Features of COPD as Predictors of Lung Cancer

Abstract

Background: 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.

Methods: 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.

Results: 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]).

Conclusions: 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.

Keywords: COPD; chest imaging; lung cancer.

Figure 1

Kaplan-Meier curve for lung cancer diagnosis, comparing subjects with no acute respiratory exacerbations reported in the 12 months prior to study enrollment (n = 387) vs those with one or more reported exacerbations (n = 87). Subjects were followed up for 8 years; those who died without lung cancer or were lost to follow-up were censored as marked. HRs are based on an unadjusted analysis of time to lung cancer diagnosis. This analysis was limited to cases with an annotated lung cancer diagnosis date and the matched control subjects. HR = hazard ratio.

Figure 2

Kaplan-Meier curve comparing subjects with no to trace visual centrilobular emphysema (n = 162) vs those with mild to advanced visual emphysema (n = 250). Subjects were followed for 8 years for a lung cancer diagnosis. Subjects who died without lung cancer or were lost to follow-up were censored as marked. HRs are based on an unadjusted analysis of time to lung cancer diagnosis. This analysis was limited to those cases with annotated lung cancer diagnosis dates, complete visual emphysema assessment, and the matched control subjects. See Figure 1 legend for expansion of abbreviation.

Figure 3

Lung cancer associations with degree of visual CLE. HRs (squares) and 95% CIs (whiskers) for the presence of each degree of visual emphysema on CT scan and study entry. GOLD = Global Initiative for Chronic Lung Disease. See Figure 1 and 2 legends for expansion of other abbreviation.

Figure 4

Overall survival for lung cancer cases (N = 169) according to GOLD stage. Kaplan-Meier curve of subjects with a known lung cancer diagnosis confirmed by review of death certificates or medical records. See Figure 3 legend for expansion of abbreviation.