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.

Estimating the Health and Economic Impact of Improved Management in Prevalent Chronic Obstructive Pulmonary Disease Populations in England, Germany, Canada, and Japan: A Modelling Study.

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations. Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings. Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care. Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size. Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement-the Mobilise-D study protocol.

BACKGROUND: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. METHODS/DESIGN: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson's Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. DISCUSSION: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. TRIAL REGISTRATION: ISRCTN12051706.

Standardisation of Clinical Assessment, Management and Follow-Up of Acute Hospitalised Exacerbation of COPD: A Europe-Wide Consensus.

BACKGROUND: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up. METHODS: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken. FINDINGS: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation. INTERPRETATION: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.

Comprehensive assessment of the safety of olodaterol 5 µg in the Respimat® device for maintenance treatment of COPD: comparison with the long-acting ß2-agonist formoterol.

This analysis provides a comprehensive clinical assessment of the long-term safety of the licensed dose of olodaterol (5 µg once daily [QD] via Respimat® inhaler) in patients with chronic obstructive pulmonary disease by exploring the occurrence of acknowledged side effects of long-acting ß2-agonists as well as those included in the olodaterol and formoterol labels. We analysed pooled data from two replicate, double-blind studies of olodaterol (5 µg QD via Respimat®) compared to formoterol (12 µg twice daily [BID]) or placebo over 48 weeks (1222.13, NCT00793624; 1222.14, NCT00796653). Patients could continue their background treatment. The analysis considered adverse events (AEs) typically associated with ß2-agonists, including cardiovascular events, as well as administration-related events. Descriptive statistics were provided for the incidence of AEs and aggregated AEs. The analysis included 1379 patients: 460 placebo, 459 olodaterol and 460 formoterol; AEs were reported by 70.9, 71.7 and 69.1% of patients, respectively. Exposure-adjusted incidence rates of cardiac AEs (arrhythmia and myocardial ischaemia) and cough were numerically lower in the olodaterol group than the formoterol group, while nasopharyngitis, throat irritation, metabolism and psychiatric disorders were numerically higher in the olodaterol group. The most frequent event in the olodaterol group was nasopharyngitis (placebo 8.0%; olodaterol 12.9%; formoterol 10.0%). Except for cough (incidence rate ratio of 0.46 [95% confidence interval 0.24, 0.89] in favour of olodaterol), there were no significant differences between active groups. In conclusion, olodaterol 5 µg QD was well tolerated over 48 weeks with a typical ß2-agonist safety profile comparable to formoterol 12 µg BID.

COPD: the patient perspective.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by nonreversible airway obstruction. Well-characterized symptoms such as exertional dyspnea and fatigue have a negative impact on patients' quality of life (QoL) and restrict physical activity in daily life. The impact of COPD symptoms on QoL is often underestimated; for example, 36% of patients who describe their symptoms as being mild-to-moderate also admit to being too breathless to leave the house. Additionally, early morning and nighttime symptoms are a particular problem. Methods are available to allow clinicians to accurately assess COPD symptoms, including patient questionnaires. Integrated approaches to COPD management, particularly pulmonary rehabilitation, are effective strategies for addressing symptoms, improving exercise capacity and, potentially, also increasing physical activity. Inhaled bronchodilators continue to be the mainstay of drug therapy in COPD, where options can be tailored to meet patients' needs with careful selection of the inhaled medication and the device used for its delivery. Overall, an integrated approach to disease management should be considered for improving QoL and subsequent patient outcomes in COPD.

Mechanisms, assessment and therapeutic implications of lung hyperinflation in COPD.

The main complaint of patients with chronic obstructive pulmonary disease (COPD) is shortness of breath with exercise, that is usually progressive. The principal mechanism that explains this symptom is the development of lung hyperinflation (LH) which is defined by an increase of functional residual capacity (FRC) above predicted values. Patients with COPD may develop static LH (sLH) because of destruction of pulmonary parenchyma and loss of elastic recoil. In addition, dynamic LH (dLH) develops when patients with COPD breathe in before achieving a full exhalation and, as a consequence, air is trapped within the lungs with each further breath. Dynamic LH may also occur at rest but it becomes clinically relevant during exercise and exacerbation. Lung hyperinflation may have an impact beyond the lungs and the effects of LH on cardiovascular function have been extensively analysed. The importance of LH makes its identification and measurement crucial. The demonstration of LH in COPD leads to the adoption of strategies to minimise its impact on the daily activities of patients. Several strategies reduce the impact of LH; the use of long-acting bronchodilators has been shown to reduce LH and improve exercise capacity. Non pharmacologic interventions have also been demonstrated to be useful. This article describes the pathophysiology of LH, its impact on the lungs and beyond and reviews the strategies that improve LH in COPD.