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Asthma genetics

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https://www.readbyqxmd.com/read/28724478/the-stoppa-twin-study-explains-the-exhaled-nitric-oxide-and-asthma-link-by-genetics-and-sensitization
#1
Björn Nordlund, Cecilia Lundholm, Vilhelmina Ullemar, Marianne van Hage, Anne K Örtqvist, Catarina Almqvist
BACKGROUND: The link between asthma and exhaled nitric oxide (FENO) is not completely understood. The aim of this study was to estimate the association between FENO and asthma, taking genetics, sensitization, and inhaled corticosteroids (ICS) into account. METHODS: A total of 681 twins (53% monozygotic [MZ] and 47% dizygotic [DZ]) from the population-based STOPPA study (mean age 12.6 years) were recruited and information on FENO (parts per billion), parental report of current asthma, sensitization to airborne allergens (Phadiatop; IgE ≥0...
August 2017: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#2
REVIEW
Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M Heller
Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation...
2017: F1000Research
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#3
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28713081/gene-polymorphism-of-xenobiotic-detoxification-in-children-with-bronchial-asthma
#4
Liudmila Y Lytvynets
INTRODUCTION: Children are the most susceptible to harmful external factors due to the incomplete development of all functional body systems. The ecological situation the problem of influence of genetic and environmental factors on the pathogenesis of chronic respiratory diseases in children and its investigation is very impotent today. Among it the bronchial asthma is a leader among bronchial and pulmonary diseases caused by the influence of pneumotropic pollutants. The aim of our research was to study the phenotypic characteristics of asthma in Pre-Carpathian children with different types of allelic gene polymorphism of the first phase of xenobiotic detoxification of microsomal epoxide hydrolases (mEPHX1)...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28712576/comparing-effectiveness-and-outcomes-in-asthma-and-cystic-fibrosis
#5
REVIEW
Michael S Schechter
As technology yields new treatments, pediatric pulmonologists need determine how best to use them and how to decide which ones are best for any specific group or individual patient. Physicians have always customized therapies based upon patient response, but the new concept of "Personalized (or precision) medicine" focuses attention to a greater degree on the individual needs of patients based on their genetic, biomarker, phenotypic, or psychosocial characteristics. The newly developed biologics for treatment of asthma and CFTR modulators for treatment of cystic fibrosis (CF) highlight this newer approach...
June 12, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28709967/advances-in-asthma-2016-designing-individualized-approaches-to-management
#6
William C Anderson, Andrea Apter, Cullen M Dutmer, Daniel A Searing, Stanley J Szefler
In this years Advances in Asthma review we discuss viral infections in asthma and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long term sequelae of childhood asthma, patient centered outcome research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine, and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase...
July 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28704396/phenotypic-chemical-and-functional-characterization-of-cyclic-nucleotide-phosphodiesterase-4-pde4-as-a-potential-anthelmintic-drug-target
#7
Thavy Long, Liliana Rojo-Arreola, Da Shi, Nelly El-Sakkary, Kurt Jarnagin, Fernando Rock, Maliwan Meewan, Alberto A Rascón, Lin Lin, Katherine A Cunningham, George A Lemieux, Larissa Podust, Ruben Abagyan, Kaveh Ashrafi, James H McKerrow, Conor R Caffrey
BACKGROUND: Reliance on just one drug to treat the prevalent tropical disease, schistosomiasis, spurs the search for new drugs and drug targets. Inhibitors of human cyclic nucleotide phosphodiesterases (huPDEs), including PDE4, are under development as novel drugs to treat a range of chronic indications including asthma, chronic obstructive pulmonary disease and Alzheimer's disease. One class of huPDE4 inhibitors that have yielded marketed drugs is the benzoxaboroles (Anacor Pharmaceuticals)...
