James MD; Department of Medicine, Kingston General
Hospital, Kingston, ON, Canada. & other Canadian sites
Vincent SG; Elbehairy AF; Phillips DB; et al

Copd: Journal of Chronic Obstructive Pulmonary Disease. 23(1):2705831,
2026 Jul 25.

Long-term smokers with persistent dyspnoea and exercise intolerance, who
are at risk for COPD, require careful clinical assessment. However, many
such individuals have only minor abnormalities on spirometry, and it is
not known if various additional tests of small airways dysfunction (SAD)
or pulmonary microvascular deficits, offer added clinical value. In this
study we wished to determine which of the available resting pulmonary
function tests (e.g. airway mechanics and lung diffusing capacity for
carbon monoxide, DLCO) best uncover the physiological underpinnings of
these troublesome respiratory symptoms. This tri-centre, prospective study
enrolled 90 volunteers: 33 non-smoker controls, 57 symptomatic smokers, 38
of whom had Global Initiative for Obstructive Lung Disease Grade 1 COPD).
Participants completed impulse oscillometry (IOS), spirometry, body
plethysmography, DLCO, single and multiple breath nitrogen washout and an
incremental cycle cardiopulmonary exercise test. Smokers had more diverse
physiological abnormalities, greater dyspnoea and exercise intolerance
than healthy controls. Stepwise multilinear regression revealed that DLCO
was the only independent predictor of dyspnoea burden (ratio of peak
dyspnoea score to peak oxygen uptake (VO2peak)), lower VO2peak, higher
ventilatory equivalent for carbon dioxide (VE/VCO2 nadir) and dynamic
inspiratory mechanical constraints (higher tidal volume to inspiratory
capacity ratio), after accounting for age, sex, height, and smoking
history. In symptomatic smokers, reduced DLCO, contributed more to the
variance in exertional dyspnoea and exercise intolerance than all airway
mechanical measurements. This attests to the added value of DLCO for
clinicians assessing the nature and extent of smoking-related lung injury
in individuals with only minor airway obstruction.