Quantitative Emphysema on Low-Dose CT Imaging of the Chest and Risk of Lung Cancer and Airflow Obstruction

An Analysis of the National Lung Screening Trial
Published:December 14, 2020DOI:


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

      Research Question

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

      Study Design and Methods

      In 7,262 participants in the CT arm of the National Lung Screening Trial, percent low attenuation area (%LAA) was defined as the percentage of lung volume with voxels less than –950 Hounsfield units on the baseline examination. Multivariable Cox proportional hazards models, adjusting for competing risks where appropriate, were built to test for association between %LAA and lung cancer incidence, lung cancer mortality, and all-cause mortality with censoring at 6 years. In addition, multivariable logistic regression models were built to test the cross-sectional association between %LAA and airflow obstruction on spirometry, which was available in 2,700 participants.


      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 (hazard ratio [HR], 1.02; 95% CI, 1.01-1.03; P = .004), lung cancer mortality (HR, 1.02; 95% CI, 1.00-1.05; P = .045), and all-cause mortality (HR, 1.01; 95% CI, 1.00-1.03; P = .042). Among participants with spirometry, 892 had airflow obstruction. The likelihood of airflow obstruction increased with every 1% increase in %LAA (odds ratio, 1.07; 95% CI, 1.06-1.09; P < .001). A %LAA cutoff of 1% had the best discriminative accuracy for airflow obstruction in participants aged > 65 years.


