Chronic obstructive pulmonary disease (COPD) is a common comorbid disease in lung cancer, estimated to affect 40-70% of lung cancer patients, depending on diagnostic criteria. As smoking exposure is found in 85-90% of those diagnosed with either COPD or lung cancer, coexisting disease could merely reflect a shared smoking exposure. Potential confounding by age, sex and pack-yr smoking history, and/or by the possible effects of lung cancer on spirometry, may result in over-diagnosis of COPD prevalence.In the present study, the prevalence of COPD (pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2+ criteria) in patients diagnosed with lung cancer was 50% compared with 8% in a randomly recruited community control group, matched for age, sex and pack-yr smoking exposure (n5602, odds ratio 11.6; p,0.0001).In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer (n5127), we found a nonsignificant increase in COPD prevalence following diagnosis (56-61%; p50.45). After controlling for important variables, the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers; this is much greater than previously reported.We conclude that COPD is both a common and important independent risk factor for lung cancer.KEYWORDS: Chronic obstructive pulmonary disease, epidemiology, lung cancer, risk, spirometry A s only 10-15% of chronic smokers get lung cancer [1], host susceptibility factors have been implicated. Age, smoking history, family history and impaired lung function have been identified as key risk factors [2]. The question that then arises is: does the association between chronic obstructive pulmonary disease (COPD) and lung cancer come down to more than a shared smoking history?Cross-sectional studies show that the prevalence of COPD is 40-70% of those diagnosed with lung cancer [3,4], although prevalence is highly dependent on diagnostic criteria, age, sex and smoking exposure [5]. As none of these studies compared the prevalence of COPD in their lung cancer cohorts with a smoking cohort matched for these variables, the significance of this finding is uncertain. Moreover, none of these studies considered that lung cancer may itself cause an obstructive effect on spirometry. It is possible that potential confounding by age, sex and packyr smoking history on COPD prevalence, and/or the possible effects of lung cancer per se on spirometry, could result in over-diagnosis of COPD and a falsely increased association between COPD and lung cancer.

The clinical utility of spirometric screening of asymptomatic smokers for early signs of air flow limitation has recently come under review. The current authors propose that reduced forced expiratory volume in one second (FEV1) is more than a measure of airflow limitation, but a marker of premature death with broad utility in assessing baseline risk of chronic obstructive pulmonary disease (COPD), lung cancer, coronary artery disease and stroke, collectively accounting for 70-80% of premature death in smokers.Reduced FEV1 identifies undiagnosed COPD, has comparable utility to that of serum cholesterol in assessing cardiovascular risk and defines those smokers at greatest risk of lung cancer. As such, reduced FEV1 should be considered a marker that identifies smokers at greatest need of medical intervention.Smoking cessation has been shown to attenuate FEV1 decline and, if achieved before the age of 45-50 yrs, may not only preserve FEV1 within normal values but substantially reduce cardiorespiratory complications of smoking.Recent findings suggest inhaled drugs (bronchodilators and corticosteroids), and possibly statins, may be effective in reducing morbidity and mortality in patients with chronic obstructive pulmonary disease. The current authors propose that spirometry has broad utility in identifying smokers who are at greatest risk of cardiorespiratory complications and greatest benefit from targeted preventive strategies, such as smoking cessation, prioritised screening and effective pharmacotherapy.

Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-kB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-a, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.

Recently, several large genome-wide association studies have identified a putative ''lung cancer'' locus in the nicotinic acetylcholine receptor subunit genes (nAChR) on 15q25. However, these findings may be confounded by the presence of chronic obstructive pulmonary disease (COPD), which is also strongly associated with smoking exposure and lung cancer. This is likely as the prevalence of COPD in lung cancer cohorts is as much as two-fold greater than that reported in smoking control populations (50 versus 20%).The present authors compared the genotype frequencies of the most strongly associated single nucleotide polymorphism (rs16969968) in the a5 subunit of the nAChR gene cluster between three matched smoking cohorts.The AA genotype was found to be more frequent and was seen in 437 (16%) lung cancer cases and 445 (14%) COPD cases compared with 475 (9%) healthy smoking controls. More importantly, when 429 lung cancer cases were divided according to spirometry results (performed within 3 months of diagnosis, prior to surgery and in the absence of effusions or collapse), the AA genotype was present in 19 and 11% of cases with and without COPD, respectively.These findings suggest that the association between the a5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the single greatest risk factor for lung cancer in smokers and is found in 50-90% of lung cancer cases. The link between COPD and lung cancer may stem in part from the matrix remodelling and repair processes underlying COPD, and the development of epithelial-mesenchymal transition (EMT) that underlies lung carcinogenesis. The Hedgehog-interacting protein (HHIP), which mediates the epithelial response (EMT) to smoking, has been implicated in COPD and lung cancer. Recent genomewide and candidate gene studies of COPD implicate genetic variants on the chromosomal 4q31 (HHIP/glycophorin A (GYPA)) locus.In a case-control study of smokers with normal lung function, COPD and lung cancer (subphenotyped for COPD), we show the GG genotype of the rs 1489759 HHIP single-nucleotide polymorphism (SNP) and the CC genotype of the rs 2202507 GYPA SNP confers a ''protective'' effect on COPD (OR 0.59, p50.006 for HHIP and OR50.65, p50.006 for GYPA) and lung cancer (OR50.70 (p50.05) for HHIP and OR 0.70 (p50.02) for GYPA).This study suggests that, in smokers, genetic variants of the 4q31 locus conferring a protective effect for COPD are also protective in lung cancer. We conclude that genetic susceptibility to lung cancer includes COPD-related gene variants.