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Background: Chronic cough affects up to 10% of the general population and was previously perceived as a comorbidity of underlying conditions, but is nowadays classified as a disease in its own entity that could confer increased risk of morbidity and mortality. We tested the hypothesis that chronic cough is associated with increased risk of COPD exacerbation, pneumonia and all-cause mortality in the general population., Methods: We identified 2801 individuals with chronic cough, defined as cough lasting >8 weeks, among 44 756 randomly selected individuals from the Copenhagen General Population Study, and recorded COPD exacerbations, pneumonia and all-cause mortality during follow-up., Results: During up to 5.9 years of follow-up (median 3.4 years), 173 individuals experienced COPD exacerbation, 767 experienced pneumonia and 894 individuals died. Individuals with chronic cough versus those without had cumulative incidences at age 80 years of 12% versus 3% for COPD exacerbation, 30% versus 15% for pneumonia, and 25% versus 13% for death from all causes. After adjustment for age, sex and smoking, individuals with chronic cough versus those without had adjusted hazard ratios of 4.6 (95% CI 2.9-7.2) for COPD exacerbation, 2.2 (1.7-2.7) for pneumonia and 1.7 (1.4-2.0) for all-cause mortality. Among current smokers aged >60 years with airflow limitation, those with versus without chronic cough had an absolute 5-year risk of 10% versus 4% for COPD exacerbation, 16% versus 8% for pneumonia and 19% versus 12% for all-cause mortality., Conclusion: Chronic cough is associated with higher risks of COPD exacerbation, pneumonia and death, independent of airflow limitation and smoking., Competing Interests: Conflict of interest: B.G. Nordestgaard has consultancies with Amarin, Akcea, Amgen, AstraZeneca, Denka Seiken, Kowa, Novartis, Novo Nordisk and Silence Therap. No conflicts of interest exist for E.M. Landt, Y. Çolak, P. Lange and M. Dahl, (Copyright ©The authors 2024.)

Background: The most recent guideline on acute pulmonary embolism (PE) indicates possible long-term sequelae such as dyspnoea and chronic thromboembolic pulmonary hypertension after a PE event. However, effects on lung function or asthma risk have not been evaluated in the general population., Methods: We tested whether individuals with a venous thromboembolism (VTE) encompassing PE and deep vein thrombosis (DVT) have reduced lung function, or greater risks of dyspnoea and asthma using data from 102 792 adults from the Copenhagen General Population Study. Diagnoses of PE, DVT and asthma were collected from the national Danish Patient Registry. Factor V Leiden and prothrombin G20210A gene variants were determined using TaqMan assays., Results: Prevalences of PE, DVT and VTE were 2.2%, 3.6% and 5.2%, respectively. Individuals with VTE had forced expiratory volume in 1 s of 92% predicted compared with 96% pred in individuals without VTE (p<0.001). Individuals with VTE versus those without had adjusted OR (95% CI) for light, moderate and severe dyspnoea of 1.4 (1.2-1.6), 1.6 (1.4-1.8) and 1.7 (1.5-1.9), respectively. Individuals with VTE versus those without had an adjusted OR for asthma of 1.6 (95% CI 1.4-1.8). Factor V Leiden and prothrombin G20210A genotype also associated with increased risk of asthma (p for trend=0.002). Population-attributable fractions of severe dyspnoea and asthma due to VTE were 3.5% and 3.0%, respectively, in the population., Conclusion: Individuals with VTE have worse lung function and higher risks of severe dyspnoea and asthma, and may account for 3.5% and 3.0% of people with severe dyspnoea and asthma, respectively, in the general population., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2023.)

Background: Individuals with α 1 -antitrypsin deficiency have increased elastase activity resulting in continuous degradation of elastin and early onset of COPD. Increased elastase activity may also affect elastic properties of the heart, which may impact risk of heart failure. We tested the hypothesis that α 1 -antitrypsin deficiency is associated with increased risk of heart failure in two large populations., Methods: In a nationwide nested study of 2209 patients with α 1 -antitrypsin deficiency and 21 869 controls without α 1 -antitrypsin deficiency matched on age, sex and municipality, we recorded admissions and deaths due to heart failure during a median follow-up of 62 years. We also studied a population-based cohort of another 102 481 individuals from the Copenhagen General Population Study including 187 patients from the Danish α 1 -Antitrypsin Deficiency Registry, all with genetically confirmed α 1 -antitrypsin deficiency., Results: Individuals with versus without α 1 -antitrypsin deficiency had increased risk of heart failure hospitalisation in the nationwide cohort (adjusted hazard ratio 2.64, 95% CI 2.25-3.10) and in the population-based cohort (1.77, 95% CI 1.14-2.74). Nationwide, these hazard ratios were highest in those without myocardial infarction (3.24, 95% CI 2.70-3.90), without aortic valve stenosis (2.80, 95% CI 2.38-3.29), without hypertension (3.44, 95% CI 2.81-4.22), without atrial fibrillation (3.33, 95% CI 2.75-4.04) and without any of these four diseases (6.00, 95% CI 4.60-7.82). Hazard ratios for heart failure-specific mortality in individuals with versus without α 1 -antitrypsin deficiency were 2.28 (95% CI 1.57-3.32) in the nationwide cohort and 3.35 (95% CI 1.04-10.74) in the population-based cohort., Conclusion: Individuals with α 1 -antitrypsin deficiency have increased risk of heart failure hospitalisation and heart failure-specific mortality in the Danish population., Competing Interests: Conflict of interest: B.G. Nordestgaard has consultancies with Amarin, Akcea, Amgen, AstraZeneca, Denka Seiken, Kowa, Novartis, Novo Nordisk and Silence Therap. Conflict of interest: No conflicts of interest exist for S.V. Winther, E.M. Landt, N. Seersholm and M. Dahl., (Copyright ©The authors 2023.)

Background: Randomised controlled trials found that low-density lipoprotein (LDL) cholesterol-lowering statins increase lung function and possibly decrease rate of exacerbations in individuals with COPD. However, it is unknown whether high levels of LDL cholesterol are associated with increased susceptibility to COPD., Methods: We tested the hypothesis that high LDL cholesterol is associated with increased risk of COPD, severe COPD exacerbation and COPD-specific mortality. We examined 107 301 adults from the Copenhagen General Population Study. COPD outcomes were ascertained at baseline and prospectively through nationwide registries., Results: In cross-sectional analysis, low LDL cholesterol was associated with increased risk of COPD (odds ratio for 1st versus 4th quartile: 1.07 (95% CI 1.01-1.14)). Prospectively, low LDL cholesterol was associated with increased risk of COPD exacerbations with hazard ratios of 1.43 (1.21-1.70) for 1st versus 4th quartile, 1.21 (1.03-1.43) for 2nd versus 4th quartile, and 1.01 (0.85-1.20) for 3rd versus 4th quartile of LDL cholesterol (p-value for trend=6×10 -6 ). Finally, low LDL cholesterol was likewise associated with increased risk of COPD-specific mortality (log-rank test: p=0.0009). Sensitivity analyses with death as competing risk provided similar results., Conclusion: Low LDL cholesterol was associated with increased risks of severe COPD exacerbation and COPD-specific mortality in the Danish general population. As this is opposite of that observed in randomised controlled trials with statins, our findings might be a result of reverse causation indicating that individuals with severe phenotypes of COPD have lower plasma levels of LDL cholesterol due to wasting., Competing Interests: Conflict of interest: J. Freyberg, E.M. Landt, S. Afzal, B.G. Nordestgaard and M. Dahl have nothing to disclose., (Copyright ©The authors 2023.)