The link between chronic obstructive pulmonary disease phenotypes and histological subtypes of lung cancer: a case-control study

Background: COPD is considered an independent risk factor for lung cancer. COPD and lung cancer are both very heterogeneous diseases, and the study herein investigates the link between COPD phenotypes and specific histological subtypes of lung cancer. Methods: This case-control study comprised 2,283 patients with newly diagnosed pathological lung cancer and 2,323 non-lung cancer controls. All participants underwent pulmonary function tests. The diagnosis of COPD was based on Global Initiative for Chronic Obstructive Lung Disease criteria. Subtypes of the two diseases were categorized according to 2015 World Health Organization classification of lung cancer and computer quantification of airway collapse on maximum expiratory flow volume. ORs were estimated using logistic regression analysis. Results: The prevalence of COPD was higher (32.8%) in lung cancer patients compared to controls (16.0%). After adjustment for age, sex, body-mass index, and smoking status, the presence of COPD significantly increased the risk of lung cancer (OR 2.88, 95% CI 2.48-3.34) and all common histological subtypes (ORs 2.04-5.26). Both emphysema-predominant and non-emphysema-predominant phenotypes of COPD significantly increased the risk of lung cancer (OR 4.43, 95% CI 2.85-6.88; OR 2.82, 95% CI 2.40-3.31). Higher risk of squamous-cell carcinoma and small-cell lung cancer was observed in patients with the emphysema-predominant than the non-emphysema-predominant phenotype (OR 1.73, 95% CI 1.03-2.89; OR 3.74, 95% CI 1.64-8.53). Conclusion: COPD was an independent risk factor for lung cancer and all common histological subtypes. Both emphysema-predominant and non-emphysema-predominant phenotypes of COPD significantly increased the risk of lung cancer. Relative to non-emphysema-predominant phenotype of COPD, emphysema-predominant phenotype had a higher risk of squamous-cell carcinoma and small-cell lung cancer.