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Background: Novel biomarkers and targeted treatments are needed for patients with chronic obstructive pulmonary disease (COPD). Objective: To test the hypothesis that high plasma immunoglobulin (Ig)E concentrations associate with increased risk of exacerbation and mortality in individuals with COPD in the general population. Methods: Among 46,598 adults in the Copenhagen General Population Study, we included 1559 with COPD, defined as forced expiratory volume in 1 second/forced vital capacity < 0.70 and forced expiratory volume in 1 second < 80% predicted in individuals aged ≥ 40 years with chronic respiratory symptoms and smoking exposure ≥ 10 pack-years, and without asthma. We assessed risk of future severe exacerbation and all-cause mortality according to baseline plasma IgE ≥ 76 IU/mL, a clinical cutoff for omalizumab treatment in severe asthma. Results: During 14 years of follow-up (median, 6.9; interquartile range, 3.4), we recorded 224 severe exacerbations and 434 deaths in 1559 individuals with COPD. Individuals with COPD with IgE ≥ 76 IU/mL vs those with < 76 IU/mL had a multivariable adjusted hazard ratio (HR) of 1.43 (95% confidence interval, 1.07-1.89) for severe exacerbation and 1.30 (1.05-1.62) for all-cause mortality. Compared with individuals with IgE < 76 IU/mL and blood eosinophils < 300 cells/µL, the multivariable adjusted HR for severe exacerbation was 1.12 (0.76-1.67) for those with IgE < 76 IU/mL and blood eosinophils ≥ 300 cells/µL, 1.62 (1.17-2.24) for IgE ≥ 76 IU/mL and blood eosinophils < 300 cells/µL, and 1.06 (0.63-1.77) for those with IgE ≥ 76 IU/mL and blood eosinophils ≥ 300 cells/µL. Corresponding HRs for all-cause mortality were 1.27 (0.99-1.63), 1.47 (1.14-1.88), and 1.17 (0.83-1.64), respectively. Conclusion: High plasma IgE was associated with an increased risk of severe exacerbation and all-cause mortality in individuals with COPD in the general population, independent of blood eosinophils.

Aims: The relevance of adherence to established dietary guidelines is repeatedly challenged. We hypothesised that non-adherence to established dietary guidelines is associated with an excess risk of cardiovascular, non-cardiovascular and all-cause mortality. Methods: We studied 100,191 white adult Danes aged 20–100 years recruited in 2003–2015 and followed up until December 2018. During follow-up equalling 865,600 person-years, 9273 individuals died. Participants’ diets were assessed at baseline by a food frequency questionnaire focusing on key foods defining a healthy diet according to Danish dietary guidelines. Individuals were divided into five categories ranging from very high to very low adherence to dietary guidelines and studied with Cox and Fine–Gray regression models. At study inclusion, we collected demographic and lifestyle characteristics by questionnaire, made a physical examination and took a blood sample. Results: Cardiovascular, non-cardiovascular and all-cause mortality increased gradually with increasing non-adherence to dietary guidelines. Cardiovascular mortality was 30% higher (95% confidence interval 7–57%), non-cardiovascular mortality 54% higher (32–79%) and all-cause mortality 43% higher (29–59%) in individuals with very low adherence to dietary guidelines compared with those with very high adherence after adjustments for age, sex, education, income, smoking, leisure time physical activity and alcohol intake. Mortality risk estimates were similar in all strata of adjusted variables. Conclusion: Non-adherence to Danish food-based dietary guidelines is associated with up to 43% increased all-cause mortality in a dose–response manner. The mortality excess was seen for both cardiovascular and non-cardiovascular causes. The public has good reasons to have confidence in and to adhere to established dietary guidelines.

ObjectiveSleep apnea and elevated plasma glucose associates with inflammation which associates with the risk of COPD exacerbations. We investigated the risk of exacerbations in individuals with COPD, witnessed sleep apneas, and elevated plasma glucose.MethodsFrom the Copenhagen City Heart Study cohort, we identified 564 individuals with COPD (forced expiratory volume in 1 sec divided by forced vital capacity, FEV1/FVCResultsWe identified 74 (13%) individuals with sleep apnea without elevated plasma glucose, 70 (12%) had elevated plasma glucose (above 6.9 mM (>125 mg/dL)) without sleep apnea and 11 individuals had the presence of both conditions. In univariable analysis, witnessed apneas together with elevated plasma glucose had a high risk of exacerbations, hazard ratio (HR) = 5.81 (2.34-14.4, p = 0.0001) compared to those without sleep apnea and without elevated plasma glucose. Multivariable analysis, adjusting for several risk factors of exacerbations, showed a similar result, HR = 3.45 (1.13-10.5, p = 0.03). Both presence of sleep apnea without elevated plasma glucose and the presence of elevated plasma glucose without sleep apnea showed no associations with the risk of exacerbations.ConclusionsWitnessed sleep apneas in COPD are associated with increased risk of exacerbations, but only among those with elevated plasma glucose.

