The Impact of Chronic Obstructive Pulmonary Disease in Lung Cancer and its Outcomes in High Risk Smokers

Abstract

Background: The existing literature suggests that Chronic Obstructive Pulmonary Disease (COPD) and lung cancer may be linked by more than smoking exposure alone. COPD is characterised by reduced expiratory flow rates and quantified as airflow limitation. The studies reported in this thesis explore the relationship between lung cancer and COPD, through several different approaches. Null Hypothesis: COPD and lung cancer are not related. Aim: To assess the relationship between COPD and lung cancer using different smoking cohorts in order to better understand if any links are evident. Methods: Using stratification of smokers according to the presence or absence of COPD, symptomatic airways disease or increasing severity of airflow limitation, to examine relationships and outcomes in lung cancer. This entailed cross-sectional and cohort study designs and covers both epidemiological and genetic approaches. Results: Using an epidemiological approach and comparing outcomes in heavy smokers, I have found the following associations- (1) COPD severity and lung cancer diagnosed prospectively are related in a linear fashion, independent of age and pack years. (Confirmatory) (2) While COPD is associated with an increased risk of lung cancer, it is also associated with more aggressive cancer, less surgery and more non-lung cancer related deaths in the context of computed tomography (CT) screening. (Novel) (3) Severe COPD is related to poorer outcomes from lung cancer screening relative to mild or asymptomatic forms of COPD. (Novel) My case-case ethnicity study found that despite comparable smoking exposure Maori develop lung cancer on average, six years younger than their Caucasian counterpart, and that this is associated with worse lung function (with loss of the expected dose-response relationship), and greater mortality, independent of stage at diagnosis. Lastly, I confirmed our earlier studies showing that COPD and lung cancer are linked at a molecular level through the nicotine acetylcholine receptor gene variant. Conclusion: I conclude that COPD has a strong relationship with lung cancer, independent of smoking that includes genetic linkage, greater risk with increasing airflow limitation albeit with poorer outcomes from screening.