Low smoking exposure and development and prognosis of COPD over four decades: A population-based cohort study.

A diagnosis of chronic obstructive pulmonary disease (COPD) is mainly considered in individuals with more than 10 pack-years of smoking. We tested the hypothesis that low smoking exposure, below the critical threshold of 10 pack-years, increases risk of COPD and leads to poor prognosis.We followed non-obstructive adult smokers from the Copenhagen City Heart Study for COPD, defined as forced expiratory volume in one second [FEV1]/forced vital capacity [FVC]<0.70 and FEV1<80% predicted, and for related clinical outcomes. First, we followed individuals for 5years according to baseline smoking for risk of developing COPD, and hereafter for up to four decades for severe exacerbations and death.In 6098 non-obstructive smokers, 1781(29%) developed COPD after 5 years follow-up; 23% in individuals with <10pack-years of smoking at baseline, 26% in those with 10-19.9pack-years, 30% in those with 20-39.9pack-years, and 39% in those with ≥40pack-years. During four decades follow-up, we recorded 620 exacerbations and 5573 deaths. Compared to individuals without COPD with <10pack-years of smoking, multivariable adjusted hazard ratios (HRs) for exacerbations were 1.94(95% confidence interval:1.36-2.77) in those without COPD with ≥10pack-years, 2.83(1.72-4.66) in those with COPD with <10pack-years, 4.34(2.93-6.43) in COPD with 10-19.9pack-years, 4.39(2.98-6.47) in COPD with 20-39.9pack-years, and 4.98(3.11-7.97) in COPD with ≥40pack-years. Corresponding HRs for all-cause mortality were 1.20(1.10-1.32), 1.33(1.14-1.56), 1.59(1.40-1.80),1.81(1.62-2.03), and 1.81(1.55-2.10), respectively.Low smoking exposure below the critical threshold of 10 pack-years increases risk of COPD in middle-aged adults within 5 years, and these individuals have increased risk of severe exacerbation and early death over four decades.

Use of sugar in coffee and tea and long-term risk of mortality in older adult Danish men: 32 years of follow-up from a prospective cohort study.

BACKGROUND: Tea and coffee are the most consumed beverages worldwide and very often sweetened with sugar. However, the association between the use of sugar in tea or coffee and adverse events is currently unclear. OBJECTIVES: To investigate the association between the addition of sugar to coffee or tea, and the risk of all-cause mortality, cardiovascular mortality, cancer mortality and incident diabetes mellitus. METHODS: Participants from the prospective Copenhagen Male Study, included from 1985 to 1986, without cardiovascular disease, cancer or diabetes mellitus at inclusion, who reported regular coffee or tea consumption were included. Self-reported number of cups of coffee and tea and use of sugar were derived from the study questionnaires. Quantity of sugar use was not reported. Primary outcome was all-cause mortality and secondary endpoints were cardiovascular mortality, cancer mortality and incident diabetes mellitus, all assessed through the Danish national registries. The association between adding sugar and all-cause mortality was analyzed by Cox regression analysis. Age, smoking status, daily alcohol intake, systolic blood pressure, body mass index, number of cups of coffee and/or tea consumed per day and socioeconomic status were included as covariates. Vital status of patients up and until 22.03.2017 was assessed. Sugar could be added to either coffee, tea or both. RESULTS: In total, 2923 men (mean age at inclusion: 63±5 years) were included, of which 1007 (34.5%) added sugar. In 32 years of follow-up, 2581 participants (88.3%) died, 1677 in the non-sugar group (87.5%) versus 904 in the sugar group (89.9%). Hazard ratio of the sugar group compared to the non-sugar group was 1.06 (95% CI 0.98;1.16) for all-cause mortality. An interaction term between number of cups of coffee and/or tea per day and adding sugar was 0.99 (0.96;1.01). A subgroup analysis of coffee-only drinkers showed a hazard ratio of 1.11 (0.99;1.26). The interaction term was 0.98 (0.94;1.02). Hazard ratios for the sugar group compared to the non-sugar group were 1.11 (95% CI 0.97;1.26) for cardiovascular disease mortality, 1.01 (95% CI 0.87;1.17) for cancer mortality and 1.04 (95% CI 0.79;1.36) for incident diabetes mellitus. CONCLUSION: In the present population of Danish men, use of sugar in tea and/or coffee was not significantly associated with increased risk of mortality or incident diabetes.

Plasma immunoglobulin E and risk of exacerbation and mortality in chronic obstructive pulmonary disease: A contemporary population-based cohort.

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.

The physical activity health paradox and risk factors for cardiovascular disease: A cross-sectional compositional data analysis in the Copenhagen City Heart Study.

BACKGROUND: Studies indicate that physical activity during leisure and work have opposite associations with cardiovascular disease (CVD) risk factors, referred to as the physical activity health paradox. We investigated how sedentary behaviour and physical activity types during leisure and work are associated with systolic blood pressure (SBP), waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) in an adult general population sample using compositional data analysis. METHODS: Participants wore accelerometers for 7 days (right thigh and iliac crest; 24 h/day) and had their SBP, WC, and LDL-C measured. Accelerometer data was analysed using the software Acti4 to derive daily time spent in sedentary behaviour and physical activity types. The measure of association was quantified by reallocating time between sedentary behaviour and 1) walking, and 2) high-intensity physical activity (HIPA; sum of climbing stairs, running, cycling, and rowing), during both domains. RESULTS: In total, 652 participants were included in the analyses (median wear time: 6 days, 23.8 h/day). During leisure, the results indicated that less sedentary behaviour and more walking or more HIPA was associated with lower SBP, while during work, the findings indicated an association with higher SBP. During both domains, the findings indicated that less sedentary behaviour and more HIPA was associated with a smaller WC and lower LDL-C. However, the findings indicated less sedentary behaviour and more walking to be associated with a larger WC and higher LDL-C, regardless of domain. CONCLUSIONS: During leisure, less sedentary behaviour and more walking or HIPA seems to be associated with a lower SBP, but, during work, it seems to be associated with a higher SBP. No consistent differences between domains were observed for WC and LDL-C. These findings highlight the importance of considering the physical activity health paradox, at least for some risk factors for CVD.

Combat Exposure and Risk of Suicide Attempt Among Danish Army Military Personnel.

Objective: The aim of this study was to estimate the association between self-reported perceived danger during deployment, measured as combat exposure or witnessing the consequences of war, and post-deployment suicide attempts among military personnel. Furthermore, the effect of post-deployment symptoms of posttraumatic stress disorder (PTSD) and/or depression on the risk of suicide attempts was also evaluated.Methods: This observational cohort study included Danish Army military personnel who returned from deployment in international missions from 1998 to 2016 and had completed a post-deployment questionnaire. Perceived exposure to danger was ascertained by self-report. Data on suicide attempt were retrieved from national registers. Adjusted Cox regression analyses were used to evaluate if military personnel indicating high level of combat exposure were more likely to have attempted suicides post-deployment than military personnel with lower levels of combat exposure.Results: Eighty-three suicide attempts were registered after homecoming among 12,218 military personnel. Perceived higher exposure to combat was associated with the risk of suicide attempt (hazard ratio = 1.08; 95% CI, 1.01-1.16). Furthermore, the association between combat exposure and suicide attempt was fully mediated by post-deployment symptoms of PTSD and/or depression. No association was found between witnessing consequences of war and the risk of post-deployment suicide attempt.Conclusions: This nationwide study found that combat exposure was associated with an increased risk of suicide attempt among military personnel. This association was, however, fully mediated by mental disorders (PTSD and/or depression). These findings suggest that better psychological follow-up of military personnel identified as having PTSD and/or depression may be warranted.

Non-adherence to established dietary guidelines associated with increased mortality: the Copenhagen General Population Study.

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.

Layer-specific global longitudinal strain and the risk of heart failure and cardiovascular mortality in the general population: the Copenhagen City Heart Study.

