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Steroid resistant asthma

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https://www.readbyqxmd.com/read/28725641/mechanisms-mediating-pediatric-severe-asthma-and-potential-novel-therapies
#1
REVIEW
Aldara Martin Alonso, Sejal Saglani
Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling). Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28697969/childhood-severe-asthma-new-insights-on-remodelling-and-biomarkers
#2
REVIEW
Sejal Saglani
Severe asthma in children is characterised by severe and multiple aeroallergen sensitisation, food allergy, eosinophilic airway inflammation and airway remodelling. However, it is a heterogeneous disease with considerable variability in the manifestation of each of these characteristics between patients. Recent data from mechanistic studies that have used translational approaches including neonatal mouse models and airway bronchoscopic samples, have shown specific molecular mediators that drive remodelling and steroid resistance in paediatric severe asthma will be discussed...
June 12, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28696809/effects-of-aspergillus-fumigatus-on-glucocorticoid-receptor-and-%C3%AE-2-adrenergic-receptor-expression-in-a-rat-model-of-asthma
#3
Xia Zhou, Ya-Jie Dang, Gui-Fang Wang, Xian-Qiao Jin
PURPOSE: Conventional inhaled corticosteroids or β2-adrenergic receptor agonists do not work well in some asthmatic populations while empirical antifungal therapy has obvious impact on those patients. The study was designed to investigate whether short-term exposure to Aspergillus fumigatus (A. fumigatus) could decrease glucocorticoid receptor (GCR) and β2-adrenergic receptor (ADRB2) expression in lung tissue of asthmatic rats. MATERIALS AND METHODS: A rat model of chronic asthma was first established by ovalbumin sensitization and challenge...
July 11, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28666799/ovatodiolide-suppresses-allergic-airway-inflammation-and-hyperresponsiveness-in-a-murine-model-of-asthma
#4
Chien-Neng Wang, Yueh-Lun Lee, Yu-Pei Lin, Wen-Hui Chung, Yew-Min Tzeng, Chen-Chen Lee
Asthma, a complex pulmonary allergic disease, major therapy is applied of drugs to control the disease, but quickly recur after the drugs are stopped. In patients with severe asthma may show steroid resistance and would benefit from the development of novel therapeutic drugs. Ovatodiolide, a unique macrocyclic diterpenoid isolated from Anisomeles indica, showed therapeutic potential for the treatment of allergic asthma. As a model of allergic inflammation, we used ovalbumin (OVA)-immunized mice, which displayed T helper cell type 2 (TH2) cytokine expression in bronchoalveolar lavage fluid (BALF), as well as airway inflammation and hyperresponsiveness (AHR)...
June 27, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28658552/mechanisms-and-treatments-for-severe-steroid-resistant-allergic-airway-disease-and-asthma
#5
REVIEW
Philip M Hansbro, Richard Y Kim, Malcolm R Starkey, Chantal Donovan, Kamal Dua, Jemma R Mayall, Gang Liu, Nicole G Hansbro, Jodie L Simpson, Lisa G Wood, Jeremy A Hirota, Darryl A Knight, Paul S Foster, Jay C Horvat
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658551/spectrum-of-t-lymphocyte-activities-regulating-allergic-lung-inflammation
#6
REVIEW
Erwin W Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28658543/modeling-th-2-responses-and-airway-inflammation-to-understand-fundamental-mechanisms-regulating-the-pathogenesis-of-asthma
#7
REVIEW
Paul S Foster, Steven Maltby, Helene F Rosenberg, Hock L Tay, Simon P Hogan, Adam M Collison, Ming Yang, Gerard E Kaiko, Philip M Hansbro, Rakesh K Kumar, Joerg Mattes
In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4(+) T-helper type-2 lymphocytes (TH 2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical TH 2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR)...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28576975/route-of-administration-affects-corticosteroid-sensitivity-of-a-combined-ovalbumin-and-lipopolysaccharide-model-of-asthma-exacerbation-in-guinea-pigs
#8
Alexander P P Lowe, Rhian S Thomas, Anthony T Nials, Emma J Kidd, Kenneth J Broadley, William R Ford
Lipopolysaccharide (LPS) contributes to asthma exacerbations and development of inhaled corticosteroid insensitivity. Complete resistance to systemic corticosteroids is rare and most patients lie on a continuum of steroid responsiveness. The objective of this study was to examine the sensitivity of combined ovalbumin- (Ova) and LPS-induced functional and inflammatory responses to inhaled and systemic corticosteroid in conscious guinea-pigs, to test the hypothesis that the route of administration affects its sensitivity...
