Association of generic health-related quality of life (EQ-5D dimensions) and inactivity with lung function in lung-healthy German adults: results from the KORA studies F4L and Age.

PURPOSE: Among patients with lung disease, decreased lung function is associated with lower health-related quality of life. However, whether this association is detectable within the physiological variability of respiratory function in lung-healthy populations is unknown. We analyzed the association of each EQ-5D-3L dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and self-reported physical inactivity with spirometric indices in lung-healthy adults. Modulating effects between inactivity and EQ-5D dimensions were considered. METHODS: 1132 non-smoking, apparently lung-healthy participants (48% male, aged 64 ± 12 years) from the population-based KORA F4L and Age surveys in Southern Germany were analyzed. Associations of each EQ-5D dimension and inactivity with spirometric indices serving as outcomes (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and mid-expiratory flow) were examined by linear regression, considering possible confounders. Interactions between EQ-5D dimensions (no problems/any problems) and inactivity (four categories of time spent engaging in exercise: inactive to most active) were assessed. RESULTS: Among all participants 42% reported no problems in any EQ-5D dimension, 24% were inactive and 32% exercised > 2 h/week. After adjustment, FEV1 was - 99 ml (95% CI - 166; - 32) and FVC was - 109 ml (95% CI - 195; - 24) lower among subjects with mobility problems. Comparable estimates were observed for usual activities. Inactivity was negatively associated with FVC (ß-coefficient: - 83 ml, 95% CI - 166; 0), but showed no interactions with EQ-5D. CONCLUSIONS: Problems with mobility or usual activities, and inactivity were associated with slightly lower spirometric parameters in lung-healthy adults, suggesting a relationship between perceived physical functioning and volumetric lung function.

Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences-Comorbidities Network Study.

RATIONALE: Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. OBJECTIVES: We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. METHODS: The ankle-brachial index was used to diagnose PAD (ankle-brachial index ≤ 0.9). The 6-minute-walk distance, health status (St. George's Respiratory Questionnaire), COPD Assessment Test, and EuroQol-5-Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences-Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. MEASUREMENTS AND MAIN RESULTS: A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I-IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences-Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6-minute-walk distance (356 [108] vs. 422 [103] m, P < 0.001) and worse health status (St. George's Respiratory Questionnaire: 49.7 [20.1] vs. 42.7 [20.0] points, P < 0.001; COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol-5-Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P < 0.001). Differences remained significant after correction for several confounders. CONCLUSIONS: In a large cohort of patients with COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

[Health Science Research with Primary Care Routine Data From Electronic Patient Records: the BeoNet Registry]. / Gesundheitswissenschaftliche Forschung mit primärärztlichen Routinedaten der elektronischen Patientenakte: das BeoNet-Register.

Reliable current information is needed for daily patient care and the health system, but comprehensive data, especially from primary care, are scarce and/or hard to access. The BeoNet Register-Database (BNR) aims to depict quality of medical care in Germany using routine data and with no additional documentation or costs for GPs. Registry design, data structure and database use will be demonstrated using chronic obstructive lung disease (COPD) as an example. The BNR is moving through pilot- and roll-out phases. Participating practices provide standardized information about (1) master data (2) practice profile (3) infrastructure and documentation systems. The routinely documented data will be pseudonymized before transmission via standardized secure interfaces to the registry database. Practices can participate in studies in cooperation with BNR if informed consent is obtained from the patients. The registry data will be linked with questionnaires on health care utilization, quality of life and disease-specific parameters. Researchers and physicians can access quasi anonymized data in specific datasets extracted from the registry. Regular automatic data quality checks and feedback from GPs, patients and researchers enhance the quality of the registry. Performance and data analysis are continuously optimized. The data security concept has been approved and ethical approval is on hand. GPs, pediatricians and pneumologists from Hanover, Munich and Heidelberg participated in the pilot phase. The registry database currently holds 98497 patient IDs and related information. BNR contains more than the standard billing data collected by health insurers. The data are applicable to a wide range of health practices, health care and economics and disease development questions. Questionnaires have been generated, tested and are being distributed. First descriptive analyses of prevalence, age and gender have been performed. Quality and validity checks have been implemented. 2016 marks the roll-out phase of the BNR. Further recruitment of practices throughout Germany, data linkage with additional questionnaires, recruitment of patients for health care research projects, quality checks and data analysis of disease-specific costs and health-related quality of life in COPD are progressing with the overall aim of improving pulmonary healthcare strategies. The floor is now open for retro- and prospective cross-sectional and longitudinal studies.

