The biomarkers suPAR and blood eosinophils are associated with hospital readmissions and mortality in asthma - a retrospective cohort study.

INTRODUCTION: Prognostic biomarkers in asthma are needed. The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with asthma control and with prognosis in acutely admitted medical patients. We investigated if suPAR and blood eosinophil counts at the time of admission for asthma are associated with readmission and mortality. METHODS: Our cohort comprised 1341 patients (median age 45.3, IQR 30.1-63.1) acutely admitted with a diagnosis of asthma to Hvidovre Hospital, Denmark (November 2013 to March 2017). Patients had suPAR and blood eosinophils measured at admission. Outcomes were 365-day readmission and all-cause mortality. Logistic regression analysis adjusted for age, sex, C-reactive protein, and Charlson comorbidity score was used to assess the association of the two biomarkers with readmission and all-cause mortality. RESULTS: Compared to event-free patients, patients who were either readmitted (n = 452, 42.3%) or died (n = 57, 5.3%) had significantly higher suPAR concentrations (p < 0.0001) and lower eosinophil counts (p = 0.0031) at admission. The highest odds of readmission or mortality were observed for patients in either the 4th suPAR quartile (p < 0.0001) or with eosinophil counts < 150 cells/µL at admission. Increasing levels of suPAR were associated with 365-day readmission (OR 1.3 [1.0-1.6]; p = 0.05) and mortality (OR 2.9 [1.7-5.1]; p = 0.0002). Eosinophil count > 300 cells/µL was significantly associated with lower odds of readmission (OR 0.64 [0.5-0.9]; p = 0.005) and lower mortality (OR 0.7 [0.6-0.9]; p = 0.0007). CONCLUSIONS: In patients acutely admitted with asthma, elevated suPAR concentrations together with blood eosinophil count < 150 cells/µL at the time of hospital admission were associated with both 365-day all-cause readmission and mortality.

Soluble urokinase plasminogen activator receptor predicts mortality in exacerbated COPD.

BACKGROUND: The inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in severe acute and chronic medical conditions and has been associated with short-term mortality. The role of suPAR in predicting risk of death following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has never been studied. We hypothesized that increased suPAR is an independent predictor of short-term mortality in patients admitted to hospital with COPD or acute respiratory failure. METHODS: This retrospective cohort study from a university hospital in the Capital Region of Denmark included 2838 acutely admitted medical patients with COPD as primary (AECOPD) or secondary diagnosis, who had plasma suPAR measured at the time of admission between November 18th, 2013 to September 30th, 2015 and followed until December 31st, 2015. Primary outcomes were 30- and 90-days all-cause mortality. Association of suPAR and mortality was investigated by Cox regression analyses adjusted for age, sex, CRP values and Charlson comorbidity index. RESULTS: For patients with AECOPD or underlying COPD, median suPAR levels were significantly higher among patients who died within 30 days compared with those who survived (5.7 ng/ml (IQR 3.8-8.1) vs. 3.6 ng/ml (2.7-5.1), P < 0.0001). Increasing suPAR levels independently predicted 30-day mortality in patients with COPD with a hazard ratio of 2.0 (95% CI 1.7-2.4) but not respiratory failure. CONCLUSIONS: In this large group of acutely admitted patients with COPD, elevated suPAR levels were associated with increased risk of mortality. The study supports the value of suPAR as a marker of poor prognosis.

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use: Results from an Observational Study (ASSESS).

This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p < 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p < 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p < 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p < 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.

Prevalence and management of pulmonary comorbidity in patients with lung and head and neck cancer.

BACKGROUND: The simultaneous presence of cancer and other medical conditions (comorbidity) is frequent. Cigarette smoking is the major risk factor for as well head and neck cancer (HNC) and lung cancer (LC) as chronic obstructive pulmonary disease (COPD). COPD is the most common comorbidity in LC patients, and presence of COPD worsens the prognosis of HNC and LC. COPD is under-diagnosed and under-treated in the Danish population. The aims of this study were to determine the prevalence of COPD in a HNC and LC population, and to determine the need and feasibility of a randomized controlled phase II trial comparing usual care with optimized medical treatment of COPD in cancer patients. MATERIAL AND METHODS: All patients with HNC or LC referred for oncologic treatment in a university hospital during a 10-month period were invited to attend a pulmonary clinic for evaluation of lung function. Patients who were found to have concomitant COPD were randomized to intervention or usual care. Primary endpoints were prevalence of COPD among the referred patients with either LC or HNC, and further whether the patients that were diagnosed with COPD already received treatment in accordance with Danish COPD guidelines. Secondary outcome was feasibility, i.e. the proportion of eligible patients that accepted follow-up in the pulmonary clinic for 24 weeks in addition to oncological treatment. The design of the randomized trail is described in detail. RESULTS: In total 130 patients of whom 65% had LC and 35% HNC have been screened during the first seven months of this ongoing trial. Sixty-eight percent of LC patients and 22% of HNC patients had COPD. All but one of 68 eligible patients accepted randomization. Nearly one third (31%) of the LC and HNC patients with COPD were diagnosed prior to study entry, and of these, only 33% were receiving correct treatment according to current guidelines. CONCLUSION: For patients with LC, and to a lesser extend HNC, there is a need for improved diagnosis and treatment of concomitant COPD. Furthermore, patients found it acceptable to be scheduled for a 24-week follow-up in a pulmonary clinic along with their oncological treatment.