AIMS: Layer-specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer-specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW ), endomyocardial (GLSEndo ), and epimyocardial (GLSEpi ) GLS in the general population. METHODS AND RESULTS: A total of 4013 citizens were included in the present study. All 4013 had two-dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow-up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex-stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02-1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04-1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. CONCLUSIONS: In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females.

Occupational lifting and risk of hypertension, stratified by use of anti-hypertensives and age - a cross-sectional and prospective cohort study.

BACKGROUND: Heavy occupational lifting is prevalent in the general working population and is sparsely reported to associate with hypertension, especially among older and hypertensive workers. We investigated if heavy occupational lifting is associated with hypertension and blood pressure (BP) in both cross-sectional and prospective study designs in the Copenhagen General Population Study, stratified by age, and use of anti-hypertensives. METHODS: Participation was conducted following the declaration of Helsinki and approved by the ethical committee (H-KF-01-144/01). By multivariable logistic and linear regression models, we investigated the association between heavy occupational lifting and hypertension, in a cross-sectional design (n = 67,363), using anti-hypertensives or BP ≥140/≥90 mmHg as outcome, and in a prospective design (n = 7020) with an above-median change in systolic BP (SBP) from baseline to follow-up and/or a shift from no use to use of anti-hypertensives as outcome, with and without stratification by age and use of anti-hypertensives. RESULTS: The odds ratio for hypertension was estimated at 0.97 (99% CI: 0.93-1.00) in the cross-sectional analysis, and at 1.08 (99% CI: 0.98-1.19) in the prospective analysis. The difference in SBP among workers with versus without heavy occupational lifting was estimated at - 0.29 mmHg (99% CI -0.82 - 0.25) in the cross-sectional and at 1.02 mmHg (99% CI -0.41 - 2.45) in the prospective analysis. No significant interaction between heavy occupational lifting and age, nor use of anti-hypertensives were shown. CONCLUSIONS: Only the prospective analysis indicated heavy occupational lifting to increase the risk of hypertension. Further research on the association between occupational lifting and hypertension are needed.

Witnessed sleep apneas together with elevated plasma glucose are predictors of COPD exacerbations.

OBJECTIVE: Sleep 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. METHODS: From the Copenhagen City Heart Study cohort, we identified 564 individuals with COPD (forced expiratory volume in 1 sec divided by forced vital capacity, FEV1/FVC<0.70), no asthma, above 40 years of age, and more than 10 pack-years of smoking history, with information on witnessed apneas and levels of plasma glucose. We prospectively recorded hospital admissions with COPD exacerbations during maximum available follow-up (26.3 years; mean 10.7 years). Cox-regression analyses were used to analyze the risk of COPD exacerbations. RESULTS: We 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. CONCLUSIONS: Witnessed sleep apneas in COPD are associated with increased risk of exacerbations, but only among those with elevated plasma glucose.

Effect of Predeployment Psychiatric Diagnoses on Postdeployment Long-Term Sickness Absence and Mental Health Problems Among Danish Military Personnel.

Military personnel may withhold information on mental health problems (MHPs) for fear of not being permitted to deploy. Past or current MHPs may, however, increase the risk of postdeployment MHPs. Using psychiatric diagnoses rather than self-report assessments in predeployment screening may be a more effective screening strategy for determining deployment fitness. This retrospective follow-up study investigated (a) the extent to which predeployment childhood and adult psychiatric diagnoses predicted postdeployment MHPs, measured as psychiatric diagnosis and the purchase of psychiatric drugs, and long-term sickness absence among formerly deployed Danish military personnel and (b) whether perceived combat exposure moderated or mediated the effect of predeployment psychiatric diagnoses. Complete data were available for 7,514 Danish military personnel who answered questions on perceived combat exposure between 6-8 months after returning from their first deployment to the Balkans, Iraq, or Afghanistan. Data on all psychiatric diagnoses given at Danish hospitals, all medicine purchases, and all sickness absences were retrieved from nationwide research registers. Personnel with predeployment psychiatric diagnoses had a statistically significant higher risk for both postdeployment long-term sickness absence, hazard ratio (HR) = 2.06, 95% CI [1.52, 2.80]; and postdeployment MHPs, HR = 2.38, 95% CI [1.73, 3.27], than personnel without a predeployment psychiatric diagnosis. Personnel with a predeployment psychiatric diagnosis demonstrated a higher risk of reporting high levels of perceived combat exposure. Perceived combat exposure was not found to moderate or mediate the effect of a predeployment psychiatric diagnosis on the two outcomes. Additional findings, limitations, and implications are discussed.

