Publications by authors named "Lies Lahousse"

120 Publications

Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation Using P-gp and/or CYP450-Interacting Drugs: a Systematic Review and Meta-analysis.

Cardiovasc Drugs Ther 2021 Oct 12. Epub 2021 Oct 12.

Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Purpose: Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.

Methods: Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.

Results: Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.

Conclusion: The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.
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http://dx.doi.org/10.1007/s10557-021-07279-8DOI Listing
October 2021

Benefits of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers on Progression of Emphysema and Lung Function Decline.

Chest 2021 Oct;160(4):1160-1162

Department of Bioanalysis, Ghent University, Ghent, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2021.06.023DOI Listing
October 2021

Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies.

Lancet Respir Med 2021 Oct 4. Epub 2021 Oct 4.

Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; COPD Centre, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements.

Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year.

Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001).

Interpretation: If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity.

Funding: The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.
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http://dx.doi.org/10.1016/S2213-2600(21)00313-1DOI Listing
October 2021

Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function.

Sci Rep 2021 Sep 29;11(1):19365. Epub 2021 Sep 29.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.
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http://dx.doi.org/10.1038/s41598-021-98120-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481467PMC
September 2021

The implementation of risk minimization measures to prevent teratogenic pregnancy outcomes related to oral retinoid and valproate use in Belgium.

Acta Clin Belg 2021 Sep 26:1-8. Epub 2021 Sep 26.

Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

Introduction: Both oral retinoid and valproate containing medicines are highly teratogenic. Their use by women of childbearing age is controlled by risk minimization measures (RMMs) introduced by the European Medicine Agency, including the pregnancy prevention programme (PPP). In 2018, the RMMs were revised as previous measures were insufficient to prevent the use of these medicines during pregnancies.

Aim & Methods: A cross-sectional survey was conducted among patients, physicians and pharmacists to evaluate the implementation of the revised RMMs in Belgium. The primary outcome was compliance with key aspects of the PPP. Differences in compliance between oral retinoid and valproate stakeholders were investigated. The relationship between potential determinants (population characteristics and RMM usage) and compliance was studied via multiple logistic regression.

Results: A total of 317 eligible patients, physicians and pharmacists participated. The majority of the studied patients fail to comply with the PPP, mainly driven by poor implementation of pregnancy testing. A large number of healthcare providers is unaware of the available educational materials.

Conclusion: It is likely that a substantial part of Belgian women of childbearing age using oral retinoids or valproate insufficiently meet the PPP requirements. We propose to better inform healthcare providers about the mandatory PPPs and available educational materials as well as to support them with the implementation of such programmes to improve the safe use of these teratogenic medicines.
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http://dx.doi.org/10.1080/17843286.2021.1983708DOI Listing
September 2021

Anti-Interleukin-5 Therapy Is Associated with Attenuated Lung Function Decline in Severe Eosinophilic Asthma Patients from the Belgian Severe Asthma Registry.

J Allergy Clin Immunol Pract 2021 09 23. Epub 2021 Sep 23.

Department of Respiratory Medicine, CHU Sart-Tilman, I(3)GIGA Research Group, University of Liège, Liège, Belgium.

Background: Asthmatics have accelerated lung function decline over time compared with healthy individuals.

Objective: To evaluate risk factors for accelerated lung function decline.

Methods: In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of post-bronchodilation forced expiratory volume in 1 s [FEV] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV decline.

Results: In the overall population (n = 318), median annual FEV decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV were associated with accelerated FEV decline.

Conclusions: Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV decline. The causality of this observation should, however, be confirmed in future prospective controlled studies.
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http://dx.doi.org/10.1016/j.jaip.2021.09.023DOI Listing
September 2021

Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications.

Allergy 2021 Sep 3. Epub 2021 Sep 3.

Emergency Department, Respiratory Medicine, University of Ferrara, University Hospital S. Anna, Ferrara, Italy.

A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long-acting β2 adrenergic bronchodilators (LABA). The addition of long-acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single-inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS-LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.
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http://dx.doi.org/10.1111/all.15076DOI Listing
September 2021

Determinants of poor inhaler technique and poor therapy adherence in obstructive lung diseases: a cross-sectional study in community pharmacies.

