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Asthma pathogenesis

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https://www.readbyqxmd.com/read/28721017/targeted-therapy-in-severe-asthma-today-focus-on-immunoglobulin-e
#1
REVIEW
Girolamo Pelaia, Giorgio Walter Canonica, Andrea Matucci, Rossella Paolini, Massimo Triggiani, Pierluigi Paggiaro
Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard "one size fits all" approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28720095/fibrocyte-measurement-in-peripheral-blood-correlates-with-number-of-cultured-mature-fibrocytes-in-vitro-and-is-a-potential-biomarker-for-interstitial-lung-disease-in-rheumatoid-arthritis
#2
Søren Andreas Just, Hanne Lindegaard, Eva Kildall Hejbøl, Jesper Rømhild Davidsen, Niels Bjerring, Søren Werner Karlskov Hansen, Henrik Daa Schrøder, Inger Marie Jensen Hansen, Torben Barington, Christian Nielsen
BACKGROUND: Interstitial lung disease (ILD) can be a severe extra-articular disease manifestation in Rheumatoid Arthritis (RA). A potential role of fibrocytes in RA associated ILD (RA-ILD) has not previously been described. We present a modified faster method for measuring circulating fibrocytes, without intracellular staining. The results are compared to the traditional culture method, where the number of monocytes that differentiate into mature fibrocytes in vitro are counted. The results are following compared to disease activity in patients with severe asthma, ILD, RA (without diagnosed ILD) and RA with verified ILD (RA-ILD)...
July 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28719697/diagnosis-and-management-of-asthma-in-adults-a-review
#3
Jennifer L McCracken, Sreenivas P Veeranki, Bill T Ameredes, William J Calhoun
Importance: Asthma affects about 7.5% of the adult population. Evidence-based diagnosis, monitoring, and treatment can improve functioning and quality of life in adult patients with asthma. Observations: Asthma is a heterogeneous clinical syndrome primarily affecting the lower respiratory tract, characterized by episodic or persistent symptoms of wheezing, dyspnea, and cough. The diagnosis of asthma requires these symptoms and demonstration of reversible airway obstruction using spirometry...
July 18, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#4
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28713081/gene-polymorphism-of-xenobiotic-detoxification-in-children-with-bronchial-asthma
#5
Liudmila Y Lytvynets
INTRODUCTION: Children are the most susceptible to harmful external factors due to the incomplete development of all functional body systems. The ecological situation the problem of influence of genetic and environmental factors on the pathogenesis of chronic respiratory diseases in children and its investigation is very impotent today. Among it the bronchial asthma is a leader among bronchial and pulmonary diseases caused by the influence of pneumotropic pollutants. The aim of our research was to study the phenotypic characteristics of asthma in Pre-Carpathian children with different types of allelic gene polymorphism of the first phase of xenobiotic detoxification of microsomal epoxide hydrolases (mEPHX1)...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28711603/mir-139-5p-inhibits-proliferation-and-promoted-apoptosis-of-human-airway-smooth-muscle-cells-by-downregulating-the-brg1-gene
#6
Huanying Zhang, Zhongmei Sun, Lianfeng Yu, Jie Sun
MicroRNAs have emerged as critical regulators in the pathogenesis of asthma. However, the role of microRNAs in asthma needs to be further elucidated. In this study, we found that miR-139-5p was greatly decreased in airway smooth muscle (ASM) cells from asthmatic humans as well as ASM cells stimulated with cytokines. Overexpression of miR-139-5p markedly suppressed ASM cell proliferation and promoted cell apoptosis, whereas knockdown of miR-139-5p had the opposite effect. Further study verified that Brg1, a chromatin remodeling factor, was upregulated in ASM cells treated with cytokines and acted as a direct target of miR-139-5p...
July 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28702704/ezrin-orchestrates-signal-transduction-in-airway-cells
#7
Lei-Miao Yin, Ting-Ting Duan, Luis Ulloa, Yong-Qing Yang
Ezrin is a critical structural protein that organizes receptor complexes and orchestrates their signal transduction. In this study, we review the ezrin-meditated regulation of critical receptor complexes, including the epidermal growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin-meditated regulation of critical pathways associated with asthma, such as the RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA) pathways...
