16 results on '"Elise M A Slob"'
Search Results
2. Genome-wide association studies of exacerbations in children using long-acting beta2-agonists
- Author
-
Esther Herrera Luis, S Vijverberg, Mariëlle W. Pijnenburg, Daniel B Hawcutt, Esteban G. Burchard, Anke H. Maitland-van der Zee, Elise M A Slob, Anne H. Neerincx, Levi B. Richards, Somnath Mukhopadhyay, Colin N. A. Palmer, Cristina Longo, Fook Tim Chew, Natalia Hernandez-Pacheco, Andrea L. Jorgensen, Gerard H. Koppelman, Elisabeth H. Bel, Maria Pino-Yanes, Javier Perez-Garcia, Yang Yie Sio, Steve Turner, Anand Kumar Andiappan, Groningen Research Institute for Asthma and COPD (GRIAC), Pediatrics, Graduate School, AII - Inflammatory diseases, APH - Personalized Medicine, Pulmonology, and Paediatric Pulmonology
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Exacerbation ,Immunology ,Single-nucleotide polymorphism ,Genome-wide association study ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,exacerbations ,Adrenal Cortex Hormones ,childhood asthma ,Internal medicine ,Administration, Inhalation ,medicine ,Humans ,Immunology and Allergy ,genetic polymorphism ,Anti-Asthmatic Agents ,030212 general & internal medicine ,Young adult ,Child ,Genetic association ,Asthma ,pharmacogenetics ,long-acting beta2-agonist ,business.industry ,medicine.disease ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,business ,Pharmacogenetics ,Imputation (genetics) ,hormones, hormone substitutes, and hormone antagonists ,Genome-Wide Association Study - Abstract
Background: Some children with asthma experience exacerbations despite long-acting beta2-agonist (LABA) treatment. While this variability is partly caused by genetic variation, no genome-wide study until now has investigated which genetic factors associated with risk of exacerbations despite LABA use in children with asthma. We aimed to assess whether genetic variation was associated with exacerbations in children treated with LABA from a global consortium. Methods: A meta-analysis of genome-wide association studies (meta-GWAS) was performed in 1,425 children and young adults with asthma (age 6-21 years) with reported regular use of LABA from six studies within the PiCA consortium using a random effects model. The primary outcome of each study was defined as any exacerbation within the past 6 or 12 months, including at least one of the following: 1) hospital admissions for asthma, 2) a course of oral corticosteroids or 3) emergency room visits because of asthma. Results: Genome-wide association results for a total of 82 996 common single nucleotide polymorphisms (SNPs, MAF ≥1%) with high imputation quality were meta-analysed. Eight independent variants were suggestively (P-value threshold ≤5 × 10−6) associated with exacerbations despite LABA use. Conclusion: No strong effects of single nucleotide polymorphisms (SNPs) on exacerbations during LABA use were identified. We identified two loci (TBX3 and EPHA7) that were previously implicated in the response to short-acting beta2-agonists (SABA). These loci merit further investigation in response to LABA and SABA use.
- Published
- 2021
3. Adolescents' experiences with patient engagement in respiratory medicine
- Author
-
Niels W.P. Rutjes, Henriette Maitland, Elise M A Slob, Susanne J. H. Vijverberg, Truus Teunissen, Christine Dedding, BC Groot, Health Economics and Health Technology Assessment, Science Communication, Graduate School, AII - Inflammatory diseases, APH - Personalized Medicine, Paediatric Pulmonology, Amsterdam institute for Infection and Immunity, Pulmonology, Ethics, Law & Medical humanities, Pediatric surgery, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, and APH - Societal Participation & Health
- Subjects
Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,SDG 16 - Peace ,Adolescent ,Cystic Fibrosis ,Youth engagement ,education ,shared decision making ,Advisory Committees ,Patient engagement ,Outcomes ,Peer support ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Patient Education as Topic ,030225 pediatrics ,Health care ,medicine ,Pulmonary Medicine ,Humans ,adolescents ,Child ,Pediatric asthma ,health care economics and organizations ,Qualitative Research ,Netherlands ,patient involvement ,Motivation ,business.industry ,SDG 16 - Peace, Justice and Strong Institutions ,Original Articles ,Asthma ,Justice and Strong Institutions ,Respiratory Medicine ,030228 respiratory system ,Family medicine ,Pediatrics, Perinatology and Child Health ,Original Article ,Female ,Thematic analysis ,Patient Participation ,business ,pediatric asthma - Abstract
