Effects of triple therapy on disease burden in patients of GOLD groups C and D: results from the observational COPD cohort COSYCONET.

BACKGROUND: Randomized controlled trials described beneficial effects of inhaled triple therapy (LABA/LAMA/ICS) in patients with chronic obstructive pulmonary disease (COPD) and high risk of exacerbations. We studied whether such effects were also detectable under continuous treatment in a retrospective observational setting. METHODS: Data from baseline and 18-month follow-up of the COPD cohort COSYCONET were used, including patients categorized as GOLD groups C/D at both visits (n = 258). Therapy groups were defined as triple therapy at both visits (triple always, TA) versus its complement (triple not always, TNA). Comparisons were performed via multiple regression analysis, propensity score matching and inverse probability weighting to adjust for differences between groups. For this purpose, variables were divided into predictors of therapy and outcomes. RESULTS: In total, 258 patients were eligible (TA: n = 162, TNA: n = 96). Without adjustments, TA patients showed significant (p < 0.05) impairments regarding lung function, quality of life and symptom burden. After adjustments, most differences in outcomes were no more significant. Total direct health care costs were reduced but still elevated, with inpatient costs much reduced, while costs of total and respiratory medication only slightly changed. CONCLUSION: Without statistical adjustment, patients with triple therapy showed multiple impairments as well as elevated treatment costs. After adjusting for differences between treatment groups, differences were reduced. These findings are compatible with beneficial effects of triple therapy under continuous, long-term treatment, but also demonstrate the limitations encountered in the comparison of controlled intervention studies with observational studies in patients with severe COPD using different types of devices and compounds.

Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians.

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.

Economic burden of bronchiectasis in Germany.

Estimates of healthcare costs for incident bronchiectasis patients are currently not available for any European country.Out of a sample of 4 859 013 persons covered by German statutory health insurance companies, 231 new bronchiectasis patients were identified in 2012. They were matched with 685 control patients by age, sex and Charlson Comorbidity Index, and followed for 3 years.The total direct expenditure during that period per insured bronchiectasis patient was EUR18 634.57 (95% CI EUR15 891.02-23 871.12), nearly one-third higher (ratio of mean 1.31, 95% CI 1.02-1.68) than for a matched control (p<0.001). Hospitalisation costs contributed to 35% of the total and were >50% higher in the bronchiectasis group (ratio of mean 1.56, 95% CI 1.20-3.01; p<0.001); on average, bronchiectasis patients spent 4.9 (95% CI 2.27-7.43) more days in hospital (p<0.001). Antibiotics expenditures per bronchiectasis outpatient (EUR413.81) were nearly 5 times higher than those for a matched control (ratio of mean 4.85, 95% CI 2.72-8.64). Each bronchiectasis patient had on average 40.5 (95% CI 17.1-43.5) sick-leave days and induced work-loss costs of EUR4230.49 (95% CI EUR2849.58-5611.20). The mortality rate for bronchiectasis and matched non-bronchiectasis patients after 3 years of follow-up was 26.4% and 10.5%, respectively (p<0.001). Mortality in the bronchiectasis group was higher among those who also had chronic obstructive lung disease than in patients with bronchiectasis alone (35.9% and 14.6%, respectively; p<0.001).Although bronchiectasis is considered underdiagnosed, the mortality and associated financial burden in Germany are substantial.

Esophageal ultrasound (EUS) assessment of T4 status in NSCLC patients.

BACKGROUND: Mediastinal and central large vessels (T4) invasion by lung cancer is often difficult to assess preoperatively due to the limited accuracy of computed tomography (CT) scan of the chest. Esophageal ultrasound (EUS) can visualize the relationship of para-esophageally located lung tumors to surrounding mediastinal structures. AIM: To assess the value of EUS for detecting mediastinal invasion (T4) of centrally located lung tumors. METHODS: Patients who underwent EUS for the diagnosis and staging of lung cancer and in whom the primary tumor was detected by EUS and who subsequently underwent surgical- pathological staging (2000-2016) were retrospectively selected from two university hospitals in The Netherlands. T status of the lung tumor was reviewed based on EUS, CT and thoracotomy findings. Surgical- pathological staging was the reference standard. RESULTS: In 426 patients, a lung malignancy was detected by EUS of which 74 subjects subsequently underwent surgical- pathological staging. 19 patients (26%) were diagnosed with stage T4 based on vascular (n=8, 42%) or mediastinal (n=8, 42%) invasion or both (n=2, 11%), one patient (5%) had vertebral involvement. Sensitivity, specificity, PPV and NPV for assessing T4 status were: for EUS (n=74); 42%, 95%, 73%, 83%, for chest CT (n=66); 76%, 61%, 41%, 88% and the combination of EUS and chest CT (both positive or negative for T4, (n=34); 83%, 100%, 100% 97%. CONCLUSION: EUS has a high specificity and NPV for the T4 assessment of lung tumors located para-esophageally and offers further value to chest CT scan.