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

      Key Words


      AUC (area under the curve), HR (hazard ratio), LDCT (low-dose CT), %LAA (percent low attenuation area)
      To read this article in full you will need to make a payment
      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Aberle D.R.
        • Adams A.M.
        • Berg C.D.
        • et al.
        Reduced lung-cancer mortality with low-dose computed tomographic screening.
        N Engl J Med. 2011; 365: 395-409
        • Morgan L.
        • Choi H.
        • Reid M.
        • Khawaja A.
        • Mazzone P.J.
        Frequency of incidental findings and subsequent evaluation in low-dose computed tomographic scans for lung cancer screening.
        Ann Am Thorac Soc. 2017; 14: 1450-1456
        • Regan E.A.
        • Lowe K.E.
        • Make B.J.
        • et al.
        Identifying smoking-related disease on lung cancer screening CT scans: increasing the value.
        Chronic Obstr Pulm Dis. 2019; 6: 233-245
        • Labaki W.W.
        • Martinez C.H.
        • Martinez F.J.
        • et al.
        The role of chest computed tomography in the evaluation and management of the patient with chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2017; 196: 1372-1379
        • Maldonado F.
        • Bartholmai B.J.
        • Swensen S.J.
        • Midthun D.E.
        • Decker P.A.
        • Jett J.R.
        Are airflow obstruction and radiographic evidence of emphysema risk factors for lung cancer? A nested case-control study using quantitative emphysema analysis.
        Chest. 2010; 138: 1295-1302
        • Gierada D.S.
        • Guniganti P.
        • Newman B.J.
        • et al.
        Quantitative CT assessment of emphysema and airways in relation to lung cancer risk.
        Radiology. 2011; 261: 950-959
        • Wilson D.O.
        • Leader J.K.
        • Fuhrman C.R.
        • Reilly J.J.
        • Sciurba F.C.
        • Weissfeld J.L.
        Quantitative computed tomography analysis, airflow obstruction, and lung cancer in the Pittsburgh lung screening study.
        J Thorac Oncol. 2011; 6: 1200-1205
        • Smith B.M.
        • Pinto L.
        • Ezer N.
        • Sverzellati N.
        • Muro S.
        • Schwartzman K.
        Emphysema detected on computed tomography and risk of lung cancer: a systematic review and meta-analysis.
        Lung Cancer. 2012; 77: 58-63
        • Johannessen A.
        • Skorge T.D.
        • Bottai M.
        • et al.
        Mortality by level of emphysema and airway wall thickness.
        Am J Respir Crit Care Med. 2013; 187: 602-608
        • Oelsner E.C.
        • Carr J.J.
        • Enright P.L.
        • et al.
        Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study.
        Thorax. 2016; 71: 624-632
        • Carr L.L.
        • Jacobson S.
        • Lynch D.A.
        • et al.
        Features of COPD as predictors of lung cancer.
        Chest. 2018; 153: 1326-1335
        • Ruparel M.
        • Quaife S.L.
        • Dickson J.L.
        • et al.
        Prevalence, symptom burden and under-diagnosis of chronic obstructive pulmonary disease in a lung cancer screening cohort.
        Ann Am Thorac Soc. 2020; 17: 869-878
        • Martinez C.H.
        • Mannino D.M.
        • Jaimes F.A.
        • et al.
        Undiagnosed obstructive lung disease in the United States: associated factors and long-term mortality.
        Ann Am Thorac Soc. 2015; 12: 1788-1795
        • Mets O.M.
        • Buckens C.F.
        • Zanen P.
        • et al.
        Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans.
        JAMA. 2011; 306: 1775-1781
        • Aberle D.R.
        • Berg C.D.
        • Black W.C.
        • et al.
        The National Lung Screening Trial: overview and study design.
        Radiology. 2011; 258: 243-253
        • Hilts M.
        • Duzenli C.
        Image filtering for improved dose resolution in CT polymer gel dosimetry.
        Med Phys. 2004; 31: 39-49
        • Tammemägi M.C.
        • Katki H.A.
        • Hocking W.G.
        • et al.
        Selection criteria for lung-cancer screening.
        N Engl J Med. 2013; 368: 728-736
        • Kovalchik S.A.
        • Tammemägi M.
        • Berg C.D.
        • et al.
        Targeting of low-dose CT screening according to the risk of lung-cancer death.
        N Engl J Med. 2013; 369: 245-254
        • Young R.P.
        • Hopkins R.J.
        • Christmas T.
        • Black P.N.
        • Metcalf P.
        • Gamble G.D.
        COPD prevalence is increased in lung cancer, independent of age, sex and smoking history.
        Eur Respir J. 2009; 34: 380-386
        • Denholm R.
        • Schuz J.
        • Straif K.
        • et al.
        Is previous respiratory disease a risk factor for lung cancer?.
        Am J Respir Crit Care Med. 2014; 190: 549-559
        • Houghton A.M.
        • Mouded M.
        • Shapiro S.D.
