Physiological Characterization of Preserved Ratio Impaired Spirometry in the CanCOLD Study: Implications for Exertional Dyspnea and Exercise Intolerance

Rationale: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. Objectives: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. Methods: We completed a cross-sectional analysis of the CanCOLD population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV1<80% predicted and FEV1/FVC≥0.7), 264 controls, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing (CPET). Measurements and Main Results: PRISm had lower total lung, vital and inspiratory capacities than controls (all p<0.05), and minimal small airway, pulmonary gas-exchange, and radiographic parenchymal lung abnormalities. Compared with control, PRISm had higher dyspnea/oxygen uptake [V̇O2] ratio at peak exercise (4.0±2.2vs2.9±1.9, Borg units/L/min, p<0.001) and lower V̇O2peak (74±22vs96±25% predicted, p<0.001). At standardized submaximal work rates, PRISm had greater tidal volume/inspiratory capacity (VT%IC, p<0.001), reflecting inspiratory mechanical constraint. In contrast to PRISm, COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas-exchange abnormalities. Despite these physiological differences between the 3 groups, the relationship between increasing dyspnea and VT%IC during CPET was similar. Resting IC significantly correlated with V̇O2peak (r=0.65, p<0.001) in the entire sample, even after adjusting for airflow limitation, gas-trapping and diffusing capacity. Conclusion: In PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates.