Frequency and severity of exacerbations of COPD associated with future Risk of exacerbations and mortality: A UK routine health care data study

Background: Studies have shown that chronic obstructive pulmonary disease (COPD) exacerbation events are related to future events; however, previous literature typically reports frequent vs infrequent exacerbations per patient-year and no studies have investigated increasing number of severe exacerbations in relation to COPD outcomes. Objective: To investigate the association between baseline frequency and severity of exacerbations and subsequent mortality and exacerbation risk in a COPD cohort. Methods: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics data were used to identify patients registered at general practices in the UK, who had a diagnosis of COPD, were over the age of 40 years, were smokers or ex-smokers and had data recorded from 2004 onwards. Frequency and severity of exacerbations in the baseline year were identified as moderate exacerbations (general practice events) and severe exacerbations (hospitalised events). Patients were categorised as having: none, 1 moderate only, 2 moderate only, 3+ moderate only, 1 severe (and any moderate), 2 severe (and any moderate), and 3+ severe (and any moderate exacerbations). Poisson regression was used to investigate the association between baseline exacerbation frequency/severity and exacerbation events and mortality over follow-up. Results: Overall, 340,515 COPD patients were included. Patients had higher rates of future exacerbations with increasing frequency and severity of baseline exacerbations compared to no baseline exacerbations. Adjusted incidence rate ratios (IRR) for patients with 1, 2, and 3+ moderate exacerbations compared to 0 exacerbations were 1.70 (95% CI 1.66– 1.74), 2.31 (95% CI 2.24– 2.37), and 3.52 (95% CI 3.43– 3.62), respectively. Patients with increased frequency of baseline exacerbations were more likely to die from all-cause, COPD-related, and cardiovascular-related mortality in a graduated fashion. Conclusion: Increasing number and severity of exacerbations were associated with increasing risk of subsequent exacerbations, all-cause mortality and COPD-related mortality. Even a single moderate event increases the risk of future events, illustrating that every exacerbation counts

An observational cohort study of exercise and education for people with chronic obstructive pulmonary disease not meeting criteria for formal pulmonary rehabilitation programmes

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Pulmonary rehabilitation (PR) is offered to patients with functional breathlessness. However, access to PR is limited. The objective of this study was to evaluate whether a 4-week education and exercise programme offered to COPD patients with Medical Research Council (MRC) dyspnoea 1–2 improves disease self-management. Patients were recruited by their GP to attend four weekly 2-h sessions provided by a multidisciplinary team. Patients completed outcome measures before and after the program. Forty-two patients entered the programme and 26 out of 42 (61.9%) completed all sessions. The Bristol COPD Knowledge Questionnaire and Patient Activation Measure improved (both p ≤ 0.001). Disease burden was not reduced according to the COPD assessment test. All patients accepted a referral for ongoing exercise. Fourteen current smokers (81.3%) accepted a referral for smoking cessation, three patients with anxiety or depression (37.5%) accepted a psychological therapies referral. The programme improved COPD disease knowledge, patient activation and stimulated referrals to further services supporting disease management. Randomised controlled trials are warranted for similar interventions for COPD patients with early stage disease

The effect of aclidinium bromide on daily respiratory symptoms of COPD, measured using the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) diary: pooled analysis of two 6-month Phase III studies.

BACKGROUND: Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD). We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS(™): COPD) scale (formerly EXACT-RS). METHODS: Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction. Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D. Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed. RESULTS: Of 1210 patients, 1167 had data available for GOLD classification. Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted. Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group. The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D. CONCLUSIONS: Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients' level of symptoms at baseline. Net treatment benefit was similar in patients with low or high levels of symptoms. TRIAL REGISTRATION: ATTAIN (ClinicalTrials.gov identifier: NCT01001494 ) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397 )

A Proposal of the European Association for the Study of Obesity to Improve the ICD-11 Diagnostic Criteria for Obesity Based on the Three Dimensions Etiology, Degree of Adiposity and Health Risk