BMJ Open Respir Res 2021 08;8(1)

Department of Bioanalysis, Ghent University, Ghent, Belgium

Background: Correct inhaler use can be challenging in real life, with incorrect use resulting in poor symptom control. The aim of this study was to examine factors associated with poor inhaler technique and poor therapy adherence among patients with obstructive lung disease in community pharmacies.

Methods: A cross-sectional study was conducted in patients with obstructive lung diseases in nine Belgian community pharmacies. Logistic regression analyses identified factors associated with poor inhaler technique and poor therapy adherence (assessed by the Test of Adherence to Inhalers and the modified Medication Possession Ratio).

Results: Seventy obstructively impaired community patients (median age 64 y, 56% females) were included and the technique of 122 inhalers was assessed. Inhaler technique scored generally poor, with half of patients making critical errors in using at least one of their inhalers. In multivariable analysis, the use of multiple devices (adjusted OR, aOR 11.68; 95% CI 3.29 to 41.51) and a diagnosis of asthma-Chronic Obstructive Pulmonary Disease overlap (ACO; aOR 7.06; 95% CI 1.15 to 43.35), were associated with making critical errors in inhaler technique independent of quality of life. Non-adherence occurred in more than one-third of patients, and occurred in up to one half of the patients when also taking overuse into account. In multivariable analysis for therapy adherence, current smoking was associated with poor therapy adherence (aOR 0.15; 95% CI 0.02 to 0.96) independently of age and poor treatment knowledge. Therapy adherence was poor in patients with asthma compared with those with ACO. Current smokers and highly educated patients seemed to be at increased risk for inhaler overuse.

Conclusions: Given the important role of a correct inhaler technique and therapy adherence in disease control, these findings emphasise the need for patient education and aiming uniformity in the inhaler device.

Trial Registration Number: B670201835229.
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http://dx.doi.org/10.1136/bmjresp-2020-000823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351493PMC
August 2021

An alternative approach for bioanalytical assay optimization for wastewater-based epidemiology of SARS-CoV-2.

Sci Total Environ 2021 May 26;789:148043. Epub 2021 May 26.

Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Wastewater-based epidemiology of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW). Unlike predecessors, method optimization of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 RNA loads. This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris, …). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering the molecular weight cut-off did not improve our limit of detection and quantification (approximately 10 copies/μL for all genes). Quantitative polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E-gene fragments. This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. dPCR showed high variability at low concentration levels (10 copies/μL), indicating that variability in bioanalytical methods for wastewater-based epidemiology of SARS-CoV-2 might be substantial. dPCR results in IWW were in line with the results found with qPCR. On average, the N2-gene fragment showed high in-sample stability in IWW for 10 days of storage at 4 °C. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene fragment proved to be less stable compared to the N2-gene fragment and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene fragment in IWW.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152210PMC
May 2021

Macrolide-associated ototoxicity: a cross-sectional and longitudinal study to assess the association of macrolide use with tinnitus and hearing loss.

J Antimicrob Chemother 2021 Sep;76(10):2708-2716

Department of Bioanalysis, Pharmaceutical Care Unit, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Background: Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity.

Objectives: To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population.

Methods: Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action.

Results: In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found.

Conclusions: Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.
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http://dx.doi.org/10.1093/jac/dkab232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446930PMC
September 2021

Incidence and predictors of asthma exacerbations in middle-aged and older adults: the Rotterdam Study.

ERJ Open Res 2021 Jul 12;7(3). Epub 2021 Jul 12.

Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

Aim: The aim of this study was to investigate occurrence and determinants of asthma exacerbations in an ageing general population.

Methods: Subjects aged 45 years or above with physician-diagnosed asthma in the Rotterdam Study, a population-based prospective cohort from January 1991 to May 2018, were assessed for asthma exacerbations. Exacerbations were defined as acute episodes of worsening asthma treated with oral corticosteroids. Cox proportional hazards analysis was used to investigate risk factors for a future exacerbation.

