Treatment and rehabilitation options for patients with COPD exacerbations against the background of continuing smoking

Background: Chronic obstructive pulmonary disease (COPD), primarily caused by smoking, is the third leading cause of death worldwide. Inhaled glucocorticosteroids (IGCS) are part of the recommended triple therapy for COPD exacerbations. However, in patients who continue to smoke, the effectiveness of corticosteroids is significantly reduced: they do not slow disease progression or suppress mediator production in alveolar macrophages due to oxidative stress, which blocks HDAC2 activity. One of solutions to this problem is the use of carbocysteine (CC). It maintains HDAC2 activity by reducing reactive oxygen species (ROS) levels and increasing glutathione (GSH) and superoxide dismutase (SOD) activity. This enhances the anti-inflammatory effect of GCS, reduces airway remodeling, and the frequency of exacerbations.

An alternative strategy is switching to electronic heated tobacco systems (EHTS). EHTS aerosol contains 90–95% fewer toxic substances (aldehydes, acrolein, and benzene) than cigarette smoke.

Objective: Comparative analysis of the effects of switching to EHTS and carbocysteine use on lung function recovery during combination therapy and rehabilitation for exacerbations of spirometric stage II (moderate) COPD in male smokers.

Materials and methods: The study included 37 men with stage II COPD during a bacterial exacerbation. All participants were active smokers with a smoking history of more than 20 years. Three groups were formed: group 1 – standard therapy + rehabilitation + carbocysteine; group 2 – standard therapy + rehabilitation + full transition to EHTS; control group: standard therapy only without smoking modification.

Standard therapy included triple inhalation therapy (long-acting beta-2-adrenergic agonist + long-acting M-anticholinergic + inhaled glucocorticosteroid), as well as appropriate antibacterial therapy based on the etiologic agent. Rehabilitation included bovhyaluronidase, azoximer, and Buteyko breathing exercises.

Results: By day 180 of follow-up, patients in groups 1 and 2 showed significant improvements in all spirometric parameters compared to baseline values. Both groups showed comparable increases in FEV1 (+17.3±2.39%), reflecting a reduction in inflammation and improved lung elasticity. In the control group, FVC, MEF 25-75, and FEV1 remained virtually unchanged. Particularly significant was the lack of increase in MEF 50 and MEF 75 flow rates — markers of distal bronchiole health. This indicates persistent exposure to tobacco combustion products and reduced HDAC2 activity, which limits the effectiveness of inhalation therapy.

Conclusion: Timely therapy adjustments (addition of carbocysteine or switching to EHTS) significantly improve clinical status and respiratory function in COPD patients who are not ready to quit smoking. Integrating harm reduction strategies into a personalized approach is an important component of secondary prevention. Further randomized prospective studies are needed to clarify the long-term benefits of fully switching to EHTS.