICS. We interpret these findings as a

References (28)

  • Q Jobsis et al.

    Hydrogen peroxide in exhaled air of healthy children: reference values

    Eur Respir J

    (1998)
  • J Arias-Diaz et al.

    Nitrite/nitrate levels in bronchoalveolar lavage fluid of lung cancer patients

    Cancer

    (1994)
  • R Louis et al.

    The relationship between airways inflammation and asthma severity

    Am J Respir Crit Care Med

    (2000)
  • PJ Sterk et al.

    Airway responsiveness: standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Report working party standardization of lung function tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society

    Eur Respir J

    (1993)
  • Cited by (87)

    • Molecular mechanisms of oxidative stress in asthma

      2022, Molecular Aspects of Medicine
      Citation Excerpt :

      Understanding how the currently available treatments for asthma, particularly corticosteroids and β2AR agonists, interact with ROS may help in the development of new therapeutic interventions. Early studies reported that corticosteroid treatment is associated with reduced levels of airway oxidative stress in asthmatic patients (Teng et al., 2011; Horvath et al., 1998; Ganas et al., 2001; Loukides et al., 2002). Also, airway ECs from corticosteroid-naïve asthmatic patients were shown to have lower CuZnSOD activity compared to cells from patients on inhaled corticosteroids (De Raeve et al., 1997).

    • Feline Asthma: Diagnostic and Treatment Update

      2020, Veterinary Clinics of North America - Small Animal Practice
    • Mitochondrial regulation of airway smooth muscle functions in health and pulmonary diseases

      2019, Archives of Biochemistry and Biophysics
      Citation Excerpt :

      In asthmatic ASM in vivo and in primary ASM culture, the generation of ROS is increased with an associated increase in the expression of adenine dinucleotide phosphate oxidase type 4 (NOX4) enzyme, resulting in oxidative stress in ASM cells. This increase in oxidative stress is correlated to the degree of airflow obstruction and airway hyperresponsiveness (AHR) [118,119]. More importantly, the antioxidant mitoubiquinone mesylate (MitoQ) reverses ozone-induced AHR and inflammation, suggesting a key role for mitochondrial ROS in the development of these pathological conditions [11].

    View all citing articles on Scopus
    View full text