Chronic cough associated with COPD exacerbation, pneumonia and death in the general population.

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.

α1-Antitrypsin deficiency associated with increased risk of heart failure.

Background: Individuals with α1-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 α1-antitrypsin deficiency is associated with increased risk of heart failure in two large populations. Methods: In a nationwide nested study of 2209 patients with α1-antitrypsin deficiency and 21 869 controls without α1-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 α1-Antitrypsin Deficiency Registry, all with genetically confirmed α1-antitrypsin deficiency. Results: Individuals with versus without α1-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 α1-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 α1-antitrypsin deficiency have increased risk of heart failure hospitalisation and heart failure-specific mortality in the Danish population.

Low-density lipoprotein cholesterol and risk of COPD: Copenhagen General Population Study.

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.

Second-Hand Smoke Exposure Associated with Risk of Respiratory Symptoms, Asthma, and COPD in 20,421 Adults from the General Population.

RATIONALE: Individuals exposed to second-hand smoking may be more susceptible to asthma and chronic obstructive pulmonary disease (COPD). We investigated the risk of respiratory symptoms, asthma, and COPD in adults exposed to second-hand smoking at different stages of life in the general population. METHODS: We identified individuals who had been exposed to second-hand smoking in childhood only, adulthood only, or lifelong in a cohort of 20,421 adults from the Danish General Suburban Population Study and recorded respiratory symptoms, lung function, asthma, and COPD as outcomes. RESULTS: Among 20,421 adults from the general population, 2,551 (12%) had been lifelong exposed to second-hand smoking, 459 (2%) had been exposed in adulthood only, and 13,998 (69%) had been exposed in childhood only; the mean ages of the three groups were 54 years, 55 years, and 57 years, respectably, compared with 56 years in non-exposed individuals (P<0.001). Equivalent values for the prevalence of current smoking were 25%, 20%, and 18% versus 12% (P<0.001). After adjustment for age, smoking, and sex, the odds ratios for wheezing, severe dyspnoea, cough on exertion, and asthma increased as a function of second-hand smoke exposure (Ps≤0.004); individuals who had been exposed to second-hand smoking lifelong, in adulthood only, or in childhood only versus non-exposed had increased odds ratios for wheezing of 1.62 (95% CI=1.41-1.87), 1.50 (1.15-1.94), and 1.16 (1.04-1.30). Corresponding values were 2.08 (1.52-2.85), 2.05 (1.22-3-44), and 1.23 (0.95-1.59) for severe dyspnoea, 1.56 (1.33-1.83), 1.53 (1.15-2.02), and 1.19 (1.05-1.35) for cough on exertion, 1.36 (1.14-1.63), 1.49 (1.09-2.05), and 1.13 (0.99-1.30) for asthma, and 1.24 (1.03-1.48), 1.25 (0.90-1.74), and 1.09 (0.96-1.24) for COPD. The population attributable fractions of asthma and COPD due to lifelong second-hand smoke exposure were 4.3% and 2.9%. CONCLUSION: Individuals exposed to lifelong second-hand smoking have increased risks of respiratory symptoms, asthma, and COPD, and may account for 4.3% and 2.9% of people with asthma and COPD in the general population.