Disease Severity Dependence of the Longitudinal Association Between CT Lung Density and Lung Function in Smokers

Abstract

Background: In smokers, the lung parenchyma is characterized by inflammation and emphysema, processes that can result in local gain and loss of lung tissue. CT measures of lung density might reflect lung tissue changes; however, longitudinal data regarding the effects of CT lung tissue on FEV₁ in smokers with and without COPD are scarce.

Methods: The 15th percentile of CT lung density was obtained from the scans of 3,390 smokers who completed baseline and 5-year follow-up of the Genetic Epidemiology of COPD (COPDGene) study visits. The longitudinal relationship between total lung capacity-adjusted lung density (TLC-PD15) and FEV₁ was assessed by using multivariable mixed models. Separate models were performed in smokers at risk, smokers with preserved ratio and impaired spirometry (PRISm), and smokers with COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging system.

Results: The direction of the relationship between lung density and lung function was GOLD stage dependent. In smokers with PRISm, a 1-g/L decrease in TLC-PD15 was associated with an increase of 2.8 mL FEV₁ (P = .02). In contrast, among smokers with GOLD III to IV COPD, a 1-g/L decrease in TLC-PD15 was associated with a decrease of 4.1 mL FEV₁ (P = .002).

Conclusions: A decline in TLC-PD15 was associated with an increase or decrease in FEV₁ depending on disease severity. The associations are GOLD stage specific, and their presence might influence the interpretation of future studies that use CT lung density as an intermediate study end point for a decline in lung function.

Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Keywords: CT scan; lung density; smoking.