Results: Out of 763 participants with asthma (mean age 61.3 years, 69.2% female), 427 (56.0%) experienced at least one exacerbation, in a mean follow-up time of 13.9 years. The mean annual exacerbation rate was 0.22. Most exacerbations occurred during winter months. Risk factors for exacerbations were a history of previous exacerbations (HR 4.25; 95% CI 3.07-5.90, p<0.001)), respiratory complaints (HR 2.18; 95% CI 1.48-3.21, p<0.001), airflow obstruction (HR 1.52; 95% CI 1.07-2.15, p=0.019), obesity (HR 1.38; 95% CI 1.01-1.87, p=0.040) and depressive symptoms (HR 1.55; 95% CI 1.05-2.29, p=0.027). Compared to those not using respiratory medication, we observed higher hazard ratios for those on short-acting β-agonists (SABA, rescue medication) only (HR 3.08, 95% CI 1.61-5.90, p=0.001) than those on controller medication (HR 2.50, 95% CI 1.59-3.92, p<0.001).

Conclusion: Many older adults with asthma suffer from at least one severe exacerbation. Previous exacerbations, use of SABA without concomitant controller medication, respiratory complaints, obesity, airway obstruction and depression are independent risk factors for exacerbations.
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http://dx.doi.org/10.1183/23120541.00126-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273296PMC
July 2021

Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long-acting beta agonists.

Am J Ind Med 2021 10 13;64(10):853-860. Epub 2021 Jul 13.

Fire Department of the City of New York, The Bureau of Health Services and the FDNY World Trade Center Health Program, Brooklyn, NY, USA.

Background: Greater than average loss of one-second forced expiratory volume (FEV ) is a risk factor for asthma, chronic obstructive pulmonary disease (COPD), and asthma/COPD overlap syndrome in World Trade Center (WTC)-exposed firefighters. Inhaled corticosteroids and long-acting beta agonists (ICS/LABA) are used to treat obstructive airways disease but their impact on FEV -trajectory in this population is unknown.

Methods: The study population included WTC-exposed male firefighters who were treated with ICS/LABA for 2 years or longer (with initiation before 2015), had at least two FEV measurements before ICS/LABA initiation and two FEV measurements posttreatment between September 11, 2001 and September 10, 2019. Linear mixed-effects models were used to estimate FEV -slope pre- and post-treatment.

Results: During follow-up, 1023 WTC-exposed firefighters were treated with ICS/LABA for 2 years or longer. When comparing intervals 6 years before and 6 years after treatment, participants had an 18.7 ml/year (95% confidence interval [CI]: 11.3-26.1) improvement in FEV -slope after adjustment for baseline FEV , race, height, WTC exposure, weight change, blood eosinophil concentration, and smoking status. After stratification by median date of ICS/LABA initiation (January 14, 2010), earlier ICS/LABA-initiators had a 32.5 ml/year (95% CI: 19.5-45.5) improvement in slope but later ICS/LABA-initiators had a nonsignificant FEV -slope improvement (7.9 ml/year, 95% CI: -0.5 to 17.2).

Conclusions: WTC-exposed firefighters treated with ICS/LABA had improved FEV slope after initiation, particularly among those who started earlier. Treatment was, however, not associated with FEV -slope improvement if started after the median initiation date (1/14/2010), likely because onset of disease began before treatment initiation. Research on alternative treatments is needed for patients with greater than average FEV -decline who have not responded to ICS/LABA.
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http://dx.doi.org/10.1002/ajim.23272DOI Listing
October 2021

Effect of β-blockers on the risk of COPD exacerbations according to indication of use: the Rotterdam Study.

ERJ Open Res 2021 Apr 28;7(2). Epub 2021 Jun 28.

Dept of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.

