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Steroid resistant asthma

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https://www.readbyqxmd.com/read/28297812/-the-regulative-effects-of-aspergillus-fumigatus-on-expression-of-glucocorticoid-receptor-in-asthmatic-rats
#1
X Zhou, Y J Dang, G F Wang, X Q Jin
Objective: To study the regulative effects of Aspergillus fumigatus (A.fumigatus) on expression of glucocorticoid receptor (GCR) in asthmatic rats. Methods: Wistar rats were randomly divided into 4 groups: a normal control group (UC), a normal control with A. fumigatus group (UC+ AF), an OVA group (OVA), and an OVA with A. fumigatus group (OVA+ AF). OVA and OVA+ AF groups were sensitized and challenged with OVA to establish asthmatic models. UC and UC+ AF groups were given normal saline as controls. After the last challenge, OVA+ AF and UC+ AF groups were given A...
March 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28252317/role-for-nlrp3-inflammasome-mediated-il-1%C3%AE-dependent-responses-in-severe-steroid-resistant-asthma
#2
Richard Y Kim, James W Pinkerton, Ama T Essilfie, Avril Ab Robertson, Katherine J Baines, Alexandra C Brown, Jemma R Mayall, Md Khadem Ali, Malcolm R Starkey, Nicole G Hansbro, Jeremy A Hirota, Lisa G Wood, Jodie L Simpson, Darryl A Knight, Peter A Wark, Peter G Gibson, Luke A J O'Neill, Matthew A Cooper, Jay C Horvat, Philip M Hansbro
RATIONALE: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive NLRP3 inflammasome and concomitant IL-1β responses occur in COPD, respiratory infections and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma...
March 2, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#3
Caini Liu, Liang Zhu, Koichi Fukuda, Suidong Ouyang, Xing Chen, Chenhui Wang, Cun-Jin Zhang, Bradley Martin, Chunfang Gu, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li
Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28131832/treatment-of-obese-asthma-in-a-mouse-model-by-simvastatin-is-associated-with-improving-dyslipidemia-and-decreasing-leptin-level
#4
Wei Han, Jun Li, Huaping Tang, Lixin Sun
Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma...
March 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#5
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28043871/bcl-2-inhibitors-reduce-steroid-insensitive-airway-inflammation
#6
Bao-Ping Tian, Li-Xia Xia, Zheng-Qiang Bao, Hao Zhang, Zhi-Wei Xu, Yuan-Yuan Mao, Chao Cao, Luan-Qing Che, Jin-Kai Liu, Wen Li, Zhi-Hua Chen, Songmin Ying, Hua-Hao Shen
BACKGROUND: Asthmatic inflammation is dominated by accumulation of either eosinophils, neutrophils, or both in the airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, whereas neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid-resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies...
December 31, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27999674/development-and-validation-of-a-novel-bioassay-to-determine-glucocorticoid-sensitivity
#7
Emily L Williams, Madeleine L Stimpson, Peter L Collins, Doyo G Enki, Ashish Sinha, Richard W Lee, Ashwin D Dhanda
BACKGROUND: Glucocorticoids (GCs) remain the first line treatment for almost all non-infectious inflammatory diseases, ranging from acute asthma to rheumatoid arthritis. However, across all conditions, patients have a variable response to GCs with approximately 30% being non-responders. This group of GC resistant patients is typically exposed to high-dose GCs and their side-effects before more appropriate immunotherapy is instituted. Hence, there is a pressing clinical need for a predictive biomarker of GC responsiveness...
2016: Biomarker Research
https://www.readbyqxmd.com/read/27888992/il-17-protein-levels-in-both-induced-sputum-and-plasma-are-increased-in-stable-but-not-acute-asthma-individuals-with-obesity
#8
Jian-Hui Chen, Ling Qin, Ying-Ying Shi, Jun-Tao Feng, Yu-Long Zheng, Yu-Feng Wan, Chuan-Qin Xu, Xiao-Mei Yang, Cheng-Ping Hu
BACKGROUND: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown. OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and stable settings...
December 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27852250/impaired-anti-inflammatory-action-of-glucocorticoid-in-neutrophil-from-patients-with-steroid-resistant-asthma
#9
Meijia Wang, Pengfei Gao, Xiaojie Wu, Yuetao Chen, Yikuan Feng, Qun Yang, Yongjian Xu, Jianping Zhao, Jungang Xie
BACKGROUND: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics. METHODS: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment...
