Lung cancer screening trials provide an opportunity to study the natural history of emphysema by using computed tomography (CT) lung density as a surrogate parameter. In the Danish Lung Cancer Screening Trial, 2,052 participants were included. At screening rounds, smoking habits were recorded and spirometry was performed. CT lung density was measured as the volume-adjusted 15th percentile density (PD15). A mixed effects model was used with former smoking males with <30 pack-yrs and without airflow obstruction (AFO) at entry as a reference group. At study entry, 893 (44%) participants had AFO. For the reference group, PD15 was 72.6 g.L-1 with an annual decline of -0.33 g.L-1. Female sex and current smoking increased PD15 at baseline, 17.3 g.L-1 (p<0.001) and 10 g.L-1 (p<0.001), respectively; and both increased the annual decline in PD15 (female: -0.3 g.L-1; current smoking: -0.4 g.L-1). The presence and severity of AFO was a strong predictor of low PD15 at baseline (Global Initiative for Chronic Obstructive Lung Disease (GOLD) I: -1.4 g. Female sex, active smoking and the presence of AFO are associated with accelerated decline in lung density.