July 13, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28701890/relationship-between-oxidative-stress-physical-activity-and-vitamin-intake-in-patients-with-asthma
#8
Akira Yamasaki, Yuji Kawasaki, Kenichi Takeda, Tomoya Harada, Yasuyuki Hasegawa, Takehito Fukushima, Ryota Okazaki, Haruhiko Makino, Yoshihiro Funaki, Yuriko Sueda, Akihiro Yamamoto, Jun Kurai, Masanari Watanabe, Eiji Shimizu
BACKGROUND: Oxidative stress plays an important role in the pathogenesis of bronchial asthma. Antioxidant nutrition and supplementation have been used to reduce oxidative stress. However, a clinical trial with antioxidant supplementation showed no beneficial effects in patients with asthma. On the other hand, physical activity is related to the prognosis of chronic obstructive pulmonary disease (COPD) and is also related to oxidant status. We investigated the relationships between oxidative stress, serum levels of vitamins, dietary vitamin intake, daily activities, and pulmonary functions in patients with asthma...
June 2017: Yonago Acta Medica
https://www.readbyqxmd.com/read/28701525/cigarette-smoke-differentially-affects-il-13-induced-gene-expression-in-human-airway-epithelial-cells
#9
Tinne C J Mertens, Anne M van der Does, Loes E Kistemaker, Dennis K Ninaber, Christian Taube, Pieter S Hiemstra
Allergic airways inflammation in asthma is characterized by an airway epithelial gene signature composed of POSTN, CLCA1, and SERPINB2 This Th2 gene signature is proposed as a tool to classify patients with asthma into Th2-high and Th2-low phenotypes. However, many asthmatics smoke and the effects of cigarette smoke exposure on the epithelial Th2 gene signature are largely unknown. Therefore, we investigated the combined effect of IL-13 and whole cigarette smoke (CS) on the Th2 gene signature and the mucin-related genes MUC5AC and SPDEF in air-liquid interface differentiated human bronchial (ALI-PBEC) and tracheal epithelial cells (ALI-PTEC)...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28689842/asthma-exacerbations-pathogenesis-prevention-and-treatment
#10
Jamee R Castillo, Stephen P Peters, William W Busse
Guideline-based management of asthma focuses on disease severity and choosing the appropriate medical therapy to control symptoms and reduce the risk of exacerbations. However, irrespective of asthma severity and often despite optimal medical therapy, patients may experience acute exacerbations of symptoms and a loss of disease control. Asthma exacerbations are most commonly triggered by viral respiratory infections, particularly with human rhinovirus. Given the importance of these events to asthma morbidity and health care costs, we will review common inciting factors for asthma exacerbations and approaches to prevent and treat these events...
July 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28680338/evaluation-of-selected-immunological-parameters-and-the-concentration-of-vitamin-d-in-children-with-asthma-case-control-study
#11
Agata Wawrzyniak, Agnieszka Lipińska-Opałka, Robert Zdanowski, Sławomir Lewicki, Piotr Murawski, Bolesław Kalicki
Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28673565/monocyte-subpopulations-study-in-patients-with-plaque-psoriasis
#12
Mariana Carvalho Costa, Bruno de Oliveira Rocha, Camilla Sampaio Paixão, Maria de Fátima Santos Paim de Oliveira, Lícia Maria Henrique da Mota, Lucas Pedreira de Carvalho
Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease, mainly manifested by skin and / or joints lesions, presenting with a wide degree of clinical severity, but generally with great impact on patients' quality of life. Despite advances in the understanding of its pathogenesis, especially regarding the participation of T-lymphocytes and the key role of TNF, the triggering factor of the disease at the molecular level remains unknown, as well as the function of other cell populations. By presenting antigens to T-lymphocytes, monocytes assume an important role in both innate and adaptive immune response...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28673400/the-environment-epigenome-and-asthma
#13
REVIEW
Ivana V Yang, Catherine A Lozupone, David A Schwartz
Asthma prevalence has been on the increase, especially in North America compared with other continents. However, the prevalence of asthma differs worldwide, and in many countries the prevalence is stable or decreasing. This highlights the influence of environmental exposures, such as allergens, air pollution, and the environmental microbiome, on disease etiology and pathogenesis. The epigenome might provide the unifying mechanism that translates the influence of environmental exposures to changes in gene expression, respiratory epithelial function, and immune cell skewing that are hallmarks of asthma...
