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Glucocorticoid asthma

Alisa M Gorbacheva, Dmitry V Kuprash, Nikita A Mitkin
Interleukin 33 (IL-33) is a cytokine constitutively expressed by various cells of barrier tissues that contribute to the development of inflammatory immune responses. According to its function as an alarmin secreted by lung and airway epithelium, IL-33 plays a significant role in pathogenesis of allergic disorders. IL-33 is strongly involved in the pathogenesis of asthma, anaphylaxis, allergy and dermatitis, and genetic variations in IL33 locus are associated with increased susceptibility to asthma. Genome-wide association studies have identified risk "T" allele of the single-nucleotide polymorphism rs4742170 located in putative IL33 enhancer area as susceptible variant for development of specific wheezing phenotype in early childhood...
December 9, 2018: International Journal of Molecular Sciences
Carlo C Campa, Rangel L Silva, Jean P Margaria, Tracey Pirali, Matheus S Mattos, Lucas R Kraemer, Diego C Reis, Giorgio Grosa, Francesca Copperi, Eduardo M Dalmarco, Roberto C P Lima-Júnior, Silvio Aprile, Valentina Sala, Federica Dal Bello, Douglas Silva Prado, Jose Carlos Alves-Filho, Claudio Medana, Geovanni D Cassali, Gian Cesare Tron, Mauro M Teixeira, Elisa Ciraolo, Remo C Russo, Emilio Hirsch
PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action...
December 12, 2018: Nature Communications
Cheng-Ping Hu, Qiu-Fen Xun, Xiao-Zhao Li, Xin-Yue Hu, Ling Qin, Ruo-Xi He, Jun-Tao Feng
Background: Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown. Methods: A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV1 ) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1-/- ) mice...
December 5, 2018: Chinese Medical Journal
Reynold A Panettieri, Dedmer Schaafsma, Yassine Amrani, Cynthia Koziol-White, Rennolds Ostrom, Omar Tliba
Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs 'rapidly' enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma...
November 26, 2018: Trends in Pharmacological Sciences
Ledina Imami, Sarah C E Stanton, Samuele Zilioli, Erin T Tobin, Allison K Farrell, Francesca Luca, Richard B Slatcher
Self-disclosure and perceived responsiveness are important building blocks of social relationships that have long-lasting consequences for health and well-being. However, the conditions under which self-disclosure and responsiveness are likely to benefit health, and how early in life these benefits arise, remain unclear. Among 141 youth (aged 10-17) with asthma, we investigated how average daily levels of self-disclosure and responsiveness are linked to positive and negative affect and the expression of the glucocorticoid receptor gene NR3C1, a marker of improved regulation of stress physiology and immune functioning...
November 28, 2018: Personality & Social Psychology Bulletin
Sina A Gharib, Ryan S McMahan, William E Eddy, Matthew E Long, William C Parks, Moira L Aitken, Anne M Manicone
BACKGROUND: Macrophage plasticity allows cells to adopt different phenotypes, a property with important implications in disorders such as cystic fibrosis (CF) and asthma. OBJECTIVE: To examine the transcriptional and functional significance of macrophage repolarization from an "M1" towards an "M2" phenotype, and assess the role of a common human genetic disorder (CF) and a prototypical allergic disease (asthma) in this transformation. METHODS: Monocyte-derived macrophages were collected from healthy and CF subjects and polarized to an M2 state using IL-4, IL-10, glucocorticoids, apoptotic PMNs, or azithromycin...
November 13, 2018: Journal of Allergy and Clinical Immunology
Yann Nguyen, Loïc Guillevin
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a systemic necrotizing vasculitis of small- and medium-size vessels, characterized by asthma and blood eosinophilia. EGPA typically occurs in patients with preexisting asthma, and involves the skin, lungs, and peripheral nerves. Poor-prognosis factors (i.e., involvement(s) of the gastrointestinal tract, heart, and/or kidney) have been assessed with the Five-Factor Score (FFS). One-third of the patients have anti-myeloperoxidase antineutrophil cytoplasm antibodies, and their presence seems to differentiate between two phenotypes, with different clinical characteristics and prognoses...