[Smoking is associated with health risks even when cessation is before the age of 30 years].

It is broadly believed that smokers who have ceased to smoke before the age of 30 years, have no excess health risk compared with never-smokers. As summarised in this review, large, prospective cohort studies show, that this holds true regarding all-cause mortality for men, whereas the risk of dying remains slightly elevated for women, who quit smoking early. The risk of lung cancer also remains elevated. Smoking also increases the risk of physical and mental problems in youth. The evidence is strongest regarding infertility, impotence, reproductive health outcomes, cardio-vascular and respiratory symptoms.

[Statins and COPD: relationship with inflammation, exacerbations and mortality].

The role of statins on the disease course of COPD is controversial. Observational studies have shown a reduction in mortality and exacerbations, but results of randomised clinical trials (RCTs) of statin treatment and its effect on adverse outcomes are conflicting. Recent meta-analyses suggest the need for further RCTs including COPD patients both with and without concurrent cardiovascular disease (CVD). As there are no known detrimental effects of statins in COPD patients, we conclude in this review, that statins should be prescribed more frequently in these patients due to the common co-morbidity with CVD.

High suPAR and Low Blood Eosinophil Count are Risk Factors for Hospital Readmission and Mortality in Patients with COPD.

Introduction: The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD. Methods: This retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein. Results: suPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40-1.85; p<0.0001) and 3.40 (95% CI 2.64-4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/µL) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39-0.62; p<0.0001) compared with patients with <150 cells/µL. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/µL) group. Conclusion: In this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.

[Environmental tobacco smoke is a risk factor for the development of chronic obstructive pulmonary disease].

The purpose of this review is to summarise the existing knowledge of the relationship between exposure to en-vironmental tobacco smoke (ETS) and the development of chronic obstructive pulmonary disease (COPD). A possible causal relationship between ETS and COPD has long been suspected. Prenatal as well as postnatal ETS can reduce the lung function of the child permanently. Albeit the causality is multifactorial, new evidence has emerged since the Surgeon General's report from 2006 and suggests, that ETS is an independent and significant risk factor for developing COPD.

Smoking reduction and biomarkers in two longitudinal studies.

AIMS: To measure reduction in exposure to smoke in two population-based studies of self-reported smoking reduction not using nicotine replacement. DESIGN: Cross-sectional analyses of biomarkers and smoking. SETTING: Data from two time-points in the Copenhagen City Heart Study (CCHS), 1981/83 and 1991/94, and the Copenhagen Male Study (CMS) in 1976 and 1985/86, respectively. PARTICIPANTS: There were 3026 adults who were smokers at both time-points in the CCHS and 1319 men smoking at both time-points in the CMS. MEASUREMENTS: Smoking status and tobacco consumption were assessed by self-completion questionnaire. Measurements of biomarkers of smoke intake were taken at the second time-point in the two studies: expired-air carbon monoxide (CO) in the CCHS and serum cotinine in the CMS. Biomarker levels in medium (15-29 g tobacco/day) and heavy (> 30 g/day) smokers at the first time-point who later reported a reduction in cigarettes per day of 50% or more without quitting were compared with continuing medium, heavy and light smokers (1-14 g/day) using linear regression. Sex (CCHS only), age, self-reported inhalation of smoke, duration of smoking, type of tobacco and amount smoked were included as covariates in multivariate models. FINDINGS: Heavy smokers who reduced did not show lower levels of biomarkers at follow-up. Medium smokers who reduced showed a reduction in cotinine but not CO. The reduction in cotinine was not commensurate with the reported reduction in consumption. CONCLUSIONS: Long-term reductions in self-reported tobacco smoking are probably associated with, at best, modest reductions in smoke exposure.

Effect of smoking reduction on lung cancer risk.

