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Asthma endotype phenotype

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https://www.readbyqxmd.com/read/29318959/novel-biological-therapies-in-severe-asthma-targeting-the-right-trait
#1
Gilda Varricchi, Giancarlo Marone, Giuseppe Spadaro, Michele Russo, Francescopaolo Granata, Arturo Genovese, Gianni Marone
Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments...
January 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29307657/a-decade-of-research-on-the-17q12-21-asthma-locus-piecing-together-the-puzzle
#2
Michelle M Stein, Emma E Thompson, Nathan Schoettler, Britney A Helling, Kevin M Magnaye, Catherine Stanhope, Catherine Igartua, Andréanne Morin, Charles Washington, Dan Nicolae, Klaus Bønnelykke, Carole Ober
Chromosome 17q12-21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first GWAS correlate with expression of two genes, ORMDL3 and GSDMB, making these prime candidate asthma genes, although recent studies have implicated GSDMA distal to and PGAP3 proximal to the core region as independent loci. We review here 10 years of studies on the 17q12-21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early onset asthma and mediated by PGAP3, ORMDL3, and/or GSDMA expression...
January 4, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29279053/unraveling-the-conundrum-of-asthma-phenotypes-and-endotypes
#3
Joseph A Bellanti, Russell A Settipane
No abstract text is available yet for this article.
January 1, 2018: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/29229196/impact-of-allergy-on-phenotypic-and-endotypic-profiles-of-nasal-polyposis
#4
G Mortuaire, I Gengler, M Balden, M Capron, G Lefèvre
OBJECTIVES: To assess the impact of allergy on clinical presentations (phenotypes) and inflammatory patterns (endotypes) of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A single-center prospective study was conducted over an 18-month period. Fifty-seven patients with refractory CRSwNP were included. The diagnosis of allergy was based on concordant skin prick tests and symptoms. Phenotypes were determined on symptom severity score, polyp size classification and Lund-Mackay CT staging...
December 8, 2017: European Annals of Otorhinolaryngology, Head and Neck Diseases
https://www.readbyqxmd.com/read/29221581/biomarkers-for-severe-eosinophilic-asthma
#5
REVIEW
Steven W Yancey, Oliver N Keene, Frank C Albers, Hector Ortega, Stewart Bates, Eugene R Bleecker, Ian Pavord
The last decade has seen the approval of several new biologics for the treatment of severe asthma-targeting specific endotypes and phenotypes. This review will examine how evidence generated from the mepolizumab clinical development program showed that blood eosinophil counts, rather than sputum or tissue eosinophil counts, evolved as a pharmacodynamic and predictive biomarker for the efficacy of treatment with mepolizumab in patients with severe eosinophilic asthma. Based on the available evidence and combined with clinical judgement, a baseline blood eosinophil threshold of 150 cells/μL or greater or a historical blood eosinophil threshold of 300 cells/μL or greater will allow selection of patients with severe eosinophilic asthma who are most likely to achieve clinically significant reductions in the rate of exacerbations with mepolizumab treatment...
December 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29189350/asthma-personalized-and-precision-medicine
#6
Giorgio W Canonica, Matteo Ferrando, Ilaria Baiardini, Francesca Puggioni, Francesca Racca, Giovanni Passalacqua, Enrico Heffler
PURPOSE OF REVIEW: In this review, we herein describe the progress in management of severe asthma, evolving from a 'blockbuster approach' to a more personalized approach targeted to the utilization of endotype-driven therapies. RECENT FINDINGS: Severe asthma characterization in phenotypes and endotypes, by means of specific biomarkers, have led to the dichotomization of the concepts of 'personalized medicine' and 'precision medicine', which are often used as synonyms, but actually have conceptual differences in meaning...
February 2018: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29106996/chronic-rhinosinusitis-endotypes-biomarkers-and-treatment-response
#7
Jose Gurrola, Larry Borish
It is increasingly recognized that chronic rhinosinusitis (CRS) comprises a spectrum of different diseases with distinct clinical presentations and pathogenic mechanisms. Defining the distinct phenotypes and endotypes of CRS impacts prognosis and most importantly is necessary as the basis for making therapeutic decisions. The need for individualized defining of pathogenic mechanisms prior to initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics where, barring an influence from their off-target anti-inflammatory pharmacological effects, an understanding of the role of individual biome predicts likelihood of therapeutic benefit...
