Phenotypic and endotypic features of COPD associated with lung cancer development.

Abstract

e13563 Background: Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with multiple phenotypes and endotypes and associated with lung cancer development. In this study, we analyzed the clinical features of COPD including various phenotypic and endotypic features from the electronic health records (EHR) as the potential risk factors for lung cancer development in a large cohort of COPD patients. Methods: We identified a COPD cohort based on electronic Medical Records and Genomics (eMERGE) network COPD cohort identification algorithms with minor modifications from the Mount Sinai Data Warehouse (2000-2020) and followed the patients on the first diagnosis of lung cancer. The development of lung cancer in COPD patients was confirmed by manual chart review. We retrieved the clinical features from EHRs and conducted Kaplan Meier (KM) analysis and multivariable Cox-regression modeling for hazard ratio (HR) analysis. Results: We found that 3.8 % of COPD patients (824 out of 21,658) developed lung cancer. While COPD patients with emphysema and smoking history (former or current) showed an increased risk of lung cancer onset, patients with concurrent asthma and corticosteroid (ICS) inhalation history showed a reduced risk of lung cancer onset (adjusted HR in Table). Interestingly, COPD patients with higher eosinophil counts showed late onset of lung cancer (>300 cells/ul, cancer rate at 5y=2.4%, p=< 0.002; 150-300 cells/ul, cancer rate at 5y=2.9%, p=0.003) when compared to patients with low eosinophils count (<150 cells/ul, cancer rate at 5y=3.4%) in a KM analysis. A multivariable analysis adjusted for age, gender, race, smoking status, COPD sub-phenotypes, severe exacerbation history, and ICS inhalation history showed a significantly lower risk of lung cancer in COPD patients with higher eosinophils count (150-300 cells/ul; HR: 0.82, 95% CI: 0.69-0.97, p=0.021 and >300 cells/ul; HR:0.72, 95% CI: 0.57-0.89, p=0.003) when compared to those with low eosinophils count (<150 cells/ul). Conclusions: Our study shows that many phenotypic and endotypic features of COPD are differentially associated with lung cancer development. High eosinophil levels, ICS usage, and concurrent asthma in COPD patients may reduce the risk of lung cancer development. [Table: see text]