Clinical Assessment of Smokers with Persistent Dyspnoea but Unremarkable Spirometry: The Added Value of Diffusing...

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, DL_CO) 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, DL_CO, 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 DL_CO was the only independent predictor of dyspnoea burden (ratio of peak dyspnoea score to peak oxygen uptake (V̇O_2peak)), lower V̇O_2peak, higher ventilatory equivalent for carbon dioxide (V̇_E/V̇CO₂ 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 DL_CO, contributed more to the variance in exertional dyspnoea and exercise intolerance than all airway mechanical measurements. This attests to the added value of DL_CO for clinicians assessing the nature and extent of smoking-related lung injury in individuals with only minor airway obstruction.