Features of COPD as Predictors of Lung Cancer

Laurie L Carr, Sean Jacobson, David A Lynch, Marilyn G Foreman, Eric L Flenaugh, Craig P Hersh, Frank C Sciurba, David O Wilson, Jessica C Sieren, Patrick Mulhall, Victor Kim, C Matthew Kinsey, Russell P Bowler

Lung cancer is a leading cause of death and hospitalization for patients with chronic obstructive lung disease, (COPD); a detailed understanding of which clinical features of COPD increase risk is needed. To identify clinical and imaging features of smokers, with and without COPD, that are associated with an increased risk of lung cancer, we performed a nested case-control study of COPDGene subjects with and without lung cancer, age 45-80, who smoked at least 10-pack years. Baseline evaluation included: spirometry, high-resolution chest CT, and respiratory questionnaires. New lung cancer diagnoses were identified over eight years of longitudinal follow-up. Lung cancer cases were matched 1:4 with control subjects for age, race, gender, and smoking history. Multiple logistic regressions were used to determine features predictive of lung cancer. Features associated with a future risk of lung cancer included: decreased FEV1/FVC (Odds Ratio (OR) 1.28 per 10% decrease, 95%CI 1.12- 1.46), visual severity of emphysema (OR 2.31, none-trace vs mild-advanced, 95%CI 1.41-3.86), and respiratory exacerbations prior to study entry (OR 1.39 per increased events, 0, 1, > 2, 95%CI 1.04-1.85). Respiratory exacerbations were also associated with small-cell lung cancer histology (OR 3.57, 95%CI, 1.47-10). The degree of COPD severity, including airflow obstruction, visual emphysema and respiratory exacerbations are independently predictive of lung cancer. These risk factors should be further studied as inclusion and exclusion criteria for the survival benefit of lung cancer screening. Studies are needed to determine if reduction in respiratory exacerbations among smokers can reduce lung cancer risk.