CONTEXT: Many smokers are unable or unwilling to completely quit smoking. A proposed means of harm reduction is to reduce the number of cigarettes smoked per day. However, it is not clear whether this strategy decreases the risk for tobacco-related diseases. OBJECTIVE: To assess the effects of smoking reduction on lung cancer incidence. DESIGN, SETTING, AND PARTICIPANTS: Observational population-based cohort study with up to 31 years of follow-up from the Copenhagen Centre for Prospective Population Studies, which administrates data from 3 longitudinal studies conducted in Copenhagen and suburbs, the Copenhagen City Heart Study, the Copenhagen Male Study, and the Glostrup Population Studies, Denmark. Participants were 11,151 men and 8563 women (N = 19,714) aged 20 to 93 years, who attended 2 consecutive examinations with a 5- to 10-year interval between 1964 and 1988. Participants underwent a physical examination and completed self-filled questionnaires about lifestyle habits. The study population was divided into 6 groups according to smoking habits: continued heavy smokers (> or =15 cigarettes/d), reducers (reduced from > or =15 cigarettes/d by minimum of 50% without quitting), continued light smokers (1-14 cigarettes/d), quitters (stopped between first and second examination), stable ex-smokers, and never smokers. MAIN OUTCOME MEASURE: Incident primary lung cancer cases assessed by record linkage with the National Cancer Registry until December 31, 2003. RESULTS: There were 864 incident lung cancers during follow-up. Using Cox regression, the adjusted hazard ratio (HR) for lung cancer in reducers was 0.73 (95% confidence interval [CI], 0.54-0.98) compared with persistent heavy smokers. The HR for light smokers was 0.44 (95% CI, 0.35-0.56); for quitters, HR 0.50 (95% CI, 0.36-0.69), for stable ex-smokers, HR 0.17 (95% CI, 0.13-0.23), and for never smokers, HR 0.09 (95% CI, 0.06-0.13). CONCLUSION: Among individuals who smoke 15 or more cigarettes per day, smoking reduction by 50% significantly reduces the risk of lung cancer.

A prospective study linked both alcohol and tobacco to Dupuytren's disease.

OBJECTIVE: To address the role of alcohol intake and tobacco smoking and the combination of the two on subsequent risk of Dupuytren's disease. STUDY DESIGN AND SETTING: Cohort study of 7,254 subjects enrolled in the Copenhagen City Heart Study (1981-1983). Both self-reported information on lifestyle and objective measures at the baseline examination were linked to presence of Dupuytren's disease at a subsequent examination (1991-1994) using multivariate logistic regression analysis. RESULTS: A total of 772 subjects had signs of Dupuytren's disease at follow-up. After adjustment for age, sex, educational level, diabetes, and either alcohol or tobacco consumption, respectively, odds ratios for having the disease increased in a dose-dependent manner with increasing levels of alcohol or tobacco intake; however, there was no statistical interaction between heavy smoking and heavy drinking. CONCLUSION: Alcohol intake and tobacco smoking are independently associated with increased risk of Dupuytren's disease, and the combination of the two conveys a very large risk.

A prospective study of the association between smoking and later alcohol drinking in the general population.

AIMS: To address the possible prospective association between smoking habits and risk of later heavy drinking in the adult population. DESIGN: Pooled population-based long-term cohort studies with repeated assessments of smoking and alcohol habits. SETTING: Copenhagen, Denmark. PARTICIPANTS: A total of 14,130 non- to moderate drinkers at baseline, who attended re-examination. MEASUREMENTS: Among the non- to moderate drinkers we addressed the relation between smoking habits at first examination and the risk of becoming a heavy and excessive drinker at follow-up. FINDINGS: Level of tobacco consumption at first examination predicted an increased risk of becoming a heavy and excessive drinker in a dose-dependent manner. Men who smoked more than 25 g of tobacco per day had adjusted odds ratios of 2.12 (95% confidence interval (CI): 1.44-3.11) and 3.95 (95% CI: 1.93-8.95) for becoming heavy and excessive drinkers, compared to participants who had never smoked. Equivalent estimates among women were 1.76 (95% CI: 1.02-3.04) and 2.21 (95% CI: 1.00-4.58), respectively. CONCLUSIONS: This study suggests that tobacco use is associated quantitatively with later risk of heavier drinking.

Impact of exercise capacity on dyspnea and health-related quality of life in patients with chronic obstructive pulmonary disease.

PURPOSE: To assess the impact of the amount of exercise training during pulmonary rehabilitation (PR) program for improvements in dyspnea and health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Data on COPD patient health, exercise capacity, dyspnea, and HRQOL were collected at the start and at the end of PR, which was provided in the ambulatory section of the hospital and lasted for 7 weeks. Pulmonary rehabilitation program included exercise training, education, smoking cessation, and diet consultation sessions. Data were analyzed using multivariable linear regression. RESULTS: Baseline data were obtained from a total of 143 patients with followup data in 108 patients available at the end of PR. The majority of the patient population had severe disease progression of COPD as exhibited by spirometry test results. Results of multivariable analyses showed that after adjustment for sociodemographic characteristics and baseline patient characteristics, changes in dyspnea and exercise capacity were directly and linearly predicted by the number of exercise training sessions attended. Changes in disease-specific and general HRQOL outcomes were not predicted by the amount of exercise training received during PR. CONCLUSIONS: Quality of life in patients with COPD is predicted by dyspnea. Thus, to further investigate the influence of exercise training on quality of life in patients with CODP, simultaneous assessment of dyspnea should be considered.

