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https://www.readbyqxmd.com/read/27931975/identification-of-il-17f-frequent-exacerbator-endotype-in-asthma
#1
Fabio L M Ricciardolo, Valentina Sorbello, Anna Folino, Fabio Gallo, Gian Mario Massaglia, Gabriella Favatà, Salvatore Conticello, Davide Vallese, Federica Gani, Mario Malerba, Gert Folkerts, Giovanni Rolla, Mirella Profita, Thais Mauad, Antonino Di Stefano, Giorgio Ciprandi
BACKGROUND: Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies. OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics in relation to exacerbation rate. METHODS: Inflammatory cells and IL-17A(+), IL-17F(+), IL-21(+), IL-22(+) and IL-23(+) cells were examined by immunohistochemistry (IHC) in cryostat sections of bronchial/nasal biopsies obtained from 33 SA (21 frequent exacerbators (FE)), 31 MA (3 FE) and 14 controls...
December 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27930984/bone-marrow-mesenchymal-stem-cells-and-their-conditioned-media-could-potentially-ameliorate-ovalbumin-induced-asthmatic-changes
#2
Mahdi Ahmadi, Reza Rahbarghazi, Mohammad Reza Aslani, Amir-Ali Shahbazfar, Masoumeh Kazemi, Rana Keyhanmanesh
BACKGROUND: The major feature of asthma is governed by chronic airway inflammation. This investigation was proposed to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. METHODS: 36 rats were classified into healthy (C) and ovalbumin (OVA)-sensitized animals (S). To sensitize, the rats were exposed to OVA over a course of 32±1days. One day after sensitization, equal six different groups were subjected to experimental procedure (n=6); Rats only received intratracheally 50ml PBS (CPT and SPT groups), 50μl conditioned medium (CM) (CST and SST groups) and 50μl PBS containing 2×10(6) rat bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCT and SCT groups)...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27928844/glucagon-like-peptide-1-receptor-expression-on-human-eosinophils-and-its-regulation-of-eosinophil-activation
#3
Patrick D Mitchell, Brittany M Salter, John Paul Oliveria, Amani El-Gammal, Damian Tworek, Steve G Smith, Roma Sehmi, Gail M Gauvreau, Marcus Butler, Paul M O'Byrne
BACKGROUND: Glucagon Like Peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones the regulate glucose metabolism. GLP-1 also has immune modulatory roles. OBJECTIVES: To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 analog on eosinophil function. METHODS: Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects...
December 8, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27923549/assessing-the-value-of-mepolizumab-for-severe-eosinophilic-asthma-a-cost-effectiveness-analysis
#4
Melanie D Whittington, R Brett McQueen, Daniel A Ollendorf, Jeffrey A Tice, Richard H Chapman, Steven D Pearson, Jonathan D Campbell
BACKGROUND: Adding mepolizumab to standard treatment with inhaled corticosteroids and controller medications could decrease asthma exacerbations and use of long-term oral steroids in patients with severe disease and increased eosinophils; however, mepolizumab is costly and its cost effectiveness is unknown. OBJECTIVE: To estimate the cost effectiveness of mepolizumab. METHODS: A Markov model was used to determine the incremental cost per quality-adjusted life year (QALY) gained for mepolizumab plus standard of care (SoC) and for SoC alone...
December 3, 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27922751/new-therapies-for-asthma-and-copd
#5
Nicholas J Gross, Peter J Barnes
Asthma and COPD (chronic obstructive pulmonary disease) are two common diseases for which current treatments are less than optimal and for which new drugs are greatly needed. Better understanding of the cellular and molecular mechanisms of these diseases has identified new targets for therapy and several new drugs are in development. Although most new treatments on the market are improvements in existing classes of drug or new combination of treatments, the clinicaltrials.gov website indicates 50 and 100 new medications for both asthma and COPD and many of these are entirely new...
December 6, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27922744/lung-pathologies-in-a-chronic-inflammation-mouse-model-are-independent-of-eosinophil-degranulation
#6
Elizabeth A Jacobsen, Sergei I Ochkur, Alfred D Doyle, William E LeSuer, Wen Li, Cheryl A Protheroe, Dana Colbert, Katie R Zellner, HuaHao H Shen, Charles G Irvin, James J Lee, Nancy A Lee
RATIONALE: The release of eosinophil granule proteins in the lungs of asthma patients has been dogmatically linked with lung remodeling and airway hyperresponsiveness (AHR). However, the demonstrated inability of established mouse models to display the eosinophil degranulation occurring in human subjects has prevented a definitive in vivo test of this hypothesis. OBJECTIVES: To demonstrate in vivo causative links between induced pulmonary histopathologies/lung dysfunction and eosinophil degranulation...
