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The order and extent of interactions across the factors affecting exertional dyspnoea (ED) and exercise intolerance (EI) in patients with chronic obstructive pulmonary disease (COPD) are not clear. We hypothesized that lung and non-lung variables were the primary variables, ED was the secondary variable and EI was the tertiary variable. Data on demographics, blood tests, cardiac imaging, lung function tests and invasive dead space fractions (V D /V T ) during incremental exercise test of 46 male COPD subjects were obtained. These variables were categorized by factor analysis and pair-wise correlation analysis was conducted. The best factor of each category was selected and then multivariate regression was conducted. Peak tidal inspiratory flow (V T /T Ipeak ), V D /V Tpeak  and tidal lung expansion capability, and resting diffusing capacity of the lungs (D L CO)% predicted were the primary pulmonary factors most related to ED, whereas body mass index (BMI), haemoglobin and cholesterol levels were the primary non-pulmonary factors. In multivariate regression analysis, V T /T Ipeak , V D /V Tpeak  and D L CO% were the primary factors most related to ED ( r2  = 0.69); ED was most related to EI ( r  = −0.74 to −0.83). Using hierarchical stratification and statistical methods may improve understanding of the pathophysiology of ED and EI in patients with COPD.KEY MESSAGESThe pathophysiology of exertional dyspnoea (ED) and exercise intolerance (EI) in chronic obstructive pulmonary disease (COPD) is complex. The order and extent of interactions across factors are not clear. In multivariate regression analysis, we found that tidal inspiratory flow, dead space fraction and resting diffusing capacity of the lungs % but not the non-pulmonary factors affected ED.Using correlation coefficients, we further found that ED was the secondary variable and EI was the tertiary variable.Hierarchical stratification of the important factors associated with ED and EI in patients with COPD clarifies their relationships and could be incorporated into management programmes and outcome studies for these patients. The pathophysiology of exertional dyspnoea (ED) and exercise intolerance (EI) in chronic obstructive pulmonary disease (COPD) is complex. The order and extent of interactions across factors are not clear. In multivariate regression analysis, we found that tidal inspiratory flow, dead space fraction and resting diffusing capacity of the lungs % but not the non-pulmonary factors affected ED. Using correlation coefficients, we further found that ED was the secondary variable and EI was the tertiary variable. Hierarchical stratification of the important factors associated with ED and EI in patients with COPD clarifies their relationships and could be incorporated into management programmes and outcome studies for these patients.

Hierarchical stratification of the factors related to exertional dyspnoea and exercise intolerance in male COPD patients