Title : Redox homeostasis as a therapeutic target in chronic obstructive pulmonary disease: Emerging strategies and preliminary clinical evidence
Abstract:
Chronic diseases characterized by persistent oxidative stress such as cardiovascular disorders, type 2 diabetes, neurodegenerative diseases, and chronic obstructive pulmonary disease (COPD) share common pathogenic pathways, including sustained inflammation and redox imbalance. However, current pharmacological approaches only partially address these mechanisms, highlighting the need for innovative therapeutic strategies. As far as COPD, recent studies reported the importance of restoration of redox homeostasis as key factor in clinical treatment .On this basis, modulation of oxidative stress through integrative approaches, including physical activity, caloric restriction, and bioactive dietary compounds, has been proposed to enhance endogenous antioxidant defenses in COPD patients. Unfortunately, these interventions are often limited by poor adherence, variability in bioavailability, and inconsistent clinical outcomes. Increasing evidence suggests that the regulation of the Nrf2/ARE pathway plays a central role in redox homeostasis and protection of lung cells and the inhibition of this pathway may contribute to the COPD progression, underscoring the importance of a well calibrate redox modulation. Among emerging strategies, controlled oxidative stimuli such as the use of ozone in medicine have been proposed as indirect activators of endogenous antioxidant systems. In fact, ozone, when administered appropriately, may induce a transient and controlled oxidative stress in cells capable of stimulating cytoprotective pathways, including Nrf2 activation. To investigate this approach, a case-control clinical study was conducted on 50 patients with moderate to severe COPD. All participants were ex-smokers in a stable phase of the disease and receiving standard pharmacological therapy (inhaled antinflammatory and/or bronchodilators). Patients were randomized into two groups: one group received standard therapy plus medical ozone therapy (major autohemotherapy protocol), while the control group received standard therapy alone.
Clinical outcomes were assessed before and after the intervention through pulmonary function tests, arterial blood gas analysis, six-minute walking test (6MWT), Borg dyspnea scale, and St. George’s Respiratory Questionnaire (SGRQ). Patients treated with ozone therapy showed a significant improvement in functional capacity, with an increase in walking distance exceeding the minimal clinically important difference (>25 m). Additionally, a reduction in perceived dyspnea and a significant improvement in quality of life scores were observed. No comparable changes were detected in the control group. Further evaluation of oxidative stress markers demonstrated a significant reduction in plasma reactive oxygen metabolites (dROMs) following ozone therapy, whereas no changes were observed in controls. These findings support the hypothesis that ozone therapy may contribute to restoring redox balance in COPD patients. Importantly, the treatment was well tolerated, with no reported adverse effects during long-term follow-up. Patients also reported subjective improvements in well-being.
In conclusion, modulation of redox homeostasis through controlled activation of endogenous antioxidant pathways represents a promising adjunctive strategy in COPD management. Although a larger randomized controlled trials are required to confirm these preliminary findings, ozone therapy, acting as a molecular redox signal, may offer clinical benefits by improving functional capacity, reducing oxidative stress, and enhancing quality of life in patients affected by chronic pulmonary diseases.