OBJECTIVE: Adolescent engagement in decision-making processes in health care and research in the field of chronic respiratory diseases is rare but increasingly recognized as important. The aim of this study was to reflect on adolescents' motives and experiences in the process of establishing an advisory council for adolescents with a chronic respiratory disease.METHODS: A qualitative evaluation study was undertaken to assess the process of starting an advisory youth council in a tertiary hospital in the Netherlands. Data collection consisted of observations of council meetings, in-depth interviews with youth council members, and moderated group discussions. Data were analyzed using thematic analysis to explore the experiences of the council members (n = 9, aged 12-18 years, all with a chronic respiratory disease). Two-hour council meetings took place in the hospital to provide solicited and unsolicited advice to improve research and care.RESULTS: Three themes were identified as motives for adolescents to engage in an advisory council: (1) experience of fun and becoming empowered by their illness; (2) the value of peer support and contact; and (3) being able to contribute to care and research. The council's output consisted of solicited advice on information leaflets for patients, study procedures, and dietary menu options for hospitalized children. The council struggled to have their unsolicited advice heard within the hospital.CONCLUSIONS: Council members experienced engagement as beneficial at the individual, group, and organizational levels. However, meaningful youth engagement requires connectedness with, and official support from, officials at all levels within an organization.
- Published
- 2021
4. Late Breaking Abstract - A randomised, double-blind, placebo controlled, clinical trial evaluating imatinib in patients with severe COVID-19
- Author
-
Josien Smits, Marleen Kemper, Jessy Van Wezenbeek, Wim Boersma, Patrick J Smeele, Lucas R Celant, Erik Duijvelaar, Wouter Hoefsloot, Pierre M Bet, Leo M. A. Heunks, M.J. Overbeek, Anton Vonk Noordegraaf, Carol Pamplona, Marry R. Smit, Laurien M.A. Oswald, Ary Serpa Neto, Jurjan Aman, Herman M.A. Hofstee, Job R Schippers, Katrien Eger, Ivo van der Lee, Janneke E Stalenhoef, Miranda Geelhoed, Arthur L E M Vanhove, Nienke Paternotte, Karin A. Boomars, Azar Kianzad, Frank W.J.M. Smeenk, Esther J. Nossent, Adinda Mieras, Elise M A Slob, Jeroen N. Wessels, Michel M. van den Heuvel, Yurika L E van Glabbeek, Chris Happé, Renate Kos, Anke-Hilse Maitland-van der Zee, Nicole P. Juffermans, Laurien Van Der Lee, Imke H Bartelink, Pieter R. Tuinman, Gert-Jan Braunstahl, Peter W.A. Kunst, Marcus J. Schultz, Laura A. Hagens, Romke Hoekstra, Niels Pronk, Lieuwe D. J. Bos, Frances Handoko-De Man, Hans P. Grotjohan, Sara Azhang, Michiel Alexander de Raaf, Liza Botros, Peter I. Bonta, Pearl Mau-Asam, Rianne J A Hoek, Harm Jan Bogaard, Job J.M.H. van Bragt, Marije Lammers, ACS - Pulmonary hypertension & thrombosis, Pulmonary medicine, ACS - Microcirculation, Clinical pharmacology and pharmacy, APH - Mental Health, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, ACS - Heart failure & arrhythmias, Internal medicine, Intensive care medicine, Surgery, and ACS - Diabetes & metabolism
- Subjects
Double blind ,Clinical trial ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Internal medicine ,medicine ,In patient ,Imatinib ,Placebo ,business ,medicine.drug - Published
- 2021
5. Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial
- Author
-
