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asthma endotypes or phenotypes

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https://www.readbyqxmd.com/read/28933920/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#1
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy Sc Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma, and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (mild, moderate and severe asthma; N=46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips and results were validated by real-time quantitative PCR...
September 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28931049/the-c5a-c5ar1-axis-controls-the-development-of-experimental-allergic-asthma-independent-of-lysm-expressing-pulmonary-immune-cells
#2
Anna V Wiese, Fanny Ender, Katharina M Quell, Konstantina Antoniou, Tillman Vollbrandt, Peter König, Jörg Köhl, Yves Laumonnier
C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1). Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs) and monocyte-derived DCs (moDCs) during the allergic effector phase using a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse...
2017: PloS One
https://www.readbyqxmd.com/read/28929787/-phenotypes-of-bronchial-asthma
#3
László Béla Nagy
It is increasingly recognized that the bronchial asthma is a heterogeneous entity, encompassing a variety of different phenotypes. The identification of specific phenotypes is the key to develop more effective personalised treatment. The earliest attempt to phenotype asthma was proposed classifying into extrinsic and intrinsic subtypes. Clinical asthma is mainly divided into allergic (atopic) and non-allergic (non-atopic) asthma. Other phenotypes are based on trigger factors. Later the phenotyping based on the predominant cellular nature of inflammation: It can be divided into eosinophilic and non-eosinohilic...
April 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28929293/predictive-biomarkers-for-asthma-therapy
#4
REVIEW
Sarah K Medrek, Amit D Parulekar, Nicola A Hanania
PURPOSE OF REVIEW: Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. RECENT FINDINGS: Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment...
September 19, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28927820/a-novel-role-for-cilia-function-in-atopy-adgrv1-and-dnah5-interactions
#5
Pierre-Emmanuel Sugier, Myriam Brossard, Chloé Sarnowski, Amaury Vaysse, Andréanne Morin, Lucile Pain, Patricia Margaritte-Jeannin, Marie-Hélène Dizier, William O C M Cookson, Mark Lathrop, Miriam F Moffatt, Catherine Laprise, Florence Demenais, Emmanuelle Bouzigon
BACKGROUND: Atopy, an endotype underlying allergic diseases, has a substantial genetic component. OBJECTIVE: Our goal was to identify novel genes associated with atopy in asthma-ascertained families. METHODS: We implemented a three-step analysis strategy in three datasets: The Epidemiological study on the Genetics and Environment of Asthma (EGEA) dataset: 1,660 subjects; The Saguenay-Lac-Saint-Jean (SLSJ) dataset: 1,138 subjects; and The Medical Research Council (MRC) dataset: 446 subjects)...
September 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28926280/mepolizumab-attenuates-airway-eosinophil-numbers-but-not-their-functional-phenotype-in-asthma
#6
Gail M Gauvreau, Roma Sehmi
No abstract text is available yet for this article.
September 19, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28925522/grandmaternal-smoking-increases-asthma-risk-in-grandchildren-a-nationwide-swedish-cohort
#7
C J Lodge, L Bråbäck, A J Lowe, S C Dharmage, D Olsson, B Forsberg
BACKGROUND: There is growing interest in exposures prior to conception as possible risk factors for offspring asthma. Although partially supported by evidence from limited human studies, current evidence is inconsistent, and based on recall of exposure status. OBJECTIVE: We aimed to investigate grandmaternal smoking during pregnancy and the risk of asthma in grandchildren using prospectively collected population-based data. METHODS: Information on grandmaternal and maternal smoking during pregnancy and grandchild use of asthma medications was collected from national Swedish registries...
September 19, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28923762/translating-basic-research-into-clinical-practice-vitamin-d-in-asthma-mechanisms-of-action-and-considerations-for-clinical-trials
#8
REVIEW
Paul E Pfeffer, Catherine M Hawrylowicz
There is increasing interest in the therapeutic utility of vitamin D in asthma, supported by a significant body of evidence on epidemiological associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunological pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterised by a failure of immune tolerance, and development of pathological responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation...
September 15, 2017: Chest
https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#9
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
#10
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/28913987/clinical-characteristics-of-exacerbation-prone-adult-asthmatics-identified-by-cluster-analysis
#11
Mi Ae Kim, Seung Woo Shin, Jong Sook Park, Soo Taek Uh, Hun Soo Chang, Da Jeong Bae, You Sook Cho, Hae Sim Park, Ho Joo Yoon, Byoung Whui Choi, Yong Hoon Kim, Choon Sik Park
PURPOSE: Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation...
