Prevalence of asthma and COPD and blood eosinophil count in a middle-aged Belgian population

Various phenotypes exist in asthma and Chronic Obstructive Pulmonary Disease (COPD). These are important to identify in order to guide treatment decisions. We aim to investigate the prevalence and clinical characteristics of obstructive airway diseases in the middle-aged population. We estimated the prevalence of COPD and/or asthma in the Asklepios cohort study (Belgium), using information from the third European Community Respiratory Health Survey (ECRHS3), medical records, and spirometry. Respiratory symptoms, respiratory medication, and current disease status distinguished clinical from sub-clinical cases. In addition, we compared the blood eosinophil count/mu L (median [IQR]) between cases and controls. Of the 2221 participants (mean age 56.1 +/- 5.9 years; 48.7% males), 138 (6.2%) participants had clinical current asthma, 22 (1.0%) participants had sub-clinical ever asthma, 102 (4.6%) had sub-clinical spirometry-defined COPD, 104 (4.6%) participants had clinical spirometry-confirmed COPD, and 11 (0.5%) had asthma and COPD overlap (ACO). Clinical current asthma (160.0 [110.0-250.0]), sub-clinical ever asthma (170.0 [110.0-230.0]), and clinical COPD (160.0 [110.0-220.0])-but less sub-clinical COPD (140.0 [90.0-210.0])-had higher eosinophil counts, compared to controls (130.0 [80.0-200.0]). We conclude that obstructive airway diseases are prevalent in the middle-aged Asklepios cohort. Moreover, the systemic eosinophil count is increased in clinical COPD cases, and in asthma cases regardless of clinical remission

Epidemiology of Comorbidities in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is defined by the Global initiative for chronic Obstructive Lung Disease (GOLD) as a common preventable and treatable disease, which is characterized by a persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response of the airways and lungs to noxious particles or gases. Since 2010, COPD is globally the third leading cause of death. Each year, approximately 200 000 to 300 000 people die in Europe because of COPD. The morbidity, economic and social impact of COPD is substantial and increasing.2 Among respiratory diseases, COPD is the leading cause of lost work days and it has an estimated cost of 3 to 4% (or 38.6 billion €) of the total health care budget in the European Union

Monoclonal antibodies in type 2 asthma : a systematic review and network meta-analysis

Since novel treatments to target eosinophilic inflammation in Type 2 asthma are emerging, we aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate. PubMed and Web of Science were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma. Thirty trials were selected involving biologics that target the IL-5 pathway, IL-13, the common IL-4 and IL-13 receptor, IL-9, IL-2 and TSLP. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis to compare effects on exacerbation rate between the different treatments. Mepolizumab, reslizumab and benralizumab significantly reduced the risk of exacerbations compared to placebo (by 47-52%, 50-60%, and 28-51% respectively). Reslizumab and benralizumab also improved lung function. Dupilumab and tezepelumab improved lung function in frequent exacerbators. Lebrikizumab had no significant effect on the number of exacerbations, symptom control or health-related quality of life. Tralokinumab improved lung function compared to placebo. Network meta-analysis of all treatment and placebo arms, showed no superiority of one biologic over the others. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n = 2051) to demonstrate significantly decreased exacerbation rates in the subgroup analysis of IL-5 acting agents compared to placebo. Monoclonal antibodies such as mepolizumab, reslizumab and benralizumab have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. However, no statistically significant superiority was observed of one biologic over the other in the network meta-analysis. More studies with direct head to head comparisons and better defined endotypes are required

Effectiveness and safety of oral anticoagulants in older patients with atrial fibrillation : a systematic review and meta-analysis

Background and Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk. Methods and Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74–0.94] for stroke/SE; HR 0.77, 95%CI [0.65–0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86–1.01] for major bleeding; HR 0.58, 95%CI [0.50–0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99–1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients. Conclusion: Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results

Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation:A nationwide cohort study