Costs and health-related quality of life in Alpha-1-Antitrypsin Deficient COPD patients.

BACKGROUND: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored genetic disease. METHODS: Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort. The medication costs of AT were excluded from all analyses to reveal differences associated with morbidity profiles. The association of AATD (with/without AT) with costs or HRQL was examined using generalized linear regression modelling (GLM) adjusting for age, sex, GOLD grade, BMI, smoking status, education and comorbidities. RESULTS: Adjusted mean direct annual costs were €6,099 in AATD patients without AT, €7,117 in AATD patients with AT (excluding costs for AT), and €7,460 in COPD patients without AATD. AATD with AT was significantly associated with higher outpatient (+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT) compared with COPD patients without AATD. There were no significant differences between groups regarding indirect costs and HRQL. CONCLUSION: Apart from AT costs, AATD patients tended to have lower, though not significant, overall costs and similar HRQL compared to COPD patients without AATD. AT was not associated with lower costs or higher HRQL. TRIAL REGISTRATION: NCT01245933.

Transfer factor for carbon monoxide in patients with COPD and diabetes: results from the German COSYCONET cohort.

BACKGROUND: An impairment of CO diffusing capacity has been shown in diabetic patients without lung disease. We analyzed how diffusing capacity in patients with COPD is affected by the concurrent diagnosis of diabetes. METHODS: Data from the initial visit of the German COPD cohort COSYCONET were used for analysis. 2575 patients with complete lung function data were included, among them 358 defined as diabetics with a reported physician diagnosis of diabetes and/or specific medication. Pairwise comparisons between groups and multivariate regression models were used to identify variables predicting the CO transfer factor (TLCO%pred) and the transfer coefficient (KCO%pred). RESULTS: COPD patients with diabetes differed from those without diabetes regarding lung function, anthropometric, clinical and laboratory parameters. Moreover, gender was an important covariate. After correction for lung function, gender and body mass index (BMI), TLCO%pred did not significantly differ between patients with and without diabetes. The results for the transfer coefficient KCO were similar, demonstrating an important role of the confounding factors RV%pred, TLC%pred, ITGV%pred, FEV1%pred, FEV1/FVC, age, packyears, creatinine and BMI. There was not even a tendency towards lower values in diabetes. CONCLUSION: The analysis of data from a COPD cohort showed no significant differences of CO transport parameters between COPD patients with and without diabetes, if BMI, gender and the reduction in lung volumes were taken into account. This result is in contrast to observations in lung-healthy subjects with diabetes and raises the question which factors, among them potential anti-inflammatory effects of anti-diabetes medication are responsible for this finding.

External Validation of Health Economic Decision Models for Chronic Obstructive Pulmonary Disease (COPD): Report of the Third COPD Modeling Meeting.