Job J.M.H. van Bragt, Michiel Alexander de Raaf, Harm Jan Bogaard, Pierre M Bet, Azar Kianzad, Merlijn Reijrink, Esther J. Nossent, Job R Schippers, Lucas R Celant, Lieuwe D. J. Bos, Jeroen N. Wessels, Mirte Muller, Chris Happé, Niels Pronk, Anton Vonk Noordegraaf, Leo M. A. Heunks, Liza Botros, E Marleen Kemper, Wim Boersma, Michel van den Heuvel, Hans P Grotjohan, Rianne J A Hoek, Carolina C Pamplona, Sara Azhang, Nicole P. Juffermans, Marry R Smit, Ivo van der Lee, Imke H Bartelink, Bas F M van Raaij, Janneke E Stalenhoef, Wouter Hoefsloot, Pieter R. Tuinman, Ariana Lammers, Katrien Eger, Boaz D Hazes, E Laurien van der Lee, Karin A T Boomars, Arthur L E M Vanhove, Frances S. de Man, Laura A Hagens, Anke-Hilse Maitland-van der Zee, Elisabeth C W Neefjes, Marcus J. Schultz, Pearl F M Mau Asam, Erik Duijvelaar, Patrick J Smeele, A. Josien Smits, Frank W J M Smeenk, Elise M A Slob, Laurien M A Oswald, Ary Serpa Neto, J. J. Miranda Geelhoed, Jessie Van Wezenbeek, Gert-Jan Braunstahl, Herman M A Hofstee, Romke Hoekstra, Peter I. Bonta, Jurjan Aman, Nienke Paternotte, Renate Kos, Ahmed A. Bayoumy, Peter W A Kunst, Maria J Overbeek, Adinda Mieras, Yurika L E van Glabbeek, Pulmonology, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, Intensive Care Medicine, Graduate School, APH - Personalized Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Pharmacy, Emergency Department, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, ACS - Microcirculation, Pulmonary Medicine, Pulmonary medicine, Clinical pharmacology and pharmacy, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Internal medicine, Intensive care medicine, and Surgery
- Subjects
Male ,Time Factors ,medicine.medical_treatment ,Severity of Illness Index ,Corrections ,law.invention ,Placebos ,0302 clinical medicine ,Randomized controlled trial ,law ,Netherlands ,media_common ,0303 health sciences ,education.field_of_study ,Middle Aged ,Combined Modality Therapy ,3. Good health ,Treatment Outcome ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,Respiratory Insufficiency ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Population ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Placebo ,Loading dose ,Capillary Permeability ,03 medical and health sciences ,Double-Blind Method ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,media_common.cataloged_instance ,European union ,education ,Protein Kinase Inhibitors ,Aged ,030304 developmental biology ,Mechanical ventilation ,SARS-CoV-2 ,business.industry ,COVID-19 ,Respiration, Artificial ,Discontinuation ,Oxygen ,Clinical trial ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,business - Abstract
Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak. Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged ≥18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1–9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020–001236–10). Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56–73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0·95 [95% CI 0·76–1·20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0·51 [0·27–0·95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0·52 (95% CI 0·26–1·05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1·07 (0·63–1·80; p=0·81). The median duration of invasive mechanical ventilation was 7 days (IQR 3–13) in the imatinib group compared with 12 days (6–20) in the placebo group (p=0·0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events. Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. 
- Published
- 2021
6. Early-life antibiotic use and risk of attention-deficit hyperactivity disorder and autism spectrum disorder: results of a discordant twin study
- Author
-
Paul Lichtenstein, Gerard H. Koppelman, Henrik Larsson, Anke H. Maitland-van der Zee, Sebastian Lundström, Aletta D. Kraneveld, Catharina E. M. van Beijsterveldt, Conor V. Dolan, Tong Gong, Susanne J. H. Vijverberg, Bronwyn K. Brew, Catarina Almqvist, Meike Bartels, Elise M A Slob, Dorret I. Boomsma, Talitha Dijs, Graduate School, AII - Inflammatory diseases, APH - Personalized Medicine, Pulmonology, Paediatric Pulmonology, Afd Pharmacology, Pharmacology, Biological Psychology, APH - Mental Health, APH - Methodology, and Groningen Research Institute for Asthma and COPD (GRIAC)
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Epidemiology ,Autism Spectrum Disorder ,Gut–brain axis ,Monozygotic twin ,discordant twin design ,ASD ,antibiotics ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,children ,Medicine ,Attention deficit hyperactivity disorder ,Humans ,ADHD ,early life ,AcademicSubjects/MED00860 ,Child ,Netherlands ,Sweden ,Discordant Twin ,business.industry ,gut-brain axis ,General Medicine ,Odds ratio ,medicine.disease ,Twin study ,Anti-Bacterial Agents ,030104 developmental biology ,Autism spectrum disorder ,Attention Deficit Disorder with Hyperactivity ,Child, Preschool ,ADHD and ASD ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Background Development of the gut-brain