December 6, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27916272/regulation-and-function-of-anaphylatoxins-and-their-receptors-in-allergic-asthma
#7
Yves Laumonnier, Anna V Wiese, Julia Figge, Christian Karsten
Allergic asthma is a disease of the airways driven by maladaptive T helper 2 (Th2) and Th17 immune response against harmless, airborne substances. The hallmarks of this disease are airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Distinct dendric cell (DC) subsets together with airway epithelial and pulmonary vascular endothelial cells play critical roles in allergen sensing and in driving T cell differentiation towards Th2 and Th17 effector or regulatory T cells (Treg)...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27913422/factor-xi-deficiency-enhances-the-pulmonary-allergic-response-to-house-dust-mite-in-mice-independent-of-factor-xii
#8
Ingrid Stroo, Jack Yang, Johannes Daan de Boer, Joris J T H Roelofs, Cornelis van 't Veer, Francis J Castellino, Sacha Zeerleder, Tom van der Poll
Asthma is associated with activation of coagulation in the airways. The coagulation system can be initiated via the extrinsic tissue factor dependent pathway or via the intrinsic pathway, in which the central player factor XI (FXI) can be either activated via active factor XII (FXIIa) or via thrombin. We aimed to determine the role of the intrinsic coagulation system, and its possible route of activation, in allergic lung inflammation induced by the clinically relevant human allergen house dust mite (HDM). Wild-type (WT), FXI knockout (KO) and FXII KO mice were subjected to repeated exposure to HDM via the airways, and inflammatory responses were compared...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27908911/biological-treatment-is-approved-for-severe-eosinophilic-asthma
#9
Susan Mayor
No abstract text is available yet for this article.
November 30, 2016: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/27906698/ige-and-eosinophils-as-therapeutic-targets-in-asthma
#10
Tanvi R Patel, Sanjiv Sur
PURPOSE OF REVIEW: Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively...
November 30, 2016: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27904530/blockade-of-il-23-ameliorates-allergic-lung-inflammation-via-decreasing-the-infiltration-of-tc17-cells
#11
Sheng Cheng, Huilong Chen, Aili Wang, Hansvin Bunjhoo, Yong Cao, Jungang Xie, Yongjian Xu, Weining Xiong
INTRODUCTION: Tc17 cells are interleukin (IL)-17-producing CD8(+) T cells and have been found to participate in the development of allergic asthma. Interleukin-23 is a cytokine that may be involved in modulating the IL-17 response via Th17 cells. This study aimed to investigate whether IL-23 also has immunomodulatory effects on Tc17 cells. MATERIAL AND METHODS: An allergic asthmatic mouse model was induced by sensitizing and challenging with ovalbumin (OVA). Anti-IL-23 antibody was administered intratracheally before challenge to the OVA-induced asthmatic mouse model...
December 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27903737/allergen-induced-cd4-t-cell-cytokine-production-within-airway-mucosal-dendritic-cell-t-cell-clusters-drives-the-local-recruitment-of-myeloid-effector-cells
#12
Tibor Z Veres, Tamás Kopcsányi, Nicholas van Panhuys, Michael Y Gerner, Zhiduo Liu, Pia Rantakari, Johannes Dunkel, Masayuki Miyasaka, Marko Salmi, Sirpa Jalkanen, Ronald N Germain
Allergic asthma develops in the mucosal tissue of small bronchi. At these sites, local cytokine production by Th2/Th17 cells is believed to be critical for the development of tissue eosinophilia/neutrophilia. Using the mouse trachea as a relevant model of human small airways, we performed advanced in vivo dynamic and in situ static imaging to visualize individual cytokine-producing T cells in the airway mucosa and to define their immediate cellular environment. Upon allergen sensitization, newly recruited CD4(+) T cells formed discrete Ag-driven clusters with dendritic cells (DCs)...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27902981/calcitriol-reduces-eosinophil-necrosis-which-leads-to-the-diminished-release-of-cytotoxic-granules
#13
Caroline Ethier, Yingqi Yu, Lisa Cameron, Paige Lacy, Francis Davoine
BACKGROUND: Asthma severity and eosinophilia correlate with a deficiency in vitamin D and its active metabolite calcitriol. Calcitriol modulates numerous leukocyte functions, but its effect on eosinophils is not fully understood. We postulated that calcitriol exerts a direct effect on eosinophil biology by modulating cell survival. METHODS: Purified peripheral blood eosinophils from atopic donors were incubated in the presence of calcitriol for up to 14 days with or without IL-5...
