Optimizing Management Beyond Triple Therapy in Stable Severe Chronic Obstructive Pulmonary Disease: Efficacy of...

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition commonly managed with triple inhaler therapy comprising long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA), and inhaled corticosteroid (ICS). Despite optimal inhalation therapy, many patients continue to experience persistent symptoms. Doxophylline, a novel xanthine derivative, offers bronchodilator and anti-inflammatory benefits with a more favorable safety profile than traditional methylxanthines.

To assess the efficacy, safety, and tolerability of oral doxophylline in addition to triple inhaler therapy in patients with stable severe COPD.

In this randomized controlled trial, 78 patients were allocated to group A (triple therapy + doxophylline 650 mg once daily) and group B (triple therapy alone). Assessment included the COPD assessment test (CAT score), C-reactive protein (CRP), spirometry parameters (FEV₁, FEV₁%, FEV₁/FVC), adverse events, and evaluations were performed on days 0 and 90.

By day 90, group A showed greater improvement in CAT score (7.94 ± 4.17 vs 10.06 ± 3.99; p = 0.033) and CRP (12.2 ± 4.47 vs 15.33 ± 5.37 mg/L; p = 0.01). Spirometry gains were comparable: FEV₁ (0.97 ± 0.23 vs 0.96 ± 0.26 L/minute; p = 0.872), FEV₁% predicted (49.10 ± 8.73 vs 48.69 ± 9.72%; p = 0.482), and FEV₁/FVC% (54.09 ± 6.57 vs 52.89 ± 6.95%; p = 0.397). Mild adverse events including palpitations (14.29%), tremors (8.57%), and nausea (2.86%) were more frequent in group A but were generally tolerated.

Adjunctive oral doxophylline significantly improved symptom burden and systemic inflammation in patients with stable severe COPD without conferring additional spirometric benefits. Although mild adverse effects were observed, doxophylline was overall well tolerated and may represent a viable adjunctive option in selected COPD patients with persistent symptoms despite optimized inhaler therapy.