Phenotyping Exertional Breathlessness Using Cardiopulmonary Cycle Exercise Testing in People With Chronic Airflow Limitation

Exertional breathlessness is a cardinal symptom of people with chronic airflow limitation (CAL) and can be evaluated using cardiopulmonary exercise testing (CPET). Does abnormally high exertional breathlessness in relation to the rate of oxygen uptake (V’O 2 ) and minute ventilation (V’ E ) indicate different underlying pathophysiological mechanisms and clinical characteristics in people with CAL? Analysis of people aged ≥40 years with CAL (post-bronchodilator FEV 1 /FVC <lower limit of normal) undergoing symptom-limited incremental cycle CPET in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Using published normative references, breathlessness phenotypes at peak exercise were categorized as abnormal (Borg 0-10 intensity rating > upper limit of normal) by V’O 2 alone, abnormal by both V’O 2 and V’ E (B-V’O 2 +V’ E ), or normal by both V’O 2 and V’ E (B-normal). Exercise physiological responses and clinical characteristics were compared between groups. We included 325 people (44% women) with CAL (FEV 1 75.4±[standard deviation] 17.5%predicted). Compared with the B-normal group (n=237[73%]), the B-V’O 2 group (n=29 [9%]) had lower pulmonary diffusing capacity and greater exercise ventilatory inefficiency, whereas the B-V’O 2 +V’ E group (n=50[15%]) had even worse lung function, dynamic critical inspiratory constraints, and exertional breathlessness along with greater symptom burden in daily life, lower physical activity, and worse health status. Exertional breathlessness phenotyped in relation to V’O 2 and V’ E using normative reference equations enable multivariable analyses of underlying symptom mechanisms and associated clinical characteristics.