Cigarette Smoke Exposure and Radiographic Pulmonary Vascular Morphology in the Framingham Heart Study

Abstract

Rationale: Cigarette smoke exposure is a risk factor for many lung diseases, and histologic studies suggest that tobacco-related vasoconstriction and vessel loss plays a role in the development of emphysema. However, it remains unclear how tobacco affects the pulmonary vasculature in general populations with a typical range of tobacco exposure, and whether these changes are detectable by radiographic methods. Objectives: To determine whether tobacco exposure in a generally healthy population manifests as lower pulmonary blood vessel volumes and vascular pruning on imaging. Methods: A total of 2,410 Framingham Heart Study participants with demographic data and smoking history underwent volumetric whole-lung computed tomography from 2008 to 2011. Automated algorithms calculated the total blood volume of all intrapulmonary vessels (TBV), smaller peripheral vessels (defined as cross-sectional area ,5 mm 2 [BV5]), and the relative fraction of small vessels (BV5/TBV). Tobacco exposure was assessed as smoking status, cumulative pack-years, and secondhand exposure. We constructed multivariable linear regression models to evaluate associations of cigarette exposure and pulmonary blood vessel volume measures, adjusting for demographic covariates, including age, sex, height, weight, education, occupation, and median neighborhood income. Results: All metrics of tobacco exposure (including smoking status, pack-years, and secondhand exposure) were consistently associated with higher absolute pulmonary blood vessel volume, higher small vessel volume, and/or higher small vessel fraction. For example, eversmokers had a 4.6 ml higher TBV (95% confidence interval [CI] = 2.9-6.3, P , 0.001), 2.1 ml higher BV5 (95% CI = 1.3-2.9, P , 0.001), and 0.28 percentage-point-higher BV5/TBV (95% CI = 0.03-0.52, P = 0.03) compared with never-smokers. These associations remained significant after adjustment for percent predicted forced expiratory volume in 1 second, cardiovascular comorbidities, and did not differ based on presence or absence of airflow obstruction. Conclusions: Using computed tomographic imaging, we found that cigarette exposure was associated with higher pulmonary blood vessel volumes, especially in the smaller peripheral vessels. Although, histologically, tobacco-related vasculopathy is characterized by vessel narrowing and loss, our results suggest that radiographic vascular pruning may not be a surrogate of these pathologic changes.

Ambient air pollution exposure and radiographic pulmonary vascular volumes

“…The study population consists of participants of the Framingham Heart Study Offspring and Third Generation cohorts who took part in the Multi-Detector CT 2 sub-study and underwent volumetric thoracic CT between 2008 and 2011 as previously described. 23 , 24 A total of 2470 participants had CT vascular data; those without assessment of any air pollutant were excluded, leaving 2428 individuals in the analysis. This study was conducted in accordance with the Declaration of Helsinki.…”

“… 22 Using a related technique in the Framingham Heart Study, we reported a similar association of tobacco exposure with higher volumes of the pulmonary vessels on CT (including the total vascular volume and the volume of the small vessels alone). 23 …”

How to Detect Tobacco-related Vasculopathy: Are We There Yet?

“…Could these differences be explained by the choice of study population? As stated here, Synn and colleagues did not use a novel analysis modality, but their study is the first one to apply it and its algorithm to a large representative and relatively healthy cohort (8). This would also explain why they found an association of smoking with higher pulmonary blood volume, which is the opposite of the previous studies.…”

“…Another explanation for the smokingassociated increase in pulmonary blood volume was explained by the authors of the study on hand as being a result of a larger appearance of the pulmonary vasculature on imaging by an increased recruitment resulting from a stronger inspiratory effort in healthy smokers. Nevertheless and despite these limitations, Synn and colleagues can reliably conclude that smoking is associated with a higher average total pulmonary vascular volume when compared with nonsmokers in the Framingham study cohort by the use of volumetric imaging (8). In the future, more studies using this modality of larger prospective cohorts of smokers are needed to determine the prognostic relevance.…”

“…In this issue of AnnalsATS, Synn and colleagues (pp. 698-706) conducted a retrospective data analysis using the Framingham Heart Study cohort to hypothesize that tobacco exposure is associated with lower pulmonary blood volumes and vascular pruning (8). Data from 2,410 participants who had undergone volumetric whole-lung tomography were used, and an automated algorithm generated 3-dimensional reconstructions of the pulmonary vascular tree and calculated the total volume of all intrapulmonary vessels.…”