Normative Reference Equations for Breathlessness Intensity during Incremental Cardiopulmonary Cycle Exercise Testing

Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0-10 category-ratio [CR10]) response in men and women aged ≥40 years during CPET, in relation to power output (W), rate of oxygen uptake (V'O2), and minute ventilation (V'E). Methods: Analysis of ostensibly healthy people aged ≥40 years undergoing a symptom-limited incremental cycle CPET (10 W/min) in the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants had <5 pack-years smoking, normal lung function and exercise capacity. The probability of each Borg CR10 breathlessness intensity rating by W, V'O2 or V'E (as absolute or relative value [% of predicted max]) was predicted using ordinal multinomial logistic regression. Model performance was evaluated by fit, calibration, discrimination (c-statistic), and externally validated in an independent sample (n=86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; mean age 65 (range 42-91) years, mean body mass index 26.3 (SD 3.8) kg/m2. Reference equations were developed for females and males separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (c-statistic males: 0.81-0.92; females: 0.81-0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings between individuals or groups, and to identify and quantify abnormal breathlessness responses (score > upper limit of normal) during CPET.