Observational studies report a reduction of COPD exacerbations in patients treated with β-blockers. In contrast, the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK COPD) randomised controlled trial which excluded COPD patients with cardiovascular conditions showed an increase in COPD exacerbations. It is unclear whether this discrepancy could be explained by underlying cardiovascular comorbidity. We examined whether the association between use of β-blockers and risk of COPD exacerbations differed between patients with and without a cardiovascular indication for β-blockers use. Within the Rotterdam Study, we followed COPD subjects until the first COPD exacerbation, or end of follow-up. Cardiovascular indication for β-blockers use was defined as a history of hypertension, coronary heart disease, atrial fibrillation and/or heart failure at baseline. The association between β-blockers use and COPD exacerbations was assessed using Cox proportional hazards models adjusted for age, sex, smoking, incident cardiovascular disease ( heart failure, hypertension, atrial fibrillation and/or coronary heart disease during follow-up), respiratory drugs and nitrates. In total, 1312 COPD patients with a mean age of 69.7±9.2 years were included. In patients with a cardiovascular indication (n=755, mean age of 70.4±8.8 years), current use of cardioselective β-blockers was significantly associated with a reduced risk of COPD exacerbations (HR 0.69, 95% CI 0.57-0.85). In contrast, in subjects without a cardiovascular indication (n=557, mean age of 68.8±9.7 years), current use of cardioselective β-blockers was not associated with an altered risk of COPD exacerbations (HR 0.94, 95% CI 0.55-1.62). Use of cardioselective β-blockers reduced the risk of exacerbations in COPD patients with concomitant cardiovascular disease. Therefore, the potential benefits of β-blockers might be confined to COPD patients with cardiovascular disease.
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http://dx.doi.org/10.1183/23120541.00624-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236616PMC
April 2021

Lung Function Impairment and the Risk of Incident Dementia: The Rotterdam Study.

J Alzheimers Dis 2021 ;82(2):621-630

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

Background: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia.

Objective: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia.

Methods: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 < 80% predicted) and in participants with COPD (FEV1/FVC < 0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80% predicted). Hazard ratios (HRs) with 95% confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype.

Results: Of 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95% CI, 1.53-4.75; adjusted HRCOPD 1.03; 95% CI, 0.61-1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC% predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95% CI, 1.31-3.98), as well as Alzheimer's disease (AD; adjusted HR 2.13; 95% CI, 1.13-4.02).

Conclusion: Participants with PRISm or a low FVC% predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC% predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.
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http://dx.doi.org/10.3233/JAD-210162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385522PMC
September 2021

Monoclonal antibodies in type 2 asthma: an updated network meta-analysis.

Minerva Med 2021 May 14. Epub 2021 May 14.

Department of Bioanalysis, Pharmaceutical Care Unit, Ghent University, Ghent, Belgium -

Introduction: Novel treatments target eosinophilic inflammation in type 2 asthma. We aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate.

Evidence Acquisition: PubMed and Embase were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma between 2019 and 2021 to update our previous meta-analysis covering studies published from 2005 to 2018. Five-hundred and sixty six publications have been identified, of which six recent trials (on top of 30 previously identified) involving mepolizumab, benralizumab, reslizumab and dupilumab met our inclusion criteria. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis including a total of 19 RCTs to compare effects on exacerbation rate between the different treatments.

Evidence Synthesis: Benralizumab significantly reduced the risk of exacerbations compared to the pooled placebo in our network meta-analysis (median effect difference: -0.520, 95% CI (-1.010- -0.048) ). No biologic showed superiority over the others in indirect comparisons. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n=2564) to demonstrate significantly decreased exacerbation rates both in the overall population and in the subgroup analysis of IL-5 acting agents compared to placebo.

Conclusions: Monoclonal antibodies have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. No biological showed superiority over the others emphasizing the need for clearly defined endotypes indicating those patients who will optimally benefit for each treatment.
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http://dx.doi.org/10.23736/S0026-4806.21.07623-0DOI Listing
May 2021

A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2021 07 28;321(1):L130-L143. Epub 2021 Apr 28.

Department of Health Sciences, University of Leicester, Leicester, United Kingdom.

Genome-wide association studies (GWASs) have identified regions associated with chronic obstructive pulmonary disease (COPD). GWASs of other diseases have shown an approximately 10-fold overrepresentation of nonsynonymous variants, despite limited exonic coverage on genotyping arrays. We hypothesized that a large-scale analysis of coding variants could discover novel genetic associations with COPD, including rare variants with large effect sizes. We performed a meta-analysis of exome arrays from 218,399 controls and 33,851 moderate-to-severe COPD cases. All exome-wide significant associations were present in regions previously identified by GWAS. We did not identify any novel rare coding variants with large effect sizes. Within GWAS regions on chromosomes 5q, 6p, and 15q, four coding variants were conditionally significant ( < 0.00015) when adjusting for lead GWAS single-nucleotide polymorphisms A common gasdermin B () splice variant (rs11078928) previously associated with a decreased risk for asthma was nominally associated with a decreased risk for COPD [minor allele frequency (MAF) = 0.46, = 1.8e-4]. Two stop variants in coiled-coil α-helical rod protein 1 (), a gene involved in regulating cell proliferation, were associated with COPD (both < 0.0001). The Z allele was associated with a random-effects odds ratio of 1.43 for COPD (95% confidence interval = 1.17-1.74), though with marked heterogeneity across studies. Overall, COPD-associated exonic variants were identified in genes involved in DNA methylation, cell-matrix interactions, cell proliferation, and cell death. In conclusion, we performed the largest exome array meta-analysis of COPD to date and identified potential functional coding variants. Future studies are needed to identify rarer variants and further define the role of coding variants in COPD pathogenesis.
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http://dx.doi.org/10.1152/ajplung.00009.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321852PMC
July 2021

