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Asthma endotype phenotype

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https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#1
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
#2
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
https://www.readbyqxmd.com/read/28913336/anti-interleukin-5-il-5-and-il-5ra-biological-drugs-efficacy-safety-and-future-perspectives-in-severe-eosinophilic-asthma
#3
REVIEW
Diego Bagnasco, Matteo Ferrando, Gilda Varricchi, Francesca Puggioni, Giovanni Passalacqua, Giorgio Walter Canonica
The definition of asthma has changed considerably in recent years, to the extent that asthma is no longer considered a single disease but a heterogeneous disorder that includes several phenotypes and, possibly, endotypes. A more detailed analysis of the immunological mechanisms underlying the pathogenesis of asthma shows interleukin 5 (IL-5) to be a crucial cytokine in several asthma phenotypes. In fact, IL-5 exerts selective action on eosinophils, which, in turn, sustain airway inflammation and worsen asthma symptoms and control...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28910134/eosinophilic-and-non-eosinophilic-asthma
#4
Tara F Carr, Amir A Zeki, Monica Kraft
Asthma can be subdivided into eosinophilic or non-eosinophilic phenotypes based on the inflammatory cellular patterns seen in sputum, blood, and airway tissue compartments. However, this level of stratification does not always produce robust clinical phenotypes as there is considerable overlap across these phenotypes when viewed from the perspective of "eosinophilia". Multiple proposed subphenotypes of asthma have instead been described within both the eosinophilic and non-eosinophilic groups. An endotype is the mechanism driving a subphenotype including those associated with eosinophilia such as early-onset allergic asthma, with and without obesity, aspirin sensitive asthma and late-onset eosinophilic asthma, allergic bronchopulmonary mycosis, and exercise-induced asthma...
September 14, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28879503/asthma-phenotypes-and-endotypes-implications-for-personalised-therapy
#5
Katrina Dean, Robert Niven
Asthma is increasingly recognised as a heterogeneous group of diseases with similar clinical presentations rather than a singular disease entity. Asthma was historically categorised by clinical symptoms; however, newer methods of subgrouping, describing and categorising the disease have sub-defined asthma. These sub-definitions are intermittently called phenotypes or endotypes, but the real meanings of these words are poorly understood. Novel treatments are currently and increasingly available, partly in the monoclonal antibody environment, and also some physical therapies (bronchial thermoplasty), but additionally small molecules are not far away from clinical practice...
September 6, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28866644/functional-phenotypes-determined-by-fluctuation-based-clustering-of-lung-function-measurements-in-healthy-and-asthmatic-cohort-participants
#6
Edgar Delgado-Eckert, Oliver Fuchs, Nitin Kumar, Juha Pekkanen, Jean-Charles Dalphin, Josef Riedler, Roger Lauener, Michael Kabesch, Maciej Kupczyk, Sven-Eric Dahlen, Erika von Mutius, Urs Frey
RATIONALE: Asthma is characterised by inflammation and reversible airway obstruction. However, these features are not always closely related. Fluctuations of daily lung function contain information on asthma phenotypes, exacerbation risk and response to long-acting β-agonists. OBJECTIVES: In search of subgroups of asthmatic participants with specific lung functional features, we developed and validated a novel clustering approach to asthma phenotyping, which exploits the information contained within the fluctuating behaviour of twice-daily lung function measurements...
September 2, 2017: Thorax
https://www.readbyqxmd.com/read/28852271/potential-biomarkers-for-nsaid-exacerbated-respiratory-disease
#7
REVIEW
Hanki Park, Youngwoo Choi, Chang-Gyu Jung, Hae-Sim Park
Asthma is a common chronic disease with several variant phenotypes and endotypes. NSAID-exacerbated respiratory disease (NERD) is one such endotype characterized by asthma, chronic rhinosinusitis (CRS) with nasal polyps, and hypersensitivity to aspirin/cyclooxygenase-1 inhibitors. NERD is more associated with severe asthma than other asthma phenotypes. Regarding diagnosis, aspirin challenge tests via the oral or bronchial route are a standard diagnostic method; reliable in vitro diagnostic tests are not available...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28797075/arginine-metabolic-endotypes-related-to-asthma-severity
#8
Weiling Xu, Suzy A A Comhair, Allison J Janocha, Abigail Lara, Lori A Mavrakis, Carole D Bennett, Satish C Kalhan, Serpil C Erzurum
AIMS: Arginine metabolism via inducible nitric oxide synthase (iNOS) and arginase 2 (ARG2) is higher in asthmatics than in healthy individuals. We hypothesized that a sub-phenotype of asthma might be defined by the magnitude of arginine metabolism categorized on the basis of high and low fraction of exhaled nitric oxide (FENO). METHODS: To test this hypothesis, asthmatics (n = 52) were compared to healthy controls (n = 51) for levels of FENO, serum arginase activity, and airway epithelial expression of iNOS and ARG2 proteins, in relation to clinical parameters of asthma inflammation and airway reactivity...
2017: PloS One
https://www.readbyqxmd.com/read/28791280/oxidative-stress-and-bronchial-asthma-in-children-causes-or-consequences
#9
REVIEW
Milos Jesenak, Maria Zelieskova, Eva Babusikova
Bronchial asthma is one of the most common chronic inflammatory diseases of the airways. In the pathogenesis of this disease, the interplay among the genes, intrinsic, and extrinsic factors are crucial. Various combinations of the involved factors determine and modify the final clinical phenotype/endotype of asthma. Oxidative stress results from an imbalance between the production of reactive oxygen species and reactive nitrogen species and the capacity of antioxidant defense mechanisms. It was shown that oxidative damage of biomolecules is strongly involved in the asthmatic inflammation...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28780940/diagnosis-and-management-of-anaphylaxis-in-precision-medicine
#10
REVIEW
Mariana Castells
Anaphylaxis is the most severe and frightening of the allergic reactions, placing patients at high risk and demanding prompt recognition and immediate management by health care providers. Yet because its symptoms imitate those of other diseases, such as asthma and urticaria, current data suggest that its diagnosis is often missed, with underuse of tryptase measurement; its treatment is delayed, with little use of epinephrine; and its underlying cause or causes are poorly investigated. Deaths from anaphylaxis are difficult to investigate because of miscoding...