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs. Methods: AF patients initiating anticoagulation between 2013–2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose. Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64–0.72)), all-cause mortality (HR 0.76, 95%CI (0.74–0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91–0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66–0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83–0.90); HR 0.86, 95%CI (0.83–0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83–0.99); HR 0.86, 95%CI (0.81–0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80–0.92)) and edoxaban (HR 0.79, 95%CI (0.72–0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively. Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran

Beta(2)-adrenergic receptor (ADRB2) gene polymorphisms and risk of COPD exacerbations : the Rotterdam study

The role of the beta(2)-adrenergic receptor (ADRB2) gene in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the association between ADRB2 variants and the risk of exacerbations in COPD patients treated with inhaled beta(2)-agonists. Within the Rotterdam Study, a population-based cohort study, we followed 1053 COPD patients until the first COPD exacerbation or end of follow-up and extracted rs1042713 (16Arg > Gly) and rs1042714 (27Gln > Glu) in ADRB2. Exposure to inhaled beta(2)-agonists was categorized into current, past, or non-use on the index date (date of COPD exacerbation for cases and on the same day of follow-up for controls). COPD exacerbations were defined as acute episodes of worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate exacerbations), or hospitalization (severe exacerbations). The associations between ADRB2 variants and COPD exacerbations were assessed using Cox proportional hazards models, adjusting for age, sex, use of inhaled corticosteroids, daily dose of beta(2)-agonists, and smoking. In current users of beta(2)-agonists, the risk of COPD exacerbation decreased by 30% (hazard ratio (HR); 0.70, 95% CI: 0.59-0.84) for each copy of the Arg allele of rs1042713 and by 20% (HR; 0.80, 95% CI: 0.69-0.94) for each copy of the Gln allele of rs1042714. Furthermore, current users carrying the Arg16/Gln27 haplotype had a significantly lower risk (HR; 0.70, 95% CI: 0.59-0.85) of COPD exacerbation compared to the Gly16/Glu27 haplotype. In conclusion, we observed that the Arg16/Gln27 haplotype in ADRB2 was associated with a reduced risk of COPD exacerbation in current users of inhaled beta(2)-agonists

Methods to assess COPD medications adherence in healthcare databases:a systematic review

Background: The Global Initiative for Chronic Obstructive Lung Disease 2023 report recommends medication adherence assessment in COPD as an action item. Healthcare databases provide opportunities for objective assessments; however, multiple methods exist. We aimed to systematically review the literature to describe existing methods to assess adherence in COPD in healthcare databases and to evaluate the reporting of influencing variables. Method: We searched MEDLINE, Web of Science and Embase for peer-reviewed articles evaluating adherence to COPD medication in electronic databases, written in English, published up to 11 October 2022 (PROSPERO identifier CRD42022363449). Two reviewers independently conducted screening for inclusion and performed data extraction. Methods to assess initiation (dispensing of medication after prescribing), implementation (extent of use over a specific time period) and/or persistence (time from initiation to discontinuation) were listed descriptively. Each included study was evaluated for reporting variables with an impact on adherence assessment: inpatient stays, drug substitution, dose switching and early refills. Results: 160 studies were included, of which four assessed initiation, 135 implementation and 45 persistence. Overall, one method was used to measure initiation, 43 methods for implementation and seven methods for persistence. Most of the included implementation studies reported medication possession ratio, proportion of days covered and/or an alteration of these methods. Only 11% of the included studies mentioned the potential impact of the evaluated variables. Conclusion: Variations in adherence assessment methods are common. Attention to transparency, reporting of variables with an impact on adherence assessment and rationale for choosing an adherence cut-off or treatment gap is recommended.</p

Cardiac impact of inhaled therapy in the largest randomised placebo-controlled trial in COPD history

SUMMIT supports the efficiency and cardiovascular safety of LABA and ICS in COPD patients at cardiovascular risk http://ow.ly/p6Is300ffoc