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Il 13 antibody severe asthma

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https://www.readbyqxmd.com/read/27836376/-new-drugs-for-severe-asthma
#1
Caroline Sattler, Roxane Malrin, Gilles Garcia, Marc Humbert
Asthma is a very frequent disease with complex and heterogenous immunological and clinical features. Daily inhaled steroids are the cornerstone of the current therapeutics sometimes associated with long-acting β2-agonist. This controller treatment is effective and allows to control asthma symptoms for the vast majority of the patients. Severe asthma is characterized by a poor level of control of symptoms, with recurrent exacerbations or a chronic airflow limitation despite an optimal management. Severe asthma remains a difficult diagnosis but we have now studies proving the clinical efficacy or promising data about monoclonal antibodies targeting IgE, IL-5, IL-4 or IL-13...
November 8, 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27766108/co-exposure-to-zymosan-a-and-heat-inactivated-asian-sand-dust-exacerbates-ovalbumin-induced-murine-lung-eosinophilia
#2
Kaori Sadakane, Takamichi Ichinose, Masataka Nishikawa, Hirohisa Takano, Takayuki Shibamoto
BACKGROUND: Epidemiological studies have implicated Asian sand dust (ASD) in the increased prevalence of respiratory disorders, including asthma. It has been observed that fungal elements such as β-glucan can be adsorbed onto ASD. In the present study, the exacerbating effect of the combined exposure to zymosan A (ZymA) containing yeast β-glucan and heat-inactivated ASD on ovalbumin (OVA)-induced murine lung eosinophilia was investigated. METHODS: BALB/c mice were repeatedly instilled intratracheally with one of eight immunogenic formulations consisting of various combinations of (1) ZymA, (2) ASD that was briefly heated to remove organic substances (H-ASD), and (3) OVA in normal saline, or each of the above alone...
2016: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/27582399/using-periostin-as-a-biomarker-in-the-treatment-of-asthma
#3
REVIEW
Kenji Izuhara, Shoichiro Ohta, Junya Ono
Periostin acts both as an extracellular matrix protein belonging to the fasciclin family and as a matricellular protein functioning in cell activation by binding to its receptors on the cell surface. It has been established that periostin is a downstream molecule of interleukin (IL)-13, a signature type 2 cytokine, and that periostin plays an important role in the pathogenesis of allergic diseases, including asthma. Based on these findings, much attention has been paid to periostin as a biomarker useful in the treatment of asthma...
November 2016: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/27499539/characterization-of-asthma-endotypes-implications-for-therapy
#4
REVIEW
Jeffrey R Stokes, Thomas B Casale
OBJECTIVE: To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers. DATA SOURCES: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (TH2)-low and TH2-high asthma. STUDY SELECTIONS: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic...
August 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27459348/biologics-targeting-il-5-il-4-or-il-13-for-the-treatment-of-asthma-an-update
#5
Garry M Walsh
INTRODUCTION: The development of monoclonal antibody-based biologics targeted at inhibition of the Th2 cytokines IL-4, IL-5 and IL-13 represent potentially effective treatments for patients with the glucocorticoid refractory eosinophilic asthma phenotype. AREAS COVERED: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. It is becoming apparent that significant clinical effects with anti-cytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account...
August 2, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27373855/patient-stratification-and-the-unmet-need-in-asthma
#6
Linda Swedin, Tiiu Saarne, Maria Rehnberg, Pernilla Glader, Magdalena Niedzielska, Gustav Johansson, Petra Hazon, Matthew C Catley
Asthma is often described as an inflammatory disease of the lungs and in most patients symptomatic treatment with bronchodilators or inhaled corticosteroids is sufficient to control disease. Unfortunately there are a proportion of patients who fail to achieve control despite treatment with the best current treatment. These severe asthma patients have been considered a homogeneous group of patients that represent the unmet therapeutic need in asthma. Many novel therapies have been tested in unselected asthma patients and the effects have often been disappointing, particularly for the highly specific monoclonal antibody-based drugs such as anti-IL-13 and anti-IL-5...
