Features of COPD as Predictors of Lung Cancer

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Lung cancer is a leading cause of death and hospitalization for patients with COPD. A detailed understanding of which clinical features of COPD increase risk is needed.


We performed a nested case-control study of Genetic Epidemiology of COPD (COPDGene) Study subjects with and without lung cancer, age 45 to 80 years, who smoked at least 10-pack years to identify clinical and imaging features of smokers, with and without COPD, that are associated with an increased risk of lung cancer. The baseline evaluation included spirometry, high-resolution chest CT scanning, and respiratory questionnaires. New lung cancer diagnoses were identified over 8 years of longitudinal follow-up. Cases of lung cancer were matched 1:4 with control subjects for age, race, sex, and smoking history. Multiple logistic regression analyses were used to determine features predictive of lung cancer.


Features associated with a future risk of lung cancer included decreased FEV1/FVC (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, and ≥ 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, was 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 the risk of lung cancer.

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