OBJECTIVES: To validate outcomes of presently available chronic obstructive pulmonary disease (COPD) cost-effectiveness models against results of two large COPD trials-the 3-year TOwards a Revolution in COPD Health (TORCH) trial and the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial. METHODS: Participating COPD modeling groups simulated the outcomes for the placebo-treated groups of the TORCH and UPLIFT trials using baseline characteristics of the trial populations as input. Groups then simulated treatment effectiveness by using relative reductions in annual decline in lung function and exacerbation frequency observed in the most intensively treated group compared with placebo as input for the models. Main outcomes were (change in) total/severe exacerbations and mortality. Furthermore, the absolute differences in total exacerbations and quality-adjusted life-years (QALYs) were used to approximate the cost per exacerbation avoided and the cost per QALY gained. RESULT: Of the six participating models, three models reported higher total exacerbation rates than observed in the TORCH trial (1.13/patient-year) (models: 1.22-1.48). Four models reported higher rates than observed in the UPLIFT trial (0.85/patient-year) (models: 1.13-1.52). Two models reported higher mortality rates than in the TORCH trial (15.2%) (models: 20.0% and 30.6%) and the UPLIFT trial (16.3%) (models: 24.8% and 36.0%), whereas one model reported lower rates (9.8% and 12.1%, respectively). Simulation of treatment effectiveness showed that the absolute reduction in total exacerbations, the gain in QALYs, and the cost-effectiveness ratios did not differ from the trials, except for one model. CONCLUSIONS: Although most of the participating COPD cost-effectiveness models reported higher total exacerbation rates than observed in the trials, estimates of the absolute treatment effect and cost-effectiveness ratios do not seem different from the trials in most models.

Relative impact of COPD and comorbidities on generic health-related quality of life: a pooled analysis of the COSYCONET patient cohort and control subjects from the KORA and SHIP studies.

BACKGROUND: Health-related quality of life (HRQL) is an important patient-reported outcome measure used to describe the burden of chronic obstructive pulmonary disease (COPD) which is often accompanied by comorbid conditions. METHODS: Data from 2275 participants in the COPD cohort COSYCONET and from 4505 lung-healthy control subjects from the population-based KORA and SHIP studies were pooled. Main outcomes were the five dimensions of the generic EQ-5D-3 L questionnaire and two EQ-5D index scores using a tariff based on valuations from the general population and an experience-based tariff. The association of COPD in GOLD grades 1-4 and of several comorbid conditions with the EQ-5D index scores was quantified by multiple linear regression models while adjusting for age, sex, education, body mass index (BMI), and smoking status. RESULTS: For all dimensions of the EQ-5D, the proportion of participants reporting problems was higher in the COPD group than in control subjects. COPD was associated with significant reductions in the EQ-5D index scores (-0.05 points for COPD grades 1/2, -0.09 for COPD grade 3, -0.18 for COPD grade 4 according to the preference-based utility tariff, all p < 0.0001). Adjusted mean index scores were 0.89 in control subjects and 0.85, 0.84, 0.81, and 0.72 in COPD grades 1-4 according to the preference-based utility tariff and 0.76, 0.71, 0.68, 0.64, and 0.58 for control subjects and COPD grades 1-4 for the experience-based tariff respectively. Comorbidities had additive negative effects on the index scores; the effect sizes for comorbidities were comparable to or smaller than the effects of COPD grade 3. No statistically significant interactions between COPD and comorbidities were observed. Score differences between COPD patients and control subjects were most pronounced in younger age groups. CONCLUSIONS: Compared with control subjects, the considerable reduction of HRQL in patients with COPD was mainly due to respiratory limitations, but observed comorbidities added linearly to this effect. Younger COPD patients showed a greater loss of HRQL and may therefore be in specific need of comprehensive disease management. TRIAL REGISTRATION: NCT01245933.

Patient Heterogeneity in Health Economic Decision Models for Chronic Obstructive Pulmonary Disease: Are Current Models Suitable to Evaluate Personalized Medicine?

OBJECTIVES: To assess how suitable current chronic obstructive pulmonary disease (COPD) cost-effectiveness models are to evaluate personalized treatment options for COPD by exploring the type of heterogeneity included in current models and by validating outcomes for subgroups of patients. METHODS: A consortium of COPD modeling groups completed three tasks. First, they reported all patient characteristics included in the model and provided the level of detail in which the input parameters were specified. Second, groups simulated disease progression, mortality, quality-adjusted life-years (QALYs), and costs for hypothetical subgroups of patients that differed in terms of sex, age, smoking status, and lung function (forced expiratory volume in 1 second [FEV1] % predicted). Finally, model outcomes for exacerbations and mortality for subgroups of patients were validated against published subgroup results of two large COPD trials. RESULTS: Nine COPD modeling groups participated. Most models included sex (seven), age (nine), smoking status (six), and FEV1% predicted (nine), mainly to specify disease progression and mortality. Trial results showed higher exacerbation rates for women (found in one model), higher mortality rates for men (two models), lower mortality for younger patients (four models), and higher exacerbation and mortality rates in patients with severe COPD (four models). CONCLUSIONS: Most currently available COPD cost-effectiveness models are able to evaluate the cost-effectiveness of personalized treatment on the basis of sex, age, smoking, and FEV1% predicted. Treatment in COPD is, however, more likely to be personalized on the basis of clinical parameters. Two models include several clinical patient characteristics and are therefore most suitable to evaluate personalized treatment, although some important clinical parameters are still missing.