July 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27334730/monoclonal-antibodies-for-the-management-of-severe-asthma
#7
Renata Rubinsztajn, Ryszarda Chazan
Asthma is a heterogeneous inflammatory disease. Most patients respond to current standard of care, i.e., bronchodilators, inhaled glucocorticosteroids and other anti-inflammatory drugs, but in some adequate asthma control cannot be achieved with standard treatments. These difficult-to-treat patients would be the target population for new biological therapies. At present, omalizumab is the only biological agent approved for the treatment of early-onset, severe IgE-dependent asthma. It is safe, effective, and well tolerated...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27165851/interleukin-4-receptor-signaling-and-its-binding-mechanism-a-therapeutic-insight-from-inhibitors-tool-box
#8
REVIEW
Zaheer Ul-Haq, Sehrish Naz, M Ahmed Mesaik
Studies on Interlukin-4 (IL-4) disclosed great deal of information about its various physiological and pathological roles. All these roles depend upon its interaction and signaling through either type-I (IL-4Rα/common γ-chain) or type-II (IL-4Rα/IL-13Rα) receptors. Another cytokine, IL-13, shares some of the functions of IL-4, because both cytokines use a common receptor subunit, IL-4Rα. Here in this review, we discuss the structural details of IL-4 and IL-4Rα subunit and the structural similarities between IL-4 and IL-13...
December 2016: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/27161908/lebrikizumab-in-the-treatment-of-asthma
#9
Stephen Bujarski, Amit D Parulekar, Nicola A Hanania
Severe asthma continues to be a major clinical problem despite the availability of effective asthma medications such as inhaled corticosteroids. Several targeted biologic therapies are emerging to treat patients with severe asthma. Areas Covered: This review provides an update of information on lebrikizumab, a novel monoclonal antibody that targets IL-13 and is currently in advanced stages of development. It describes the role of IL-13, a key effector cytokine in Type 2 (T2) airway inflammation in asthma and discusses the results of recent phase 2 trials investigating lebrikizumab's efficacy and safety in patients with severe asthma...
May 10, 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/26895179/pharmacological-therapy-of-bronchial-asthma-the-role-of-biologicals
#10
REVIEW
Sebastian Heck, Juliane Nguyen, Duc-Dung Le, Robert Bals, Quoc Thai Dinh
Bronchial asthma is a heterogeneous, complex, chronic inflammatory and obstructive pulmonary disease driven by various pathways to present with different phenotypes. A small proportion of asthmatics (5-10%) suffer from severe asthma with symptoms that cannot be controlled by guideline therapy with high doses of inhaled steroids plus a second controller, such as long-acting β2 agonists (LABA) or leukotriene receptor antagonists, or even systemic steroids. The discovery and characterization of the pathways that drive different asthma phenotypes have opened up new therapeutic avenues for asthma treatment...
2015: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/26635789/estrogen-signaling-modulates-allergic-inflammation-and-contributes-to-sex-differences-in-asthma
#11
REVIEW
Aleksander Keselman, Nicola Heller
Asthma is a chronic airway inflammatory disease that affects ~300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or "hard-to-treat" asthma...
2015: Frontiers in Immunology
https://www.readbyqxmd.com/read/26473724/respiratory-syncytial-virus-disease-is-mediated-by-age-variable-il-33
#12
Jordy Saravia, Dahui You, Bishwas Shrestha, Sridhar Jaligama, David Siefker, Greg I Lee, Jeffrey N Harding, Tamekia L Jones, Cynthia Rovnaghi, Bindiya Bagga, John P DeVincenzo, Stephania A Cormier
Respiratory syncytial virus (RSV) is the most common cause of infant hospitalizations and severe RSV infections are a significant risk factor for childhood asthma. The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive. Using an age-appropriate mouse model of RSV, we show that IL-33 plays a critical role in the immunopathogenesis of severe RSV, which is associated with higher group 2 innate lymphoid cells (ILC2s) specifically in neonates. Infection with RSV induced rapid IL-33 expression and an increase in ILC2 numbers in the lungs of neonatal mice; this was not observed in adult mice...
October 2015: PLoS Pathogens
https://www.readbyqxmd.com/read/26343937/therapeutic-approaches-to-asthma-chronic-obstructive-pulmonary-disease-overlap-syndromes
#13
REVIEW
Peter J Barnes
The recognition that there are some patients with features of asthma and chronic obstructive pulmonary disease (COPD) has highlighted the need to develop more specific treatments for these clinical phenotypes. Some patients with COPD have predominantly eosinophilic inflammation and might respond to high doses of inhaled corticosteroids and newly developed specific antieosinophil therapies, including blocking antibodies against IL-5, IL-13, IL-33, and thymic stromal lymphopoietin, as well as oral chemoattractant receptor-homologous molecule expressed on TH2 cells antagonists...
September 2015: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26331583/treatment-of-severe-asthma-entering-the-era-of-targeted-therapy
#14
REVIEW
Amanda R van Buul, Christian Taube
INTRODUCTION: It is estimated that 5 - 10% of asthma patients suffer from severe asthma. Severe asthma is associated with increased morbidity and mortality. These patients are not controlled with currently available treatments and therefore additional treatment options are needed. Asthma is a heterogeneous disease, and different asthma patient groups probably have different underlying pathophysiology. Novel therapies with, for example, monoclonal antibodies that target certain immunological pathways have become available...
