Floriani AF; S. Valentino Hospital, Montebelluna, Italy.
Menzella F

Expert Review of Respiratory Medicine. 20(8):963-974, 2026 Aug.

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.