Sedentary work and risk of venous thromboembolism.

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.

Does occupational lifting affect the risk of hypertension? Cross-sectional and prospective associations in the Copenhagen City Heart Study.

Objective The aim of this study was to investigate cross-sectional and prospective associations between heavy occupational lifting and hypertension. Methods Data from the third, fourth and fifth examinations of the Copenhagen City Heart Study were included. Multivariable logistic regression models were applied to adjust for sex, age, body mass index (BMI), smoking, education, self-rated cardiorespiratory fitness, vital exhaustion and baseline blood pressure, and were used to estimate (i) the cross-sectional association between heavy occupational lifting and hypertension, defined as using anti-hypertensives or having a systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg, and (ii) the prospective association between heavy occupational lifting and risk of becoming a systolic blood pressure case, defined as an above median change (from baseline to follow-up) and/or a shift from no use of anti-hypertensives at baseline to use of anti-hypertensives at a ten-year follow-up. Results Both cross-sectional [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.94-1.20] and prospective (OR 1.10, 95% CI 0.92-1.31) analysis indicated no relations. Explorative prospective analyses suggested linear associations between heavy occupational lifting and systolic blood pressure among participants using anti-hypertensives. Exposure to heavy occupational lifting tended to increase the incidence of hypertension (OR 1.30, 95% CI 0.97-1.73) among participants ≥50 years. Conclusions No associations were seen among the general population. Positive associations were seen among users of anti-hypertensives and participants ≥50 years, indicating these groups as vulnerable to increases in blood pressure when exposed to occupational lifting.

Influence of errors in job codes on job exposure matrix-based exposure assessment in the register-based occupational cohort DOC*X.

Objective Job-exposure matrices (JEM) may be efficient for exposure assessment in occupational epidemiological studies, but they rely on valid job information. We evaluated the agreement between JEM-based exposure estimates according to self-reported job titles converted to DISCO-88 codes and according to register-based DISCO-88 codes in the Danish Occupational Cohort with eXposure data (DOC*X). Furthermore, we evaluated the agreement between these two sets of DISCO-88 codes. Methods We used JEM regarding wood dust, lifting, standing/walking, arm elevation >90°, and noise from DOC*X. Participants from previous questionnaire studies were assigned JEM-based exposure estimates using (i) self-reported job titles converted to DISCO-88 codes and (ii) DISCO-88 codes registered in DOC*X, in four time periods (1976-78: N=7707; 1981-83: N=2193; 1991-94: N=2664; 2004: N=11 782). Agreement between the exposure estimates and between the DISCO-88 codes (four-digit levels, 1-4) was evaluated by kappa (κ) statistics. Sensitivities were calculated using the self-reported observation as the gold standard. Results We found substantial agreement (κ>0.60) between exposure estimates for all types of job-exposures and all time periods except for one κ. Low sensitivity (30-65%) was found for the period 1981-83, but for the other time periods the sensitivities varied between 60-91%. For individual 4-digit DISCO-88 codes, the sensitivities varied substantially and overall the sensitivities increased by lower digit level of DISCO-88. Conclusion The validity of the DISCO-88 codes in DOC*X was generally high. Substantial agreement was found for the JEM-based exposure estimates and the DISCO-88 codes per se, although the DISCO-88 code-specific agreement varied across digit levels and time periods.