Burden of non-tuberculous mycobacterial pulmonary disease in Germany.

The objective of this study was to estimate the burden of disease in incident patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD).A sample of 7 073 357 anonymised persons covered by German public statutory health insurances was used to identify patients with NTM-PD. In total, 125 patients with newly diagnosed NTM-PD in 2010 and 2011 were matched with 1250 control patients by age, sex and Charlson Comorbidity Index, and followed for 39 months.The incidence rate for NTM-PD was 2.6 per 100 000 insured persons (95% CI 2.2-3.1). The mortality rate for patients with NTM-PD and the control group in the observational period was 22.4% and 6%, respectively (p<0.001). Mean direct expenditure per NTM-PD patient was €39 559.60 (95% CI 26 916.49-52 202.71), nearly 4-fold (3.95, 95% CI 3.73-4.19) that for a matched control (€10 006.71, 95% CI 8907.24-11 106.17). Hospitalisations were three times higher in the NTM-PD group and accounted for 63% of the total costs. Attributable annual direct costs and indirect work-loss costs in NTM-PD patients were €9093.20 and €1221.05 per control patient, respectively. Only 74% of NTM-PD patients received antibiotics and nearly 12% were prescribed macrolide monotherapy.Although NTM-PD is considered rare, the attributable mortality and financial burden in Germany are high. Efforts to heighten awareness of appropriate therapy are urgently needed.

An official American Thoracic Society and European Respiratory Society policy statement: disparities in respiratory health.

Health disparities, defined as a significant difference in health between populations, are more common for diseases of the respiratory system than for those of other organ systems, because of the environmental influence on breathing and the variation of the environment among different segments of the population. The lowest social groups are up to 14 times more likely to have respiratory diseases than are the highest. Tobacco smoke, air pollution, environmental exposures, and occupational hazards affect the lungs more than other organs and occur disproportionately in ethnic minorities and those with lower socioeconomic status. Lack of access to quality healthcare contributes to disparities. The executive committees of the American Thoracic Society (ATS) and European Respiratory Society (ERS) established a writing committee to develop a policy on health disparities. The document was reviewed, edited, and approved by their full executive committees and boards of directors of the societies. This document expresses a policy to address health disparities by promoting scientific inquiry and training, disseminating medical information and best practices, and monitoring and advocating for public respiratory health. The ERS and the ATS have strong international commitments and work with leaders from governments, academia, and other organisational bodies to address and reduce avoidable health inequalities. Their training initiatives improve the function of healthcare systems and health equality. Both the ATS and the ERS support all aspects of this document, confer regularly, and act together when possible, but the activities to bring about change may vary because of the differences in the continents where the two organisations carry out most of their activities. The ATS and ERS pledge to frame their actions to reduce respiratory health disparities. The vision of the ATS and ERS is that all persons attain better and sustained respiratory health. They call on all their members and other societies to join in this commitment.

An official American Thoracic Society/European Respiratory Society policy statement: disparities in respiratory health.

BACKGROUND: Health disparities, defined as a significant difference in health between populations, are more common for diseases of the respiratory system than for those of other organ systems, because of the environmental influence on breathing and the variation of the environment among different segments of the population. The lowest social groups are up to 14 times more likely to have respiratory diseases than are the highest. Tobacco smoke, air pollution, environmental exposures, and occupational hazards affect the lungs more than other organs, and occur disproportionately in ethnic minorities and those with lower socioeconomic status. Lack of access to quality health care contributes to disparities. METHODS: The executive committees of the American Thoracic Society (ATS) and European Respiratory Society (ERS) established a writing committee to develop a policy on health disparities. The document was reviewed, edited, and approved by the full executive committees and boards of directors of the societies. RESULTS: This document expresses a policy to address health disparities by promoting scientific inquiry and training, disseminating medical information and best practices, and monitoring and advocating for public respiratory health. ERS and ATS have strong international commitments, and work with leaders from governments, academia, and organizations to address and reduce avoidable health inequalities. Their training initiatives improve the function of health care systems and health equality. Both the ATS and ERS support all aspects of this document, confer regularly, and act together when possible, but the activities to bring about change may vary because of the differences in the continents where the two organizations carry out most of their activities. CONCLUSIONS: The ATS and ERS pledge to frame their actions to reduce respiratory health disparities. The vision of the ATS and ERS is that all persons attain better and sustained respiratory health. They call on all their members and other societies to join in this commitment.

