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Asthma pharmacogenetics

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https://www.readbyqxmd.com/read/29551627/susceptibility-to-corticosteroid-induced-adrenal-suppression-a-genome-wide-association-study
#1
Daniel B Hawcutt, Ben Francis, Daniel F Carr, Andrea L Jorgensen, Peng Yin, Naomi Wallin, Natalie O'Hara, Eunice J Zhang, Katarzyna M Bloch, Amitava Ganguli, Ben Thompson, Laurence McEvoy, Matthew Peak, Andrew A Crawford, Brian R Walker, Joanne C Blair, Jonathan Couriel, Rosalind L Smyth, Munir Pirmohamed
BACKGROUND: A serious adverse effect of corticosteroid therapy is adrenal suppression. Our aim was to identify genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression. METHODS: We enrolled children with asthma who used inhaled corticosteroids as part of their treatment from 25 sites across the UK (discovery cohort), as part of the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) study. We included two validation cohorts, one comprising children with asthma (PASS study) and the other consisting of adults with chronic obstructive pulmonary disorder (COPD) who were recruited from two UK centres for the Pharmacogenomics of Adrenal Suppression in COPD (PASIC) study...
March 15, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29509491/whole-genome-sequencing-of-pharmacogenetic-drug-response-in-racially-diverse-children-with-asthma
#2
Angel Cy Mak, Marquitta J White, Walter L Eckalbar, Zachary A Szpiech, Sam S Oh, Maria Pino-Yanes, Donglei Hu, Pagé Goddard, Scott Huntsman, Joshua Galanter, Ann Chen Wu, Blanca E Himes, Soren Germer, Julia M Vogel, Karen L Bunting, Celeste Eng, Sandra Salazar, Kevin L Keys, Jennifer Liberto, Thomas J Nuckton, Thomas A Nguyen, Dara G Torgerson, Pui-Yan Kwok, Albert M Levin, Juan C Celedón, Erick Forno, Hakon Hakonarson, Patrick M Sleiman, Amber Dahlin, Kelan G Tantisira, Scott T Weiss, Denise Serebrisky, Emerita Brigino-Buenaventura, Harold J Farber, Kelley Meade, Michael A Lenoir, Pedro C Avila, Saunak Sen, Shannon M Thyne, William Rodriguez-Cintron, Cheryl A Winkler, Andrés Moreno-Estrada, Karla Sandoval, Jose R Rodriguez-Santana, Rajesh Kumar, L Keoki Williams, Nadav Ahituv, Elad Ziv, Max A Seibold, Robert B Darnell, Noah Zaitlen, Ryan D Hernandez, Esteban G Burchard
Rationale Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. Objective To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. Methods We performed the first whole genome sequencing (WGS) pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. Measurements and Main Results We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (p < 3...
March 6, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29380695/how-to-control-asthma-with-personalized-management-where-do-we-stand-now
#3
Meng Wang, Yuan Yao, Shanqun Jiang, Fang Tao, Rui Tang, Jinlu Sun
Asthma is one of the most significant diseases worldwide and causes overwhelming costs physically and economically. The heterogeneity of asthma has been a hot topic, and an increasing amount of research has been conducted on this issue. The study of asthma has revealed various groups of asthma patients who share phenotypic characteristics that naturally elicit the need for personalized asthma therapy. Clinical evidence has shown that a 'one size fits all' approach does not apply to all asthma patients because of the large variability in treatment responses to asthma medication...
January 28, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29361392/preschool-wheeze-genes-and-treatment
#4
REVIEW
Chinedu Nwokoro, Jonathan Grigg
Preschool wheeze is a common but poorly understood cause of respiratory morbidity that is both distinct from and overlaps with infantile bronchiolitis and school age asthma. Attempts at classification by epidemiology, pathophysiology, therapeutic response and clinical phenotype are imperfect and yet fundamental to both treatment choice and research design. The four main therapeutic classes for preschool wheeze, namely beta2 agonists, anticholinergics, corticosteroids and leukotriene modifiers are employed with variable and often scanty evidence base, with evidence for a genetic influence on response variations...
December 5, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/29345236/glcci1-polymorphism-rs37973-and-asthma-treatment-response-to-inhaled-corticosteroids
#5
M Rijavec, M Žavbi, A Lopert, M Fležar, P Korošec
BACKGROUND: Asthma treatment response is highly variable and pharmacogenetic markers that predict treatment response would be one step closer to personalized treatment. GWAS studies have shown that polymorphisms GLCCI1 could be associated with asthma treatment response to inhaled corticosteroids (ICS). MATERIAL AND METHODS: We genotyped rs37973 of GLCCI1 in 208 adult asthma patients treated with ICS. Change in % predicted FEV1 was analysed after short-term (3 months) and after long-term (at least 3 years) treatment...