November 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28913985/asthma-biomarkers-do-they-bring-precision-medicine-closer-to-the-clinic
#12
REVIEW
Ioana Agache, Liliana Rogozea
Measurement of biomarkers has been incorporated within clinical research of asthma to characterize the population and to associate the disease with environmental and therapeutic effects. Regrettably, at present, there are no specific biomarkers, none is validated or qualified, and endotype-driven choices overlap. Biomarkers have not yet reached clinical practice and are not included in current asthma guidelines. Last but not least, the choice of the outcome upholding the value of the biomarkers is extremely difficult, since it has to reflect the mechanistic intervention while being relevant to both the disease and the particular person...
November 2017: Allergy, Asthma & Immunology Research
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
#13
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/28912381/invariant-natural-killer-t-cells-promote-immunogenic-maturation-of-lung-dendritic-cells-in-mouse-models-of-asthma
#14
Qing He, Linlin Liu, Qiaoyu Yang, Ailing Wang, Shuo Chen, Ruiyun Li, Yi Huang, Guqin Zhang, Xuhong Ding, Hongying Yu, Suping Hu, Hanxiang Nie
Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, co-culture experiments, and adoptive transfer of iNKT cells in mouse models of asthma...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28911045/azole-resistant-aspergillosis-epidemiology-molecular-mechanisms-and-treatment
#15
REVIEW
Anuradha Chowdhary, Cheshta Sharma, Jacques F Meis
Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28910142/distinct-phenotypes-of-smokers-with-fixed-airflow-limitation-identi%C3%AF-ed-by-cluster-analysis-of-severe-asthma
#16
Satoshi Konno, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M Ito, Sally E Wenzel, Masaharu Nishimura
RATIONALE: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any priori hypotheses. OBJECTIVE: To explore novel severe asthma phenotypes by cluster analysis when including smoking asthmatics. METHODS: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics...
September 14, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28910134/eosinophilic-and-non-eosinophilic-asthma
#17
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/28906154/moving-toward-consensus-on-diagnosis-and-management-of-severe-asthma-in-adults
#18
Daniel Colodenco, Oscar Palomares, Carlos Celis, Alan Kaplan, Christian Domingo
Asthma is a considerable health problem with an increasing global prevalence. The burden of severe asthma is expected to notably increase in the following years. Some misleading concepts that sometimes appear in the literature can drive the physician responsible for the patient's management to make incorrect decisions. Furthermore, some of the concepts that appear in the literature and in the guidelines may be not be clear to understand, to follow or to adapt to the regional and local realities. This could again drive the physicians responsible of the patient's management to make incorrect clinical judgements...
September 14, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28904353/toll-like-receptor%C3%A2-2-induced-cytotoxic-t-lymphocyte-associated-protein%C3%A2-4-regulates-aspergillus-induced-regulatory-t-cells-with-pro-inflammatory-characteristics
#19
Ruud P H Raijmakers, Evelien G G Sprenkeler, Floor E Aleva, Cor W M Jacobs, Thirumala-Devi Kanneganti, Leo A B Joosten, Frank L van de Veerdonk, Mark S Gresnigt
Patients with cystic fibrosis, chronic obstructive pulmonary disease, severe asthma, pre-existing pulmonary lesions, and severely immunocompromised patients are susceptible to develop infections with the opportunistic pathogenic fungus Aspergillus fumigatus, called aspergillosis. Infections in these patients are associated with persistent pro-inflammatory T-helper (TH)2 and TH17 responses. Regulatory T-cells, natural suppressor cells of the immune system, control pro-inflammatory T-cell responses, but can also contribute to disease by shifting to a pro-inflammatory TH17-like phenotype...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903951/managing-problematic-severe-asthma-beyond-the-guidelines
#20
REVIEW
Katharine C Pike, Mark L Levy, John Moreiras, Louise Fleming
This review discusses issues related to managing problematic severe asthma in children and young people. A small minority of children have genuinely severe asthma symptoms which are difficult to control. Children with genuinely severe asthma need investigations and treatments beyond those described within conventional guidelines. However, the majority of children with poor symptom control despite high-intensity treatment achieve improvement in their asthma control once attention has been paid to the basics of asthma management...
September 13, 2017: Archives of Disease in Childhood
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