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https://www.readbyqxmd.com/read/28212463/efficacy-and-tolerability-of-an-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-in-copd-patients-phase-ii-study-results
#1
Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28211191/cigarette-smoking-increases-bronchial-mucosal-il-17a-expression-in-asthmatics-which-acts-in-concert-with-environmental-aeroallergens-to-engender-neutrophilic-inflammation
#2
Leonard Quok Chean Siew, Shih-Ying Wu, Sun Ying, Christopher John Corrigan
BACKGROUND: Mild asthmatics who smoke cigarettes may develop unstable disease and neutrophilic infiltration of the airways, features more usually associated with severe asthmatic disease. The mechanisms giving rise to this response remain unclear. OBJECTIVE: To address the hypothesis that smoking increases bronchial mucosal production of IL-17A which acts on bronchial epithelial cells directly and in concert with other environmental stimuli to induce the production of IL-6 and neutrophil chemotaxins...
February 17, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28209625/association-of-blood-eosinophil-and-blood-neutrophil-counts-with-asthma-exacerbations-in-the-copenhagen-general-population-study
#3
Signe Vedel-Krogh, Sune Fallgaard Nielsen, Peter Lange, J Rgen Vestbo, B Rge Gr Nne Nordestgaard
BACKGROUND: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS: From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma...
February 16, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28208871/clinical-utility-of-fractional-exhaled-nitric-oxide-feno-as-a-biomarker-to-predict-severity-of-disease-and-response-to-inhaled-corticosteroid-ics-in-asthma-patients
#4
Revathy Neelamegan, Vinodkumar Saka, Kadhiravan Tamilarasu, Manju Rajaram, Sandhiya Selvarajan, Adithan Chandrasekaran
INTRODUCTION: Bronchial asthma is a common chronic inflammatory airway disease diagnosed and is based on symptomatic history and Pulmonary Function Tests (PFT). Fractional exhaled Nitric Oxide (FeNO) is exclusively a non-invasive biomarker of on-going eosinophilic airway inflammation which remains unpredictable only with PFTs. FeNO measurement is recommended in predicting asthma severity and Inhaled Corticosteroid (ICS) response but further research is required to understand its clinical utility and agreement with current recommendations in a specific population...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28207927/attenuated-airway-hyperresponsiveness-and-mucus-secretion-in-hdm-exposed-igf1r-deficient-mice
#5
S Piñeiro-Hermida, J A Gregory, I P López, R Torrens, C Ruíz-Martínez, M Adner, J G Pichel
BACKGROUND: Asthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR) and inflammation. IGFs have been reported to play a role in asthma but little is known about how the Insulin-like Growth Factor 1 Receptor (IGF1R) affects asthma pathobiology. METHODS: Female Igf1r-deficient and control mice were intranasally challenged with house dust mite (HDM) extract or PBS five days per week for four weeks. Lung function measurements, and bronchioalveolar lavage fluid (BALF), serum and lungs were collected on day 28 for further cellular, histological and molecular analysis...
February 16, 2017: Allergy
https://www.readbyqxmd.com/read/28205598/lyn-regulates-mucus-secretion-and-muc5ac-via-the-stat6-signaling-pathway-during-allergic-airway-inflammation
#6
Xiaoyun Wang, Yin Li, Deyu Luo, Xing Wang, Yun Zhang, Zhigang Liu, Nanshan Zhong, Min Wu, Guoping Li
Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203435/recent-developments-in-the-role-of-reactive-oxygen-species-in-allergic-asthma
#7
REVIEW
Jingjing Qu, Yuanyuan Li, Wen Zhong, Peisong Gao, Chengping Hu
Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28202124/-effect-of-heat-shock-factor-1-on-airway-hyperresponsiveness-and-airway-inflammation-in-mice-with-allergic-asthma
#8
Jing Wang, Li-Hong Xin, Wei Cheng, Zhen Wang, Wen Zhang
OBJECTIVE: To investigate the effect of heat shock factor 1 (HSF1) on airway hyperresponsiveness and airway inflammation in mice with asthma and possible mechanisms. METHODS: A total of 36 mice were randomly divided into four groups: control, asthma, HSF1 small interfering RNA negative control (siHSF1-NC), and siHSF1 intervention (n=9 each). Ovalbumin (OVA) sensitization and challenge were performed to induce asthma in the latter three groups. The mice in the siHSF1-NC and siHSF1 groups were treated with siHSF1-NC and siHSF1, respectively...
