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https://www.readbyqxmd.com/read/28645995/mepolizumab-for-the-treatment-of-severe-eosinophilic-asthma
#1
REVIEW
Mara N Poulakos, Shawna M Cargill, Melissa F Waineo, Allen L Wolford
PURPOSE: Published data on the pharmacology, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety of the interleukin-5 antagonist mepolizumab are reviewed. SUMMARY: Asthma of the eosinophilic phenotype is characterized by persistent eosinophilic airway inflammation promoted primarily by T-helper type 2 cytokines, the key regulator of eosinophils. Patients with severe eosinophilic asthma are burdened by the need to administer high doses of corticosteroids to help manage their symptoms...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28644104/the-association-between-blood-eosinophil-count-and-benralizumab-efficacy-for-patients-with-severe-uncontrolled-asthma-subanalyses-of-the-phase-iii-sirocco-and-calima-studies
#2
Mitchell Goldman, Ian Hirsch, James G Zangrilli, Paul Newbold, Xiao Xu
OBJECTIVE: Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β2-agonists (ICS/LABA) significantly reduced asthma exacerbations, improved lung function, and reduced symptoms for patients with severe, uncontrolled asthma with blood eosinophil counts ≥300 cells/µL in the Phase III SIROCCO and CALIMA studies. To understand the efficacy and safety of benralizumab for patients with eosinophil-driven disease with blood eosinophil counts lower than 300 cells/µL, we evaluated the effect of applying an eosinophil cutoff of ≥150 cells/µL...
June 23, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28641549/relevance-of-cat-and-dog-sensitization-by-skin-prick-testing-in-childhood-eczema-and-asthma
#3
Kam Lun E Lun Hon, Kathy Yin Ching Tsang, Ting Fan Leung
BACKGROUND: Household animal dander has been implicated as aeroallergen in childhood atopic diseases. Many parents seek healthcare advice if household pet keeping may be detrimental in atopic eczema (AE) and atopies. AIM: We investigated if skin sensitization by cat/dog dander was associated with disease severity and quality of life in children with AE. METHODS: Demographics, skin prick test (SPT) results, disease severity (Nottingham eczema severity score NESS), Children Dermatology Life Quality Index (CDLQI), blood IgE and eosinophil counts of a cohort of AE patients were reviewed...
June 14, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28634005/semaphorin-3e-alleviates-hallmarks-of-house-dust-mite-induced-allergic-airway-disease
#4
Hesam Movassagh, Lianyu Shan, Jonathan S Duke-Cohan, Andrew J Halayko, Jude E Uzonna, Abdelilah S Gounni
Semaphorins are an essential family of guidance cues ubiquitously expressed in various organs, which play diverse developmental, homeostatic, and pathological roles. Semaphorin 3E (Sema3E), initially identified as a neuronal chemorepellent, is involved in the regulation of cell migration, proliferation, and angiogenesis. However, expression and function of Sema3E in allergic asthma has not been extensively investigated. We determined the expression of Sema3E in the airways and its effect on airway inflammation, hyperresponsiveness, and remodeling as pathological features of allergic asthma provoked by house dust mite in vivo...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28628664/effects-of-diesel-exhaust-particle-exposure-on-a-murine-model-of-asthma-due-to-soybean
#5
Daniel Alvarez-Simón, Xavier Muñoz, Susana Gómez-Ollés, Miquel de Homdedeu, María-Dolores Untoria, María-Jesús Cruz
BACKGROUND: Exposure to soybean allergens has been linked to asthma outbreaks. Exposure to diesel exhaust particles (DEP) has been associated with an increase in the risk of asthma and asthma exacerbation; however, in both cases the underlying mechanisms remain poorly understood, as does the possible interaction between the two entities. OBJECTIVE: To investigate how the combination of soybean allergens and DEP can affect the induction or exacerbation of asthma in a murine model...
2017: PloS One
https://www.readbyqxmd.com/read/28627361/incorporating-the-airway-microbiome-into-asthma-phenotyping-moving-towards-personalized-medicine-for-non-eosinophilic-asthma
#6
EDITORIAL
J Durack, H A Boushey, Y J Huang
No abstract text is available yet for this article.
June 13, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28626990/exhaled-breath-profiles-in-the-monitoring-of-loss-of-control-and-clinical-recovery-in-asthma
#7
Paul Brinkman, Marianne A van de Pol, Marije G Gerritsen, Lieuwe D Bos, Tamara Dekker, Barbara S Smids, Anirban Sinha, Christof J Majoor, Marlous M Sneeboer, Hugo H Knobel, Teunis J Vink, Frans H de Jongh, René Lutter, Peter J Sterk, Niki Fens
BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography / mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma...