axis in early life may be disturbed by antibiotic use. It has been hypothesized that this disturbance may contribute to development of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit hyperactivity disorder. We aimed to assess the association between antibiotic use in early life and the risk of developing attention-deficit hyperactivity disorder or autism spectrum disorder, while controlling for shared genetic and environmental factors in a discordant twin design. Methods We conducted a cohort study in twins (7–12 years; 25 781 twins) from the Netherlands Twin Register (NTR) and a replication study in the Childhood and Adolescent Twin Study in Sweden (CATSS; 7946 9-year-old twins). Antibiotic use was recorded before age 2 years. Attention-deficit hyperactivity disorder and autism spectrum disorder were parent-reported in the Netherlands Twin Register and register-based in the Childhood and Adolescent Twin Study in Sweden. Results Early-life antibiotic use was associated with increased risk of attention-deficit hyperactivity disorder development [pooled odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02-1.17] and autism spectrum disorder (pooled OR 1.15, 95% CI 1.06-1.25) in a case-control design. When restricting to monozygotic twin pairs discordant for the outcome, associations disappeared for both disorders in both cohorts (attention-deficit hyperactivity disorder OR 0.90, 95% CI 0.48-1.69 and OR 0.80, 95% CI 0.37-1.76, and autism spectrum disorder OR 0.66, 95% CI 0.38-1.16 and OR 0.29, 95% CI 0.02-4.50, respectively). Conclusions Our findings suggest that the association between early-life antibiotic use and risk of attention-deficit hyperactivity and autism spectrum disorder may be confounded by shared familial environment and genetics.
- Published
- 2021
7. Bronchial airway inducible expression and methylation QTL mapping identifies a single nucleotide polymorphism predicting inhaled corticosteroids response heterogeneity
- Author
-
Leila Karimi, Patrícia Soares, Pieter S. Hiemstra, Uroš Potočnik, Maarten van den Berge, Steve Turner, Antonio Espuela Ortiz, Wim Timens, Katia M.C. Verhamme, Anke-Hilse Maitland-van der Zee, Esther Herrera-Luis, Cristina Longo, Alen Faiz, Cyrielle Maroteau, Maria Del Pino Yanes, Merve Kutlu, Elise M A Slob, Esteban G. Burchard, Colin N. A. Palmer, Gerard H. Koppelman, Fook Tim Chew, Marielle W. Pijnenburg, Susanne J. H. Vijverberg, and Somnath Mukhopadhyay
- Subjects
business.industry ,Single-nucleotide polymorphism ,Locus (genetics) ,Quantitative trait locus ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Expression quantitative trait loci ,DNA methylation ,Medicine ,SNP ,030212 general & internal medicine ,Allele ,business ,Allele frequency - Abstract
Objectives: We aimed to identify genetic variants affecting gene expression and methylation changes in airway wall biopsies before and after ICS and investigate whether these are associated with poor response to ICS. Methods: Quantitative Trait Locus (QTL) Mapping profiling of paired bronchial biopsies from 42 COPD patients, was performed prior to and 6 months post ICS use. The window size was 1Mb flanking gene limits and the false discovery rate was used to adjust for multiple comparisons. Association between SNPs and gene expression (eQTL) or gene methylation (meQTL) changes upon ICS use was evaluated. Subsequently, a candidate-gene study was conducted in asthma patients treated with ICS to investigate whether these SNPs are associated with ICS response. Poor ICS response was defined as presence of exacerbations despite ICS use in the last 6-12 months. Logistic regressions were used to test the association and Bonferroni correction was applied. Results: 18 eQTL and 57 meQTL SNPs were associated with ICS response. When these SNPs were tested in asthma patients (3,722 children for eQTL and 1,166 children for meQTL), the only significant variant was the meQTL SNP rs7220099, an intergenic variant at locus 17q12 with an allele frequency of 33% and a lung eQTL for TBC1 domain family member 3D. The G allele increased the risk of exacerbations (pooled OR: 1.39 95%CI 1.19-1.63, p-value = 2.4 x 10-5). Conclusions: Our results show that gene expression and methylation profiling prior and post ICS use are quite different between asthma and COPD but still may help to find functional SNPs predicting ICS response.