July 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28673013/coumarins-from-the-roots-of-angelica-dahurica-cause-anti-allergic-inflammation
#14
Dong Li, Li Wu
Allergic inflammation is induced by allergens and leads to various allergic diseases, including rhinitis, asthma and conjunctivitis. Histamine is important in the pathogenesis of an immunoglobulin E-dependent allergic reaction and results in the secretion of cytokines associated with inflammation. Angelica dahurica (A. dahurica) is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. The present study investigated the chemical constituents from A. dahurica and evaluated their reductive effect on allergic inflammation...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28672989/altered-expression-of-regulatory-t-and-th17-cells-in-murine-bronchial-asthma
#15
Jianbo Zhu, Xiaoying Liu, Wenxia Wang, Xiuhe Ouyang, Wentao Zheng, Qingyuan Wang
Alteration of the careful balance of the ratio of Th1/Th2 cell subsets impacts immune function and plays an important role in the pathogenesis of asthma. There is little research on the impact of changes on the balance of the regulatory T (Treg)/Th17 subset ratio and its possible repercussions for asthma. This investigation used a murine model of asthma to measure the expression levels of Treg and Th17 cells and the levels of their transcription factors Foxp3 and retinoic acid receptor-related orphan nuclear receptor (ROR)γt in bronchial asthma while assessing indexes of airway inflammation...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28669635/neuropsychiatry-phenotype-in-asthma-psychological-stress-induced-alterations-of-the-neuroendocrine-immune-system-in-allergic-airway-inflammation
#16
REVIEW
Isao Ohno
Since the recognition of asthma as a syndrome with complex pathophysiological signs and symptoms, recent research has sought to classify asthma phenotypes based on its clinical and molecular pathological features. Psychological stress was first recognized as a potential immune system modulator of asthma at the end of the 19th century. The activation of the central nervous system (CNS) upon exposure to psychological stress is integral for the initiation of signal transduction processes. The stress hormones, including glucocorticoids, epinephrine, and norepinephrine, which are secreted following CNS activation, are involved in the immunological alterations involved in psychological stress-induced asthma exacerbation...
June 29, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28667163/leukotriene-c4-potentiates-il-33-induced-group-2-innate-lymphoid-cell-activation-and-lung-inflammation
#17
Sean J Lund, Alex Portillo, Kellen Cavagnero, Rachel E Baum, Luay H Naji, Jana H Badrani, Amit Mehta, Michael Croft, David H Broide, Taylor A Doherty
Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation...
June 30, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28667070/pathogenesis-of-asthma-implications-for-precision-medicine
#18
REVIEW
Richard J Russell, Christopher Brightling
The pathogenesis of asthma is complex and multi-faceted. Asthma patients have a diverse range of underlying dominant disease processes and pathways despite apparent similarities in clinical expression. Here, we present the current understanding of asthma pathogenesis. We discuss airway inflammation (both T2(HIGH) and T2(LOW)), airway hyperresponsiveness (AHR) and airways remodelling as four key factors in asthma pathogenesis, and also outline other contributory factors such as genetics and co-morbidities. Response to current asthma therapies also varies greatly, which is probably related to the inter-patient differences in pathogenesis...
July 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28665693/critical-role-of-irak-m-in-regulating-antigen-induced-airway-inflammation
#19
Mingqiang Zhang, Wei Chen, Weixun Zhou, Yan Bai, Jinming Gao
Asthma is an airway epithelium disorder involving allergic lung inflammation. IRAK-M is a negative regulator of Toll-like receptor (TLR) signaling on airway epithelial cells and macrophages and known to limit overproduction of cytokines during the inflammatory process. However, the direct role of IRAK-M on asthma pathogenesis is unclear. In the present study, we found significant elevation of IRAK-M expression in mouse lungs following ovalbumin (OVA) exposure. Compared to wild type (WT) mice, IRAK-M knockout (KO) mice responded to OVA challenge with significantly worse infiltration of airway inflammatory cells, greater airway responsiveness, higher proinflammatory cytokine levels in lung homogenates, and more prominent Th2 and Th17 deviation...
June 30, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28659824/hypersensitivity-of-vagal-pulmonary-afferents-induced-by-tumor-necrosis-factor-alpha-in-mice
#20
Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee
Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice...
2017: Frontiers in Physiology
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