August 2018: Seminars in Respiratory and Critical Care Medicine
Ying Tang, Caiyun Zhang, Zhigang Zhang, Jinhui Tian
OBJECTIVE: To determine the efficacy and safety of current maintenance therapies consisting of different regimens of long-acting β2-agonists (LABA) with inhaled corticosteroids (ICS) in patients with asthma. METHODS: A network meta-analysis (NMA) was conducted after a comprehensive search for relevant studies in the PubMed, Cochrane Library, and Embase databases up to January 1, 2017. Randomized clinical trials comparing LABA combined with ICS in patients with asthma were selected...
October 25, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
X Shi, R H Qiu, Z D Lai, M Z Qiu, S S Wei, J X Xie, X X Zhang, F G Deng, J Li, Y Y Gu, L Dai, Q L Zhang, N F Zhang, S Y Li, R C Chen
Objective: To improve the clinical recognition of eosinophilic granulomatosis with polyangiitis(EGPA) in clinical manifestations, diagnosis and treatment. Methods: The clinical manifestations, pathological characteristic, imaging manifestations, diagnosis and the therapy of three patients with EGPA were presented. Results: These 3 patients had asthma-like symptoms and extrapulmonary manifestations of systemic vasculitis. They were 20, 40 and 44 years old. All of them were female.They denied exposure or contact...
October 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
Lina Jankauskaitė, Valdonė Misevičienė, Laimutė Vaidelienė, Rimantas Kėvalas
Studies of human airway virome are relatively recent and still very limited. Culture-independent microbial techniques showed growing evidence of numerous viral communities in the respiratory microbial ecosystem. The significance of different acute respiratory viruses is already known in the pathogenesis of chronic conditions, such as asthma, cystic fibrosis (CF), or chronic obstructive lung disease (COPD), and their exacerbations. Viral pathogens, such as influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, or rhinovirus, have been associated with impaired immune response, acute exacerbations, and decrease in lung function in chronic lung diseases...
October 13, 2018: Medicina
Rodney D Britt, Michael A Thompson, Sarah K Sasse, Christina M Pabelick, Anthony N Gerber, Y S Prakash
Corticosteroids are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show corticosteroid (CS) resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previous studies have demonstrated that Th1 cytokines, such as TNFα and IFNγ, promote corticosteroid resistance in adult human airway smooth muscle (ASM)...
October 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Zhang Quan-San, Xu Xiaohong, Li Ying, Sun Zhaojia
Objective This study aimed to investigate the pathogenesis of geriatric asthma through immunoglobulin E (IgE), interleukin-17A (IL-17A), IL-17F, and glucocorticoid receptor-β (GR-β) expression. Methods We studied 51 geriatric male patients with asthma and 50 young male patients with asthma. We also included 21 normal geriatric males and 21 normal young males. All geriatric and young patients were divided into groups according to pulmonary function. Levels of cytokines, such as IgE, IL-17A, IL-17F, and GR-β, were measured...
October 10, 2018: Journal of International Medical Research
Kristin A Lambert, Alanna N Roff, Ronaldo P Panganiban, Scott Douglas, Faoud T Ishmael
BACKGROUND: MicroRNAs (miRNAs) are emerging as central regulators of inflammation, but their role in asthma and airway epithelial cells is not well studied. Glucocorticoids are the cornerstone of therapy in asthma and other inflammatory disease, yet their mechanisms of action are not completely elucidated, and it is not clear whether miRNAs modulate their effects. OBJECTIVE: We aimed to identify miRNAs that regulate cytokine and chemokine expression in airway epithelial cells and whether these miRNAs are subject to the effects of glucocorticoids...
2018: PloS One
Aleksandar Perić, Cveta Špadijer Mirković, Danilo Vojvodić
Clara cell protein 16 (CC16) is a small protein mainly produced by non-ciliated Clara cells in the respiratory epithelium. It has an anti-inflammatory role in chronic upper and lower airway eosinophilic inflammations. Decreased levels of CC16 are found in the nasal secretions and plasma of patients with chronic eosinophilic inflammatory disorders, such as asthma, allergic rhinitis, and chronic rhinosinusitis with or without nasal polyps, as well as in people exposed to high levels of air pollutants. Intranasal corticosteroid administration suppresses chronic inflammation of the nasal mucosa driven by eosinophils and stimulates local CC16 production...
