Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Pharmacological Treatment of AECOPD New Perspectives

Abstract: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are major drivers of morbidity, mortality, disease progression, and healthcare utilization worldwide. Evolving definitions of COPD and exacerbations, along with emerging evidence on risk stratification and treatment optimization, have prompted updates in clinical practice, most recently reflected in the 2026 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. This review summarizes contemporary perspectives on AECOPD, with a focus on updated definitions, epidemiology, predictors, clinical impact, and current pharmacological and nonpharmacological management strategies, including emerging preventive therapies. A narrative review of published literature, international guidelines, and major clinical trials was conducted, emphasizing evidence relevant to the assessment, treatment, and prevention of AECOPD. Particular attention was given to severity classification and guideline-directed therapeutic approaches. AECOPD is associated with substantial short- and long-term mortality, accelerated lung function decline, increased cardiovascular risk, and high readmission rates. The 2026 GOLD guidelines lower the threshold for high-risk classification, recognizing that even a single moderate exacerbation increases future risk. Acute management remains centered on short-acting bronchodilators, short courses of systemic corticosteroids, and antibiotics when indicated, with treatment of intensity guided by clinical severity and physiological derangements. Adjunctive supportive measures and early postdischarge interventions are critical to improving outcomes. While biologics, macrolides, Roflumilast, and Ensifentrine have no established role in the acute setting, they play an important role in exacerbation prevention as part of individualized, biomarker-informed maintenance strategies. AECOPD should be viewed as a sentinel event that necessitates both effective acute management and reassessment of long-term therapy. Early intervention, severity-based treatment, and postexacerbation optimization of maintenance therapy are essential to reduce recurrence, limit disease progression, and improve survival and quality of life in patients with COPD.