Assessing health-related quality of life in COPD: comparing generic and disease-specific instruments with focus on comorbidities.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient's health-related quality of life (HRQL). While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health. This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George's Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments. METHODS: Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions. Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences. RESULTS: In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease. Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions. The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions. For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL. CONCLUSION: All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities. Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.

Cost-effectiveness models for chronic obstructive pulmonary disease: cross-model comparison of hypothetical treatment scenarios.

OBJECTIVES: To compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios. METHODS: COPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared. RESULTS: Seven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively. CONCLUSIONS: Mortality was the most important factor determining the differences in cost-effectiveness outcomes between models.

Health-related quality of life and chronic obstructive pulmonary disease in early stages - longitudinal results from the population-based KORA cohort in a working age population.

BACKGROUND: It is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL. This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities. METHODS: In the population-based KORA F4 study (2006-08) 1,321 participants aged 41-61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities. For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999-2001) and the F4L follow-up study (2010). Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups. RESULTS: 7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1. Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered. Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (-3.5 (p=0.008) in F4, -3.3 (p=0.014) in S4 and -4.7 (p=0.003) in F4L) compared to the group without airflow limitation. The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer. Over ten years, a small decline in PCS-12 was observed in all groups. This decline was larger in participants with COPD grade 2+, but insignificant. Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found. CONCLUSION: Despite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades. Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients.

The association of smoking status with healthcare utilisation, productivity loss and resulting costs: results from the population-based KORA F4 study.

BACKGROUND: Smoking is seen as the most important single risk to health today, and is responsible for a high financial burden on healthcare systems and society. This population-based cross-sectional study compares healthcare utilisation, direct medical costs, and costs of productivity losses for different smoking groups: current smokers, former smokers, and never smokers. METHODS: Using a bottom-up approach, data were taken from the German KORA F4 study (2006/2008) on self-reported healthcare utilisation and work absence due to illness for 3,071 adults aged 32-81 years. Unit costs from a societal perspective were applied to utilisation. Utilisation and resulting costs were compared across different smoking groups using generalised linear models to adjust for age, sex, education, alcohol consumption and physical activity. RESULTS: Average annual total costs per survey participant were estimated as €3,844 [95% confidence interval: 3,447-4,233], and differed considerably between smoking groups with never smokers showing €3,237 [2,802-3,735] and former smokers causing €4,398 [3,796-5,058]. There was a positive effect of current and former smoking on the utilisation of healthcare services and on direct and indirect costs. Total annual costs were more than 20% higher (p<0.05) for current smokers and 35% higher (p<0.01) for former smokers compared with never smokers, which corresponds to annual excess costs of €743 and €1,108 per current and former smoker, respectively. CONCLUSIONS: Results indicate that excess costs for current and former smokers impose a large burden on society, and that previous top-down cost approaches produced lower estimates for the costs of care for smoking-related diseases. Efforts must be focused on prevention of smoking to achieve sustainable containment on behalf of the public interest.

Real-world treatment of German patients with recurrent and advanced endometrial cancer with a post-platinum treatment: a retrospective claims data analysis.

