Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by acute exacerbations that accelerate disease progression, increase hospitalizations, and elevate mortality. Effective management focuses on preventing these exacerbations owing to their significant impact on long-term outcomes. This review compiles current evidence regarding pharmacologic interventions aimed at reducing exacerbations, which include inhaled therapies, oral treatments, and novel agents. Established inhaled agents, such as long-acting beta-agonists, long-acting muscarinic antagonists, and combinations of inhaled corticosteroids, are fundamental, with the personalized selection based on patient-specific factors like blood eosinophil levels and history of exacerbations. Oral treatments, including roflumilast and azithromycin, confer additional benefits for patients with particular characteristics, such as chronic bronchitis or frequent exacerbations. Roflumilast effectively reduces exacerbations as a phosphodiesterase 4 (PDE-4) inhibitor in conjunction with inhaled therapies, while azithromycin provides anti-inflammatory and antimicrobial properties, particularly advantageous for elderly former smokers. Innovative therapies such as ensifentrine, a dual PDE-3/4 inhibitor, and dupilumab, which targets type 2 inflammation, demonstrate potential for lowering exacerbations in specific subgroups. This body of evidence endorses a personalized, phenotype-driven approach to COPD management, aimed at optimizing therapeutic strategies to decrease exacerbation frequency and enhance patient outcomes.