Pulmonary Abnormalities and Carotid Atherosclerosis in Ex-Smokers without Airflow Limitation

Abstract

It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- (72 ± 6 years) and 27 ex-smokers (73 ± 9 years), who provided written informed consent to spirometry, plethysmography, ³He magnetic resonance imaging (MRI) and carotid ultrasound (US) and, for ex-smokers alone, thoracic X-ray computed tomography (CT). Ex-smokers had significantly greater ³He ventilation defect percent (VDP = 7%, p = 0.001) and carotid total plaque volume (TPV = 250 mm³, p = 0.002) than never-smokers, although there were no significant differences for spirometry or plethysmography, and CT airway and emphysema measurements were normal. There were univariate relationships for ³He VDP with carotid intima media thickness (IMT, r = 0.42, p = 0.004), TPV (r = 0.41, p = 0.006) and vessel wall volume (VWV, r = 0.40, p = 0.007). Multivariate models that included age, BMI, FEV₁, DL_CO and VDP showed that only VDP significantly predicted IMT (β = 0.41, p = 0.001), VWV (β = 0.45, p = 0.003) and TPV (β = 0.38, p = 0.005). In summary, there was imaging evidence of mild airways disease and carotid plaque burden that were related and significantly greater in ex-smokers without airflow limitation than in never-smokers.

Keywords:

• atherosclerosis
• COPD
• magnetic resonance imaging
• tobacco
• ultrasound

Acknowledgments

We thank D. Buchanan and S. Blamires, CCRC, RPT, for 3DUS measurements, clinical coordination and clinical database management and T. Szekeres, RTMR, for MRI of research volunteers.

D. Pike was supported by a Canadian Institutes of Health Research (CIHR) Strategic Training Program and G. Parraga gratefully acknowledges support from a CIHR New Investigator Award. Ongoing research funding from a CIHR Team Grant CIF#97687 (Thoracic Imaging Network of Canada, TinCAN) is also gratefully acknowledged.