January 17, 2018: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/29251255/effects-of-genetic-factors-to-inhaled-corticosteroid-response-in-children-with-asthma-a-literature-review
#6
Huong Duong-Thi-Ly, Ha Nguyen-Thi-Thu, Long Nguyen-Hoang, Hanh Nguyen-Thi-Bich, Timothy J Craig, Sy Duong-Quy
Numerous studies have examined the association between pharmacogenetic effects and the response to inhaled corticosteroids (ICS) in patients with asthma. In fact, several single nucleotide polymorphisms of a number of candidate genes have been identified that might influence the clinical response to ICS in children with asthma. Their direct or indirect effects depend on their role in the inflammatory process in asthma or the anti-inflammatory action of corticosteroids, respectively. Among the genes identified, variants in T-box 21 ( TBX21) and Fc fragment of IgE receptor II ( FCER2) contribute indirectly to the variability in the response to ICS by altering the inflammatory mechanisms in asthma, while other genes such as corticotropin releasing hormone receptor 1 ( CRHR1), nuclear receptor subfamily 3 group C member 1 ( NR3C1), stress induced phosphoprotein 1 ( STIP1), dual specificity phosphatase 1 (DUSP1), glucocorticoid induced 1 (GLCCI1), histone deacetylase 1 (HDAC), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and vascular endothelial growth factors (VEGF) directly affect this variability through the anti-inflammatory mechanisms of ICS...
December 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/29229094/no-genetic-association-detected-with-mepolizumab-efficacy-in-severe-asthma
#7
Lynn Condreay, Mathias Chiano, Hector Ortega, Natalie Buchan, Elizabeth Harris, Eugene R Bleecker, Philip J Thompson, Marc Humbert, Peter Gibson, Steven Yancey, Soumitra Ghosh
BACKGROUND AND OBJECTIVES: Treatment with mepolizumab, a humanized monoclonal antibody to interleukin-5, reduces the rate of asthma exacerbations and the requirement for systemic glucocorticoids while maintaining asthma control. Treatment decisions are guided by predictors of response, including blood eosinophil thresholds in patients with frequent exacerbations despite intensive anti-inflammatory and controller treatment. Identification of additional predictors of response could aid treatment decisions...
November 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/29115880/treatment-response-heterogeneity-in-asthma-the-role-of-genetic-variation
#8
Susanne J H Vijverberg, Niloufar Farzan, Elise M A Slob, Anne H Neerincx, Anke H Maitland-van der Zee
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...
January 2018: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28992739/pharmacogenetic-and-pharmacogenomic-considerations-of-asthma-treatment
#9
REVIEW
Maria Gabriella Matera, Barbara Rinaldi, Luigino Calzetta, Mario Cazzola
Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors. Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as β2 -AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described...
November 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28776467/pharmacogenetics-and-the-treatment-of-asthma
#10
María Isidoro-García, Almudena Sánchez-Martín, Asunción García-Sánchez, Catalina Sanz, Belén García-Berrocal, Ignacio Dávila
Heterogeneity defines both the natural history of asthma as well as patient's response to treatment. Pharmacogenomics contribute to understand the genetic basis of drug response and thus to define new therapeutic targets or molecular biomarkers to evaluate treatment effectiveness. This review is initially focused on different genes so far involved in the pharmacological response to asthma treatment. Specific considerations regarding allergic asthma, the pharmacogenetics aspects of polypharmacy and the application of pharmacogenomics in new drugs in asthma will also be addressed...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28639505/rationale-and-design-of-the-multiethnic-pharmacogenomics-in-childhood-asthma-consortium
#11
Niloufar Farzan, Susanne J Vijverberg, Anand K Andiappan, Lambang Arianto, Vojko Berce, Natalia Blanca-López, Hans Bisgaard, Klaus Bønnelykke, Esteban G Burchard, Paloma Campo, Glorisa Canino, Bruce Carleton, Juan C Celedón, Fook Tim Chew, Wen Chin Chiang, Michelle M Cloutier, Denis Daley, Herman T Den Dekker, F Nicole Dijk, Liesbeth Duijts, Carlos Flores, Erick Forno, Daniel B Hawcutt, Natalia Hernandez-Pacheco, Johan C de Jongste, Michael Kabesch, Gerard H Koppelman, Vangelis G Manolopoulos, Erik Melén, Somnath Mukhopadhyay, Sara Nilsson, Colin N Palmer, Maria Pino-Yanes, Munir Pirmohamed, Uros Potočnik, Jan A Raaijmakers, Katja Repnik, Maximilian Schieck, Yang Yie Sio, Rosalind L Smyth, Csaba Szalai, Kelan G Tantisira, Steve Turner, Marc P van der Schee, Katia M Verhamme, Anke H Maitland-van der Zee
AIM: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. MATERIALS & METHODS: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. RESULTS: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium...
July 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28442499/absorption-distribution-metabolism-and-excretion-of-the-oral-prostaglandin-d2-receptor-2-dp2-antagonist-fevipiprant-qaw039-in-healthy-volunteers-and-in-vitro
#12
David Pearson, H Markus Weiss, Yi Jin, Jan Jaap van Lier, Veit J Erpenbeck, Ulrike Glaenzel, Peter End, Ralph Woessner, Fabian Eggimann, Gian Camenisch
Fevipiprant is a novel oral prostaglandin D2 receptor 2 (DP2; also known as CRTh2) antagonist, which is currently in development for the treatment of severe asthma and atopic dermatitis. We investigated the absorption, distribution, metabolism, and excretion properties of fevipiprant in healthy subjects after a single 200 mg oral dose of [(14)C]-radiolabeled fevipiprant. Fevipiprant and metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and radioactivity measurements, and mechanistic in vitro studies were performed to investigate clearance pathways and covalent plasma protein binding...