Objective Prolonged seated immobility during long-distance flights is related to an increased risk of venous thromboembolism (VTE), but little, if anything, is known about the risk related to sedentary work. The objective of this paper was to examine the risk of VTE according to sitting posture at work. Methods This prospective study includes a total of 78 936 participants from the Copenhagen City Heart Study and the Copenhagen General Population Study, all without previous thromboembolic events and aged <65 years. An assessment of the number of hours spent in sitting position at work was assigned each participant at baseline using a job exposure matrix. VTE was identified through national patient registries. Survival analyses were performed to determine the risk of VTE according to sedentary position at work with adjustment for a range of known determinants including lifestyle and coagulation factors. Results During the follow-up period of 582 411 person years (mean follow-up, 7.4 years) 911 participants experienced their first VTE event. Multivariable adjusted analyses showed no difference in risk of VTE between occupational sitting ≥6.5 hours/day and occupational sitting ≤3.5 hours/day (hazard ratio 1.11, 95% confidence interval 0.92-1.34). Conclusion This study does not support the hypothesis that sedentary work is a risk factor for VTE in the general population. Whether certain occupations with particularly high exposure to immobilized sitting positions are associated with thromboembolic events is not addressed.

Introduction We examined changes in smoking habits in the general population according to prevalence and incidence of chronic diseases affected by smoking. Methods We included 12283 individuals enrolled from 2003 in the Copenhagen General Population Study and re-examined from 2014. Participants were classified as either healthy or suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, heart disease or stroke. Results At entry, smoking prevalence was 15.4%in healthy participants, 29.8%with COPD, 15.8%with asthma, 21.7%with diabetes mellitus, 17.2%with ischemic heart disease/heart failure and 18.6%in participants with previous stroke. Smoking prevalence declined during the 10 years of observation. Among healthy subjects who developed one of the above mentioned diseases during follow-up, those who developed COPD had the highest initial smoking prevalence (51.5%). Quit rates were highest in those who developed asthma resulting in smoking prevalence of 8.2%versus 27.7%in COPD. After adjustment for age, smoking severity and genotype previously associated with heavy smoking (CHRNA3 rs1051730 AA), significant predictors of quitting were new diagnosis of ischemic heart disease/heart failure (OR=2.33, 95%CI: 1.61-3.42), new diagnosis of asthma (OR=1.84, 95%CI: 1.18-2.90) and low number of pack-years. Conclusions Individuals with prevalent smoking related diseases continued to smoke more than healthy individuals. Incident heart disease and asthma, but not incident COPD, stroke or diabetes were associated with a higher chance of quitting. Special focus on smokers with COPD, asthma, diabetes, stroke and ischemic heart disease/heart failure is warranted to decrease smoking prevalence in these groups. Smokers with a new diagnosis of diabetes, stroke and COPD need special smoking cessation support.

BACKGROUND: Previous findings regarding physical activity and risk of incident atrial fibrillation (AF) are controversial, focusing on leisure-time physical activity (LTPA) and without distinguishing it from occupational physical activity (OPA). Our aim was to study the association between physical activity and risk of AF, with special attention to the possible divergent effects of OPA and LTPA.METHODS AND RESULTS: In a prospective, observational cohort study, 17,196 subjects were included from the Copenhagen Population Register. All participants had a physical examination, a 12-lead electrocardiogram (ECG), and answered a questionnaire regarding health and physical activity. Participants without previously diagnosed AF who answered adequately regarding OPA and LTPA were included. LTPA and OPA were each graded into four levels. Follow-up were carried out between 1981-1983, 1991-1994, and 2001-2003. Information regarding hospitalization and mortality was drawn from the National Patient Registry and the Registry of Causes of Death. Outcome was incident AF as determined by follow-up ECG or register diagnosis. In univariable Cox regression analysis all sub-groups of OPA had a significant higher risk of AF compared to moderate OPA. When adjusting for confounders, the risk remained significantly increased for high OPA (hazard ratio (HR) 1.21 (95% confidence interval (CI) 1.02-1.43), p = 0.028), and very high OPA (HR 1.39 (95% CI 1.03-1.88), p = 0.034). We found no significant association between LTPA and incident AF.CONCLUSIONS: High and very high OPA were associated with a significantly increased risk of incident AF. LTPA was not associated with risk of incident AF.