Ventilation Heterogeneity in Ex-smokers without Airflow Limitation

Abstract

Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP). Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation≤-950 HU, RA950) and airway morphology (wall area percent [WA%], lumen area [LA] and LA normalized to body surface area [LA/BSA]). In 42 ex-smokers, there was abnormally elevated VDP and no significant differences for pulmonary function, RA950, or airway measurements compared to 18 ex-smokers with normal VDP. Ex-smokers with abnormally elevated VDP reported significantly greater (3)He ADC in the apical lung (right upper lobe [RUL], P=.02; right middle lobe [RML], P=.04; and left upper lobe [LUL], P=.009). Whole lung (r=0.40, P=.001) and lobar VDP (RUL, r=0.32, P=.01; RML, r=0.46, P=.002; right lower lobe [RLL], r=0.38, P=.003; LUL, r=0.35, P=.006; and left lower lobe, r=0.37, P=.004) correlated with regional (3)He ADC. Although whole-lung VDP and CT airway morphology measurements were not correlated, regional VDP was correlated with RUL LA (r=-0.37, P=.004), LA/BSA (r=-0.42, P=.0008), RLL WA% (r=0.28, P=.03), LA (r=-0.28, P=.03), and LA/BSA (r=-0.37, P=.004). Abnormally elevated VDP in ex-smokers without airflow limitation was coincident with very mild emphysema detected using MRI and regional airway remodeling detected using CT representing a subclinical obstructive lung disease phenotype.