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Asthma phenotype

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https://www.readbyqxmd.com/read/29053714/atopic-asthmatic-immune-phenotypes-associated-with-airway-microbiota-and-airway-obstruction
#1
Benjamin A Turturice, Halvor S McGee, Brian Oliver, Melissa Baraket, Brian T Nguyen, Christian Ascoli, Ravi Ranjan, Asha Rani, David L Perkins, Patricia W Finn
BACKGROUND: Differences in asthma severity may be related to inflammation in the airways. The lower airway microbiota has been associated with clinical features such as airway obstruction, symptom control, and response to corticosteroids. OBJECTIVE: To assess the relationship between local airway inflammation, severity of disease, and the lower airway microbiota in atopic asthmatics. METHODS: A cohort of young adult, atopic asthmatics with intermittent or mild/moderate persistent symptoms (n = 13) were assessed via bronchoscopy, lavage, and spirometry...
2017: PloS One
https://www.readbyqxmd.com/read/29052232/different-functional-genes-of-upper-airway-microbiome-associated-with-natural-course-of-childhood-asthma
#2
Bong-Soo Kim, Eun Lee, Min-Jung Lee, Mi-Jin Kang, Jisun Yoon, Hyun-Ju Cho, Jaehyun Park, Sungho Won, So Yeon Lee, Soo-Jong Hong
BACKGROUND: Microbial colonization of the airway plays a role in the pathogenesis of asthma; however, the effect of the upper airway microbiome on childhood asthma is not fully understood. We analyzed the metagenome of airway microbiome to understand the associated role of upper airway microbiome with the natural course of childhood asthma. METHODS: Nasopharyngeal swabs were collected from children with asthma, those in asthma remission, and control groups. High-throughput sequencing was used to examine the structure and functional dynamics of the airway microbiome with respect to asthma phenotypes...
October 20, 2017: Allergy
https://www.readbyqxmd.com/read/29051276/precision-medicine-in-airway-diseases-moving-to-clinical-practice
#3
Alvar Agustí, Mona Bafadhel, Richard Beasley, Elisabeth H Bel, Rosa Faner, Peter G Gibson, Renaud Louis, Vanessa M McDonald, Peter J Sterk, Mike Thomas, Claus Vogelmeier, Ian D Pavord
On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often overlap and that both require individualised assessment and treatment. This paper summarises the presentations and discussions that took place during the seminar. Specifically, we discussed the need for a new taxonomy of human diseases, the role of different players in this scenario (exposome, genes, endotypes, phenotypes, biomarkers and treatable traits) and a number of unanswered key questions in the field...
October 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29049049/treatable-traits-of-chronic-airways-disease
#4
James Fingleton, Jo Hardy, Richard Beasley
PURPOSE OF REVIEW: To describe the rationale on which the treatable traits approach to the management of airways disease is based and the issues that need to be considered for its implementation in clinical practice. RECENT FINDINGS: In clinical practice, treatable traits can be classified according to both endotypes and phenotypes, broadly grouped within pulmonary, extrapulmonary, environmental and behavioural factors. Specific investigations and treatments are undertaken for each of the traits rather than a 'one size fits all' stepwise approach to pharmacological treatment which currently represents the core of asthma and chronic obstructive pulmonary disease (COPD) guidelines...
October 18, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29048949/discovering-pediatric-asthma-phenotypes-based-on-response-to-controller-medication-using-machine-learning
#5
Mindy K Ross, Jinsung Yoon, Auke van der Schaar, Mihaela van der Schaar
RATIONALE: Pediatric asthma has variable underlying inflammation and symptom control. Approaches to address this heterogeneity such as clustering methods to find phenotypes and predicting outcomes have been investigated. However, clustering based upon the relationship between treatment and clinical outcome has not been performed. Also, machine learning approaches for long-term outcome prediction in pediatric asthma have not been studied in depth. OBJECTIVES: Our objectives were to use our novel machine learning algorithm, Predictor Pursuit (PP) to discover pediatric asthma phenotypes based on treatment response to different asthma controller medications, to predict outcomes of children with asthma over time, and to identify the most indicative features of asthma control for the discovered pediatric phenotypes...
October 19, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29048927/early-origins-of-asthma-role-of-microbial-dysbiosis-and-metabolic-dysfunction
#6
Fernando D Martinez, Stefano Guerra
Asthma is a developmental disease that affects airway growth and is characterized by inappropriate responses to a variety of environmental stimuli. Recent advances point to two altered early life pathways as major determinants of asthma risk. In the "microbial" pathway, pre- and post-natal exposures to microbiota-loaded farm environments block gene-virus interactions (e.g., interactions between risk alleles in chromosome 17q21 and lower respiratory illnesses [LRI] by rhinovirus) that are associated with asthma development...
