Beyond Spirometry: Linking Wasted Ventilation to Exertional Dyspnea in the Initial Stages of COPD
J. Alberto Neder,
Giles Santyr,
Brandon Zanette,
Miranda Kirby,
Marina Pourafkari,
Matthew D. James,
Sandra G. Vincent,
Carrie Ferguson,
Chu-Yi Wang,
Nicolle J. Domnik,
Devin B. Phillips,
Janos Porszasz,
William W. Stringer,
Denis E. O’Donnell
Affiliations
J. Alberto Neder
Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen’s University and Kingston Health Sciences Centre, Kingston, Canada
Giles Santyr
Translational Medicine Department, Faculty of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Canada
Brandon Zanette
Translational Medicine Department, Faculty of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Canada
Miranda Kirby
Department of Physics, Faculty of Science, Toronto Metropolitan University, Toronto, Canada
Marina Pourafkari
Department of Radiology and Diagnostic Imaging, Kingston Health Sciences Centre, Kingston, Canada
Matthew D. James
Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen’s University and Kingston Health Sciences Centre, Kingston, Canada
Sandra G. Vincent
Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen’s University and Kingston Health Sciences Centre, Kingston, Canada
Carrie Ferguson
The Lundquist Institute for Biomedical Innovation, Harbor U.C.L.A Medical Centre, Torrance, CA, USA
Chu-Yi Wang
The Lundquist Institute for Biomedical Innovation, Harbor U.C.L.A Medical Centre, Torrance, CA, USA
Nicolle J. Domnik
Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen’s University and Kingston Health Sciences Centre, Kingston, Canada
Devin B. Phillips
School of Kinesiology and Health Science, York University, Toronto, Canada
Janos Porszasz
The Lundquist Institute for Biomedical Innovation, Harbor U.C.L.A Medical Centre, Torrance, CA, USA
William W. Stringer
The Lundquist Institute for Biomedical Innovation, Harbor U.C.L.A Medical Centre, Torrance, CA, USA
Denis E. O’Donnell
Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen’s University and Kingston Health Sciences Centre, Kingston, Canada
AbstractExertional dyspnea, a key complaint of patients with chronic obstructive pulmonary disease (COPD), ultimately reflects an increased inspiratory neural drive to breathe. In non-hypoxemic patients with largely preserved lung mechanics – as those in the initial stages of the disease – the heightened inspiratory neural drive is strongly associated with an exaggerated ventilatory response to metabolic demand. Several lines of evidence indicate that the so-called excess ventilation (high ventilation-CO2 output relationship) primarily reflects poor gas exchange efficiency, namely increased physiological dead space. Pulmonary function tests estimating the extension of the wasted ventilation and selected cardiopulmonary exercise testing variables can, therefore, shed unique light on the genesis of patients’ out-of-proportion dyspnea. After a succinct overview of the basis of gas exchange efficiency in health and inefficiency in COPD, we discuss how wasted ventilation translates into exertional dyspnea in individual patients. We then outline what is currently known about the structural basis of wasted ventilation in “minor/trivial” COPD vis-à-vis the contribution of emphysema versus a potential impairment in lung perfusion across non-emphysematous lung. After summarizing some unanswered questions on the field, we propose that functional imaging be amalgamated with pulmonary function tests beyond spirometry to improve our understanding of this deeply neglected cause of exertional dyspnea. Advances in the field will depend on our ability to develop robust platforms for deeply phenotyping (structurally and functionally), the dyspneic patients showing unordinary high wasted ventilation despite relatively preserved FEV1.