Pharmacological Treatment in Chronic Obstructive Pulmonary Disease

Dyspnea and exercise limitation are the dominant symptoms of patients with chronic obstructive pulmonary disease (COPD) and progress relentlessly as the disease advances. Effective management of these disabling symptoms awaits a better understanding of their underlying physiology. Recent research has identified a number of physiological mechanisms that can be targeted for therapeutic manipulation. Thus, interventions that improve dynamic ventilatory mechanics during exercise or reduce ventilatory demand (relative to capacity) will consistently improve exertional symptoms and physical performance even in patients with severe COPD. In this review we will attempt to provide a physiological construct to explain how modern bronchodilator therapy effectively relieves dyspnea and improves exercise endurance in COPD. We will then discuss new advances in our understanding of how oxygen enrichment of the inspired air results in impressive improvements of exertional symptoms and exercise performance even in patients without significant activityinduced arterial oxygen desaturation. Finally, we will demonstrate how combining therapies that improve airflow dynamics with those that alter the central neural drive to breathe have additive and clinically meaningful benefits in patients with advanced COPD.