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Steroid resistant asthma

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https://www.readbyqxmd.com/read/29332144/long-acting-%C3%AE-2-agonists-in-asthma-enantioselective-safety-studies-are-needed
#1
Glenn A Jacobson, Sharanne Raidal, Morten Hostrup, Luigino Calzetta, Richard Wood-Baker, Mark O Farber, Clive P Page, E Haydn Walters
Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection...
January 13, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29321968/achalasia-with-massive-oesophageal-dilation-causing-tracheomalacia-and-asthma-symptoms
#2
Ana Gomez-Larrauri, Simon Galloway, Rob Niven
Achalasia is an uncommon oesophageal motor disorder characterized by failure of relaxation of the lower oesophageal sphincter and muscle hypertrophy, resulting in a loss of peristalsis and a dilated oesophagus. Gastrointestinal symptoms are invariably present in all cases of achalasia observed in adults. We report a case of a 34 year-old female patient with long standing history of asthma-like symptoms, labelled as uncontrolled and steroid resistant asthma with no gastrointestinal manifestations. Thoracic CT scan revealed a massive oesophagus due to achalasia, which caused severe tracheomalacia as a result of tracheal compression...
2018: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/29288933/targeting-the-renin-angiotensin-system-as-novel-therapeutic-strategy-for-pulmonary-diseases
#3
REVIEW
Wan Shun Daniel Tan, Wupeng Liao, Shuo Zhou, Dan Mei, Wai-Shiu Fred Wong
The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome...
December 27, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29288381/modulation-of-the-il-23-il-17-axis-by-fenofibrate-ameliorates-the-ovalbumin-lipopolysaccharide-induced-airway-inflammation-and-bronchial-asthma-in-rats
#4
Samah M Elaidy, Soha S Essawy, Mona A Hussain, Mohamed K El-Kherbetawy, Eman R Hamed
The overlapping between asthmatic subtypes, including both CD4+ T helper (TH)2 and TH17 cells, is found in the natural course of allergic asthma, especially in exacerbations and severe and insensitive forms to steroids, which are in need of new molecular therapies. In the TH2-subset mediated asthma, fenofibrate displays therapeutic promises, besides evidenced therapeutic effects on TH17-mediated colitis and myocarditis. Therefore, the effects of fenofibrate versus dexamethasone on IL-23/IL-17 axis in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced airway inflammation and bronchial asthma in rats were explored...
December 30, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29233147/neutrophil-extracellular-traps-are-downregulated-by-glucocorticosteroids-in-lungs-in-an-equine-model-of-asthma
#5
Amandine Vargas, Roxane Boivin, Patricia Cano, Yoana Murcia, Isabelle Bazin, Jean-Pierre Lavoie
BACKGROUND: Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway...
December 12, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29220719/house-dust-mite-allergen-causes-certain-features-of-steroid-resistant-asthma-in-high-fat-fed-obese-mice
#6
Vijay Pal Singh, Ulaganathan Mabalirajan, Kunal Pratap, Devika Bahal, Deepanshu Maheswari, Atish Gheware, Aabha Bajaj, Lipsa Panda, Ashish Jaiswal, Arjun Ram, Anurag Agrawal
Obesity is a high risk factor for diseases such as cardiovascular, metabolic syndrome and asthma. Obese-asthma is another emerging phenotype in asthma which is typically refractive to steroid treatment due to its non-classical features such as non-eosinophilic cellular inflammation. The overall increased morbidity, mortality and economical burden in asthma is mainly due to steroid resistant asthma. In the present study, we used high fat diet induced obese mice which when sensitized with house dust mite (HDM) showed steroid resistant features...
December 4, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29167232/identification-of-ifn-%C3%AE-and-il-27-as-critical-regulators-of-respiratory-syncytial-virus-induced-exacerbation-of-allergic-airways-disease-in-a-mouse-model
#7
Thi Hiep Nguyen, Steven Maltby, Hock L Tay, Fiona Eyers, Paul S Foster, Ming Yang
Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown...
November 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29130617/dendritic-cell-phenotype-in-severe-asthma-reflects-clinical-responsiveness-to-glucocorticoids
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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