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

• DOI: 10.1164/rccm.202307-1184oc
• Publication Date: 2024-01-03T17:54:42Z
• Authors: 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; Jean Bourbeau; Wan C. Tan; J. Mark FitzGerald; Don D. Sin; Darcy D. Marciniuk; Denis E. O’Donnell; Paul Hernandez; Kenneth R. Chapman; Brandie Walker; Shawn Aaron; François Maltais; Jonathon Samet; Milo Puhan; Qutayba Hamid; James C. Hogg; Dany Doiron; Palmina Mancino; Pei Zhi Li; Dennis Jensen; Carolyn Baglole; Yvan Fortier; Julia Yang; Jeremy Road; Joe Comeau; Adrian Png; Kyle Johnson; Harvey Coxson; Miranda Kirby; Jonathon Leipsic; Cameron Hague; Mohsen Sadatsafavi; Teresa To; Andrea Gershon; Zhi Song; Andrea Benedetti; Christine Lo; Sarah Cheng; Elena Un; Cynthia Fung; Wen Tiang Wang; Liyun Zheng; Faize Faroon; Olga Radivojevic; Sally Chung; Carl Zou; Jacinthe Baril; Laura Labonté; Patricia McClean; Nadeen Audisho; Curtis Dumonceaux; Lisette Machado; Scott Fulton; Kristen Osterling; Denise Wigerius; Kathy Vandemheen; Gay Pratt; Amanda Bergeron; Matthew McNeil; Kate Whelan; Cynthia Brouillard; Ron Clemens; Janet Baran; Candice Leuschen
• Keywords: Male; Pulmonary Disease, Chronic Obstructive; Canada; Dyspnea; Cross-Sectional Studies; Exercise Tolerance; Spirometry; Forced Expiratory Volume; Exercise Test; Humans; Female; Middle Aged; Aged

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 (Canadian Cohort Obstructive Lung Disease) 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 control participants, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing. Measurements and Main Results: Individuals with PRISm had lower total lung, vital, and inspiratory capacities than healthy controls (all P < 0.05) and minimal small airway, pulmonary gas exchange, and radiographic parenchymal lung abnormalities. Compared with healthy controls, individuals with PRISm had higher dyspnea/[Formula: see text]o2 ratio at peak exercise (4.0 ± 2.2 vs. 2.9 ± 1.9 Borg units/L/min; P < 0.001) and lower [Formula: see text]o2peak (74 ± 22% predicted vs. 96 ± 25% predicted; P < 0.001). At standardized submaximal work rates, individuals with PRISm had greater Vt/inspiratory capacity (Vt%IC; P < 0.001), reflecting inspiratory mechanical constraint. In contrast to participants with PRISm, those with COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas exchange abnormalities. Despite these physiological differences among the three groups, the relationship between increasing dyspnea and Vt%IC during cardiopulmonary exercise testing was similar. Resting IC significantly correlated with [Formula: see text]o2peak (r = 0.65; P < 0.001) in the entire sample, even after adjusting for airflow limitation, gas trapping, and diffusing capacity. Conclusions: In individuals with 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. Clinical trial registered with www.clinicaltrials.gov (NCT00920348).