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Steroid resistant asthma

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https://www.readbyqxmd.com/read/29130617/dendritic-cell-phenotype-in-severe-asthma-reflects-clinical-responsiveness-to-glucocorticoids
#1
Emma S Chambers, Alexandra M Nanzer, Paul E Pfeffer, David F Richards, Adrian R Martineau, Christopher J Griffiths, Christopher J Corrigan, Catherine M Hawrylowicz
BACKGROUND: Subsets of patients with severe asthma remain symptomatic despite prolonged, high dosage glucocorticoid therapy. We hypothesised that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. OBJECTIVE: To compare peripheral blood leukocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid sensitive (SS) and steroid resistant (SR) asthmatics...
November 11, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29124506/heart-rate-variability-biofeedback-does-not-substitute-for-asthma-steroid-controller-medication
#2
Paul M Lehrer, Charles G Irvin, Shou-En Lu, Anthony Scardella, Beatrix Roehmheld-Hamm, Milisyaris Aviles-Velez, Jessica Graves, Evgeny G Vaschillo, Bronya Vaschillo, Flavia Hoyte, Harold Nelson, Frederick S Wamboldt
Despite previous findings of therapeutic effects for heart rate variability biofeedback (HRVB) on asthma, it is not known whether HRVB can substitute either for controller or rescue medication, or whether it affects airway inflammation. Sixty-eight paid volunteer steroid naïve study participants with mild or moderate asthma were given 3 months of HRVB or a comparison condition consisting of EEG alpha biofeedback with relaxing music and relaxed paced breathing (EEG+), in a two-center trial. All participants received a month of intensive asthma education prior to randomization...
November 9, 2017: Applied Psychophysiology and Biofeedback
https://www.readbyqxmd.com/read/29108648/cyclosporin-a-indirectly-attenuates-activation-of-group-2-innate-lymphoid-cells-in-papain-induced-lung-inflammation
#3
Fujimi Kudo, Masashi Ikutani, Masanori Iseki, Satoshi Takaki
Cyclosporin A (CsA) is a well-known immunosuppressant that is used against steroid-resistant asthma. Group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells produce Th2 cytokines including IL-5 and play important roles in asthma pathogenesis. Here, we studied the effects of CsA in allergen-induced lung inflammation in mice and found that CsA decreased the number of lung ILC2s and attenuated papain-induced activation of ILC2s accompanied with IL-5 expression. The ILC2 suppression mediated by CsA was not observed in culture or in lymphocyte-deficient Rag2(-/-) mice...
October 27, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29106996/chronic-rhinosinusitis-endotypes-biomarkers-and-treatment-response
#4
Jose Gurrola, Larry Borish
It is increasingly recognized that chronic rhinosinusitis (CRS) comprises a spectrum of different diseases with distinct clinical presentations and pathogenic mechanisms. Defining the distinct phenotypes and endotypes of CRS impacts prognosis and most importantly is necessary as the basis for making therapeutic decisions. The need for individualized defining of pathogenic mechanisms prior to initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics where, barring an influence from their off-target anti-inflammatory pharmacological effects, an understanding of the role of individual biome predicts likelihood of therapeutic benefit...
October 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29079741/combined-x-ray-crystallography-and-computational-modeling-approach-to-investigate-the-hsp90-c-terminal-peptide-binding-to-fkbp51
#5
Rajnish Kumar, Martin Moche, Bengt Winblad, Pavel F Pavlov
FK506 binding protein of 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) co-chaperone involved in the regulation of steroid hormone receptors activity. It is known for its role in various regulatory pathways implicated in mood and stress-related disorders, cancer, obesity, Alzheimer's disease and corticosteroid resistant asthma. It consists of two FKBP12 like active peptidyl prolyl isomerase (PPIase) domains (an active FK1 and inactive FK2 domain) and one tetratricopeptide repeat (TPR) domain that mediates interaction with Hsp90 via its C-terminal MEEVD peptide...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29027379/impact-of-omalizumab-in-children-from-a-middle-income-country-with-severe-therapy-resistant-asthma-a-real-life-study
#6
Paulo M Pitrez, Rodrigo G de Souza, Cristian Roncada, Joao P Heinzmann-Filho, Giovana Santos, Leonardo A Pinto, Marcus H Jones, Renato T Stein
BACKGROUND: Severe asthma in children is a global health problem. Severe therapy-resistant asthma (STRA) in children is a major clinical challenge due to persistent symptoms despite high doses of corticosteroids and results in high public health costs. Omalizumab (anti-IgE monoclonal antibody) has been described as an effective add-on therapy in these patients. The characteristics of children with STRA from low- and middle-income countries have scarcely been reported, and no real-life study has been published on the effects of omalizumab in this group of patients...