October 19, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29047170/irf-1-snps-influence-the-risk-for-childhood-allergic-asthma-a-critical-role-for-pro-inflammatory-immune-regulation
#7
Katja Landgraf-Rauf, Andreas Boeck, Diana Raedler, Elisabeth Klucker, Vanessa Vogelsang, Susanne Schmidt, Sonja Kunze, Claudia Weissenbacher, Anke Graessel, Carsten Schmidt-Weber, Erika von Mutius, Michaela Schedel, Bianca Schaub
BACKGROUND: Allergic and non-allergic childhood asthma has been characterized by distinct immune mechanisms. While interferon regulating factor 1 (IRF-1) polymorphisms (SNPs) influence atopy risk, the effect of SNPs on asthma phenotype-specific immune mechanisms is unclear. We assessed whether IRF-1 SNPs modify distinct immune regulatory pathways in allergic and non-allergic childhood asthma (AA/NA). METHODS: In the CLARA study, asthma was characterized by doctor's diagnosis and AA vs NA by positive or negative specific IgE...
October 19, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/29046734/epigenome-wide-association-study-of-asthma-and-wheeze-in-childhood-and-adolescence
#8
Ryan Arathimos, Matthew Suderman, Gemma C Sharp, Kimberley Burrows, Raquel Granell, Kate Tilling, Tom R Gaunt, John Henderson, Susan Ring, Rebecca C Richmond, Caroline L Relton
BACKGROUND: Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis. METHODS: Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29040053/periostin-as-a-biomarker-for-nasal-polyps-in-chronic-rhinosinusitis
#9
Alice Z Maxfield, Lukas D Landegger, Christopher D Brook, Ashton E Lehmann, Adam P Campbell, Regan W Bergmark, Konstantina M Stankovic, Ralph Metson
Objective Periostin is an extracellular matrix protein that is elevated in the sinonasal tissues of patients with chronic rhinosinusitis (CRS). The purpose of this study was to determine whether serum periostin could serve as a molecular biomarker of nasal polyp burden in sinonasal disease. Study Design Prospective cohort study. Setting Academic medical center. Subjects and Methods Serum periostin levels were measured by ELISA on blood samples collected from patients undergoing sinus surgery for CRS (n = 71), further stratified by phenotype as defined by nasal polyps and asthma...
October 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29038841/the-maternal-microbiome-during-pregnancy-and-allergic-disease-in-the-offspring
#10
REVIEW
Peter J Vuillermin, Laurence Macia, Ralph Nanan, Mimi Lk Tang, Fiona Collier, Susanne Brix
There is substantial epidemiological and mechanistic evidence that the increase in allergic disease and asthma in many parts of the world in part relates to changes in microbial exposures and diet acting via the composition and metabolic products of the intestinal microbiome. The majority of research in this field has focused on the gut microbiome during infancy, but it is increasingly clear that the maternal microbiome during pregnancy also has a key role in preventing an allergy-prone immune phenotype in the offspring...
October 16, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/29038036/overexpression-of-notch-ligand-delta-like-1-by-dendritic-cells-enhances-their-immunoregulatory-capacity-and-exerts-antiallergic-effects-on-th2-mediated-allergic-asthma-in-mice
#11
Chen-Chen Lee, Chu-Lun Lin, Sy-Jye Leu, Yueh-Lun Lee
Dendritic cells (DCs) are professional antigen-presenting cells, and Notch ligand Delta-like-1 (DLL1) on DCs was implicated in type 1T helper (Th1) differentiation. In this study, we produced genetically engineered bone marrow-derived DCs that expressed DLL1 (DLL1-DCs) by adenoviral transduction. DLL1-DCs exerted a fully mature phenotype, and had positive effects on expression levels of interleukin (IL)-12 and costimulatory molecules. Coculture of allogeneic T cells with ovalbumin (OVA)-pulsed DLL1-DCs enhanced T cell proliferative responses and promoted Th1 cell differentiation...
October 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29038008/fibrinogen-cleavage-products-and-tlr4-promote-the-generation-of-programmed-cell-death-1-ligand-2-pd-l2-dendritic-cells-in-allergic-asthma
#12
Minkyoung Cho, Jeong-Eun Lee, Hoyong Lim, Hyun-Woo Shin, Roza Khalmuratova, Garam Choi, Hyuk Soon Kim, Wahn Soo Choi, Young-Jun Park, Inbo Shim, Byung-Seok Kim, Chang-Yuil Kang, Jae-Ouk Kim, Shinya Tanaka, Masato Kubo, Yeonseok Chung
BACKGROUND: Inhaled protease allergens preferentially trigger Th2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on the induction of Th2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce Th2-favorable DCs in the airway remains unclear. OBJECTIVE: We sought to determine a subset of DCs responsible for Th2 cell responses in allergic asthma and the mechanism by which protease allergens induce the DC subset in the airway...