Secular trends in smoking in relation to prevalent and incident smoking-related disease: A prospective population-based study.

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.

Prognosis of COPD depends on severity of exacerbation history: A population-based analysis.

BACKGROUND: Differences in previous exacerbation history may influence prognosis of chronic obstructive pulmonary disease (COPD). We hypothesized that prognosis differs between individuals with a history of only medically treated exacerbations (moderate exacerbations) and those with a history of hospitalised exacerbations (severe exacerbations). METHODS: We included 98 614 adults from the Copenhagen General Population Study and assessed risk of moderate and severe exacerbations, pneumonia hospitalisation, and respiratory and all-cause mortality from 2003 until 2013 according to exacerbation history. RESULTS: Among 6545 individuals with COPD, 6290 had no exacerbations in the preceding year, 109 had one moderate exacerbation, 108 had two or more moderate exacerbations, and 38 had one or more severe exacerbations. During 9.4 years of follow-up, we observed 926 moderate and 244 severe exacerbations, 477 pneumonias, and 707 deaths, including 69 from respiratory disease. Compared to individuals without previous exacerbations, lung function and symptom adjusted hazard ratios (HRs) for future moderate exacerbation were 4.68 (95% confidence interval:3.31-6.62) for individuals with one previous moderate exacerbation, 21 (13-33) for individuals with two or more previous moderate exacerbations, and 5.30 (3.44-8.15) for individuals with one or more previous severe exacerbations. Corresponding HRs were 1.62(0.78-3.34), 1.29(0.57-2.89), and 5.43 (2.56-12) for severe exacerbation, 1.86(1.06-3.27), 1.74(1.01-2.99), and 4.85 (2.94-8.02) for pneumonia, 0.53(0.10-2.99), 1.65(0.53-5.17), and 2.98 (1.14-7.83) for respiratory mortality, and 1.34(0.79-2.29), 1.57(1.00-2.47), and 1.49 (0.85-2.62) for all-cause mortality, respectively. CONCLUSION: Individuals with COPD and a history of hospitalised exacerbations carried the poorest prognosis compared to those with a history of only medically treated exacerbations, suggesting difference in risk profile.

Living alone is associated with all-cause and cardiovascular mortality: 32 years of follow-up in the Copenhagen Male Study.

AIMS: As a consequence of modern urban life, an increasing number of individuals are living alone. Living alone may have potential adverse health implications. The long-term relationship between living alone and all-cause and cardiovascular mortality, however, remains unclear. METHODS AND RESULTS: Participants from The Copenhagen Male Study were included in 1985-86 and information about conventional behavioural, psychosocial, and environmental risk factors were collected. Socioeconomic position (SEP) was categorized into four groups. Multivariable Cox-regression models were performed with follow-up through the Danish National Registries. A total of 3346 men were included, mean (standard deviation) age 62.9 (5.2) years. During 32.2 years of follow-up, 89.4% of the population died and 38.9% of cardiovascular causes. Living alone (9.6%) was a significant predictor of mortality. Multivariable risk estimates were [hazard ratio (95% confidence interval)] 1.23 (1.09-1.39), P = 0.001 for all-cause mortality and 1.36 (1.13-1.63), P = 0.001 for cardiovascular mortality. Mortality risk was modified by SEP. Thus, there was no association in the highest SEP but for all other SEP categories, e.g. highest SEP for all-cause mortality 1.01 (0.7-1.39), P = 0.91 and 0.94 (0.6-1.56), P = 0.80 for cardiovascular mortality; lowest SEP 1.58 (1.16-2.19), P = 0.004 for all-cause mortality and 1.87 (1.20-2.90), P = 0.005 for cardiovascular mortality. Excluding participants dying within 5 years of inclusion (n = 274) did not change estimates, suggesting a minimal influence of reverse causation. CONCLUSIONS: Living alone was an independent risk factor for all-cause and cardiovascular mortality with more than three decades of follow-up. Individuals in middle- and lower SEPs were at particular risk. Health policy initiatives should target these high-risk individuals.