- Published
- 2020
8. Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study
- Author
-
Bronwyn K. Brew, Paul Lichtenstein, Chantal J A R Kats, Patrick Magnusson, Tong Gong, Gerard H. Koppelman, Mariëlle W. Pijnenburg, Conor V. Dolan, Catarina Almqvist, Meike Bartels, Cristina Longo, Elise M A Slob, Dorret I. Boomsma, Anke H. Maitland-van der Zee, Susanne J. H. Vijverberg, Toos C. E. M. van Beijsterveldt, Graduate School, AII - Inflammatory diseases, APH - Personalized Medicine, Pulmonology, Paediatric Pulmonology, Pediatrics, Groningen Research Institute for Asthma and COPD (GRIAC), Biological Psychology, APH - Methodology, and APH - Mental Health
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Netherlands Twin Register (NTR) ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Dizygotic twin ,Eczema ,Disease ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Child ,Asthma ,Netherlands ,Retrospective Studies ,Sweden ,Discordant Twin ,business.industry ,Confounding ,Infant, Newborn ,Infant ,Retrospective cohort study ,medicine.disease ,Twin study ,Anti-Bacterial Agents ,030104 developmental biology ,030228 respiratory system ,Child, Preschool ,Etiology ,business - Abstract
RationaleEarly-life antibiotic use has been associated with the development of atopic diseases, but the aetiology remains unclear. To elucidate the aetiology, we used a discordant twin design to control for genetic and environmental confounding.MethodsWe conducted a retrospective cohort study in twins aged 3–10 years from the Netherlands Twin Register (NTR, n=35 365) and a replication study in twins aged 9 years from the Childhood and Adolescent Twin Study in Sweden (CATSS, n=7916). Antibiotic use was recorded at age 0–2 years. Doctor-diagnosed asthma and eczema were reported by parents when children were aged 3–12 years in both cohorts. Individuals were included in unmatched analyses and in co-twin control analyses with disease discordant twin pairs.ResultsEarly-life antibiotic use was associated with increased risk of asthma (NTR OR 1.34, 95% CI 1.28–1.41; CATSS OR 1.45, 95% CI 1.34–1.56) and eczema (NTR OR 1.08, 95% CI 1.03–1.13; CATSS OR 1.07, 95% CI 1.01–1.14) in unmatched analyses. Co-twin analyses in monozygotic and dizygotic twin pairs showed similar results for asthma (NTR OR 1.54, 95% CI 1.20–1.98; CATSS OR 2.00, 95% CI 1.28–3.13), but opposing results for eczema in the NTR (OR 0.99, 95% CI 0.80–1.25) and the CATSS (OR 1.67, 95% CI 1.12–2.49). The risk of asthma increased for antibiotics prescribed for respiratory infections (CATSS OR 1.45, 95% CI 1.34–1.56), but not for antibiotics commonly used for urinary tract/skin infections (CATSS OR 1.02, 95% CI 0.88–1.17).ConclusionChildren exposed to early-life antibiotic use, particularly prescribed for respiratory infections, may be at higher risk of asthma. This risk can still be observed when correcting for genetic and environmental factors. Our results could not elucidate whether the relationship between early-life antibiotic use and eczema is confounded by familial and genetic factors.
- Published
- 2020
9. Genomics and Pharmacogenomics of Severe Childhood Asthma
- Author
-
Anke H. Maitland-van der Zee, Gerard H. Koppelman, Susanne J. H. Vijverberg, Klaus Bønnelykke, and Elise M A Slob
- Subjects
business.industry ,Pharmacogenomics ,medicine ,Genomics ,Disease ,Epigenetics ,Heritability ,medicine.disease ,Bioinformatics ,business ,Twin study ,Pharmacogenetics ,Asthma - Abstract
Twin studies have shown that asthma has a heritability of more than 50%, indicating that genetic factors play a major role in its pathogenesis and are an important key to understanding the underlying disease mechanisms. Heritability is higher for childhood compared to adult asthma, and genetics also seem to be partly responsible for determining symptom severity, suggesting that genetic studies might be particularly relevant in relation to severe childhood asthma. Furthermore, the poor response to standard treatments in severe asthma indicates that this phenotype might be associated with distinct underlying mechanisms, potentially driven by genetics, separating it from milder disease. In addition to studying the genetic code (or genome), the study of genomics includes methodological approaches such as epigenetics (of importance for gene regulation) and transcriptomics (studies of gene expression). All of these are “mechanistic tools” with the potential to increase understanding of basic disease processes and provide the basis for improved treatment. In this chapter we will focus on (1) genomic approaches contributing to our understanding of disease mechanisms and (2) genomic approaches used to predict and understand differences in treatment response between individuals, also termed pharmacogenomics. Since relatively few genomic studies have focused specifically on the phenotype of severe childhood asthma, we will also discuss the implications of results from studies on milder disease and studies of severe asthma in adults.