PURPOSE: Endometrial cancer (EC) is the sixth most common malignancy among females worldwide. Due to limited therapeutic options, treatment of advanced or recurrent disease is associated with poor outcomes. The aim of this study was to describe the real-world treatment of patients with advanced or recurrent EC who received a systemic treatment following platinum-based chemotherapy. METHODS: This retrospective cohort study was based on anonymized German claims data covering the period between January 1, 2010, and June 30, 2020. Patients with EC who started an anticancer treatment following platinum-based chemotherapy were observed for a minimum follow-up of 12 months. Available claims data were used to describe patient characteristics, subsequent treatment lines, healthcare resource utilization, and overall survival (OS) of patients. RESULTS: Out of 713 patients with advanced or recurrent EC and who had received a platinum-based treatment, 201 (mean age: 68.9 years) with a post-platinum-based treatment were identified and observed. The median OS in this population was 335.0 days. Of the 201 patients, 79 patients (39.3%) received a second line of treatment (LOT), and 21 patients (10.4%) had 3 or more treatment lines. In the LOTs following platinum-based chemotherapy, more than 70 different treatment regimens were observed. The hospitalization rate was generally high, with 5.2 hospitalizations per patient-year in the follow-up period. CONCLUSION: The wide variety of therapeutic regimens applied in patients in Germany who progressed after platinum-based therapy confirms the lack of therapeutic strategy for these patients, and the poor prognosis highlights the urgent need for new treatment strategies.

Are health risk attitude and general risk attitude associated with healthcare utilization, costs and working ability? Results from the German KORA FF4 cohort study.

BACKGROUND: Risk attitudes influence decisions made under uncertainty. This paper investigates the association of risk attitudes with the utilization of preventive and general healthcare services, work absence and resulting costs to explore their contribution to the heterogeneity in utilization. METHODS: Data of 1823 individuals (56.5 ± 9.5 years), participating in the German KORA FF4 population-based cohort study (2013/2014) were analyzed. Individuals' general and health risk attitude were measured as willingness to take risk (WTTR) on 11-point scales. Utilization of preventive and medical services and work absence was assessed and annual costs were calculated from a societal perspective. Generalized linear models with log-link function (logistic, negative-binomial and gamma regression) adjusted for age, sex, and height were used to analyze the association of WTTR with the utilizations and costs. RESULTS: Higher WTTR was significantly associated with lower healthcare utilization (physician visits, physical therapy, and medication intake), work absence days and indirect costs. Regarding preventive services, an overall negative correlation between WTTR and utilization was examined but this observation remained non-significant except for the outcome medical check-up. Here, higher WTTR was significantly associated with a lower probability of participation. For all associations mentioned, Odds Ratios ranged between 0.90 and 0.79, with p < 0.05. Comparing the two risk attitudes (general and regarding health) we obtained similar results regarding the directions of associations. CONCLUSIONS: We conclude that variations in risk attitudes contribute to the heterogeneity of healthcare utilization. Thus, knowledge of their associations with utilization might help to better understand individual decision-making - especially in case of participation in preventive services.

Determinants of healthcare utilization and costs in COPD patients: first longitudinal results from the German COPD cohort COSYCONET.

Background: In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET. Material and methods: Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history. Results: Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all p<0.05). Conclusions: Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time.

The revised GOLD 2017 COPD categorization in relation to comorbidities.

INTRODUCTION: The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. METHODS: We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. RESULTS: Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. CONCLUSIONS: These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates.

The contribution of symptoms and comorbidities to the economic impact of COPD: an analysis of the German COSYCONET cohort.