February 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28198394/cockroach-protease-allergen-induces-allergic-airway-inflammation-via-epithelial-cell-activation
#9
Sagar L Kale, Komal Agrawal, Shailendra Nath Gaur, Naveen Arora
Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197964/up-regulated-exosomal-mirna-140-3p-in-cml-patients-with-musculoskeletal-pain-associated-with-discontinuation-of-tyrosine-kinase-inhibitors
#10
Michiyo Asano, Tomohiro Umezu, Seiichiro Katagiri, Chiaki Kobayashi, Tetsuzo Tauchi, Moritaka Gotoh, Keiko Ando, Seiichi Okabe, Junko H Ohyashiki, Kazuma Ohyashiki
We analyzed the exosomal miRNA from peripheral blood from CML patients with musculoskeletal pain after stopping tyrosine kinase inhibitors to identify possible factors related to this manifestation. Exosomal miRNA profiling using TaqMan low-density array revealed that exosomal miR-140-3p was significantly elevated in CML patients showing musculoskeletal pain, when compared to those without such pain (P = 0.0336) or healthy individuals (P = 0.0022). All five CML patients with musculoskeletal pain and increased exosomal miR-140-3p levels sustained deep molecular responses: four of them achieved symptom relief and a significant decrease in exosomal miR-140-3p levels was evident...
February 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28196763/il-33-dysregulates-regulatory-t-treg-cells-and-impairs-established-immunological-tolerance-in-the-lungs
#11
Chien-Chang Chen, Takao Kobayashi, Koji Iijima, Fan-Chi Hsu, Hirohito Kita
BACKGROUND: Airway exposure to environmental antigens generally leads to immunological tolerance. A fundamental question remains: why is airway tolerance compromised in patients with allergic airway diseases? Interleukin (IL)-33 promotes innate and adaptive type 2 immunity and may provide the answer to this question. OBJECTIVE: The goal of this study was to investigate the roles IL-33 plays in altering regulatory T (Treg) cells in the lungs and in affecting previously established airway immunological tolerance...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28196638/japanese-guidelines-for-adult-asthma-2017
#12
REVIEW
Masakazu Ichinose, Hisatoshi Sugiura, Hiroyuki Nagase, Masao Yamaguchi, Hiromasa Inoue, Hironori Sagara, Jun Tamaoki, Yuji Tohda, Mitsuru Munakata, Kohei Yamauchi, Ken Ohta
Adult bronchial asthma is characterized by chronic airway inflammation, and presents clinically with variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma induces airway remodeling, leading to intractable asthma. The number of patients with asthma has increased; however, the number of patients who die of asthma has decreased (1.2 per 100,000 patients in 2015). The goal of asthma treatment is to enable patients with asthma to attain normal pulmonary function and lead a normal life, without any symptoms...
February 11, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28195747/do-aging-factors-influence-the-clinical-presentation-and-management-of-chronic-rhinosinusitis
#13
Axel E Renteria, Leandra Mfuna Endam, Martin Desrosiers
Objective/Hypothesis Chronic rhinosinusitis (CRS) is a complex inflammatory disease of the upper respiratory airways resulting from the dysregulation of immunity and epithelial defenses. More recently, the contribution of an altered nasal microbiome to the development of CRS has also been proposed. However, the impact of aging on the development of CRS has been long overlooked. Here we propose, in a hypothesis piece, that aging can influence the physiopathology of CRS and its subsequent management in an elderly population...
February 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28195657/pulmonary-function-and-airway-inflammation-among-dairy-parlor-workers-after-exposure-to-inhalable-aerosols
#14
Matthew W Nonnenmann, David Gimeno Ruiz de Porras, Jeffrey Levin, David Douphrate, Vijay Boggaram, Joshua Schaffer, Michael Gallagher, Madeleine Hornick, Stephen Reynolds
BACKGROUND: Inhalation exposure to organic dust causes lung inflammation among agricultural workers. Due to changes in production and work organization, task-based inhalation exposure data, including novel lung inflammation biomarkers, will inform exposure recommendations for dairy farm workers. METHODS: Linear regression was used to estimate the associations of airborne exposure to dust concentration, endotoxin, and muramic acid with pulmonary outcomes (i.e., FEV1 , exhaled nitric oxide)...