Diagnostic criteria for complex medical conditions caused by a multitude of both genetic and environmental factors should be descriptive and avoid any attribution of causality. Furthermore, the wording used to describe a disorder should be evidence-based and avoid stigmatization of the affected individuals. Both terminology and categorizations should be readily comprehensible for healthcare professionals and guide clinical decision making. Uncertainties with respect to diagnostic issues and their implications may be addressed to direct future clinical research. In this context, the European Association of the Study of Obesity (EASO) considers it an important endeavor to review the current ICD-11 Beta Draft for the definition of overweight and obesity and to propose a substantial revision. We aim to provide an overview of the key issues that we deem relevant for the discussion of the diagnostic criteria. We first discuss the current ICD-10 criteria and those proposed in the ICD 11 Beta Draft. We conclude with our own proposal for diagnostic criteria, which we believe will improve the assessment of patients with obesity in a clinically meaningful way

Combined transcriptomic-(1)H NMR metabonomic study reveals yhat monoethylhexyl phthalate stimulates adipogenesis and glyceroneogenesis in human adipocytes

Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl phthalate (MEHP) is of particular concern since it was shown to activate the peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 murine preadipocytes. In the present work, we used an untargeted, combined transcriptomic-(1)H NMR-based metabonomic approach to describe the overall effect of MEHP on primary cultures of human subcutaneous adipocytes differentiated in vitro. MEHP stimulated rapidly and selectively the expression of genes involved in glyceroneogenesis, enhanced the expression of the cytosolic phosphoenolpyruvate carboxykinase, and reduced fatty acid release. These results demonstrate that MEHP increased glyceroneogenesis and fatty acid reesterification in human adipocytes. A longer treatment with MEHP induced the expression of genes involved in triglycerides uptake, synthesis, and storage; decreased intracellular lactate, glutamine, and other amino acids; increased aspartate and NAD, and resulted in a global increase in triglycerides. Altogether, these results indicate that MEHP promoted the differentiation of human preadipocytes to adipocytes. These mechanisms might contribute to the suspected obesogenic effect of MEHP

European Association for the Study of Obesity Position Statement on the Global COVID-19 Pandemic

open18openFrühbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie JFrühbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie

European association for the study of obesity position statement on the global COVID-19 pandemic

COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, was declared a pandemic by the World Health Organization on March 12, 2020. The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about this global health challenge and its significant impacts on individuals, families, communities, health systems, nations, and wider society

Accumulation of Polychlorinated Biphenyls in Adipocytes: Selective Targeting to Lipid Droplets and Role of Caveolin-1

Background : Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that preferentially accumulate in lipid-rich tissues of contaminated organisms. Although the adipose tissue constitutes a major intern reservoir of PCBs and recent epidemiological studies associate PCBs to the development of obesity and its related disorders, little is known about the mechanisms involved in their uptake by the adipose tissue and their intracellular localization in fat cells

Strain-Specific Differences in the Genetic Control of Two Closely Related Mycobacteria

The host response to mycobacterial infection depends on host and pathogen genetic factors. Recent studies in human populations suggest a strain specific genetic control of tuberculosis. To test for mycobacterial-strain specific genetic control of susceptibility to infection under highly controlled experimental conditions, we performed a comparative genetic analysis using the A/J- and C57BL/6J-derived recombinant congenic (RC) mouse panel infected with the Russia and Pasteur strains of Mycobacterium bovis Bacille Calmette Guérin (BCG). Bacillary counts in the lung and spleen at weeks 1 and 6 post infection were used as a measure of susceptibility. By performing genome-wide linkage analyses of loci that impact on tissue-specific bacillary burden, we were able to show the importance of correcting for strain background effects in the RC panel. When linkage analysis was adjusted on strain background, we detected a single locus on chromosome 11 that impacted on pulmonary counts of BCG Russia but not Pasteur. The same locus also controlled the splenic counts of BCG Russia but not Pasteur. By contrast, a locus on chromosome 1 which was indistinguishable from Nramp1 impacted on splenic bacillary counts of both BCG Russia and Pasteur. Additionally, dependent upon BCG strain, tissue and time post infection, we detected 9 distinct loci associated with bacillary counts. Hence, the ensemble of genetic loci impacting on BCG infection revealed a highly dynamic picture of genetic control that reflected both the course of infection and the infecting strain. This high degree of adaptation of host genetics to strain-specific pathogenesis is expected to provide a suitable framework for the selection of specific host-mycobacteria combinations during co-evolution of mycobacteria with humans