June 19, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#8
Katharina M Quell, Christian M Karsten, Anna Kordowski, Larissa Nogueira Almeida, Daria Briukhovetska, Anna V Wiese, Jing Sun, Fanny Ender, Konstantina Antoniou, Torsten Schröder, Inken Schmudde, Johann L Berger, Peter König, Tillman Vollbrandt, Yves Laumonnier, Jörg Köhl
C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3(-/-) and C3aR(-/-) mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28624608/obesity-s-impact-on-asthma-extends-to-diagnostic-criteria
#9
Njira Lugogo, Cynthia L Green, Noah Agada, Siyi Zhang, Susanne Meghdadpour, Run Zhou, Siyun Yang, Kevin J Anstrom, Elliot Israel, Richard Martin, Robert F Lemanske, Homer Boushey, Stephen C Lazarus, Stephen I Wasserman, Mario Castro, William Calhoun, Stephen P Peters, Emily DiMango, Vernon Chinchilli, Nikolina Icitovic, Susan Kunselman, Tonya S King, Monica Kraft
BACKGROUND: The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthma is increasingly common. However, the impact of obesity on these markers is unknown. OBJECTIVES: We aimed to determine the impact of obesity on conventional markers of inflammation in asthma. METHODS: We performed secondary analysis of data from 652 patients previously enrolled in two ACRN trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE, blood eosinophils and FeNO in relationship to sputum eosinophils (>2%), as well as to determine if cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the three weight groups...
June 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28624607/obese-asthmatics-have-decreased-surfactant-protein-a-levels-mechanisms-and-implications
#10
Njira Lugogo, Dave Francisco, Kenneth J Addison, Akarsh Manne, William Pederson, Jennifer L Ingram, Cynthia L Green, Benjamin T Suratt, James J Lee, Mary E Sunday, Monica Kraft, Julie G Ledford
BACKGROUND: Eosinophils are prominent in some individuals with asthma and are elevated in the submucosa in a subgroup of obese asthmatics. Surfactant protein-A (SP-A) modulates host responses to infectious and environmental insults. OBJECTIVE: To determine if SP-A levels are altered in obese asthma patients compared to a control group and to determine the implications of these alterations in SP-A levels in asthma. METHODS: Bronchoalveolar lavage fluid from 23 lean, 12 overweight and 20 obese subjects were examined for SP-A...
June 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28620605/regulation-of-eosinophil-recruitment-and-activation-by-galectins-in-allergic-asthma
#11
REVIEW
Savita P Rao, Xiao Na Ge, P Sriramarao
Eosinophils are differentiated granulocytes that are recruited from the bone marrow to sites of inflammation via the vascular system. Allergic asthma is characterized by the presence of large numbers of eosinophils in the lungs and airways. Due to their capacity to rapidly release inflammatory mediators such as cytokines, chemokines, growth factors, and cytotoxic granule proteins upon stimulation, eosinophils play a critical role in pro-inflammatory processes in allergen-exposed lungs. Identifying key players and understanding the molecular mechanisms directing eosinophil trafficking and recruitment to inflamed airways is a key to developing therapeutic strategies to limit their influx...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28616286/severe-and-uncontrolled-asthma-in-china-a-cross-sectional-survey-from-the-australasian-severe-asthma-network
#12
Gang Wang, Fang Wang, Peter G Gibson, Michael Guo, Wei-Jie Zhang, Peng Gao, Hong-Ping Zhang, Erin S Harvey, Hui Li, Jie Zhang
BACKGROUND: Severe asthma is largely unexplored in the Chinese population. Patients with asthma underwent systematic evaluation, by investigating the characteristics of uncontrolled asthma and of asthma treated with three different controller therapies. METHODS: This multi-centre, real-world study was conducted from March 2014 to September 2015. Adults with stable asthma underwent assessment of medication use, asthma control, quality of life, psychological symptoms, work productivity and activity impairment, bronchodilator response and sputum induction...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28614923/-serum-levels-of-periostin-and-their-influencing-factors-in-the-beta-lactam-antibiotic-enterprise-workers
#13
S S Gao, Z S Song, Q Jia, X Li, C L Li, X W Chen, C B Zheng
Objective: To observe serum levels of periostin, ECP, IgE in the antibiotic enterprise workers, and study the role of periostin, ECP, IgE in the development of allergic inflammation. Methods: 90 cases with asthma or rhinitis were enrolled as disease group, another 117 workers exposed to 7-ACA、6-APA dust without suffering from allergic illness, are chosen as group of dust exposed, and 192 healthy workers who didn't contact dust were chosen as control group. Questionnaires were used to learn their basic information...
April 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28614630/prevalence-of-atopic-disease-in-patients-with-eosinophilic-esophagitis
#14
Michael S Benninger, Madeleine Strohl, Chantal E Holy, Andrea L Hanick, Paul C Bryson
BACKGROUND: The objective of this work was to evaluate prevalence of eosinophilic esophagitis (EoE) in the United States, and analyze prevalence of atopic disease in patients with EoE. The study design was a retrospective administrative database analysis in U.S.-based outpatient settings. METHODS: A retrospective claims analysis in the inpatient and outpatient setting (using MarketScan) was conducted to analyze prevalence of atopic disease diagnoses in patients with EoE in 2012, and timing of those diagnoses vs EoE...
