Bidirectional Clinical Interactions among Exacerbations and Comorbidities in COPD: A Narrative Review.

Abstract: Acute deteriorations of respiratory symptoms in people with chronic obstructive pulmonary disease (COPD), known as exacerbations, worsen COPD severity (e.g., speed up lung function decline), and increase hospital admissions, healthcare costs, and mortality risk. The prevention, diagnosis, and treatment of exacerbations remain challenging due to the heterogeneous nature of these events. This complexity is further compounded by the high prevalence of multiple comorbidities and incompletely understood underlying mechanisms. Exacerbations of COPD and comorbidities are linked through bidirectional relationships, characterized by mutual adverse impacts, overlapping clinical manifestations, and increased susceptibility to the other condition. The identification and management of comorbidities are pivotal for effective disease management. Although current clinical frameworks, that is, models that integrate clinical features and biomarker-based identification of exacerbations to guide risk stratification and management, represent promising approaches to improve patient outcomes, multimorbidity is insufficiently incorporated. This narrative review provides an overview of the complex clinical associations of comorbidities in COPD, with a particular focus on exacerbations. It highlights differences in comorbidity prevalence among exacerbators, explores clinical interrelationships, and underscores the importance of multimorbidity-oriented management.