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Jens Ellingsen, 1 Gunnar Johansson, 2 Kjell Larsson, 3 Karin Lisspers, 2 Andrei Malinovschi, 4 Björn Ställberg, 2 Marcus Thuresson, 5 Christer Janson 1 1Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 2Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 3Integrative Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 4Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden; 5Statisticon AB, Uppsala, SwedenCorrespondence: Jens EllingsenDepartment of Medical Sciences, Respiratory, Allergy and Sleep Research, Akademiska Sjukhuset, Uppsala SE-751 85, SwedenTel +46 18 611 13 93Fax +46 18 611 02 28Email jens.ellingsen@medsci.uu.seBackground: Life expectancy is significantly shorter for patients with chronic obstructive pulmonary disease (COPD) than the general population. Concurrent diseases are known to infer an increased mortality risk in those with COPD, but the effects of pharmacological treatments on survival are less established. This study aimed to examine any associations between commonly used drugs, comorbidities and mortality in Swedish real-world primary care COPD patients.Methods: Patients with physician-diagnosed COPD from a large primary care population were observed retrospectively, utilizing primary care records and mandatory Swedish national registers. The time to all-cause death was assessed in a stepwise multiple Cox proportional hazards regression model including demography, socioeconomic factors, exacerbations, comorbidities and medication.Results: During the observation period (1999– 2009) 5776 (32.5%) of 17,745 included COPD patients died. Heart failure (hazard ratio [HR]: 1.88, 95% confidence interval [CI]: 1.74– 2.04), stroke (HR: 1.52, 95% CI: 1.40– 1.64) and myocardial infarction (HR: 1.40, 95% CI: 1.24– 1.58) were associated with an increased risk of death. Use of inhaled corticosteroids (ICS; HR: 0.79, 95% CI: 0.66– 0.94), beta-blockers (HR: 0.86, 95% CI: 0.76– 0.97) and acetylsalicylic acid (ASA; HR: 0.87, 95% CI: 0.77– 0.98) was dose-dependently associated with a decreased risk of death, whereas use of long-acting muscarinic antagonists (LAMA; HR: 1.33, 95% CI: 1.14– 1.55) and N-acetylcysteine (NAC; HR: 1.26, 95% CI: 1.08– 1.48) were dose-dependently associated with an increased risk of death in COPD patients.Conclusion: This large, retrospective, observational study of Swedish real-world primary care COPD patients indicates that coexisting heart failure, stroke and myocardial infarction were the strongest predictors of death, underscoring the importance of timely recognition and treatment of comorbidities. A decreased risk of death associated with the use of ICS, beta-blockers and ASA, and an increased risk associated with the use of LAMA and NAC, was also found.Keywords: observational, LAMA, inhaled corticosteroids, beta-blockers, acetylsalicylic acid, chronic obstructive pulmonary disease

Martin Sandelin,1 Stéphanie Mindus,1 Marcus Thuresson,2 Karin Lisspers,3 Björn Ställberg,3 Gunnar Johansson,3 Kjell Larsson,4 Christer Janson1 1Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 2Statisticon AB, Uppsala, Sweden; 3Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 4Lung and Allergy Research Unit, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden Background: The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers. Methods: To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients. Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392). Results: Of the total cohort, 19,894 patients were included in the study. Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population. In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41–0.71), while the risk of lung cancer increased with increasing age. A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37–0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15–2.16). Conclusion: In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk. The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies. Keywords: asthma, NSCLC, risk factor, ACO, inhaled corticosteroids