November 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28923762/vitamin-d-in-asthma-mechanisms-of-action-and-considerations-for-clinical-trials
#7
REVIEW
Paul E Pfeffer, Catherine M Hawrylowicz
There is increasing interest in the therapeutic utility of vitamin D in asthma, which is supported by a significant body of evidence on epidemiologic associations between vitamin D insufficiency and worse asthma control. In support of a causal relationship, vitamin D beneficially modulates diverse immunologic pathways in heterogeneous asthma endotypes, regulating the actions of lymphocytes, mast cells, antigen-presenting cells, and structural cells to dampen excessive inflammatory responses. Allergic asthma is characterized by a failure of immune tolerance and the development of pathologic responses to inhaled aeroallergens, and vitamin D has been extensively shown to support immune regulation...
September 18, 2017: Chest
https://www.readbyqxmd.com/read/28880396/drug-repurposing-to-treat-asthma-and-allergic-disorders-progress-and-prospects
#8
REVIEW
Robert L Kruse, Kristine Vanijcharoenkarn
Allergy and atopic asthma have continued to become more prevalent in modern society despite the advent of new treatments, representing a major global health problem. Common medications such as antihistamines and steroids may have undesirable long-term side effects and lack efficacy in some resistant patients. Biologic medications are increasingly given to treat resistant patients, but they can represent high costs, complex dosing and management, and are not widely available around the world. The field needs new, cheap and convenient treatment options in order to bring better symptom relief to patients...
September 7, 2017: Allergy
https://www.readbyqxmd.com/read/28851976/linoleic-acid-metabolite-leads-to-steroid-resistant-asthma-features-partially-through-nf-%C3%AE%C2%BAb
#9
Lipsa Panda, Atish Gheware, Rakhshinda Rehman, Manish K Yadav, B S Jayaraj, SubbaRao V Madhunapantula, Padukudru Anand Mahesh, Balaram Ghosh, Anurag Agrawal, Ulaganathan Mabalirajan
Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826280/severe-therapy-resistant-asthma-in-children-translational-approaches-to-uncover-sub-phenotypes
#10
Aldara Martin Alonso, Valentina Fainardi, Sejal Saglani
Paediatric severe therapy resistant asthma (STRA) affects a very small proportion of all children with asthma, but results in significant morbidity, has a high risk of mortality and utilises approximately half of all healthcare resources for childhood asthma. children with STRA need add-on 'beyond guidelines' therapies because of poor control despite maximal conventional treatments and optimisation of basic asthma management. however, STRA is heterogeneous with marked phenotypic variation between patients and mechanisms from adult severe asthma cannot be extrapolated to children...
August 21, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28765890/fine-particulate-matter-aggravates-allergic-airway-inflammation-through-thymic-stromal-lymphopoietin-activation-in-mice
#11
Yan Liu, Gan-Zhu Feng, Qiang Du, Xiao-Xiang Jin, Xing-Ran Du
Fine particulate matter (PM2.5) has been linked to exacerbation of allergic airway inflammation in mice. However, the mechanism underlying exposure to PM2.5 and subsequent and adverse effects remains to be fully elucidated. Therefore, the present study aimed to investigate the effects of PM2.5 by different levels on airway inflammation in mouse models of in allergic and steroid‑resistant asthma. BALB/c mice were nasally instilled with PBS (control) or 10, 31.6 or 100 µg PM2.5, and randomly assigned into nine groups...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28755856/th9-cells-induce-steroid-resistant-bronchial-hyperresponsiveness-in-mice
#12
Mayumi Saeki, Osamu Kaminuma, Tomoe Nishimura, Noriko Kitamura, Akio Mori, Takachika Hiroi
BACKGROUND: Reduced responsiveness to corticosteroid therapy is a major problem for patients with severe asthma. Although Th9 cells, along with Th2 cells, facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains unknown. In this study, we investigated the effect of dexamethasone (Dex) on antigen-induced airway inflammation in Th9 cell-transferred mice. METHODS: Ovalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4(+) T cells of DO11...
July 26, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28725641/mechanisms-mediating-pediatric-severe-asthma-and-potential-novel-therapies
#13
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
#14
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...
September 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
#15
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...
May 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28666799/ovatodiolide-suppresses-allergic-airway-inflammation-and-hyperresponsiveness-in-a-murine-model-of-asthma
#16
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
#17
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
#18
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
#19
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
#20
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. This study aimed 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 sensitivity. Guinea pigs were sensitized to Ova and challenged with inhaled Ova alone or combined with LPS...
August 2017: Journal of Pharmacology and Experimental Therapeutics
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