September 1, 2018: Arhiv za Higijenu Rada i Toksikologiju
Yitian Liu, Bo Ji, Guozhen Zhao, Hang Su, Yunpeng Ge, Jian Dai, Yawen Lu, Reiko Sakurai, Virender K Rehan
Perinatal nicotine exposure can not only lead to lung dysplasia in offspring, but also cause epigenetic changes and induce transgenerational asthma. Previous studies have shown that electro-acupuncture (EA) applied to "Zusanli" (ST 36) can improve the lung morphology and correct abnormal expression of lung development-related protein in perinatal nicotine exposure offspring. However, it is still unclear whether ST 36 has a specific therapeutic effect and how maternal acupuncture can protect the offspring from pulmonary dysplasia...
September 28, 2018: Biochemical and Biophysical Research Communications
Elizabeth Daniel, Alanna Roff, Man-Hsun Hsu, Ronaldo Panganiban, Kristin Lambert, Faoud Ishmael
RATIONALE: MicroRNAs (miRNAs) are emerging as important regulators of allergic inflammation and potential therapeutic targets. We sought to identify which miRNAs are expressed in CD4+ T-cells and determine whether allergic stimuli or glucocorticoids alter their expression. METHODS: After IRB approval, blood was collected from dust mite (DM) allergic rhinitis subjects (n=20), non-allergic controls (n=8), and asthmatics (n=16). Peripheral blood mononuclear cells were incubated with dust mite extract (DME), diluent control, or DME + dexamethasone (0...
2018: American Journal of Clinical and Experimental Immunology
Anna Gungl, Valentina Biasin, Jochen Wilhelm, Andrea Olschewski, Grazyna Kwapiszewska, Leigh M Marsh
Background: Asthma is a complex chronic inflammatory disease characterised by airway inflammation, remodelling and hyperresponsiveness (AHR). Members of the AP-1 transcription factor family play important roles in the activation of the immune system and the control of cellular responses; however, their role in the development of asthma has not been well studied. We aimed to investigate the role of the lesser known AP-1 family member, Fra2 in experimental asthma. Methods: Phenotypic characterisation and gene expression profiling was performed on Fra2 (TG) overexpressing and wild-type mice...
2018: Frontiers in Immunology
Jasmine I Caulfield, Michael J Caruso, Rebecca A Bourne, Nicole R Chirichella, Laura C Klein, Timothy Craig, Robert H Bonneau, Avery August, Sonia A Cavigelli
In developing youth, allergic asthma is the most common chronic condition, with 9%-10% of youth affected. Asthma onset during childhood and adolescence is further associated with other health issues, particularly psychiatric conditions. To understand causal mechanisms by which developmental asthma may lead to altered behavior, brain and health trajectories, we developed a mouse model of developmental allergic asthma. In the current study, we tested for potential long-term effects of developmental asthma on adult lung function and behavior and brain gene expression associated with emotion and stress regulation...
2018: Frontiers in Behavioral Neuroscience
Tianhua Li, Ningning Qi, Xiaona Gao, Haili Yu
In this report, we summarize our experience of rescuing four children with severe type A H3N2 influenza from January to February 2017 in Weifang People's Hospital, Shandong Province, China for reference in clinical treatment. Two boys and two girls, ranging in age from 3 months to 6 years, with fever, cough, and asthma, were admitted to the pediatric intensive care unit. All children had severe pulmonary infection with respiratory distress. Three children had myocardial damage, two had liver damage, and one had encephalitis...
September 13, 2018: Journal of International Medical Research
Garry M Walsh
Severe or refractory asthma is seen in approximately 5% of asthmatic subjects who have unsatisfactory symptom control despite adherence to high-dose inhaled glucocorticoid therapies resulting in significant morbidity, reduced quality of life and health-care cost implications. Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level requiring specifically targeted treatments to block the key pathways of the disease. Monoclonal antibody-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5, and IL-13 have considerable potential as effective treatments for severe asthma...
November 2018: Expert Review of Respiratory Medicine
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