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asthma endotypes or phenotypes

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https://www.readbyqxmd.com/read/28093362/hypoxia-inducible-factor-1%C3%AE-inhibition-modulates-airway-hyperresponsiveness-and-nitric-oxide-levels-in-a-balb-c-mouse-model-of-asthma
#1
Carola Dewitz, Elisa McEachern, Stephanie Shin, Kathryn Akong, Dale G Nagle, David H Broide, Praveen Akuthota, Laura E Crotty Alexander
: Hypoxia inducible factor (HIF)-1α is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-1α regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-1α inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype. Systemic treatment with HIF-1α antagonist YC-1 suppressed the increase in HIF-1α expression seen in control AIAD mice...
January 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28092287/current-and-future-management-of-the-young-child-with-early-onset-wheezing
#2
Allison J Burbank, Stanley J Szefler
PURPOSE OF REVIEW: In this review, we discuss current thinking in relation to available guidelines for the care of preschool-aged children with recurrent wheezing, while highlighting the gaps in our knowledge and discussing changes that could occur over the next 5 years. RECENT FINDINGS: The Asthma Predictive Index as well as allergen-specific IgE, peripheral eosinophil count and exhaled nitric oxide are perhaps underutilized sources of information that can assist in predicting progression to asthma and response to therapies...
January 13, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28090286/novel-methods-in-pulmonary-hypertension-phenotyping-in-the-age-of-precision-medicine-2015-grover-conference-series
#3
REVIEW
Jarrod W Barnes, Adriano R Tonelli, Gustavo A Heresi, Jennie E Newman, Noël E Mellor, David E Grove, Raed A Dweik
Among pulmonary vascular diseases, pulmonary hypertension (PH) is the best studied and has been the focus of our work. The current classification of PH is based on a relatively simple combination of patient characteristics and hemodynamics. This leads to inherent limitations, including the inability to customize treatment and the lack of clarity from a more granular identification based on individual patient phenotypes. Accurate phenotyping of PH can be used in the clinic to select therapies and determine prognosis and in research to increase the homogeneity of study cohorts...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28089872/identification-of-airway-mucosal-type-2-inflammation-by-clinical-biomarkers-in-asthma
#4
Philip E Silkoff, Michel Laviolette, Dave Singh, J Mark FitzGerald, Steven Kelsen, Vibeke Backer, Celeste M Porsbjerg, Pierre-Olivier Girodet, Patrick Berger, Joel N Kline, Geoffrey Chupp, Vedrana S Susulic, Elliot S Barnathan, Frédéric Baribaud, Matthew J Loza
BACKGROUND AND OBJECTIVE: The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled mild, moderate and severe asthma, and non-atopic healthy controls. We explored this dataset to define Type-2 inflammation based on airway-mucosal IL-13-driven gene expression and how this related to clinically-accessible biomarkers. METHODS: IL-13-driven gene expression was evaluated in several human cell lines. We then defined Type-2 status in 25 healthy subjects, 28 mild, 29 moderate, and 26 severe asthmatics, based on airway-mucosal expression of 1) CC-motif chemokine ligand (CCL)-26, (the most differentially expressed gene), 2) periostin, or 3) a multi-gene IL-13 in-vitro signature (IVS)...
January 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28089081/asthma-chronic-obstructive-pulmonary-disease-overlap-syndrome-literature-review-and-contributions-towards-a-portuguese-consensus
#5
D Araújo, E Padrão, M Morais-Almeida, J Cardoso, F Pavão, R B Leite, A C Caldas, A Marques
INTRODUCTION: Phenotypic overlap between the two main chronic airway pulmonary diseases, asthma and chronic obstructive pulmonary disease (COPD), has been the subject of debate for decades, and recently the nomenclature of asthma-COPD overlap syndrome (ACOS) was adopted for this condition. The definition of this entity in the literature is, however, very heterogeneous, it is therefore important to define how it applies to Portugal. METHODS: A literature review of ACOS was made in a first phase resulting in the drawing up of a document that was later submitted for discussion among a panel of chronic lung diseases experts, resulting in reflexions about diagnosis, treatment and clinical guidance for ACOS patients...
January 6, 2017: Revista Portuguesa de Pneumologia
https://www.readbyqxmd.com/read/28087917/-reasearch-progress-on-the-role-of-neutrophils-in-asthma
#6
Tingting Li, Yuehai Ke, Hongqiang Cheng
Asthma is a phenotypically heterogeneous chronic disease of the airways. Studies have found that neutrophils are crucial to airway inflammation in acute asthma, persistent asthma, particularly in asthma of poor response to glucocorticoid treatment. The role of neutrophils in development of bronchial asthma is complex, as they can release a potent source of cytokines and inflammatory mediators participating in asthma. Differing from eosinophilic inflammatory asthma, neutrophilic inflammatory asthma is not depend on helper T (Th)2 cells, but may be related to Th1 and Th17 cells...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087381/prevalence-risk-factors-and-clinical-outcomes-of-atopic-and-nonatopic-asthma-among-rural-children
#7
Joshua A Lawson, Luan M Chu, Donna C Rennie, Louise Hagel, Chandima P Karunanayake, Punam Pahwa, James A Dosman
BACKGROUND: Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification. OBJECTIVE: To compare atopic and nonatopic asthma in rural children with regard to risk factors and clinical outcomes. METHODS: We conducted a cross-sectional study in rural Saskatchewan, Canada, in 2011...