- Published
- 2019
10. Treatment response heterogeneity in asthma: the role of genetic variation
- Author
-
Niloufar Farzan, Elise M A Slob, Anne H. Neerincx, Anke H. Maitland-van der Zee, and Susanne J. H. Vijverberg
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Treatment response ,03 medical and health sciences ,0302 clinical medicine ,Adrenal Cortex Hormones ,Genetic variation ,Administration, Inhalation ,medicine ,Immunology and Allergy ,Asthmatic patient ,Humans ,Anti-Asthmatic Agents ,Genotyping ,Asthma ,business.industry ,Public Health, Environmental and Occupational Health ,Genetic Variation ,Asthma medication ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,030228 respiratory system ,Pharmacogenetics ,Pharmacogenomics ,Immunology ,Leukotriene Antagonists ,Receptors, Adrenergic, beta-2 ,business - Abstract
Introduction: Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes.Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short- and long-acting beta-2 agonists (SABA/LABA), inhaled corticosteroids (ICS) and leukotriene modifiers. This review shows that various genetic variants have been identified, but none are currently used to guide asthma treatment. One of the most promising genetic variants is the Arg16 variant in the ADRB2 gene to guide LABA treatment in asthmatic children.Expert commentary: Poor replication of initially promising results and the low fraction of variability accounted for by single genetic variants inhibit pharmacogenetic findings to reach the asthma clinic. Nevertheless, the identification of genetic variation influencing treatment response does provide more insights in the complex processes underlying response and might identify novel targets for treatment. There is a need to report measures of clinical validity, to perform precision-medicine guided trials, as well as to understand how genetic variation interacts with environmental factors. In addition, systems biology approaches might be able to show a more complete picture of these complex interactions
- Published
- 2018
11. Early-Life Antibiotics Use Increases the Risk of Asthma and Eczema: A Discordant Twin Study
- Author
-
Dorret I. Boomsma, Gerard H. Koppelman, C. J. A. R. Kats, Marielle W. Pijnenburg, Susanne J. H. Vijverberg, T. C. E. M. van Beijsterveldt, A. H. Maitland-van der Zee, and Elise M A Slob
- Subjects
Discordant Twin ,Pediatrics ,medicine.medical_specialty ,business.industry ,medicine.drug_class ,Antibiotics ,Medicine ,business ,medicine.disease ,Early life ,Asthma - Published
- 2019
12. Precision medicine in childhood asthma
- Author
-
Elise M A Slob, Anke-Hilse Maitland-van der Zee, Mariëlle W. Pijnenburg, Gerard H. Koppelman, Groningen Research Institute for Asthma and COPD (GRIAC), and Pediatrics
- Subjects
medicine.medical_specialty ,Immunology ,Omalizumab ,Disease ,Immunoglobulin E ,Adrenal Cortex Hormones ,medicine ,Immunology and Allergy ,Humans ,Precision Medicine ,Intensive care medicine ,Child ,Lung ,Asthma ,Biological Products ,biology ,business.industry ,medicine.disease ,Precision medicine ,Respiratory Function Tests ,Pharmacogenetics ,Pharmacogenomics ,Exhaled nitric oxide ,biology.protein ,business ,Biomarkers ,medicine.drug - Abstract
PURPOSE OF REVIEW: Childhood asthma is a heterogeneous disease and many children have uncontrolled disease. Therefore an individualized approach is needed to improve asthma outcomes in children. Precision medicine using clinical characteristics, biomarkers, and the rapidly involving field of genomics and pharmacogenomics aims to achieve asthma control and reduce future risks with less side-effects in individual children with asthma.RECENT FINDINGS: It is not yet possible to select treatment options on clinical characteristics. Novel monoclonal antibodies are efficacious in patients with severe, eosinophilic asthma. Reduced lung function growth and early decline is a prevalent finding in children with persistent asthma. Pharmacogenetic studies have identified children at risk for cortisol suppression when using inhaled corticosteroids.SUMMARY: Clinical characteristics and simple biomarkers like eosinophils, IgE, and the fraction of exhaled nitric oxide may be used in clinical practice for a basic precision medicine approach, deciding which children will have the best chance to respond to inhaled corticosteroids and to the biologicals omalizumab and mepolizumab.Further application of pharmacogenomics and breathomics needs additional studies before they can be applied as tools for precision medicine in individual children with asthma.