        Common origins of lung cancer and COPD.
        Nat Med. 2008; 14: 1023-1024
        • Kim C.F.
        • Jackson E.L.
        • Woolfenden A.E.
        • et al.
        Identification of bronchioalveolar stem cells in normal lung and lung cancer.
        Cell. 2005; 121: 823-835
        • Murakami J.
        • Ueda K.
        • Sano F.
        • Hayashi M.
        • Nishimoto A.
        • Hamano K.
        Pulmonary emphysema and tumor microenvironment in primary lung cancer.
        J Surg Res. 2016; 200: 690-697
        • Wilson D.O.
        • Weissfeld J.L.
        • Balkan A.
        • et al.
        Association of radiographic emphysema and airflow obstruction with lung cancer.
        Am J Respir Crit Care Med. 2008; 178: 738-744
        • Zulueta J.J.
        • Wisnivesky J.P.
        • Henschke C.I.
        • et al.
        Emphysema scores predict death from COPD and lung cancer.
        Chest. 2012; 141: 1216-1223
        • Bankier A.A.
        • De Maertelaer V.
        • Keyzer C.
        • Gevenois P.A.
        Pulmonary emphysema: subjective visual grading versus objective quantification with macroscopic morphometry and thin-section CT densitometry.
        Radiology. 1999; 211: 851-858
        • Cavigli E.
        • Camiciottoli G.
        • Diciotti S.
        • et al.
        Whole-lung densitometry versus visual assessment of emphysema.
        Eur Radiol. 2009; 19: 1686-1692
        • Group C.O.C.W.
        • Barr R.G.
        • Berkowitz E.A.
        • et al.
        A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation.
        COPD. 2012; 9: 151-159
        • Patz Jr., E.F.
        • Greco E.
        • Gatsonis C.
        • Pinsky P.
        • Kramer B.S.
        • Aberle D.R.
        Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial.
        Lancet Oncol. 2016; 17: 590-599
        • Yong P.C.
        • Sigel K.
        • de-Torres J.P.
        • et al.
        The effect of radiographic emphysema in assessing lung cancer risk.
        Thorax. 2019; 74: 858-864
        • Labaki W.W.
        • Han M.K.
        Artificial intelligence and chest imaging. Will deep learning make us smarter?.
        Am J Respir Crit Care Med. 2018; 197: 148-150
        • Gonzalez G.
        • Ash S.Y.
        • Vegas-Sanchez-Ferrero G.
        • et al.
        Disease staging and prognosis in smokers using deep learning in chest computed tomography.
        Am J Respir Crit Care Med. 2018; 197: 193-203
        • Riley C.M.
        • Sciurba F.C.
        Diagnosis and outpatient management of chronic obstructive pulmonary disease: a review.
        JAMA. 2019; 321: 786-797
        • Kochanek K.D.
        • Murphy S.
        • Xu J.
        • Arias E.
        Mortality in the United States, 2016.
        NCHS Data Brief. 2017; : 1-8
        • de-Torres J.P.
        • Wisnivesky J.P.
        • Bastarrika G.
        • Wilson D.O.
        • Celli B.R.
        • Zulueta J.J.
        The prevalence of obstructive lung disease in a lung cancer screening cohort: analysis of the National Lung Screening Trial-American College of Radiology Image Network Cohort.
        Ann Am Thorac Soc. 2019; 16: 641-644
        • Han M.K.
        • Kim M.G.
        • Mardon R.
        • et al.
        Spirometry utilization for COPD: how do we measure up?.
        Chest. 2007; 132: 403-409
        • Cao P.
        • Jeon J.
        • Levy D.T.
        • et al.
        Potential impact of cessation interventions at the point of lung cancer screening on lung cancer and overall mortality in the United States.
        J Thorac Oncol. 2020; 15: 1160-1169
        • Ruparel M.
        • Quaife S.L.
        • Dickson J.L.
        • et al.
        Evaluation of cardiovascular risk in a lung cancer screening cohort.
        Thorax. 2019; 74: 1140-1146
        • Gonzalez J.
        • Henschke C.I.
        • Yankelevitz D.F.
        • et al.
        Emphysema phenotypes and lung cancer risk.
        PLoS One. 2019; 14e0219187
        • Mouronte-Roibas C.
        • Fernandez-Villar A.
        • Ruano-Ravina A.
        • et al.
        Influence of the type of emphysema in the relationship between COPD and lung cancer.
        Int J Chron Obstruct Pulmon Dis. 2018; 13: 3563-3570
        • Smith B.M.
        • Austin J.H.
        • Newell Jr., J.D.
        • et al.
        Pulmonary emphysema subtypes on computed tomography: the MESA COPD study.
        Am J Med. 2014; 127 (94 e97-23)
      1. Global Initiative for Chronic Obstructive Lung Disease 2020 Report.
        • Bae K.
        • Jeon K.N.
        • Lee S.J.
        • et al.
        Severity of pulmonary emphysema and lung cancer: analysis using quantitative lobar emphysema scoring.
        Medicine (Baltimore). 2016; 95e5494
        • Boueiz A.
        • Chang Y.
        • Cho M.H.
        • et al.
        Lobar emphysema distribution is associated with 5-year radiological disease progression.
        Chest. 2018; 153: 65-76