March 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28195210/cigarette-smoke-attenuates-phagocytic-ability-of-macrophages-through-down-regulating-milk-fat-globule-egf-factor-8-mfg-e8-expressions
#15
Yueqin Wang, Guangwei Luo, Jie Chen, Rui Jiang, Jianhua Zhu, Na Hu, Wei Huang, Guilian Cheng, Min Jia, Bingtao Su, Nian Zhang, Tianpen Cui
Chronic obstructive pulmonary disease (COPD) is one of the most common inflammatory diseases resulting from habitual smoking. Impaired clearance of apoptotic cell by airway macrophages contributes to lung inflammation. Milk fat globule-EGF factor 8 (MFG-E8), as a link between apoptotic cells and phagocytes, facilitates clearance of apoptotic cells and attenuates inflammation. We sought to investigate altered expression and potential role of MFG-E8 in COPD. In this study, apoptosis was increased and the level of MFG-E8 was decreased while HMGB1 expression was increased in lung tissues of CS-exposed mice...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194607/il-17a-monoclonal-antibody-partly-reverses-the-glucocorticoids-insensitivity-in-mice-exposed-to-ozonec
#16
Xia Fei, Peng-Yu Zhang, Xue Zhang, Guo-Qing Zhang, Wu-Ping Bao, Ying-Ying Zhang, Min Zhang, Xin Zhou
Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0...
February 13, 2017: Inflammation
https://www.readbyqxmd.com/read/28194433/mitochondrial-camkii-inhibition-in-airway-epithelium-protects-against-allergic-asthma
#17
Sara C Sebag, Olha M Koval, John D Paschke, Christopher J Winters, Omar A Jaffer, Ryszard Dworski, Fayyaz S Sutterwala, Mark E Anderson, Isabella M Grumbach
Excessive ROS promote allergic asthma, a condition characterized by airway inflammation, eosinophilic inflammation, and increased airway hyperreactivity (AHR). The mechanisms by which airway ROS are increased and the relationship between increased airway ROS and disease phenotypes are incompletely defined. Mitochondria are an important source of cellular ROS production, and our group discovered that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is present in mitochondria and activated by oxidation...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28192144/maternal-house-dust-mite-exposure-during-pregnancy-enhances-severity-of-hdm-induced-asthma-in-murine-offspring
#18
Phoebe K Richgels, Amnah Yamani, Claire A Chougnet, Ian P Lewkowich
BACKGROUND: Atopic status of the mother and maternal exposure to environmental factors is associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens like house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development...
February 9, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28191699/ndrg1-is-important-to-maintain-the-integrity-of-airway-epithelial-barrier-through-claudin-9-expression
#19
Yasuhiro Gon, Shuichiro Maruoka, Hiroyuki Kishi, Yutaka Kozu, Kuroda Kazumichi, Yasuyuki Nomura, Ikuko Takeshita, Takeshi Oshima, Shu Hashimoto
Impairment of epithelial barrier integrity caused by environmental triggers is associated with the pathogenesis of airway inflammation. Using human airway epithelial cells, we attempted to identify molecule(s) that promote airway epithelial barrier integrity. Microarray analyses were conducted using the Affimetrix human whole genome gene chip, and we identified the N-myc downstream-regulated gene 1 (NDRG1) gene, which was induced during the development of the epithelial cell barrier. Immunohistochemical analysis revealed strong NDRG1 expression in ciliated epithelial cells in nasal tissues sampled from patients with chronic rhinosinusitis (CRS), and the low expression of NDRG1 was observed in goblet cells or damaged epithelial cells...
February 13, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28191362/the-anti-inflammatory-effect-of-alpha-1-antitrypsin-in-rhinovirus-infected-human-airway-epithelial-cells
#20
Di Jiang, Reena Berman, Qun Wu, Connor Stevenson, Hong Wei Chu
OBJECTIVE: Excessive airway inflammation is seen in chronic obstructive pulmonary disease (COPD) patients experiencing acute exacerbations, which are often associated with human rhinovirus (HRV) infection. Alpha-1 antitrypsin (A1AT) has anti-inflammatory function in endothelial cells and monocytes, but its anti-inflammatory effect has not been investigated in COPD airway epithelial cells. We determined A1AT's anti-inflammatory function in COPD airway epithelial cells and the underlying mechanisms such as the role of caspase-1...
December 2016: Journal of Clinical & Cellular Immunology
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