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Steroid resistant asthma

Michael C Peters, Sheena Kerr, Eleanor M Dunican, Prescott G Woodruff, Merritt L Fajt, Bruce D Levy, Elliot Israel, Brenda R Phillips, David T Mauger, Suzy A Comhair, Serpil C Erzurum, Mats W Johansson, Nizar N Jarjour, Andrea M Coverstone, Mario Castro, Annette T Hastie, Eugene R Bleecker, Sally E Wenzel, John V Fahy
BACKGROUND: Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients on high dose inhaled corticosteroids (ICS) is uncertain. OBJECTIVE: To determine if airway type 2 inflammation persists in patients treated with ICS and to evaluate the clinical features of patients with steroid resistant airway type-2 inflammation. METHODS: We used qPCR to generate a composite metric of type-2 cytokine gene expression (type 2 Gene Mean, "T2GM") in induced sputum cells from healthy controls, severe asthma patients on ICS (n=174), and non-severe asthma patients on ICS (n=85)...
March 7, 2018: Journal of Allergy and Clinical Immunology
Virginia Mirra, Silvia Montella, Francesca Santamaria
BACKGROUND: The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly "severe therapy-resistant" asthmatics by a proper filtering process...
February 21, 2018: BMC Pediatrics
Zeyu Zeng, Xixi Lin, Rongying Zheng, Hui Zhang, Weixi Zhang
Severe airway hyperresponsiveness (AHR) is a clinical feature of asthma, which has been associated with obesity and has shown a poor response to standard asthma treatments such as glucocorticoids. Numerous studies have shown that Interleukin (IL)-17 producing CD4 + T cells (Th17 cells), which could be inhibited by celastrol, is essential in mediating steroid-resistant AHR. The following study investigates the impact of celastrol and its mechanism on the regulation of AHR in murine model of obesity and asthma...
2018: Frontiers in Pharmacology
Michael J McGeachie, George L Clemmer, Boris Hayete, Heming Xing, Karl Runge, Ann Chen Wu, Xiaofeng Jiang, Quan Lu, Bruce Church, Iya Khalil, Kelan Tantisira, Scott Weiss
BACKGROUND: Variation in response to the most commonly used class of asthma controller medication, inhaled corticosteroids (ICS), presents a serious challenge in asthma management, particularly for steroid-resistant patients who display little or no response to treatment. OBJECTIVE: We applied a systems-biology approach to primary clinical and genomic data to identify and validate genes that modulate steroid response in children with asthma. METHODS: We selected 104 ICS-treated asthmatic non-Hispanic white children and determined a Steroid Responsiveness Endophenotype (SRE) using observations of six clinical measures over four years...
January 30, 2018: Journal of Allergy and Clinical Immunology
Elena Janeva-Jovanovska, Dejan Dokic, Biserka Jovkovska-Kaeva, Gorica Breskovska, Zlatica Goseva, Jordan Minov, Dejan Trajkov, Magdalena Dimitrova-Genadieva, Beti Zafirovska-Ivanovska
BACKGROUND: Recently epidemiological studies showed that low vitamin D is linked to airway hyperresponsiveness, decreased lung function, poor asthma control, and steroid-resistant asthma. AIM: We investigated the relationship between Vitamin D, inflammation with circulating IL-33 and lung function in 30 patients with severe uncontrolled asthma. MATERIALS AND METHODS: The study included 30 patients with severe uncontrolled asthma. In each of them were measured serum levels of IL-33 and Vitamin D by the ELISA method...
December 15, 2017: Open Access Macedonian Journal of Medical Sciences
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
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
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
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
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
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...
February 2018: International Immunopharmacology
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
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
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
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
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 affects prognosis and, most importantly, is necessary as the basis for making therapeutic decisions. The need for individualized definitions of pathogenic mechanisms before initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics, where, barring an influence from their off-target anti-inflammatory pharmacologic effects, an understanding of the role of the individual biome predicts likelihood of therapeutic benefit...
December 2017: Journal of Allergy and Clinical Immunology
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
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
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
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
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