April 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28293925/genetic-signatures-of-asthma-exacerbation
#13
REVIEW
Heung Woo Park, Kelan G Tantisira
Asthma exacerbation (AE) usually denotes worsening of asthma symptoms that requires intense management to prevent further deterioration. AE has been reported to correlate with clinical and demographic factors, such as race, gender, and treatment compliance as well as environmental factors, such as viral infection, smoking, and air pollution. In addition, recent observations suggest that there are likely to be genetic factors specific to AE. Understanding genetic factors specific to AE is essential to develop therapy tailored for exacerbation-prone asthma...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28112586/genetic-variation-in-the-glucocorticoid-pathway-involved-in-interindividual-differences-in-the-glucocorticoid-treatment
#14
REVIEW
Qian-Qian Song, Wan-Ying Xie, Yong-Jun Tang, Jun Zhang, Jie Liu
Glucocorticoids (GCs) are widely used for treating asthma, rheumatoid arthritis, nephrotic syndrome, acute lymphoblastic leukemia and other autoimmune diseases. However, in a subgroup of patients, failure to respond to GCs is known as GC resistance or GC insensitivity. This represents an important barrier to effective treatment and a clinical problem requiring an urgent solution. Genetic variation in the GC pathway is a significant factor in interindividual differences in GC treatment. This article reviews the pharmacogenetics of GCs in diverse diseases based on the GC pathway...
February 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27878470/%C3%AE-2-agonists
#15
REVIEW
Charlotte K Billington, Raymond B Penn, Ian P Hall
History suggests β agonists, the cognate ligand of the β2 adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27820743/anticholinergic-drugs-in-asthma-therapy
#16
Maria D'Amato, Carolina Vitale, Antonio Molino, Maurizia Lanza, Gennaro D'Amato
PURPOSE OF REVIEW: Current guidelines recommend a stepwise approach for pharmacological therapy aimed to achieve and maintain asthma control. Despite these recommendations, at least 50% of patients continue to be uncontrolled with risk of asthma exacerbations that can often be serious and are associated with deterioration of quality of life. In recent years, the interest in anticholinergic bronchodilators, which have been primarily used in the treatment of chronic obstructive pulmonary disease, has increased patients with uncontrolled asthma...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27808589/challenges-for-drug-discovery-and-development-in-china
#17
REVIEW
Kam Lun Hon, Vivian W Y Lee
The drug development industry is restructuring worldwide in terms of the research and development process. As with pharmaceuticals in the west, China faces major challenges for drug discovery and development. Areas covered: In this review, the authors discuss anti-cancer, anti-allergy, anti-infectious, and proprietary Chinese Medicines (pCM) for various chronic diseases (such as the allergic diseases: eczema, asthma and allergic rhinitis), which remain the contemporary therapeutic strategies that are being explored and developed...
January 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27790783/pharmacogenomics-of-inhaled-corticosteroids-and-leukotriene-modifiers-a-systematic-review
#18
REVIEW
N Farzan, S J H Vijverberg, H G Arets, J A M Raaijmakers, A H Maitland-van der Zee
BACKGROUND: Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited. OBJECTIVE: To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and leukotriene modifiers (LTMs) in patients with asthma. METHODS: Articles published between 1999 and June 2015 were searched using PubMed and EMBASE...
February 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27764000/pharmacogenetics-of-asthma-toward-precision-medicine
#19
Elin T G Kersten, Gerard H Koppelman
PURPOSE OF REVIEW: Although currently available drugs to treat asthma are effective in most patients, a proportion of patients do not respond or experience side-effects; which is partly genetically determined. Pharmacogenetics is the study of how genetic variations influence drug response. In this review, we summarize prior results and recent studies in pharmacogenetics to determine if we can use genetic profiles for personalized treatment of asthma. RECENT FINDINGS: The field of pharmacogenetics has moved from candidate gene studies in single populations toward genome-wide association studies and meta-analysis of multiple studies...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27712769/genetic-and-epigenetic-components-of-aspirin-exacerbated-respiratory-disease
#20
REVIEW
Amber Dahlin, Scott T Weiss
Aspirin-exacerbated respiratory disease (AERD) severity and its clinical phenotypes are characterized by genetic variation within pathways for arachidonic acid metabolism, inflammation, and immune responses. Epigenetic effects, including DNA methylation and histone protein modification, contribute to regulation of many genes that contribute to inflammatory states in AERD. The development of noninvasive, predictive clinical tests using data from genetic, epigenetic, pharmacogenetic, and biomarker studies will improve precision medicine efforts for AERD and asthma treatment...
November 2016: Immunology and Allergy Clinics of North America
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