January 10, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28076986/utilising-exhaled-nitric-oxide-information-to-enhance-diagnosis-and-therapy-of-respiratory-disease-current-evidence-for-clinical-practice-and-proposals-to-improve-the-methodology
#8
Marieann Högman, Lauri Lehtimäki, Anh Tuan Dinh-Xuan
A non-invasive tool to diagnose respiratory diseases and to follow treatment has long been looked-for. Exhaled nitric oxide (NO) is a promising marker of inflammation in asthma but nearly 25-years of research has shown that it works in only certain endotypes of asthma. The modelling of NO dynamics of the lung can give more information than a single FENO value. Areas covered: The estimation of the NO production in the conducting airways and in the gas exchange area has given new insight of the NO production in diseases beyond asthma...
January 11, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28076799/adenylyl-cyclase-type-9-gene-polymorphisms-are-associated-with-asthma-and-allergy-in-brazilian-children
#9
Helena M P Teixeira, Neuza M Alcantara-Neves, Maurício Barreto, Camila A Figueiredo, Ryan S Costa
Asthma is a chronic inflammatory disease of the respiratory tract. This heterogeneous disease is caused by the interaction of interindividual genetic variability and environmental factors. The gene adenylyl cyclase type 9 (ADCY9) encodes a protein called adenylyl cyclase (AC), responsible for producing the second messenger cyclic AMP (cAMP). cAMP is produced by T regulatory cells and is involved in the down-regulation of T effector cells. Failures in cAMP production may be related to an imbalance in the regulatory immune response, leading to immune-mediated diseases, such as allergic disorders...
January 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28070732/the-clinical-and-laboratory-spectrum-of-dedicator-of-cytokinesis-8-immunodeficiency-syndrome-in-patients-with-a-unique-mutation
#10
Arnon Broides, Amarilla B Mandola, Jacov Levy, Baruch Yerushalmi, Vered Pinsk, Michal Eldan, George Shubinsky, Nurit Hadad, Rachel Levy, Amit Nahum, Miriam Ben-Harosh, Atar Lev, Amos Simon, Raz Somech
Mutations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency usually diagnosed as autosomal recessive hyper IgE syndrome. We sought to reveal the varying manifestations in patients with a unique mutation in DOCK8 gene by a retrospective medical record review. Ten patients from five consanguineous families and three tribes were included. Seven patients were homozygous for the c.C5134A, p.S1711X mutation, and the remaining three patients were their siblings manifesting hyper IgE syndrome features without a genetic diagnosis...
January 10, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28069248/race-is-associated-with-differences-in-airway-inflammation-in-patients-with-asthma
#11
Sharmilee M Nyenhuis, Jerry A Krishnan, Alalia Berry, William J Calhoun, Vernon M Chinchilli, Linda Engle, Nicole Grossman, Fernando Holguin, Elliot Israel, Rick A Kittles, Monica Kraft, Stephen C Lazarus, Erik B Lehman, David T Mauger, James N Moy, Stephen P Peters, Wanda Phipatanakul, Lewis J Smith, Kaharu Sumino, Stanley J Szefler, Michael E Wechsler, Sally Wenzel, Steven R White, Steven J Ackerman
BACKGROUND: African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear. OBJECTIVE: We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS-, respectively). METHODS: We performed a secondary analysis of self-identified African American and white subjects with asthma enrolled in clinical trials conducted by the National Heart, Lung, and Blood Institute-sponsored Asthma Clinical Research Network and AsthmaNet...
December 31, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28069025/interaction-of-biomedical-nanoparticles-with-the-pulmonary-immune-system
#12
REVIEW
Fabian Blank, Kleanthis Fytianos, Emilie Seydoux, Laura Rodriguez-Lorenzo, Alke Petri-Fink, Christophe von Garnier, Barbara Rothen-Rutishauser
Engineered nanoparticles (NPs) offer site-specific delivery, deposition and cellular uptake due to their unique physicochemical properties and were shown to modulate immune responses. The respiratory tract with its vast surface area is an attractive target organ for innovative immunomodulatory therapeutic applications by pulmonary administration of such NPs, enabling interactions with resident antigen-presenting cells (APCs), such as dendritic cells and macrophages. Depending on the respiratory tract compartment, e...
January 9, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28068996/non-linear-parameters-of-specific-resistance-loops-to-characterise-obstructive-airways-diseases
#13
Marko Topalovic, Vasileios Exadaktylos, Thierry Troosters, Geert Celis, Jean-Marie Aerts, Wim Janssens
BACKGROUND: Specific resistance loops appear in different shapes influenced by different resistive properties of the airways, yet their descriptive ability is compressed to a single parameter - its slope. We aimed to develop new parameters reflecting the various shapes of the loop and to explore their potential in the characterisation of obstructive airways diseases. METHODS: Our study included 134 subjects: Healthy controls (N = 22), Asthma with non-obstructive lung function (N = 22) and COPD of all disease stages (N = 90)...