October 13, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29036019/targeting-the-interleukin-4-and-interleukin-13-pathways-in-severe-asthma-current-knowledge-and-future-needs
#13
Amit D Parulekar, Christina C Kao, Zuzana Diamant, Nicola A Hanania
PURPOSE OF REVIEW: Severe asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) asthma. This article reviews the signaling pathway of IL-4 and IL-13 and highlights its targeted therapy in severe asthma. RECENT FINDINGS: Several clinical trials of biologics targeting the IL-4/IL-13 pathway have recently been completed. In patients with severe, uncontrolled asthma, targeting IL-13 alone with biologics including lebrikizumab and tralokinumab has not shown consistent reduction in asthma exacerbations...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29036018/precision-medicine-in-asthma-linking-phenotypes-to-targeted-treatments
#14
Kian F Chung
PURPOSE OF REVIEW: Asthma is a heterogeneous disease consisting of different phenotypes that are driven by different mechanistic pathways. The purpose of this review is to emphasize the important role of precision medicine in asthma management. RECENT FINDINGS: Despite asthma heterogeneity, the approach to management has been on the basis of disease severity, with the most severe patients reserved for the maximum treatments with corticosteroids and bronchodilators...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29035619/personalized-medicine-with-biologics-for-severe-type-2-asthma-current-status-and-future-prospects
#15
Marie Godar, Christophe Blanchetot, Hans de Haard, Bart N Lambrecht, Guy Brusselle
Asthma affects more than 300 million people worldwide and poses a large socioeconomic burden, particularly in the 5% to 10% of severe asthmatics. So far, each entry of new biologics in clinical trials has led to high expectations for treating all severe asthma forms, but the outcome has only been successful if the biologic, as add-on treatment, targeted specific patient subgroups. Indeed, we now realize that asthma is a heterogeneous disease with multiple phenotypes, based on distinct pathophysiological mechanisms, called endotypes...
October 16, 2017: MAbs
https://www.readbyqxmd.com/read/29027824/a-computable-phenotype-for-asthma-case-identification-in-adult-and-pediatric-patients-external-validation-in-the-chicago-area-patient-outcomes-research-network-capricorn
#16
Majid Afshar, Valerie G Press, Rachel G Robison, Abel N Kho, Sindhura Bandi, Ashvini Biswas, Pedro C Avila, Harsha Vardhan Madan Kumar, Byung Yu, Edward T Naureckas, Sharmilee M Nyenhuis, Christopher D Codispoti
OBJECTIVE: Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined...
October 13, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29025889/characterisation-of-asthma-subgroups-associated-with-circulating-ykl-40-levels
#17
Jose L Gomez, Xiting Yan, Carole T Holm, Nicole Grant, Qing Liu, Lauren Cohn, Vera Nezgovorova, Deborah A Meyers, Eugene R Bleecker, Gina M Crisafi, Nizar N Jarjour, Linda Rogers, Joan Reibman, Geoffrey L Chupp
The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341)...
October 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29020468/comparative-features-of-asthma-with-frequent-or-infrequent-exacerbations-a-longitudinal-study-of-retrospective-and-prospective-events
#18
Marie-Ève Boulay, Claudia Pruneau-Pomerleau, Hélène Villeneuve, Francine Deschesnes, Lyne Ringuette, Louis-Philippe Boulet
BACKGROUND: A "frequent exacerbator phenotype" has been described, mostly in the population of patients with severe asthma. Further data are needed on such exacerbation-prone patients in milder asthma. AIM: To compare the characteristics of frequent and nonfrequent exacerbators in asthma of different severities and to assess the stability of the exacerbator status. METHODS: This was an observational study comparing baseline data from frequent (≥2 exacerbations in the past year) and nonfrequent (<2 exacerbations in the past year) exacerbators...
October 11, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29017221/-biologicals-in-the-treatment-of-bronchial-asthma
#19
I Haasler, C Taube
Biologicals are a therapeutic option for patients with severe asthma. Difficult asthma in patients with untreated comorbidities or persistent trigger factors is much more common than severe refractory asthma. Optimized medical treatment, adherence to medication, elimination of trigger factors and treatment of comorbidities are essential before escalating the therapy with a biological. A careful phenotyping of patient with severe asthma is necessary because all available biological are only effective in certain phenotypes of the disease...
October 2017: Pneumologie
https://www.readbyqxmd.com/read/29016970/a-genome-by-environment-interaction-classifier-for-precision-medicine-personal-transcriptome-response-to-rhinovirus-identifies-children-prone-to-asthma-exacerbations
#20
Vincent Gardeux, Joanne Berghout, Ikbel Achour, A Grant Schissler, Qike Li, Colleen Kenost, Jianrong Li, Yuan Shang, Anthony Bosco, Donald Saner, Marilyn J Halonen, Daniel J Jackson, Haiquan Li, Fernando D Martinez, Yves A Lussier
Objective: To introduce a disease prognosis framework enabled by a robust classification scheme derived from patient-specific transcriptomic response to stimulation. Materials and Methods: Within an illustrative case study to predict asthma exacerbation, we designed a stimulation assay that reveals individualized transcriptomic response to human rhinovirus. Gene expression from peripheral blood mononuclear cells was quantified from 23 pediatric asthmatic patients and stimulated in vitro with human rhinovirus...
November 1, 2017: Journal of the American Medical Informatics Association: JAMIA
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