• Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI.
• Department of Biostatistics, University of Michigan, Ann Arbor, MI.
• Imbio LLC, Minneapolis, MN.
• Department of Internal Medicine, Michigan State University, East Lansing, MI.
• Department of Radiology, University of Michigan, Ann Arbor, MI.
• Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI; Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, MI.
• Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI; Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY.
• Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI. Electronic address: mrking@med.umich.edu.

BACKGROUND: Lung cancer risk prediction models do not routinely incorporate imaging metrics available on low-dose computed tomography (LDCT) of the chest ordered for lung cancer screening.

RESEARCH QUESTION: What is the association between quantitative emphysema measured on LDCT and lung cancer incidence and mortality, all-cause mortality, and airflow obstruction in individuals who currently or formerly smoked undergoing lung cancer screening?

STUDY DESIGN AND METHODS: In 7,262 participants in the CT arm of the National Lung Screening Trial, % low attenuation area (%LAA) was defined as the percent of lung volume with voxels < -950 Hounsfield Units on the baseline exam. We built multivariable Cox proportional hazards models, adjusting for competing risks where appropriate, to test for association between %LAA and lung cancer incidence, lung cancer mortality and all-cause mortality with censoring at 6 years. We also built multivariable logistic regression models to test the cross-sectional association between %LAA and airflow obstruction on spirometry which was available in 2,700 participants.

RESULTS: The median %LAA was 0.8% (interquartile range: 0.2%-2.7%). Every 1% increase in %LAA was independently associated with higher hazards of lung cancer incidence (HR 1.02; 95% CI 1.01-1.03; p=0.004), lung cancer mortality (HR 1.02; 95% CI 1.00-1.05; p=0.045) and all-cause mortality (HR 1.01; 95% CI 1.00-1.03; p=0.042). Among participants with spirometry, 892 had airflow obstruction. The likelihood of airflow obstruction increased with every 1% increase in %LAA (OR=1.07; 95% CI 1.06-1.09; p<0.001). A %LAA cutoff of 1% had the best discriminative accuracy for airflow obstruction in participants older than 65 years.

INTERPRETATION: Quantitative emphysema measured on LDCT of the chest can be leveraged to improve lung cancer risk prediction and help diagnose COPD in individuals who currently or formerly smoked undergoing lung cancer screening.