Midlife Cardiorespiratory Fitness and the Long-Term Risk of Mortality: 46 Years of Follow-Up.

BACKGROUND: A high cardiorespiratory fitness (CRF) level is recommended to promote healthy aging. However, the association between CRF and very-long-term prognosis is unclear, and reverse causation may bias results in studies with shorter follow-up. OBJECTIVES: This study investigated the association between CRF and mortality in middle-aged, employed men free of cardiovascular disease (CVD). METHODS: Participants from the Copenhagen Male Study, established in 1970 to 1971, were included and stratified into 4 age-adjusted maximal oxygen consumption (Vo2max) categories: below the lower limit of normal (lowest 5%); low normal (45%); high normal (45%); and above the upper limit of normal (top 5%). Vo2max was estimated by using a bicycle ergometer. Multivariable restricted mean survival time models were performed for all-cause and cardiovascular mortality using Danish national registers. RESULTS: A total of 5,107 men with a mean age of 48.8 ± 5.4 years were included in the study. During the 46 years of follow-up, 4,700 (92%) men died; 2,149 (42.1%) of the men died of CVD. Compared with below the lower limit of normal CRF, low normal CRF was associated with 2.1 years (95% confidence interval [CI]: 0.7 to 3.4; p = 0.002), high normal with 2.9 years (95% CI: 1.5 to 4.2; p < 0.001), and above upper limit of normal with 4.9 years (95% CI: 3.1 to 6.7; p < 0.001) longer mean life expectancy. Each unit increase in Vo2max was associated with a 45-day (95% CI: 30 to 61; p < 0.001) increase in longevity. Estimates for cardiovascular mortality were similar to all-cause mortality. Results were essentially unchanged when excluding individuals who died within the first 10 years of follow-up, suggesting a minimal role of reverse causation. CONCLUSIONS: CRF was significantly related to longevity over the course of 4 decades in middle-aged, employed men free of CVD. The benefits of higher midlife CRF extend well into the later part of life.

Combined value of exhaled nitric oxide and blood eosinophils in chronic airway disease: the Copenhagen General Population Study.

We investigated whether the combination of increased exhaled nitric oxide fraction (FeNO) level and blood eosinophil count had an additive value in chronic airway disease in the general population.We included 4677 individuals aged 20-100 years from the Copenhagen General Population Study. Based on pre- and post-bronchodilator spirometry, self-reported asthma and smoking history, participants were subdivided into healthy never-smokers (n=1649), healthy ever-smokers (n=1581), asthma (n=449), chronic obstructive pulmonary disease (COPD) (n=404), asthma-COPD overlap (ACO) (n=138) and nonspecific airflow limitation (n=456).Compared to individuals with FeNO <25 ppb and blood eosinophils <0.3×109 cells·L-1, age- and sex-adjusted odds ratios (95% CI) for wheezing were 1.54 (1.29-1.84) for individuals with FeNO ≥25 ppb or blood eosinophils ≥0.3×109 cells·L-1 and 2.14 (1.47-3.10) for individuals with FeNO ≥25 ppb and blood eosinophils ≥0.3×109 cells·L-1 Corresponding odds ratios were 1.13 (0.91-1.41) and 1.83 (1.20-2.79) for sputum production, 1.54 (1.22-1.94) and 3.26 (2.16-4.94) for asthma, 1.03 (0.80-1.32) and 0.67 (0.36-1.27) for COPD and 1.32 (0.88-1.96) and 2.14 (1.05-4.36) for ACO. Among individuals reporting respiratory symptoms, predicting the type of chronic airway disease did not differ between the two biomarkers and did not improve by combining them.Combination of FeNO and blood eosinophils may have an additive value in characterising chronic airway disease in the general population but still needs to be investigated further with regard to clinical application.

Correction: The Single-Breath Diffusing Capacity of CO and NO in Healthy Children of European Descent.

[This corrects the article DOI: 10.1371/journal.pone.0113177.].