Effect of polymorphism rs1799752 on protein levels of ACE2, the SARS-CoV-2 entry receptor, in alveolar lung epithelium.

ERJ Open Res 2021 Apr 19;7(2). Epub 2021 Apr 19.

Laboratory for Translational Research in Obstructive Pulmonary Diseases, Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

https://bit.ly/3k6aAE8.
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http://dx.doi.org/10.1183/23120541.00940-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917434PMC
April 2021

The impact of underweight and obesity on outcomes in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis on the obesity paradox.

Clin Cardiol 2021 May 26;44(5):599-608. Epub 2021 Mar 26.

Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.

Although obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF-related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta-analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73-0.87]; RR 0.63, 95%CI [0.57-0.70]; and RR 0.42, 95%CI [0.31-0.57], respectively) and all-cause mortality (RR 0.73, 95%CI [0.64-0.83]; RR 0.61, 95%CI [0.52-0.71]; and RR 0.56, 95%CI [0.47-0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to <30, ≥30 and ≥40 kg/m , respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to <25 kg/m ). In contrast, thromboembolic (RR 1.92, 95%CI [1.28-2.90]) and mortality (RR 3.57, 95%CI [2.50-5.11]) risks were significantly increased in underweight anticoagulated AF patients (BMI <18.5 kg/m ). In overweight and obese anticoagulated AF patients, the risks of major bleeding (RR 0.86, 95%CI [0.76-0.99]; and RR 0.88, 95%CI [0.79-0.98], respectively) and intracranial bleeding (RR 0.75, 95%CI [0.58-0.97]; and RR 0.57, 95%CI [0.40-0.80], respectively) were also significantly lower compared to normal BMI patients, while similar risks were observed in underweight and morbidly obese patients. This meta-analysis demonstrated lower thromboembolic and mortality risks with increasing BMI. However, as this paradox was driven by results from randomized studies, while observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.
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http://dx.doi.org/10.1002/clc.23593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119828PMC
May 2021

Epigenome-wide association study on diffusing capacity of the lung.

ERJ Open Res 2021 Jan 15;7(1). Epub 2021 Mar 15.

Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

Background: Epigenetics may play an important role in the pathogenesis of lung diseases. However, little is known about the epigenetic factors that influence impaired gas exchange at the lung.

Aim: To identify the epigenetic signatures of the diffusing capacity of the lung measured by carbon monoxide uptake (the diffusing capacity of the lung for carbon monoxide ( )).

Methods: An epigenome-wide association study (EWAS) was performed on diffusing capacity, measured by carbon monoxide uptake ( ) and per alveolar volume ( ) (as / ), using the single-breath technique in 2674 individuals from two population-based cohort studies. These were the Rotterdam Study (RS, the "discovery panel") and the Framingham Heart Study (FHS, the "replication panel"). We assessed the clinical relevance of our findings by investigating the identified sites in whole blood and by lung tissue specific gene expression.

Results: We identified and replicated two CpG sites (cg05575921 and cg05951221) that were significantly associated with / and one (cg05575921) suggestively associated with . Furthermore, we found a positive association between aryl hydrocarbon receptor repressor () gene (cg05575921) hypomethylation and gene expression of exocyst complex component 3 () in whole blood. We confirmed that the expression of in lung tissue is positively associated with / and .

Conclusions: We report on epigenome-wide associations with diffusing capacity in the general population. Our results suggest EXOC3 to be an excellent candidate, through which smoking-induced hypomethylation of might affect pulmonary gas exchange.
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http://dx.doi.org/10.1183/23120541.00567-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957297PMC
January 2021

Sarcopenia in older people with chronic airway diseases: the Rotterdam study.