2015: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/26144372/semaphorin-7a-plays-a-critical-role-in-ige-mediated-airway-inflammation-in-mice
#15
Nobuaki Mizutani, Takeshi Nabe, Shin Yoshino
Elevated allergen-specific IgE levels are a hallmark of allergic asthma, a disease involving chronic airway inflammation characterized by airway hyperresponsiveness (AHR); neutrophilic airway inflammation is found in patients with severe asthma. Furthermore, we have reported that interleukin (IL)-33 and IL-17A contribute to IgE-mediated AHR through neutrophilic inflammation in mice. Meanwhile, semaphorins regulating neuronal and immune function have been focused on in several diseases. Here, we investigated whether semaphorin 7A (SEMA7A) is related to IgE-mediated neutrophilic inflammation in mice...
October 5, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26076339/asthma-phenotyping-a-necessity-for-improved-therapeutic-precision-and-new-targeted-therapies
#16
REVIEW
Kian Fan Chung
Asthma is a common heterogeneous disease with a complex pathophysiology that carries a significant mortality rate and high morbidity. Current therapies based on inhaled corticosteroids and long-acting β-agonists remain effective in a large proportion of patients with asthma, but ~10% (considered to have 'severe asthma') do not respond to these treatments even at high doses or with the use of oral corticosteroids. Analytical clustering methods have revealed phenotypes that include dependence on high-dose corticosteroid treatment, severe airflow obstruction and recurrent exacerbations associated with an allergic background and late onset of disease...
February 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/26065426/b7-h3-promotes-pathogenesis-of-autoimmune-disease-and-inflammation-by-regulating-the-activity-of-different-t-cell-subsets
#17
Liqun Luo, Gefeng Zhu, Haiying Xu, Sheng Yao, Gang Zhou, Yuwen Zhu, Koji Tamada, Lanqing Huang, Andrew D Flies, Megan Broadwater, William Ruff, Jan M A van Deursen, Ignacio Melero, Zhou Zhu, Lieping Chen
B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively...
2015: PloS One
https://www.readbyqxmd.com/read/26006019/bronchial-lesions-of-mouse-model-of-asthma-are-preceded-by-immune-complex-vasculitis-and-induced-bronchial-associated-lymphoid-tissue-ibalt
#18
Ian C Guest, Stewart Sell
We systematically examined by immune histology the lungs of some widely used mouse models of asthma. These models include sensitization by multiple intraperitoneal injections of soluble ovalbumin (OVA) or of OVA with alum, followed by three intranasal or aerosol challenges 3 days apart. Within 24 h after a single challenge there is fibrinoid necrosis of arterial walls with deposition of immunoglobulin (Ig) and OVA and infiltration of eosinophilic polymorphonuclear cells that lasts for about 3 days followed by peribronchial B-cell infiltration and slight reversible goblet cell hypertrophy (GCHT)...
August 2015: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/25838086/immunopathology-of-chronic-rhinosinusitis
#19
REVIEW
Atsushi Kato
Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses which persists for at least 12 weeks. CRS can be divided into two phenotypes dependent on the presence of nasal polyps (NPs); CRS with NPs (CRSwNP) and CRS without NPs (CRSsNP). Immunological patterns in the two diseases are known to be different. Inflammation in CRSsNP is rarely investigated and limited studies show that CRSsNP is characterized by type 1 inflammation. Inflammation in CRSwNP is well investigated and CRSwNP in Western countries shows type 2 inflammation and eosinophilia in NPs...
April 2015: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/25826377/g-protein-coupled-estrogen-receptor-agonist-suppresses-airway-inflammation-in-a-mouse-model-of-asthma-through-il-10
#20
Masamichi Itoga, Yasunori Konno, Yuki Moritoki, Yukiko Saito, Wataru Ito, Mami Tamaki, Yoshiki Kobayashi, Hiroyuki Kayaba, Yuta Kikuchi, Junichi Chihara, Masahide Takeda, Shigeharu Ueki, Makoto Hirokawa
Estrogen influences the disease severity and sexual dimorphism in asthma, which is caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERαβ), G-protein-coupled estrogen receptor (GPER) was recently established as an estrogen receptor on the cell membrane. Although GPER is associated with immunoregulatory functions of estrogen, the pathophysiological role of GPER in allergic inflammatory lung disease has not been examined. We investigated the effect of GPER-specific agonist G-1 in asthmatic mice...
2015: PloS One
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