December 1, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27899427/a-56-year-old-woman-with-breathlessness
#14
Alastair J Moss, Marc R Dweck, Peter D O'Kane
CLINICAL INTRODUCTION: A 56-year-old female with adult-onset asthma was admitted to the cardiology service with intermittent left-sided chest pain and progressive dyspnoea. Twelve months prior to this admission, she had received a course of prednisolone for bilateral anterior uveitis. Physical examination was unremarkable with blood sampling revealing a marked eosinophilia (eosinophil count 17.3×10(9)/L) and a perinuclear antineutrophil cytoplasmic antibody staining pattern on indirect immunofluorescence microscopy (myeloperoxidase antibodies 83 IU/mL)...
November 29, 2016: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/27899011/nasal-lavage-blood-or-sputum-which-is-best-for-phenotyping-asthma
#15
Camyla F de Farias, Maria M F Amorim, Michel Dracoulakis, Lilian B Caetano, Ilka L Santoro, Ana L G Fernandes
BACKGROUND AND OBJECTIVE: Determination of asthma phenotypes, particularly inflammatory phenotypes, helps guide treatment and management of this heterogeneous disease. Induced sputum cytology has been the gold standard for determination of inflammatory phenotypes, but sputum induction is fairly invasive and technically challenging. Blood and nasal lavage cytology have been suggested as substitutes, but have not been fully verified. The aim of this study is to determine the accuracy of blood and nasal lavage cytometry as indicators of inflammatory phenotypes in asthma...
November 29, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27895167/pgi2-controls-pulmonary-nk-cells-that-prevent-airway-sensitization-to-house-dust-mite-allergen
#16
Bryan Simons, Maria E Ferrini, Sophia Carvalho, David J P Bassett, Zeina Jaffar, Kevan Roberts
In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI2 and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e., PGI2 IP receptor-deficient [IP(-/-)]) were compared with wild type (WT) mice. Surprisingly, IP(-/-) mice had increased numbers of pulmonary CD3(-)NK1.1(+)Ly49b(+) NK cells producing IFN-γ that was inversely associated with the number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Rα and IL-13 compared with WT animals...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27889561/inhibition-of-interleukin-5-induced-false-positive-anti-drug-antibody-responses-against-mepolizumab-through-the-use-of-a-competitive-blocking-antibody
#17
Karen Liao, Erik Meyer, Thomas N Lee, Amy Loercher, Daniel Sikkema
Mepolizumab, a humanized IgG1 monoclonal antibody that blocks native homodimeric interleukin-5 (IL-5) from binding to the IL-5 receptor, has recently been approved for treatment of severe eosinophilic asthma. Our initial immunogenicity assay method for phase I and II studies utilized a bridging electrochemiluminescence format with biotin and ruthenium-labelled mepolizumab linked by anti-drug antibodies (ADA). We discovered that IL-5 significantly increased in dosed subjects from a phase II study and that the increased IL-5 was in the form of a drug-bound complex...
November 24, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27886852/-cold-air-and-or-talking-as-cough-triggers-a-sign-for-the-diagnosis-of-cough-variant-asthma
#18
Yoshihiro Kanemitsu, Hisako Matsumoto, Nuriamina Osman, Tsuyoshi Oguma, Tadao Nagasaki, Yumi Izuhara, Isao Ito, Tomoko Tajiri, Toshiyuki Iwata, Akio Niimi, Michiaki Mishima
BACKGROUND: Fractional exhaled nitric oxide (FeNO) is considered an alternative marker of eosinophilic airway inflammation and is sometimes incorporated in the diagnosis of asthma. However, many patients with cough variant asthma (CVA) demonstrate an FeNO in the normal range. Therefore, additional information is needed to confirm the diagnosis of CVA, particularly in patients with low FeNO levels. We aimed to investigate the feasibility of using cough triggers to help diagnose CVA. METHODS: We studied 163 patients presenting with prolonged/chronic cough alone (including 104 CVA patients) who underwent FeNO measurements and an airway responsiveness test, and answered a questionnaire listing 18 cough triggers...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27885827/a-mathematical-modeling-approach-to-understanding-the-effect-of-anti-interleukin-therapy-on-eosinophils
#19
T Karelina, V Voronova, O Demin, G Colice, B M Agoram
Emerging T-helper type 2 (Th2 ) cytokine-based asthma therapies, such as tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL-5), have shown differences in their blood eosinophil (EOS) response. To better understand these effects, we developed a mathematical model of EOS dynamics. For the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an increase of 30% and 10% in total and activated EOS in the blood, respectively, and a decrease in the total and activated EOS in the airways...
November 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27883241/neutrophil-autophagy-and-extracellular-dna-traps-contribute-to-airway-inflammation-in-severe-asthma
#20
Duy Le Pham, Ga-Young Ban, Seung-Hyun Kim, Yoo Seob Shin, Young-Min Ye, Yong-Joon Chwae, Hae-Sim Park
BACKGROUND: Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. OBJECTIVES: We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs)...
November 24, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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