ERJ Open Res 2021 Jan 8;7(1). Epub 2021 Mar 8.

Dept of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Sarcopenia is a heterogeneous skeletal muscle disorder involving the loss of muscle mass and function. However, the prevalence of sarcopenia based on the most recent definition remains to be determined in older people with chronic airway diseases. The aim was to evaluate sarcopenia prevalence and association with chronic airway diseases and its lung function in an older population, using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. We performed a cross-sectional analysis in 5082 participants (mean age 69.0±8.8 years, 56% females) from the Rotterdam Study. Participants with interpretable spirometry and an available assessment of sarcopenia were included. The appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS) were assessed using dual-energy X-ray absorptiometry (DXA) and a hydraulic hand dynamometer, respectively. We analysed the association between sarcopenia and chronic airway diseases by using regression models adjusted for age, sex, smoking status, total fat percentage and other relevant confounders. Participants with chronic airway diseases had higher prevalence of probable sarcopenia (12.0%, 95% CI 10.2-13.8) and confirmed sarcopenia (3.0%, 95% CI 2.1-3.9) than without. Chronic airway diseases were associated with "probable sarcopenia" (OR 1.28, 95% CI 1.02-1.60), "confirmed sarcopenia" (OR 2.13, 95% CI 1.33-3.43), reduced HGS (β -0.51 (-0.90--0.11)) and reduced ASMI (β -0.19 (-0.25--0.14)). Forced expiratory volume in 1 s <80% was associated with lower HGS (β -1.03 (-1.75--0.31)) and lower ASMI (β -0.25 (-0.36--0.15)) than forced expiratory volume in 1 s ≥80%. Sarcopenia was prevalent and associated with chronic airway diseases among older population. These results suggest the need for early diagnosis of sarcopenia in older people with chronic airway diseases by applying EWGSOP2 recommendations.
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http://dx.doi.org/10.1183/23120541.00522-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938051PMC
January 2021

Pharmacogenetics of inhaled corticosteroids and exacerbation risk in adults with asthma.

Clin Exp Allergy 2021 Jan 11. Epub 2021 Jan 11.

Department of Bioanalysis, Ghent University, Ghent, Belgium.

Background: Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses.

Objective: We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment.

Methods: We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population-based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome.

Results: rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P < 0.005). In contrast, rs1134481 T allele within TBXT (chromosome 6, member of a family associated with embryonic lung development) showed better response with ICS. rs37973 G allele (GLCCI1) showed a significantly poorer response on ICS within the discovery cohort, which was also significant but in the opposite direction in the replication cohort.

Conclusion: rs242941 in CRHR1 was associated with poor ICS response. Conversely, TBXT variants were associated with improved ICS response. These associations may reveal specific endotypes, potentially allowing prediction of exacerbation risk and ICS response.
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http://dx.doi.org/10.1111/cea.13829DOI Listing
January 2021

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis.

Cardiovasc Drugs Ther 2021 Jan 11. Epub 2021 Jan 11.

Department of Bioanalysis, Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

Purpose: Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed.

Methods And Results: After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients.

Conclusion: The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m) and on differences between NOACs in these patients.
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http://dx.doi.org/10.1007/s10557-020-07122-6DOI Listing
January 2021

A pragmatic randomized controlled trial to improve inhaler technique using mHealth.

Clin Transl Allergy 2020 Dec 7;10(1):59. Epub 2020 Dec 7.

Department of Bioanalysis, Pharmaceutical Care Unit, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

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http://dx.doi.org/10.1186/s13601-020-00363-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722438PMC
December 2020

Impact of a single non-sex-related stroke risk factor on atrial fibrillation and oral anticoagulant outcomes: a systematic review and meta-analysis.

Open Heart 2020 12;7(2)

Department of Bioanalysis, Pharmaceutical Care Unit, Ghent University, Ghent, Belgium.