Background: Although patients with COPD often have various comorbidities and symptoms, limited data are available on the contribution of these aspects to health care costs. This study analyzes the association of frequent comorbidities and common symptoms with the annual direct and indirect costs of patients with COPD. Methods: Self-reported information on 33 potential comorbidities and symptoms (dyspnea, cough, and sputum) of 2,139 participants from the baseline examination of the German COPD cohort COSYCONET was used. Direct and indirect costs were calculated based on self-reported health care utilization, work absence, and retirement. The association of comorbidities, symptoms, and COPD stage with annual direct/indirect costs was assessed by generalized linear regression models. Additional models analyzed possible interactions between COPD stage, the number of comorbidities, and dyspnea. Results: Unadjusted mean annual direct costs were €7,263 per patient. Other than COPD stage, a high level of dyspnea showed the strongest driving effect on direct costs (+33%). Among the comorbidities, osteoporosis (+38%), psychiatric disorders (+36%), heart disease (+25%), cancer (+24%), and sleep apnea (+21%) were associated with the largest increase in direct costs (p<0.01). A sub-additive interaction between advanced COPD stage and a high number of comorbidities reduced the independent cost-driving effects of these factors. For indirect costs, besides dyspnea (+34%), only psychiatric disorders (+32%) and age (+62% per 10 years) were identified as significant drivers of costs (p<0.04). In the subsequent interaction analysis, a high number of comorbidities was found to be a more crucial factor for increased indirect costs than single comorbidities. Conclusion: Detailed knowledge about comorbidities in COPD is useful not only for clinical purposes but also to identify relevant cost factors and their interactions and to establish a ranking of major cost drivers. This could help in focusing therapeutic efforts on both clinically and economically important comorbidities in COPD.

Relationship of hyperlipidemia to comorbidities and lung function in COPD: Results of the COSYCONET cohort.

Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1-4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV1) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication.

Impact of chronic ischemic heart disease on the health care costs of COPD patients - An analysis of German claims data.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) has a substantial impact on health care systems worldwide. Particularly, cardiovascular diseases such as ischemic heart disease (IHD) are frequent in individuals with COPD, but the economic consequences of combined COPD and IHD are by large unknown. Therefore, our study has the objective to investigate excess costs of IHD in COPD patients. METHODS: Out of German Statutory Health Insurance claims data we identified 26,318 COPD patients with and 10,287 COPD patients without IHD based on ICD-10 codes (COPD J44; IHD I2[0,1,2,5]) of the year 2011 and matched 9986 of them in a 1:1 ratio based on age and gender. Then, we investigated health care service expenditures in 2012 via Generalized Linear Models. Moreover, we evaluated a potential non-linear association between health care expenditures and age in a gender-stratified Generalized Additive Model. RESULTS: The prevalence of IHD in individuals with COPD increases with rising age up to a share of 50%. COPD patients with IHD cause adjusted mean annual per capita health care service expenditures of ca. €7400 compared with ca. €5800 in COPD patients without IHD. Moreover, excess costs of IHD have an inverse u-shape, peaking in the early (men) respectively late seventies (women). CONCLUSIONS: IHD in COPD patients is associated with excess costs of ca. € 1,500, with the exact amount varying age- and gender-dependently. Subgroups with high excess costs indicate medical need that calls for efficient care strategies, considering COPD and IHD together particularly between 70 and 80 years of age.

Cost burden of type 2 diabetes in Germany: results from the population-based KORA studies.

OBJECTIVE: To examine the impact of type 2 diabetes on direct and indirect costs and to describe the effect of relevant diabetes-related factors, such as type of treatment or glycaemic control on direct costs. DESIGN: Bottom-up excess cost analysis from a societal perspective based on population-based survey data. PARTICIPANTS: 9160 observations from 6803 individuals aged 31-96 years (9.6% with type 2 diabetes) from the population-based KORA (Cooperative Health Research in the Region of Augsburg) studies in Southern Germany. OUTCOME MEASURES: Healthcare usage, productivity losses, and resulting direct and indirect costs. METHODS: Information on diabetes status, biomedical/sociodemographic variables, medical history and on healthcare usage and productivity losses was assessed in standardised interviews and examinations. Healthcare usage and productivity losses were costed with reference to unit prices and excess costs of type 2 diabetes were calculated using generalised linear models. RESULTS: Individuals with type 2 diabetes had 1.81 (95% CI 1.56 to 2.11) times higher direct (€3352 vs €1849) and 2.07 (1.51 to 2.84) times higher indirect (€4103 vs €1981) annual costs than those without diabetes. Cardiovascular complications, a long diabetes duration and treatment with insulin were significantly associated with increased direct costs; however, glycaemic control was only weakly insignificantly associated with costs. CONCLUSIONS: This study illustrates the substantial direct and indirect societal cost burden of type 2 diabetes in Germany. Strong effort is needed to optimise care to avoid progression of the disease and costly complications.