January 9, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28065276/using-imaging-as-a-biomarker-for-asthma
#14
REVIEW
Abhaya Trivedi, Chase Hall, Eric A Hoffman, Jason C Woods, David S Gierada, Mario Castro
There have been significant advancements in the various imaging techniques being used for the evaluation of asthmatic patients, both from a clinical and research perspective. Imaging characteristics can be used to identify specific asthmatic phenotypes and provide a more detailed understanding of endotypes contributing to the pathophysiology of the disease. Computed tomography, magnetic resonance imaging, and positron emission tomography can be used to assess pulmonary structure and function. It has been shown that specific airway and lung density measurements using computed tomography correlate with clinical parameters, including severity of disease and pathology, but also provide unique phenotypes...
January 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28063044/characterization-of-group-2-innate-lymphoid-cells-in-allergic-airway-inflammation-models-in-the-mouse
#15
Bobby W S Li, Dior M J M Beerens, Maarten D Brem, Rudi W Hendriks
Allergic asthma is a chronic inflammatory lung disease mediated by type 2 cytokines produced by T helper 2 (Th2) cells as well as the recently discovered group 2 innate lymphoid cells (ILC2). Due to a lack of unique markers, the accurate phenotypic characterization and quantification of ILC2 requires a comprehensive panel of fluorescently labeled antibodies. The markers that are currently used to characterize ILC2 have not been standardized and often vary between research groups, which poses significant challenges when comparing data...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28054016/data-set-on-a-study-of-gene-expression-in-peripheral-samples-to-identify-biomarkers-of-severity-of-allergic-and-nonallergic-asthma
#16
Selene Baos, David Calzada, Lucía Cremades, Joaquín Sastre, Joaquín Quiralte, Fernando Florido, Carlos Lahoz, Blanca Cárdaba
This article contains information related to the research article entitled "Biomarkers associated with disease severity in allergic and nonallergic asthma" (S. Baos, D. Calzada, L. Cremades, J. Sastre, J. Quiralte, F. Florido, C. Lahoz, B. Cárdaba, In press). Specifically, the clinical criteria stablished for selecting the study population (n=104 subjects) are described. Moreover, this article describes the criteria for selecting the 94 genes to be analyzed in PBMCs (peripheral blood mononuclear cells), it is provided a description of these genes and a Table with the genes most differentially expressed by clinical phenotypes and, finally it is detailed the experimental methodology followed for studying the protein expression of MSR1 (macrophage scavenger receptor 1), one of the genes evaluated in the research...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28049124/personalised-medicine-in-asthma-from-curative-to-preventive-medicine
#17
REVIEW
Laurent Guilleminault, Hakima Ouksel, Chantal Belleguic, Yannick Le Guen, Patrick Germaud, Emilie Desfleurs, Christophe Leroyer, Antoine Magnan
The concept of asthma has changed substantially in recent years. Asthma is now recognised as a heterogeneous entity that is complex to treat. The subdivision of asthma, provided by "cluster" analyses, has revealed various groups of asthma patients who share phenotypic features. These phenotypes underlie the need for personalised asthma therapy because, in contrast to the previous approach, treatment must be tailored to the individual patient. Determination of the patient's asthma phenotype is therefore essential but sometimes challenging, particularly in elderly patients with a multitude of comorbidities and a complex exposure history...
January 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28045928/altered-epithelial-gene-expression-in-peripheral-airways-of-severe-asthma
#18
Akul Singhania, Hitasha Rupani, Nivenka Jayasekera, Simon Lumb, Paul Hales, Neil Gozzard, Donna E Davies, Christopher H Woelk, Peter H Howarth
Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2...
2017: PloS One
https://www.readbyqxmd.com/read/28044257/targeted-therapy-for-severe-asthma-identifying-the-right-patients
#19
Kathy Low, Philip G Bardin
Asthma affects over 300 million people worldwide. Most asthmatics are well controlled with inhaled corticosteroids and long-acting beta-agonists; however, a proportion of patients are unresponsive and attain limited disease control. This group represents a considerable healthcare and financial burden, particularly patients who experience frequent exacerbations and require hospital admission. Development of new biological agents and disease biomarkers has provided novel avenues for treatment. These treatments have been highly successful, reducing exacerbations and yielding modest improvements in quality of life and lung function...
January 2, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28036144/revisiting-type-2-high-and-type-2-low-airway-inflammation-in-asthma-current-knowledge-and-therapeutic-implications
#20
Douglas Robinson, Marc Humbert, Roland Buhl, Alvaro A Cruz, Hiromasa Inoue, Stephan Korom, Nicola A Hanania, Parameswaran Nair
Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. Type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems...
December 30, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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