Aims: Oral anticoagulants (OACs) are crucial for treating atrial fibrillation (AF) patients at high thromboembolic risk. However, in AF patients at intermediate thromboembolic risk with a single non-sex-related stroke risk factor (CHADS-VASc score 1 in men, 2 in women), guidelines advise to consider starting anticoagulation, which may result in OAC non-initiation due to underestimation of the thromboembolic risk of a single stroke risk factor and overestimation of the OAC-related bleeding risk. A critical appraisal of the role of OACs and the benefit-risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in this patient subgroup are needed.

Methods And Results: This systematic review provides an overview of literature on the effectiveness and safety of OACs in AF patients with a single non-sex-related stroke risk factor after searching Medline and Embase. Differences between individual stroke risk factors regarding the ischaemic stroke risk in non-anticoagulated AF patients are identified in a meta-analysis, demonstrating the highest increased risk in patients aged 65-74 years old or with diabetes mellitus, followed by heart failure, hypertension and vascular disease. Furthermore, meta-analysis results favour NOACs over VKAs, given their equal effectiveness and superior safety in AF patients at intermediate thromboembolic risk (HR 0.93, 95% CI 0.65 to 1.34 for stroke or systemic embolism; HR 0.60, 95% CI 0.45 to 0.80 for major bleeding; HR 0.48, 95% CI 0.14 to 1.59 for intracranial bleeding; HR 0.58, 95% CI 0.47 to 0.71 for mortality).

Conclusion: Our systematic review with meta-analysis favours the use of anticoagulation in AF patients with a single non-sex-related stroke risk factor, especially when age ≥65 years or diabetes mellitus is present, with a preference for NOACs over VKAs.
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http://dx.doi.org/10.1136/openhrt-2020-001465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759963PMC
December 2020

Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study.

Int J Environ Res Public Health 2020 12 4;17(23). Epub 2020 Dec 4.

Pulmonary, Critical Care and Sleep Medicine Division, Department of Medicine and Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.
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http://dx.doi.org/10.3390/ijerph17239056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730939PMC
December 2020

Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation according to the drug labelling and the EHRA Practical Guide.

Int J Cardiol 2021 04 3;328:97-103. Epub 2020 Dec 3.

Pharmaceutical Care Unit, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.

Background: This study aimed to evaluate the prevalence of potential drug-drug interactions (DDIs) and the appropriateness of direct oral anticoagulant (DOAC) dosing according to both the Summary of Product Characteristics (SmPC) and the European Heart Rhythm Association (EHRA) Practical Guide in a 'real-world' sample of non-valvular atrial fibrillation (NVAF) patients.

Methods And Results: Data of a cross-sectional observational study in a primary care sample of 654 long-term DOAC users were used for this sub-analysis. A total of 262 potential DDIs were identified in 220 patients (33.6%). Pharmacodynamic DDIs were present in 163 patients (24.9%) and pharmacokinetic DDIs in 82 patients (12.5%). One-third of patients (33.8%) received reduced DOAC dose. According to the dosing recommendations in the SmPC, 81.7% of DOACs were dosed appropriately. According to the EHRA recommendations, 76.6% of DOACs were dosed appropriately. Dosing recommendations were consistent for 90.7% of patients, with both the SmPC and EHRA Practical Guide considering DOACs dosed appropriately in 74.5% of patients, overdosed in 7.8%, underdosed in 7.6% and contraindicated in 0.8%. However, for the remaining 9.3% dosing recommendations differed between SmPC and EHRA.

Conclusions: This 'real-world' analysis of DOAC dosing demonstrated that in about one-third of NVAF patients potential DDIs were present. In 18.3% and 23.4% of patients, DOACs were dosed inappropriately according to the SmPC and EHRA Practical Guide respectively. In almost 10% of the study population dosing advice was inconsistent between both references. More research is needed to ensure appropriate DOAC dosing in this 'grey zone' population.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.062DOI Listing
April 2021

Current developments and future directions in COPD.

Eur Respir Rev 2020 Dec 2;29(158). Epub 2020 Dec 2.

Division of Pulmonary Rehabilitation, Istituti Clinici Scientifici Maugeri, IRCCS, Tradate, Italy.

The European Respiratory Society journals publish respiratory research and policy documents of the highest quality, offering a platform for the exchange and promotion of scientific knowledge. In this article, focusing on COPD, the third leading cause of death globally, we summarise novel research highlights focusing on the disease's underlying mechanisms, epidemiology and management, with the aim to inform and inspire respiratory clinicians and researchers.
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http://dx.doi.org/10.1183/16000617.0289-2020DOI Listing
December 2020

Blood eosinophil level and lung function trajectories: cross-sectional and longitudinal studies in European cohorts.