August 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#11
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/28689840/severe-asthma-phenotypes-how-should-they-guide-evaluation-and-treatment
#12
Anne M Fitzpatrick, Wendy C Moore
Although patients with "severe" asthma tend to be characterized by ongoing symptoms and airway inflammation despite treatment with high doses of inhaled and systemic corticosteroids, there is increasing recognition of marked phenotypic heterogeneity within affected patients. Although "precision medicine" approaches for patients with severe asthma are needed, there are many hurdles that must be overcome in daily practice. The National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) has been at the forefront of phenotype discovery in severe asthma for the past decade...
July 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28686637/endotypes-of-difficult-to-control-asthma-in-inner-city-african-american-children
#13
K R Brown, R Z Krouse, A Calatroni, C M Visness, U Sivaprasad, C M Kercsmar, E C Matsui, J B West, M M Makhija, M A Gill, H Kim, M Kattan, D Pillai, J E Gern, W W Busse, A Togias, A H Liu, G K Khurana Hershey
African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19)...
2017: PloS One
https://www.readbyqxmd.com/read/28683596/reslizumab-in-the-treatment-of-inadequately-controlled-asthma-in-adults-and-adolescents-with-elevated-blood-eosinophils-clinical-trial-evidence-and-future-prospects
#14
Jorge Máspero
Eosinophils have long been implicated as playing a central role in the pathophysiology of asthma in many patients, and eosinophilic asthma is now recognized as an important asthma endotype. Eosinophil differentiation, maturation, migration, and survival are primarily under the control of interleukin-5 (IL-5). Reslizumab is a humanized monoclonal (immunoglobulin G4/κ) antibody that binds with high affinity to circulating human IL-5 and downregulates the IL-5 signaling pathway, potentially disrupting the maturation and survival of eosinophils...
July 1, 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28658564/a-clustering-approach-to-identify-and-characterize-the-asthma-and-chronic-obstructive-pulmonary-disease-overlap-phenotype
#15
Keita Hirai, Toshihiro Shirai, Masayuki Suzuki, Taisuke Akamatsu, Takahito Suzuki, Ichiro Hayashi, Akito Yamamoto, Takefumi Akita, Satoru Morita, Kazuhiro Asada, Daiki Tsuji, Kazuyuki Inoue, Kunihiko Itoh
BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood. OBJECTIVE: To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach. METHODS: This study assessed pathophysiological parameters, including mRNA expression levels of T helper cell-related transcription factors, namely, TBX21 (Th1), GATA3 (Th2), RORC (Th17), and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n = 152) and in COPD patients (n = 50)...
June 28, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28658552/mechanisms-and-treatments-for-severe-steroid-resistant-allergic-airway-disease-and-asthma
#16
REVIEW
Philip M Hansbro, Richard Y Kim, Malcolm R Starkey, Chantal Donovan, Kamal Dua, Jemma R Mayall, Gang Liu, Nicole G Hansbro, Jodie L Simpson, Lisa G Wood, Jeremy A Hirota, Darryl A Knight, Paul S Foster, Jay C Horvat
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28635659/divergent-how-ige-axis-contributes-to-the-continuum-of-allergic-asthma-and-anti-ige-therapies
#17
REVIEW
Óscar Palomares, Silvia Sánchez-Ramón, Ignacio Dávila, Luis Prieto, Luis Pérez de Llano, Marta Lleonart, Christian Domingo, Antonio Nieto
Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28622052/biologic-treatment-eligibility-for-real-world-patients-with-severe-asthma-the-ideal-study
#18
Frank C Albers, Hana Müllerová, Necdet B Gunsoy, Ji-Yeon Shin, Linda M Nelsen, Eric S Bradford, Sarah M Cockle, Robert Y Suruki
OBJECTIVES: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice...
June 16, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28583261/cellular-and-noncellular-bloodborne-biomarkers-in-asthma
#19
REVIEW
Hannah Sinz, Harald Renz, Chrysanthi Skevaki
OBJECTIVE: To provide an overview of studied cellular and noncellular blood-derived asthma biomarkers. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles discussing cellular and noncellular bloodborne asthma biomarkers. RESULTS: Discussed asthma biomarkers include peripheral blood cell counts of T cells, fibrocytes, or granulocytes, as well as levels of cytokines, periostin, IgE, and lipid mediators with or without stimulation...
June 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28550983/the-influence-of-asthma-and-or-hay-fever-on-pregnancy-data-from-the-1995-national-survey-of-family-growth
#20
Paul C Turkeltaub, Jooyoung Cheon, Erika Friedmann, Richard F Lockey
BACKGROUND: Asthma is associated with adverse pregnancy outcomes. At the same time there is a worldwide increase in asthma and hay fever. OBJECTIVE: This study addresses whether asthma and/or hay fever adversely influence pregnancy outcomes. METHODS: Data from the 1995 National Survey of Family Growth that include a history of diagnosed asthma, hay fever, and adverse pregnancy outcomes in 10,847 women representative of the US population aged 15 to 44 years were analyzed...
May 24, 2017: Journal of Allergy and Clinical Immunology in Practice
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