- Published
- 2019
13. What do we need to transfer pharmacogenetics findings into the clinic?
- Author
-
Elise M A Slob, Marielle W. Pijnenburg, Susanne J. H. Vijverberg, Gerard H. Koppelman, Anke-Hilse Maitland-van der Zee, Groningen Research Institute for Asthma and COPD (GRIAC), and Pediatrics
- Subjects
0301 basic medicine ,medicine.medical_specialty ,precision medicine ,infrastructure ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,IMPLEMENTATION ,Electronic Health Records ,Humans ,Medical physics ,pharmacogenetics ,Pharmacology ,business.industry ,MEDICINE ,Decision Support Systems, Clinical ,Precision medicine ,GENOTYPE ,030104 developmental biology ,Point-of-Care Testing ,030220 oncology & carcinogenesis ,Molecular Medicine ,TRIAL ,HEALTH ,business ,Pharmacogenetics - Published
- 2018
14. Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: A systematic review
- Author
-
Zulfan Zazuli, Marielle W. Pijnenburg, Niloufar Farzan, Colin N. A. Palmer, Nadia M. B. Oliveri, Gerard H. Koppelman, Anke H. Maitland van der Zee, Elise M A Slob, Susanne J. H. Vijverberg, Pediatrics, AII - Inflammatory diseases, Graduate School, APH - Personalized Medicine, Pulmonology, and Paediatric Pulmonology
- Subjects
0301 basic medicine ,medicine.medical_specialty ,bronchodilator ,medicine.drug_class ,Immunology ,GENE POLYMORPHISMS ,THERAPY ,law.invention ,03 medical and health sciences ,FEV1/FVC ratio ,SALMETEROL ,0302 clinical medicine ,Randomized controlled trial ,law ,Bronchodilator ,Internal medicine ,Administration, Inhalation ,genetic polymorphism ,Immunology and Allergy ,Medicine ,Humans ,Anti-Asthmatic Agents ,SEVERE EXACERBATIONS ,BETA-AGONIST ,BETA-2-ADRENERGIC RECEPTOR ,Adrenergic beta-2 Receptor Agonists ,Asthma ,FORMOTEROL ,Polymorphism, Genetic ,business.industry ,medicine.disease ,Clinical trial ,long-acting beta-agonist ,BETA(2)-ADRENOCEPTOR ,030104 developmental biology ,030228 respiratory system ,ADRB2 ,Pharmacogenetics ,Pediatrics, Perinatology and Child Health ,Observational study ,Salmeterol ,Receptors, Adrenergic, beta-2 ,business ,CLINICAL-TRIALS ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Adenylyl Cyclases - Abstract
BACKGROUND: Long-acting beta2-agonists (LABA) are recommended in asthma therapy; however, not all asthma patients respond well to LABA. We performed a systematic review on genetic variants associated with LABA response in patients with asthma. METHODS: Articles published until April 2017 were searched by two authors using PubMed and EMBASE. Pharmacogenetic studies in patients with asthma and LABA response as an outcome were included. RESULTS: In total, 33 studies were included in this systematic review; eight focused on children (n = 6051). Nineteen studies were clinical trials, while 14 were observational studies. Studies used different outcomes to define LABA response, for example, lung function measurements (FEV1 , PEF, MMEF, FVC), exacerbations, quality of life, and asthma symptoms. Most studies (n = 30) focused on the ADRB2 gene, encoding the beta2-adrenergic receptor. Thirty studies (n = 14 874) addressed ADRB2 rs1042713, 7 ADRB2 rs1042714 (n = 1629), and 3 ADRB2 rs1800888 (n = 1892). The association of ADRB2 rs1042713 and rs1800888 with LABA response heterogeneity was successfully replicated. Other variants were only studied in three studies but not replicated. One study focused on the ADCY9 gene. Five studies and a meta-analysis found an increased risk of exacerbations in pediatrics using LABA carrying one or two A alleles (OR 1.52 [1.17; 1.99]). These results were not confirmed in adults. CONCLUSIONS: ADRB2 rs1042713 variant is most consistently associated with response to LABA in children but not adults. To assess the clinical value of ADRB2 rs1042713 in children with asthma using LABA, a randomized clinical trial with well-defined outcomes is needed.