Chronic obstructive pulmonary disease and exacerbations: patient insights from the global Hidden Depths of COPD survey.

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations. METHODS: We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today's working-age COPD population. RESULTS: Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors. The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity. Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation. While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered. A high proportion of patients (39%) took a 'wait and see' approach to exacerbations.Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD. However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD. CONCLUSIONS: To reduce the adverse effects of COPD on patients' quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations.

How to integrate multiple comorbidities in guideline development: article 10 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

BACKGROUND: Professional societies, like many other organizations around the world, have recognized the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 10th of a series of 14 articles that were prepared to advise guideline developers in respiratory and other diseases. This article deals with how multiple comorbidities (co-existing chronic conditions) may be more effectively integrated into guidelines. METHODS: In this review we addressed the following topics and questions using chronic obstructive pulmonary disease (COPD) as an example. (1) How important are multiple comorbidities for guidelines? (2) How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities? (3) What are the implications of multiple comorbidities for pharmacological treatment? (4) What are the potential changes induced by multiple comorbidities in guidelines? (5) What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials? Our conclusions are based on available evidence from the published literature, experience from guideline developers, and workshop discussions. We did not attempt to examine all Clinical Practice Guidelines (CPGs) and relevant literature. Instead, we selected CPGs generated by prominent professional organizations and relevant literature published in widely read journals, which are likely to have a high impact on clinical practice. RESULTS AND CONCLUSIONS: A widening gap exists between the reality of the care of patients with multiple chronic conditions and the practical clinical recommendations driven by CPGs focused on a single disease, such as COPD. Guideline development panels should aim for multidisciplinary representation, especially when contemplating recommendations for individuals aged 65 years or older (who often have multiple comorbidities), and should evaluate the quality of evidence and the strength of recommendations targeted at this population. A priority area for research should be to assess the effect of multiple concomitant medications and assess how their combined effects are altered by genetic, physiological, disease-related, and other factors. One step that should be implemented immediately would be for existing COPD guidelines to add new sections to address the impact of multiple comorbidities on screening, diagnosis, prevention, and management recommendations. Research should focus on the possible interaction of multiple medications. Furthermore, genetic, physiological, disease-related, and other factors that may influence the directness (applicability) of the evidence for the target population in clinical practice guidelines should be examined.

Reporting and publishing guidelines: article 12 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

INTRODUCTION: Professional societies, like many other organizations around the world, have recognized the need to use rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the twelfth of a series of 14 articles that were prepared to advise guideline developers in respiratory and other diseases. This article discusses the reporting and publishing of guidelines. METHODS: The authors formulated and discussed the following questions on the reporting and publishing of guidelines. (1) What should be reported in guidelines? (2) How should guidelines be written? (3) How should the bottom-line message be conveyed? (4) How should guidelines be packaged? (5) Where should guidelines be published? (6) Who benefits from the publication of guidelines? (7) What information should be vetted by the editor(s)? (8) How should guidelines be peer reviewed? We conducted a review of the literature, looking for systematic reviews and methodological research that addressed these questions, but we did not conduct a full systematic review. Our conclusions are based on the available evidence from the published literature and logical arguments from experienced guideline developers. RESULTS AND DISCUSSION: There is little empirical evidence that addresses the reporting and publishing of guidelines. A standard format for reporting guidelines is desirable to ensure that guidelines are comprehensive and that all of the information necessary to judge their quality is presented. In addition, guidelines should contain concise evidence-based recommendations. To facilitate the use of guidelines by consumers, it is preferable to publish them in journals that serve the target audience and to package them in multiple ways. Editors and peer reviewers should ensure that reporting standards have been met, potential conflicts of interest have been adequately addressed and made public, and that the recommendations address important clinical questions.

Cost-effectiveness of Internet-based self-management compared with usual care in asthma.