November 16, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27815425/stat6-regulates-the-development-of-eosinophilic-versus-neutrophilic-asthma-in-response-to-alternaria-alternata
#10
Andrea C Valladao, Charles W Frevert, Lisa K Koch, Daniel J Campbell, Steven F Ziegler
Human asthma is a heterogeneous disease characterized by the expression of both Th2 and Th17 cytokines. In vitro and in vivo studies have shown a reciprocal regulation between Th2 and Th17 pathways, suggesting a potential induction of neutrophil-promoting Th17 inflammation in the absence of a Th2 response. Alternaria alternata is a clinically relevant allergen that is associated with severe and fatal asthma exacerbations. Exposure to A. alternata is characterized by a predominant Th2 response, but can also induce the production of factors associated with Th17 responses (e...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27801710/glucocortiosteroid-subsensitivity-and-asthma-severity
#11
Manali Mukherjee, Sarah Svenningsen, Parameswaran Nair
PURPOSE OF REVIEW: Glucocorticosteroids (GCSs) remain the cornerstone of therapy for treating the inflammatory component of asthma. Clinical response to GCS is heterogeneous, varying both within asthma 'endotypes', as well as the same individual. Different factors and micro-environment can alter the canonical GCS-induced signalling pathways leading to reduced efficacy, collectively termed as GCS subsensitivity, which includes the entire spectrum of steroid insensitivity and steroid resistance...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27798418/t2-low-asthma-current-approach-to-diagnosis-and-therapy
#12
Konstantinos Samitas, Eleftherios Zervas, Mina Gaga
PURPOSE OF REVIEW: Asthma is a heterogeneous disease not only on a clinical but also on a mechanistic level. For a long time, the molecular mechanisms of asthma were considered to be driven by type 2 helper T cells (Th2) and eosinophilic airway inflammation; however, extensive research has revealed that T2-low subtypes that differ from the dominant T2 paradigm are also common. RECENT FINDINGS: Research into asthma pathways has led to the recognition that some asthma phenotypes show absence of T2 inflammation or alternate between T2 and non-T2 responses...
January 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/27757507/the-obesity-related-pathology-and-th17-cells
#13
REVIEW
Yusuke Endo, Koutaro Yokote, Toshinori Nakayama
Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases...
April 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27746241/intraepithelial-neutrophils-in-pediatric-severe-asthma-are-associated-with-better-lung-function
#14
Cecilia K Andersson, Alexandra Adams, Prasad Nagakumar, Cara Bossley, Atul Gupta, Daphne De Vries, Afiqah Adnan, Andrew Bush, Sejal Saglani, Clare M Lloyd
BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in pediatric asthma is unknown. OBJECTIVES: We sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA). METHODS: Children with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4...
October 13, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27742828/cytokine-induced-glucocorticoid-resistance-from-eosinophil-activation-protein-phosphatase-5-modulation-of-glucocorticoid-receptor-phosphorylation-and-signaling
#15
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27741157/the-role-of-vitamin-d-in-allergic-diseases-in-children
#16
Michele Miraglia Del Giudice, Annalisa Allegorico
The role of vitamin D in calcium and phosphate homeostasis is well known; however, in addition to traditional functions, vitamin D modulates a variety of processes, and evidence shows that it has an important role in different allergic diseases such as asthma, atopic dermatitis, and food allergy. Vitamin D acts by binding to the vitamin D receptor, which is present in a variety of tissues; for this reason it is considered a hormone. One of the most important functions is to modulate the immune system response, both innate and adaptive, by suppressing Th2-type response and increasing natural killer cells...
November 2016: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27685608/omalizumab-in-patient-with-aspirin-exacerbated-respiratory-disease-and-chronic-idiopathic-urticaria
#17
Federica Porcaro, Antonio Di Marco, Renato Cutrera
Aspirin hypersensitivity associated with chronic rhinosinusitis-with or without nasal polyposis-and asthma resistant to conventional therapy defines the aspirin-exacerbated respiratory disease (AERD). We describe the case of a 15-year-old female patient with adverse reaction to aspirin, chronic rhinosinusitis, and severe asthma. She also experienced chronic idiopathic urticaria worsened by non-steroidal anti-inflammatory drug administration. AERD was diagnosed based on clinical history and symptoms. Given the poor responsiveness to standard therapy for respiratory and cutaneous symptoms, omalizumab was administered for 24 weeks with control of respiratory symptoms and short term improvement of cutaneous symptoms...
September 29, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27650241/allergy-medications-during-pregnancy
#18
REVIEW
Alexei Gonzalez-Estrada, Stephen A Geraci
Allergic diseases are common in women of childbearing age. Both asthma and atopic conditions may worsen, improve or remain the same during pregnancy. Primary care physicians commonly encounter women receiving multiple medications for pre-existing atopic conditions, who then become pregnant and require medication changes to avoid potential fetal injury or congenital malformations. Each medication should be evaluated; intranasal and inhaled steroids are relatively safe to continue during pregnancy (budesonide is the drug of choice), second-generation antihistamines of choice are cetirizine and loratadine, leukotriene receptor antagonists are safe, sparing use of oral decongestants during the first trimester and omalizumab may be used for both uncontrolled asthma and for antihistamine-resistant urticaria...
September 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27621904/evaluation-of-airway-resistance-in-primary-small-cell-carcinoma-of-the-trachea-by-mostgraph-a-case-study
#19
Eri Hagiwara, Yasuhiro Gon, Kentaro Hayashi, Mai Takahashi, Yuko Iida, Hisato Hiranuma, Yoshiko Nakagawa, Tsukasa Hataoka, Kenji Mizumura, Shuichiro Maruoka, Tetsuo Shimizu, Noriaki Takahashi, Shu Hashimoto
The case subject was a 58-year-old woman who presented to our hospital with a chief complaint of respiratory discomfort. Wheezing could be heard in both lungs; treatment was initiated with inhaled steroids for suspected bronchial asthma. However, 1 week later, the respiratory discomfort had not improved and the wheezing sound had progressed to the neck area. Upper airway obstruction was suspected; therefore, chest computed tomography (CT) was performed, revealing tracheal stenosis caused by a tumor in the upper airway...
August 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27582398/eicosanoid-mediators-in-the-airway-inflammation-of-asthmatic-patients-what-is-new
#20
REVIEW
Marek Sanak
Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays...
November 2016: Allergy, Asthma & Immunology Research
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