ERJ Open Res 2020 Oct 5;6(4). Epub 2020 Oct 5.

Dept of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

Background: Elevated blood eosinophils have been associated with lower lung function and are believed to be associated with accelerated lung function decline.

Method: Blood eosinophils were measured in four cohorts: <45 years cohort within the Vlagtwedde-Vlaardingen (V&V) study, the Uppsala cohort of the European Community Respiratory Health Survey (ECRHS-Uppsala; <45 years), ≥45 years cohort within the V&V study, and the Rotterdam study (≥45 years). Blood eosinophils at baseline were classified as normal (<300 cells·μL) or elevated (≥300 cells·μL). Lung function was measured at baseline and follow-up with spirometry: forced expiratory volume in 1 s (FEV), vital capacity (VC) and their ratio FEV/VC. The association between blood eosinophils and lung function was tested cross-sectionally using linear regression and longitudinally using a mixed model, both adjusted for age, sex, height, pack-years smoking and smoking status. Stratified analyses were done for asthma.

Results: Elevated blood eosinophils were associated with lower FEV (regression coefficient -147 mL (95% CI -188 to -105 mL)), VC (-120 mL (-165 to -75 mL)) and FEV/VC (-1.3% (-1.9% to -0.6%)) at baseline in the two <45 years cohorts, and with lower FEV (-70 mL (-112 to -27 mL)) and FEV/VC (-1.8% (-2.6% to -1.0%)) in the two ≥45 years cohorts. Elevated blood eosinophils were associated with an accelerated decline in FEV (-5.5 mL·year (95% CI -10.5 to -0.5 mL·year)) and VC (-6.4 mL·year (-11.26 to -1.5 mL·year)) compared to normal blood eosinophils in the younger asthmatic subjects in the longitudinal studies.

Conclusion: Elevated blood eosinophils are associated with lower lung function in the general population and with an accelerated lung function decline among asthmatic individuals.
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http://dx.doi.org/10.1183/23120541.00320-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533380PMC
October 2020

Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Front Pharmacol 2020 9;11:583311. Epub 2020 Sep 9.

Pharmaceutical Care Unit, Department of Bioanalysis, Ghent University, Ghent, Belgium.

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 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.
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http://dx.doi.org/10.3389/fphar.2020.583311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509201PMC
September 2020

Pharmacogenetics in clinical practice: current level of knowledge among Flemish physicians and pharmacists.

Pharmacogenomics J 2021 02 26;21(1):78-84. Epub 2020 Aug 26.

Department of Bioanalysis, Pharmaceutical Care Unit, Ghent University, Ghent, Belgium.

Over the past decade, pharmacogenetics (PGx) became an essential tool for personalized medicine although its clinical implementation is still limited. We aimed to assess the current level of knowledge, applications, and expectations of Flemish pharmacists and physicians towards PGx and determine the factors that influence healthcare professionals' knowledge of PGx, aiming to guide future implementation initiatives. A web-based cross-sectional survey was conducted from 8 March 2019 to 8 April 2019, targeting pharmacists, physicians, and trainees of both professions. Ten questions were used to assess the participants' knowledge about PGx. Multivariable linear regression was used to assess the association of profession, experience, practice setting, and prior education with the level of PGx knowledge. In total, 201 Flemish healthcare providers participated, including 100 pharmacists, 73 physicians, and 28 trainees. The majority (78%) of participants were unfamiliar with the basic principles of PGx and its application in clinical practice. The mean percentage of correct answers achieved for the knowledge assessment questions was 34%. Only 9% had counseled patients, while 8% assisted other healthcare professionals on PGx tests the past year. Participants' PGx knowledge was significantly affected by their profession, practice setting, and level of prior education independent of years of experience. These findings provide insight into factors affecting the knowledge of PGx and the current level of PGx implementation in Flemish clinical practice. This may form a basis for developing educational initiatives to enhance the clinical application of PGx in Flanders.
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http://dx.doi.org/10.1038/s41397-020-00180-xDOI Listing
February 2021
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