July 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28696379/obesity-and-asthma-a-missing-link
#8
REVIEW
Mª Amelia Gomez-Llorente, Raquel Romero, Natalia Chueca, Ana Martinez-Cañavate, Carolina Gomez-Llorente
Obesity and asthma are two chronic conditions that affect millions of people. Genetic and lifestyle factors such as diet, physical activity, and early exposure to micro-organisms are important factors that may contribute to the escalating prevalence of both conditions. The prevalence of asthma is higher in obese individuals. Recently, two major phenotypes of asthma with obesity have been described: one phenotype of early-onset asthma that is aggravated by obesity, and a second phenotype of later-onset asthma that predominantly affects women...
July 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28684600/frontline-science-corticotropin-releasing-factor-receptor-subtype-1-is-a-critical-modulator-of-mast-cell-degranulation-and-stress-induced-pathophysiology
#9
Saravanan Ayyadurai, Amelia J Gibson, Susan D'Costa, Elizabeth L Overman, Laura J Sommerville, Ashwini C Poopal, Emily Mackey, Yihang Li, Adam J Moeser
Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and disease pathophysiology remains poorly understood. Here, we investigated the role of corticotropin-releasing factor receptor subtype 1 (CRF1) in mast cell degranulation and associated disease pathophysiology...
July 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28683659/towards-non-conventional-methods-of-designing-register-based-epidemiological-studies-an-application-to-pediatric-research
#10
Tong Gong, Bronwyn Brew, Arvid Sjölander, Catarina Almqvist
AIMS: Various epidemiological designs have been applied to investigate the causes and consequences of fetal growth restriction in register-based observational studies. This review seeks to provide an overview of several conventional designs, including cohort, case-control and more recently applied non-conventional designs such as family-based designs. We also discuss some practical points regarding the application and interpretation of family-based designs. METHODS: Definitions of each design, the study population, the exposure and the outcome measures are briefly summarised...
July 2017: Scandinavian Journal of Public Health
https://www.readbyqxmd.com/read/28675761/estimating-the-causal-effect-of-body-mass-index-on-hay-fever-asthma-and-lung-function-using-mendelian-randomization
#11
Tea Skaaby, Amy E Taylor, Betina H Thuesen, Rikke K Jacobsen, Nele Friedrich, Line Tang Møllehave, Susanne Hansen, Sofus C Larsen, Uwe Völker, Matthias Nauck, Henry Völzke, Torben Hansen, Oluf Pedersen, Torben Jørgensen, Lavinia Paternoster, Marcus Munafò, Niels Grarup, Allan Linneberg
BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as un-confounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC)...
July 4, 2017: Allergy
https://www.readbyqxmd.com/read/28673399/environmental-determinants-of-allergy-and-asthma-in-early-life
#12
REVIEW
Allison J Burbank, Amika K Sood, Matthew J Kesic, David B Peden, Michelle L Hernandez
Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures...
July 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28668238/genetic-variants-and-risk-of-asthma-in-an-american-indian-population
#13
Lyle G Best, Crystal Azure, Alexandre Segarra, Kendra J Enright, Shawn Hamley, Dara Jerome, Marcia A O'Leary, Rae A O'Leary, Ashley Parisien, Kayana Trottier, Joseph M Yracheta, Dara G Torgerson
BACKGROUND: Asthma is recognized as a complex, multifactorial disease with a genetic component that is well recognized. Certain genetic variants are associated with asthma in a number of populations. OBJECTIVE: To determine whether the same variants increase the risk of asthma among American Indian children. METHODS: The electronic medical records of an Indian Health Service facility identified all children between 6 and 17 years of age with case-defining criteria for asthma (n = 108)...
July 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28667070/pathogenesis-of-asthma-implications-for-precision-medicine
#14
REVIEW
Richard J Russell, Christopher Brightling
The pathogenesis of asthma is complex and multi-faceted. Asthma patients have a diverse range of underlying dominant disease processes and pathways despite apparent similarities in clinical expression. Here, we present the current understanding of asthma pathogenesis. We discuss airway inflammation (both T2(HIGH) and T2(LOW)), airway hyperresponsiveness (AHR) and airways remodelling as four key factors in asthma pathogenesis, and also outline other contributory factors such as genetics and co-morbidities. Response to current asthma therapies also varies greatly, which is probably related to the inter-patient differences in pathogenesis...