BACKGROUND: Effectiveness of Internet-based self-management in patients with asthma has been shown, but its cost-effectiveness is unknown. We conducted a cost-effectiveness analysis of Internet-based asthma self-management compared with usual care. METHODOLOGY AND PRINCIPAL FINDINGS: Cost-effectiveness analysis alongside a randomized controlled trial, with 12 months follow-up. Patients were aged 18 to 50 year and had physician diagnosed asthma. The Internet-based self-management program involved weekly on-line monitoring of asthma control with self-treatment advice, remote Web communications, and Internet-based information. We determined quality adjusted life years (QALYs) as measured by the EuroQol-5D and costs for health care use and absenteeism. We performed a detailed cost price analysis for the primary intervention. QALYs did not statistically significantly differ between the Internet group and usual care: difference 0.024 (95% CI, -0.016 to 0.065). Costs of the Internet-based intervention were $254 (95% CI, $243 to $265) during the period of 1 year. From a societal perspective, the cost difference was $641 (95% CI, $-1957 to $3240). From a health care perspective, the cost difference was $37 (95% CI, $-874 to $950). At a willingness-to-pay of $50,000 per QALY, the probability that Internet-based self-management was cost-effective compared to usual care was 62% and 82% from a societal and health care perspective, respectively. CONCLUSIONS: Internet-based self-management of asthma can be as effective as current asthma care and costs are similar. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79864465.

Patient preferences for asthma therapy: a discrete choice experiment.

AIM: This study was designed to capture patient preferences for different aspects of asthma treatment from people with asthma in the UK, the Netherlands and Spain. METHODS: Asthma patients from the UK (n=124), the Netherlands (n=269) and Spain (n=86) participated in the survey. Patients' preferences and willingness to pay for a particular number of preventer inhalers, in relation to days per week with symptoms, days requiring reliever medication, risk of side effects, and requirement for a visit to their general practitioner (GP) or the Emergency Room (ER), were recorded. RESULTS: Participants were willing to pay euro 35/month to avoid a day with symptoms, euro 109/month to avoid asthma attacks that required emergency visits to their GP or the ER, and euro 94/month to achieve total avoidance of asthma symptoms compared with their current state. CONCLUSIONS: This study presents European data regarding the importance to patients of different attributes of asthma and its treatment. Study participants placed high values on the avoidance of symptoms, and asthma attacks requiring medical attendance.

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

Burden and clinical features of chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality and represents a substantial economic and social burden throughout the world. It is the fifth leading cause of death worldwide and further increases in its prevalence and mortality are expected in the coming decades. The substantial morbidity associated with COPD is often underestimated by health-care providers and patients; likewise, COPD is frequently underdiagnosed and undertreated. COPD develops earlier in life than is usually believed. Tobacco smoking is by far the major risk for COPD and the prevalence of the disease in different countries is related to rates of smoking and time of introduction of cigarette smoking. Contribution of occupational risk factors is quite small, but may vary depending on a country's level of economic development. Severe deficiency for alpha-1-antitrypsin is rare and the impact of other genetic factors on the prevalence of COPD has not been established. COPD should be considered in any patient presenting with cough, sputum production, or dyspnoea, especially if an exposure to risk factors for the disease has been present. Clinical diagnosis needs to be confirmed by standardised spirometric tests in the presence of not-fully-reversible airflow limitation. COPD is generally a progressive disease. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations. Smoking cessation is the only intervention shown to slow the decline. If exposure is stopped, the disease may still progress due to the decline in lung function that normally occurs with aging, and some persistence of the inflammatory response.

Assessment of microvascular leakage via sputum induction: the role of substance P and neurokinin A in patients with asthma.

Microvascular leakage is an important feature of inflammation. However, the assessment of vascular leakage has seldom been used to monitor airway inflammation in asthma. The aim of this study was to determine the effect of inhaled substance P, a potent neurokinin 1 (NK1) agonist and mediator of plasma extravasation, on markers of microvascular leakage in induced sputum from patients with asthma. In a crossover study, sputum was induced before and 30 minutes after inhalation of substance P or neurokinin A (as control) by 12 subjects with atopic and mild, steroid-naive asthma. The levels of alpha2-macroglobulin, ceruloplasmin, albumin, and fibrinogen were determined in induced sputum as markers of leakage. Substance P induced a significant increase in the levels of alpha2-macroglobulin, ceruloplasmin, and albumin in induced sputum (median fold change, 3.1, 2.2, and 2.9, respectively) (p < 0.013), whereas inhaled neurokinin A was not able to induce significant changes (p > 0.31). The increase in sputum leakage markers was not associated with the cumulative dose of substance P (p > 0.12). These results indicate that NK1 receptor stimulation causes a rapid increase in microvascular leakage as shown in induced sputum in patients with asthma. This investigational model of "dual induction" (first leakage, then sputum) may therefore be useful to test the antiexudative effect of newly develop drugs, such as NK1 antagonists.