Time for proper physiological assessment: the role of cardiopulmonary exercise testing in helping step-up therapy in difficult-to-treat and severe asthma

INTRODUCTION: Persistent exertional dyspnea remains a major unmet need in patients with difficult-to-treat and severe asthma, even in the era of optimized inhaled therapy and biologics. Resting lung function and inflammatory biomarkers often fail to explain exercise intolerance, leading to empirical step-up therapy without clear physiological justification. AREAS COVERED: This review discusses the role of cardiopulmonary exercise testing (CPET) in the evaluation of exertional dyspnea in difficult-to-treat and severe asthma, within the treatable traits framework. The review focuses on the main CPET-derived physiological patterns, including ventilatory limitation, dynamic hyperinflation, ventilatory inefficiency, dysfunctional breathing, deconditioning, cardiovascular limitation, exercise-induced laryngeal obstruction, and normal exercise physiology. It also examines how CPET may influence step-up decisions, support trait-directed interventions, and inform pharmacoeconomic considerations. A pragmatic clinical framework for selective integration of CPET into severe asthma assessment is proposed. EXPERT OPINION: CPET may represent a valuable physiological adjunct in selected patients with difficult-to-treat or severe asthma and persistent exertional dyspnea insufficiently explained by resting assessments. Its integration into the assessment pathway may help contextualize symptoms, distinguish asthma-driven exercise limitation from non-inflammatory or non-asthmatic causes of dyspnea, and support more mechanism-based management. However, current evidence supports CPET primarily as a tool for physiological phenotyping and trait reclassification rather than as a prospectively validated guide to treatment escalation, biologic stewardship, or long-term outcome improvement.