Is chronic obstructive pulmonary disease associated with increased arterial stiffness?

OBJECTIVE: We hypothesize that airflow limitation is associated with increasing arterial stiffness and that having COPD increases a non-invasive measure of arterial stiffness - the aortic augmentation index (AIx) - independently of other CVD risk factors. METHODS: This population study is based on 3374 subjects from the Copenhagen City Heart Study; 494 had COPD. We used multiple linear regression analyses to examine the association between COPD and AIx adjusted for CVD risk factors. Furthermore, we analyzed the association between AIx and FEV(1), FVC and FEV(1)/FVC in the entire population. RESULTS: AIx was higher in subjects with COPD than in subjects without: 25.7 vs. 21.0 (p < 0.001) in men and 33.6 vs. 29.4 (p < 0.001) in women. We found no increase in AIx with COPD adjusted for CVD risk factors: difference 0.63 (-0.26 to 1.52, p = 0.16). In sensitivity analyses in subjects younger than 60 years with exclusion of mild COPD from the analyses, COPD was associated with an increase in AIx in men only of 4.1 (0.88-7.22, p = 0.007). AIx had a curvilinear association with FEV(1) and FVC but no association with the FEV(1)/FVC ratio. CONCLUSION: AIx and COPD are only weakly associated. In the general population, this finding argues against increased arterial stiffness, as measured by AIx, being a complication of COPD.

Aortic augmentation index: reference values in a large unselected population by means of the SphygmoCor device.

BACKGROUND: Arterial stiffness and pulse wave reflection are associated with cardiovascular disease (CVD). Pulse wave analyses (PWAs) allow the estimation of the central augmentation index (AIx), a measurement of pulse wave reflection. To understand the predictive role of AIx, reference values for AIx are needed. METHODS: This population study is based on 4,561 subjects from The Copenhagen City Heart Study, an ongoing epidemiological survey started in 1976, including subjects randomly chosen from the population in Copenhagen, Denmark. We calculated and internally validated reference values of AIx measured by the SphygmoCor device in a cohort without known CVD or diabetes, and with low risk of CVD according to HeartScore using gender-specific multiple regression analyses adjusting for age, heart rate, and height. RESULTS: AIx was significantly higher in women than in men, 30% vs. 22%, (P < 0.001) and the increase in AIx with age was curvilinear. There were 972 subjects in the low-risk cohort with mean AIx 28% in women (N = 565) and 18% in men (N = 407) (P < 0.001). We report the following internally validated reference equations for AIx: men: AIx = 79.20 + 0.63 (age) - 0.002 (age(2)) - 0.28 (heart rate) - 0.39 (height). Women: AIx = 56.28 + 0.90 (age) - 0.005 (age(2)) - 0.34 (heart rate) - 0.24 (height). AIx appeared to increase with increasing risk of CVD according to HeartScore. CONCLUSIONS: We report a novel and internally validated gender-specific equation including age, heart rate, and height to calculate reference values for AIx.

Childhood social circumstances and health behaviour in midlife: the Metropolit 1953 Danish male birth cohort.

BACKGROUND: It has been suggested that the association between social disadvantage in childhood and adult mortality could come about through processes related to the family environment in which the child is raised. This study examines the relationship of fathers' social class with health behaviour in middle age and assesses the potential mediating role of cognitive function, educational status and social integration in young adulthood in these relationships. METHODS: We used data from the Metropolit cohort which includes 11 532 Danish men born in 1953 with information on fathers' social class at participants' birth and assessments of cognitive performance, education and social integration in early adulthood. In 2004, 6292 of these men participated in a follow-up survey on health and behaviour. Logistic regression was used to investigate the association of father's social class with smoking, alcohol drinking, leisure-time physical activity and the intake of fruit and vegetables in midlife. RESULTS: Middle-aged men with fathers from higher social classes were more often ex-smokers, wine drinkers and daily consumers of fruit or vegetables than men with working class fathers. Leisure activities and high alcohol consumption were not related to father's social class. Cognitive function and educational achievement at age 18 attenuated the association of father's social class with adult behaviour, while indicators of social integration had very little impact on the associations. CONCLUSIONS: Father's social class influences adult smoking, alcohol preference and food intake, and a major part of the effect is mediated through cognitive function and education.