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

Devin B Phillips; Matthew D James; Sandra G Vincent; Amany F Elbehairy; J Alberto Neder; Miranda Kirby; Josuel Ora; Andrew G Day; Wan C Tan; Jean Bourbeau; Denis E O'Donnell

doi:10.1164/rccm.202307-1184OC

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

Am J Respir Crit Care Med. 2024 Jan 3. doi: 10.1164/rccm.202307-1184OC. Online ahead of print.

Authors

Devin B Phillips¹, Matthew D James², Sandra G Vincent³, Amany F Elbehairy^{4

5}, J Alberto Neder², Miranda Kirby^{6

7}, Josuel Ora⁸, Andrew G Day⁹, Wan C Tan¹⁰, Jean Bourbeau^{11

12}, Denis E O'Donnell¹³

Affiliations

¹ York University, 7991, Toronto, Ontario, Canada.
² Queen's University, 4257, Medicine, Kingston, Ontario, Canada.
³ Queen's University, Medicine, Kingston, Ontario, Canada.
⁴ Manchester University NHS Foundation Trust, 5293, Manchester, United Kingdom of Great Britain and Northern Ireland.
⁵ Alexandria University Faculty of Medicine, 68789, Department of Chest Diseases, Alexandria, Egypt.
⁶ Ryerson University, Physics, Toronto, Ontario, Canada.
⁷ United States.
⁸ Queen's University, Kingston, Ontario, Canada.
⁹ Kingston Health Sciences Hospital Research Institute, Kingston, Ontario, Canada.
¹⁰ Providence Heart & Lung Institute, University of British Columbia, St Paul's Hospital, UBC James Hogg Research Centre, Vancouver, British Columbia, Canada.
¹¹ Montreal Chest Institute, CORE, Montreal, Quebec, Canada.
¹² McGill University Health Centre, 54473, Montreal, Quebec, Canada.
¹³ Queen's University, Division of Respiratory and Critical Care Medicine, Department of Medicine, Kingston, Ontario, Canada; odonnell@queensu.ca.

PMID: 38170674
DOI: 10.1164/rccm.202307-1184OC

Abstract

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 V̇O_2peak (74±22vs96±25% predicted, p<0.001). At standardized submaximal work rates, PRISm had greater tidal volume/inspiratory capacity (V_T%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 V_T%IC during CPET was similar. Resting IC significantly correlated with V̇O_2peak (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.

Keywords: dyspnea; exercise capacity; preserved ratio impaired spirometry; pulmonary function; spirometry.