Erdosteine, but Not N-Acetylcysteine, is Associated with Improved Homogeneity of Alveolar Ventilation in Patients with Mild-to-Moderate COPD Treated with LABA/LAMA.

Purpose: Ventilation inhomogeneity and impaired alveolar ventilation (VA) are important abnormalities in chronic obstructive pulmonary disease (COPD) and may persist despite optimized bronchodilator therapy. Volumetric capnography (VCap) assesses uneven ventilation distribution in peripheral lung units. This study compared erdosteine and N-acetylcysteine (NAC), added to long-acting β2-agonist/long-acting muscarinic antagonist (LABA/LAMA) therapy, on VCap-derived indices and VA in mild-to-moderate COPD. Patients and Methods: This retrospective study analyzed anonymized data from clinically stable patients receiving LABA/LAMA therapy. Patients were classified according to treatment received during the preceding four weeks: erdosteine 600 mg/day plus LABA/LAMA, NAC 600 mg/day plus LABA/LAMA, or LABA/LAMA alone. VCap indices ─ time to peak tidal expiratory flow/expiratory time ratio (TPTEF/TEX), Phase 2/Phase 3 angle (S2/S3 angle), dead-space-to-tidal-volume ratio (VD/VT) ─ and VA were assessed at baseline and after four weeks. Comparisons were performed using analysis of variance and adjusted linear mixed-effects models. Results: A total of 127 patients were included: 45 received erdosteine, 41 NAC, and 41 LABA/LAMA alone. Baseline characteristics were comparable among groups. After four weeks, addition of erdosteine to treatment with dual bronchodilation was associated with improvements in all investigated outcomes, including increases in TPTEF/TEX (+56.5%) and VA (+8.9%), together with reductions in S2/S3 angle (-10.4°) and VD/VT ratio (-13.5%). Changes observed with the addition of NAC to dual bronchodilation were negligible and did not differ from those observed with LABA/LAMA alone (all pairwise comparisons p>0.05). Between-group differences consistently favored erdosteine for all outcomes (all p<0.001) and remained clinically relevant after adjustment for potential confounders. Conclusion: In mild-to-moderate COPD patients receiving optimized LABA/LAMA therapy, erdosteine, but not NAC, was associated with significantly improved ventilation homogeneity and VA. These findings suggest that the addition of erdosteine to dual bronchodilator therapy could provide additional clinical benefits.