June 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28543931/severe-asthma-in-children
#9
REVIEW
Andrew Bush, Louise Fleming, Sejal Saglani
Most children with asthma have their disease easily controlled if low-dose inhaled corticosteroids (ICSs) are regularly and correctly administered. If a child presents with asthma which is apparently resistant to therapy with high-dose ICS and other controllers, then they have problematic severe asthma. However, in light of the UK National Review of Asthma Deaths, definitions of severe asthma based solely on the levels of prescribed treatment are too narrow. A detailed assessment of all such children should be performed...
May 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28483577/formoterol-and-fluticasone-propionate-combination-improves-histone-deacetylation-and-anti-inflammatory-activities-in-bronchial-epithelial-cells-exposed-to-cigarette-smoke
#10
M Ferraro, M Gjomarkaj, L Siena, S Di Vincenzo, E Pace
BACKGROUND: The addition of long-acting beta2-agonists (LABAs) to corticosteroids improves asthma control. Cigarette smoke exposure, increasing oxidative stress, may negatively affect corticosteroid responses. The anti-inflammatory effects of formoterol (FO) and fluticasone propionate (FP) in human bronchial epithelial cells exposed to cigarette smoke extracts (CSE) are unknown. AIMS: This study explored whether FP, alone and in combination with FO, in human bronchial epithelial cellline (16-HBE) and primary bronchial epithelial cells (NHBE), counteracted some CSE-mediated effects and in particular some of the molecular mechanisms of corticosteroid resistance...
May 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28481622/cardiomyocytes-of-the-heart-and-pulmonary-veins-novel-contributors-to-asthma
#11
Stephen Sai Folmsbee, Cara J Gottardi
Recent genome-wide association studies have implicated both cardiac and pulmonary vein-related genes in the pathogenesis of asthma. Since cardiac cells are not present in lung airways or viewed to affect the immune system, interpretation of these findings in the context of more well-established contributors to asthma has remained challenging. However, cardiomyocytes are present in the lung, specifically along pulmonary veins, and recent murine models suggest that cardiac cells lining pulmonary veins may contribute to allergic airway disease...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-from-patients-with-severe-asthma-the-role-of-thymic-stromal-lymphopoietin
#12
Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M Gorska, Richard J Martin, Rafeul Alam
BACKGROUND: Type 2 innate lymphoid cells (ILC2s) represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown. OBJECTIVE: We sought to assess steroid resistance of human blood and airway ILC2s from asthmatic patients and to examine its mechanism of induction. METHODS: We studied human blood and lung ILC2s from asthmatic patients and control subjects using flow cytometry and ELISA. RESULTS: Dexamethasone inhibited (P = ...
April 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28401621/mouse-models-of-severe-asthma-understanding-the-mechanisms-of-steroid-resistance-tissue-remodelling-and-disease-exacerbation
#13
REVIEW
Steven Maltby, Hock L Tay, Ming Yang, Paul S Foster
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e...
April 11, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28370266/inhaled-steroids-reduce-pain-and-svcam-levels-in-individuals-with-sickle-cell-disease-a-triple-blind-randomized-trial
#14
Jeffrey Glassberg, Caterina Minnitti, Caroline Cromwell, Lawrence Cytryn, Thomas Kraus, Gwen S Skloot, Jason T Connor, Adeeb H Rahman, William J Meurer
Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper-reactivity) is an intrinsic component of Sickle Cell Disease (SCD) and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 nonasthmatic individuals with SCD...
July 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28356505/target-practice-in-severe-asthma
#15
Stephanie A Christenson
The NLRP3 inflammasome/caspase-1/IL-1β axis may be a therapeutic target in severe steroid-resistant asthma.
March 29, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28297812/-the-regulative-effects-of-aspergillus-fumigatus-on-expression-of-glucocorticoid-receptor-in-asthmatic-rats
#16
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
#17
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
#18
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
#19
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
#20
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
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