- Published
- 2018
15. Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients
- Author
-
Mervyn Singer, Elise M A Slob, Rob Shulman, and APH - Personalized Medicine
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Hyperkalemia ,Critical Illness ,Cardiac index ,Hemodynamics ,Hypokalemia ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,0302 clinical medicine ,Intensive care ,London ,medicine ,Humans ,Insulin ,Myocardial infarction ,Intensive care medicine ,Aged ,Retrospective Studies ,Heart Failure ,Clinical Audit ,Hypocalcemia ,business.industry ,Incidence ,030208 emergency & critical care medicine ,Middle Aged ,medicine.disease ,Discontinuation ,Glucose ,Heart failure ,Anesthesia ,Hyperglycemia ,Potassium ,Female ,medicine.symptom ,business - Abstract
Purpose To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage. Materials and methods A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0 Units insulin/kg/h) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. Results Of 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72 h, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia ( 20 mmol/l), hypokalaemia ( 7 mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted. Conclusions High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation.
- Published
- 2016
16. Comparison of antibiotic dosing recommendations for neonatal sepsis from established reference sources
- Author
-
T. F. W. Wolfs, Elise M A Slob, T. B. Y. Liem, Carin M. A. Rademaker, J. U. M. Termote, and Antoine C. G. Egberts
- Subjects
0301 basic medicine ,Neonatal intensive care unit ,vancomycin ,Pharmaceutical Science ,Pharmacy ,Dosing variation ,dose calculation ,Toxicology ,Efficacy ,0302 clinical medicine ,Antibiotics ,meropenem ,newborn ,newborn sepsis ,dose response ,Medication Errors ,Pharmacology (medical) ,antibiotic agent ,030212 general & internal medicine ,ceftazidime ,Netherlands ,Neonatal sepsis ,Dosing recommendations ,article ,Anti-Bacterial Agents ,priority journal ,penicillin G ,Research Article ,medicine.drug ,medicine.medical_specialty ,cefotaxime ,030106 microbiology ,gentamicin ,Meropenem ,Drug Administration Schedule ,Medical Order Entry Systems ,Sepsis ,03 medical and health sciences ,Intensive Care Units, Neonatal ,medicine ,Humans ,controlled study ,Dosing ,Neonatology ,human ,Intensive care medicine ,outcome assessment ,Pharmacology ,business.industry ,Infant, Newborn ,Neonates ,reference value ,recommended drug dose ,Decision Support Systems, Clinical ,medicine.disease ,major clinical study ,drug efficacy ,ampicillin ,business - Abstract
Background Incorrect dosing is the most frequent prescribing error in neonatology, with antibiotics being the most frequently prescribed medicines. Computer physician order entry and clinical decision support systems can create consistency contributing to a reduction of medication errors. Although evidence-based dosing recommendations should be included in such systems, the evidence is not always available and subsequently, dosing recommendations mentioned in guidelines and textbooks are often based on expert opinion. Objective To compare dosage recommendations for antibiotics in neonates with sepsis provided by eight commonly used and well-established international reference sources. Setting An expert team from our Dutch tertiary care neonatal intensive care unit selected eight well-established international reference sources. Method Daily doses of the seven most frequently used antibiotics in the treatment of neonatal sepsis, classified by categories for birth weight and gestational age, were identified from eight well-respected reference sources in neonatology/pediatric infectious diseases. Main outcome measure Standardized average daily dosage. Results A substantial variation in dosage recommendations of antibiotics for neonatal sepsis between the reference sources was shown. Dosage recommendations of ampicillin, ceftazidime, meropenem and vancomycin varied more than recommendations for benzylpenicillin, cefotaxime and gentamicin. One reference source showed a larger variation in dosage recommendations in comparison to the average recommended daily dosage, compared to the other reference sources. Conclusion Antibiotic dosage recommendations for neonates with sepsis can be derived from important reference sources and guidelines. Further exploration to overcome variation in dosage recommendations is necessary to obtain standardized dosage regimens.
- Published
- 2018
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.