Effect of Emphysema on Lung Cancer Risk in Smokers: A Computed Tomography–Based Assessment

The contribution of emphysema to lung cancer risk has been recognized, but the effect size needs to be further defined. In this study, 565 primary lung cancer cases were enrolled though a prospective lung cancer cohort at Mayo Clinic, and 450 controls were smokers participating in a lung cancer screening study in the same institution using spiral computed tomography (CT). Cases and controls were frequency matched on age, gender, race, smoking status, and residential region. CT imaging using standard protocol at the time of lung cancer diagnosis (case) or during the study (control) was assessed for emphysema by visual scoring CT analysis as a percentage of lung tissue destroyed. The clinical definition of emphysema was the diagnosis recorded in the medical documentation. Using multiple logistic regression models, emphysema (≥5% on CT) was found to be associated with a 3.8-fold increased lung cancer risk in Caucasians, with higher risk in subgroups of younger (<65 years old, OR = 4.64), heavy smokers (≥40 pack-years, OR = 4.46), and small-cell lung cancer (OR = 5.62). When using >0% or ≥10% emphysema on CT, lung cancer risk was 2.79-fold or 3.33-fold higher than controls. Compared with CT evaluation (using criterion ≥5%), the sensitivity, specificity, positive and negative predictive values, and the accuracy of the clinical diagnosis for emphysema in controls were 19%, 98%, 73%, 84%, and 83%, respectively. These results imply that an accurate evaluation of emphysema could help reliably identify individuals at greater risk of lung cancer among smokers. Cancer Prev Res; 4(1); 43–50. ©2010 AACR.

[1]  D. Lomas,et al.  What can naturally occurring mutations tell us about the pathogenesis of COPD? , 2009, Thorax.

[2]  D. Mannino,et al.  Global burden of COPD: risk factors, prevalence, and future trends , 2007, The Lancet.

[3]  J. Gurney,et al.  Pathophysiology of obstructive airways disease. , 1998, Radiologic clinics of North America.

[4]  E. Schachter Tuberculin negative tuberculosis. , 2015, The American review of respiratory disease.

[5]  David O Wilson,et al.  Association of radiographic emphysema and airflow obstruction with lung cancer. , 2008, American journal of respiratory and critical care medicine.

[6]  N. Müller,et al.  "Density mask". An objective method to quantitate emphysema using computed tomography. , 1988, Chest.

[7]  Gorka Bastarrika,et al.  Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. , 2007, Chest.

[8]  W. Bamlet,et al.  Alpha 1-Antitrypsin Deficiency Carriers , Tobacco Smoke , Chronic Obstructive Pulmonary Disease , and Lung Cancer Risk , 2008 .

[9]  S. Thibodeau,et al.  Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. , 2005, Chest.

[10]  P. Calverley,et al.  COPD: early detection and intervention. , 2000, Chest.

[11]  J. Brody,et al.  Chronic obstructive pulmonary disease, inflammation, and lung cancer , 2006 .

[12]  M. Spitz,et al.  Opposing effects of emphysema, hay fever, and select genetic variants on lung cancer risk. , 2005, American journal of epidemiology.

[13]  P. Tønnesen How to reduce smoking among teenagers , 2002, European Respiratory Journal.

[14]  S. Mayne,et al.  Previous lung disease and risk of lung cancer among men and women nonsmokers. , 1999, American journal of epidemiology.

[15]  Anne-Marie Sykes,et al.  CT screening for lung cancer: five-year prospective experience. , 2005, Radiology.

[16]  Zhifu Sun,et al.  Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression. , 2004, The Lancet. Oncology.

[17]  W. Blot,et al.  Lung cancer among women in north-east China. , 1990, British Journal of Cancer.

[18]  J. Boice,et al.  Preexisting lung disease and lung cancer among nonsmoking women. , 1992, American journal of epidemiology.

[19]  E. Hoffman,et al.  Quantification of pulmonary emphysema from lung computed tomography images. , 1997, American journal of respiratory and critical care medicine.

[20]  D. Mannino COPD and lung cancer have come a long way ...baby. , 2007, American journal of respiratory and critical care medicine.

[21]  Avrum Spira,et al.  State of the art. Chronic obstructive pulmonary disease, inflammation, and lung cancer. , 2006, Proceedings of the American Thoracic Society.

[22]  N. Müller,et al.  Lung nodule enhancement at CT: multicenter study. , 2000, Radiology.

[23]  L. Donnelly,et al.  The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? , 2007, Pharmacology & therapeutics.

[24]  P. Paré,et al.  The growing burden of chronic obstructive pulmonary disease and lung cancer in women: examining sex differences in cigarette smoke metabolism. , 2007, American journal of respiratory and critical care medicine.

[25]  M. Martinetti,et al.  "The sarcoidosis map": a joint survey of clinical and immunogenetic findings in two European countries. , 1995, American journal of respiratory and critical care medicine.

[26]  J. Gurney,et al.  Regional distribution of emphysema: correlation of high-resolution CT with pulmonary function tests in unselected smokers. , 1992, Radiology.

[27]  J. Samet,et al.  Personal and family history of respiratory disease and lung cancer risk. , 1986, The American review of respiratory disease.

[28]  J. Lubin,et al.  Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. , 2001, International journal of epidemiology.

[29]  F. Gómez,et al.  Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease , 2002, Current opinion in pulmonary medicine.

[30]  S. Wacholder,et al.  Chronic Obstructive Pulmonary Disease and Altered Risk of Lung Cancer in a Population-Based Case-Control Study , 2009, PloS one.

[31]  M. Hasegawa,et al.  Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease , 2007, Thorax.

[32]  F. Martinez,et al.  Differential Diagnosis of Chronic Airflow Obstruction , 2000, The Journal of asthma : official journal of the Association for the Care of Asthma.

[33]  T. Lesnick,et al.  Alpha1-antitrypsin deficiency allele carriers among lung cancer patients. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[34]  J. Gurney,et al.  The correlation of emphysema or airway obstruction with the risk of lung cancer: a matched case-controlled study , 2002, European Respiratory Journal.

[35]  P. Gevenois,et al.  Quantitative computed tomography assessment of lung structure and function in pulmonary emphysema. , 2001, The European respiratory journal.

[36]  G. McVey,et al.  Screening for lung cancer using low dose CT scanning: results of 2 year follow up , 2005, Thorax.

[37]  W. Bamlet,et al.  Alpha1-antitrypsin deficiency carriers, tobacco smoke, chronic obstructive pulmonary disease, and lung cancer risk. , 2008, Archives of internal medicine.

[38]  S. Swensen,et al.  Lung cancer screening with CT: Mayo Clinic experience. , 2003, Radiology.

[39]  C. la Vecchia,et al.  Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes , 2009, European Respiratory Journal.

[40]  Stephen J. Swensen,et al.  CT Reconstruction Algorithm Selection in the Evaluation of Solitary Pulmonary Nodules , 1995, Journal of computer assisted tomography.

[41]  R. Loddenkemper,et al.  Patterns of distribution and clearance of aerosols in patients with bronchiectasis. , 2015, The American review of respiratory disease.

[42]  R. Brownson,et al.  Previous lung disease and lung cancer risk among women (United States) , 2000, Cancer Causes & Control.