July 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28659663/a-role-of-the-abcc4-gene-polymorphism-in-airway-inflammation-of-asthmatics
#15
Sailesh Palikhe, Udval Uuganbayar, Hoang Kim Tu Trinh, Ga-Young Ban, Eun-Mi Yang, Hae-Sim Park, Seung-Hyun Kim
The ATP-binding cassette subfamily C member 4 gene encodes a transmembrane protein involved in the export of proinflammatory molecules, including leukotriene, prostaglandin, and sphingosine-1-phosphate across the plasma membrane. Those metabolites play important roles in asthma. We investigated the potential associations between ABCC4 gene polymorphisms and asthma phenotype. In total, 270 asthma patients and 120 normal healthy controls were enrolled for a genetic association study. Two polymorphisms (-1508A>G and -642C>G) in the ABCC4 promoter were genotyped...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28658728/-mediators-of-inflammatory-response-in-asthma-and-its-association-with-obesity
#16
Gustavo Galicia-Negrete, Ramcés Falfán-Valencia
There is an increase in the prevalence of asthma and obesity, constituting a public health problem at national and global levels. The association between the two pathologies has not been clearly determined; however, a certain synergy has been proposed, which leads to more severe bronchospasms, longer recovery time, and more prolonged use of medications in obese asthmatic patients. The discovery of leptin, an adipokine that is directly related to the amount of total body fat and the production of proinflammatory cytokines, has generated greater interest in white adipose tissue...
April 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28658558/the-atopic-march-current-insights-into-skin-barrier-dysfunction-and-epithelial-cell-derived-cytokines
#17
REVIEW
Hongwei Han, Florence Roan, Steven F Ziegler
Atopic dermatitis often precedes the development of other atopic diseases. The atopic march describes this temporal relationship in the natural history of atopic diseases. Although the pathophysiological mechanisms that underlie this relationship are poorly understood, epidemiological and genetic data have suggested that the skin might be an important route of sensitization to allergens. Animal models have begun to elucidate how skin barrier defects can lead to systemic allergen sensitization. Emerging data now suggest that epithelial cell-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 may drive the progression from atopic dermatitis to asthma and food allergy...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658556/epigenetic-regulation-of-t-helper-cell-differentiation-memory-and-plasticity-in-allergic-asthma
#18
REVIEW
Damon J Tumes, Magdalene Papadopoulos, Yusuke Endo, Atsushi Onodera, Kiyoshi Hirahara, Toshinori Nakayama
An estimated 300 million people currently suffer from asthma, which causes approximately 250 000 deaths a year. Allergen-specific T-helper (Th) cells produce cytokines that induce many of the hallmark features of asthma including airways hyperreactivity, eosinophilic and neutrophilic inflammation, mucus hypersecretion, and airway remodeling. Cytokine-producing Th subsets including Th1 (IFN-γ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17), Th22 (IL-22), and T regulatory (IL-10) cells have all been suggested to play a role in the development of asthma...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658551/spectrum-of-t-lymphocyte-activities-regulating-allergic-lung-inflammation
#19
REVIEW
Erwin W Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28644028/understanding-the-effects-of-genotype-growing-year-and-breeding-on-tunisian-durum-wheat-allergenicity-1-the-baker-s-asthma-case
#20
Fatma Boukid, Barbara Prandi, Stefano Sforza, Rhouma Sayar, Yong Weon Seo, Mondher Mejri, Ines Yacoubi
Baker's asthma is a serious airway disease triggered by wheat protein CM3 α-amylase/trypsin inhibitor. The purpose of the present study was to investigate the impact of genotype and crop year on allergen CM3 α-amylase/trypsin inhibitor associated with baker's asthma. A historical series of Tunisian durum wheat (100 accessions), derived from three crop years, was used to compare the amount of CM3 from landraces to advanced cultivars. CM3 protein quantification was assessed after an enzymatic cleavage of the soluble protein extracts on a UPLC/ESI-MS system, using a marker peptide for its quantification...
July 3, 2017: Journal of Agricultural and Food Chemistry
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