June 14, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28612233/targeting-the-pgd2-crth2-dp1-signaling-pathway-in-asthma-and-allergic-disease-current-status-and-future-perspectives
#15
Maciej Kupczyk, Piotr Kuna
Prostaglandin D2 (PGD2) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD2 are mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th2) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th2-type cytokines (interleukin [IL]-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils...
June 13, 2017: Drugs
https://www.readbyqxmd.com/read/28610668/evaluation-of-the-psychometric-properties-of-the-st-george-s-respiratory-questionnaire-in-patients-with-severe-asthma
#16
Linda M Nelsen, Margaret Vernon, Hector Ortega, Sarah M Cockle, Steven W Yancey, Guy Brusselle, Frank C Albers, Paul W Jones
PURPOSE: Limited data exist on the quantitative validity of the St George's Respiratory Questionnaire (SGRQ) in asthma populations. This study evaluated the psychometric properties of the SGRQ in patients with severe asthma. METHODS: This was a post-hoc analysis of pooled data from MENSA (N = 576; NCT01691508) and SIRIUS (N = 135; NCT01691521), two randomized, placebo controlled trials of mepolizumab in patients with severe asthma. Patients completed the SGRQ at Baseline and Exit (MENSA Week 32; SIRIUS Week 24)...
July 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28609567/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-the-novel-crth2-antagonist-bi-1021958-at-single-oral-doses-in-healthy-men-and-multiple-oral-doses-in-men-and-women-with-well-controlled-asthma
#17
Andy Fowler, Rüdiger Koenen, James Hilbert, Jon Blatchford, Dominik Kappeler, Ewald Benediktus, Chester Wood, Abhya Gupta
BI 1021958, a novel antagonist of the chemoattractant-receptor-homologous molecule (CRTH2), targets airway inflammation in asthma by inhibiting prostaglandin binding to CRTH2 receptors. Two phase 1 studies assessed BI 1021958 safety/tolerability and pharmacokinetics (PK)/pharmacodynamics (PD) following single doses in healthy men and multiple doses in men/women with well-controlled asthma. Studies 1 had 2 parts: a placebo-controlled, fixed-sequence, single-blind, single-rising-dose part (n = 56) and a randomized, 2-way crossover, open-label, repeated-dose part studying the food effect on PK/PD (n = 12)...
June 13, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28608279/the-recombinant-fusion-protein-of-cholera-toxin-b-and-neutrophil-activating-protein-expressed-on-bacillus-subtilis-spore-surface-suppresses-allergic-inflammation-in-mice
#18
Hui Dong, Yanmei Huang, Shuwen Yao, Bingshao Liang, Yan Long, Yongqiang Xie, Jialiang Mai, Sitang Gong, Zhenwen Zhou
The neutrophil-activating protein of Helicobacter pylori (HP-NAP) has been identified as a modulator with anti-Th2 inflammation activity, and cholera toxin B (CTB) is a mucosal adjuvant that can also induce antigen tolerance. In this study, we constructed a CTB-NAP fusion protein on the surface of Bacillus subtilis spore and evaluate the efficiency of oral administration of the recombinant CTB-NAP spores in preventing asthma in mice. Oral administration of recombinant CTB or CTB-NAP spores significantly decreased serum ovalbumin (OVA)-specific IgE (p < 0...
June 12, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28606589/regulatory-effects-of-interleukin-il-15-on-allergen-induced-airway-obstruction
#19
Sathisha Upparahalli Venkateshaiah, Xiang Zhu, Priya Rajavelu, Rituraj Niranjan, Murli Manohar, Alok K Verma, Joseph A Lasky, Anil Mishra
BACKGROUND: Airway obstruction is a physiologic feature of asthma and IL-15 may have an important role in the pathogenesis of asthma. OBJECTIVE: We tested the hypothesis that regulation of IL-15 is critical for the preservation of allergen-induced airway hyperresponsiveness (AHR), airway resistance and compliance in response to methacholine. METHODS: Airway inflammation, AHR, resistance and compliance were assessed in IL-15- gene deficient mice and IL-15 overexpressing mice in an allergen-induced murine model of asthma...
June 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28605217/differences-between-preschoolers-with-asthma-and-allergies-in-urban-and-rural-environments
#20
Daniel A Marfortt, Dario Josviack, Alejandro Lozano, Eduardo Cuestas, Luis Agüero, Jose A Castro-Rodriguez
OBJECTIVE: The influence of living in a rural or urban environment on asthma and allergic diseases in school-children provide conflicting results; moreover none of these studies included exclusively preschoolers. The aim of the present study was to evaluate if recurrent wheezing preschoolers from rural or urban areas differ in asthma, allergic diseases, and atopy. METHODS: A cross-sectional-study in Rafaela, Argentina, on 143 preschoolers with recurrent wheezing from rural and urban settings was performed (2010-2012)...
June 12, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
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