October 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29077521/new-approaches-for-identifying-and-testing-potential-new-anti-asthma-agents
#8
Amelia Licari, Riccardo Castagnoli, Ilaria Brambilla, Alessia Marseglia, Maria Angela Tosca, Gian Luigi Marseglia, Giorgio Ciprandi
Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities...
October 27, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29059087/controversies-and-opportunities-in-severe-asthma
#9
Marc Humbert, William Busse, Nicola A Hanania
PURPOSE OF REVIEW: Despite currently available treatments, many asthma patients remain inadequately controlled, but identifying distinct patient populations (phenotypes/endotypes) may optimize their management. This review discusses some of the controversies and opportunities for improved disease control in severe asthma. RECENT FINDINGS: Currently approved anti-immunoglobulin E and anti-interleukin 5 biologics, which target specific pathways instead of using a 'one size fits all' strategy, are efficacious and well tolerated therapies for severe asthma...
January 2018: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29051276/precision-medicine-in-airway-diseases-moving-to-clinical-practice
#10
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
#11
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/29040053/periostin-as-a-biomarker-for-nasal-polyps-in-chronic-rhinosinusitis
#12
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/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...
January 2018: 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...
January 2018: MAbs
https://www.readbyqxmd.com/read/28992358/role-of-galectin-3-in-the-pathophysiology-underlying-allergic-lung-inflammation-in-a-timp-1-knockout-model-of-murine-asthma
#16
Manoj J Mammen, Mark F Sands, Elaine Abou-Jaoude, Ravikumar Aalinkeel, Jessica L Reynolds, Neil U Parikh, Umesh Sharma, Stanley A Schwartz, Supriya D Mahajan
Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyper-responsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Utilizing a Tissue inhibitors of metalloproteinase-1 (TIMP-1) knockout murine allergic asthma model, we previously showed that Tissue inhibitors of metalloproteinase-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation, and TH2 cytokine gene and protein expression following sensitization with ovalbumin...
October 9, 2017: Immunology
https://www.readbyqxmd.com/read/28976216/how-should-treatment-approaches-differ-depending-on-the-severity-of-asthma
#17
Maciej Kupczyk, Piotr Kuna
Asthma is nowadays regarded as a syndrome of various overlapping phenotypes with defined clinical characteristics, different underlying inflammatory mechanisms, identifiable genetic background, environmental risk factors and possible biomarkers. There are no doubts that due to the diversity of asthma, a 'one size fits all' management of the disease is no longer valid. Areas covered: Nowadays asthma management is based on the control of the disease, and the goals of asthma treatment are defined as good symptom control, decreased future risk of exacerbations, fixed airflow limitation, and side-effects of treatment...
December 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28954768/personalised-medicine-in-asthma-time-for-action-number-1-in-the-series-personalised-medicine-in-respiratory-diseases-edited-by-renaud-louis-and-nicolas-roche
#18
Kian Fan Chung
Asthma is a heterogeneous disease comprising several phenotypes driven by different pathways. To define these phenotypes or endotypes (phenotypes defined by mechanisms), an unbiased approach to clustering of various omics platforms will yield molecular phenotypes from which composite biomarkers can be obtained. Biomarkers can help differentiate between these phenotypes and pinpoint patients suitable for specific targeted therapies - the basis for personalised medicine. Biomarkers need to be linked to point-of-care biomarkers that may be measured readily in exhaled breath, blood or urine...
September 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#19
REVIEW
Francesco Menzella, Carla Galeone, Francesca Bertolini, Claudia Castagnetti, Nicola Facciolongo
The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28918658/the-role-of-upper-airway-pathology-as-a-co-morbidity-in-severe-asthma
#20
Amelia Licari, Ilaria Brambilla, Maria De Filippo, Dimitri Poddighe, Riccardo Castagnoli, Gian Luigi Marseglia
Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple co-morbidities and risk factors. Several co-morbidities may contribute to worsen asthma control and complicate diagnostic and therapeutic management of severe asthmatic patients. Areas covered: A prevalent cluster of chronic upper airway co-morbid diseases is recognized in severe asthma. Evaluation for these disorders should always be considered in clinical practice. The aim of this review is to provide an updated overview of the prevalence, the pathogenetic mechanisms, the clinical impact and the therapeutic options for upper airway pathology in severe asthma, focusing on chronic rhinosinusitis and allergic rhinitis...
September 16, 2017: Expert Review of Respiratory Medicine
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