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Steroid resistant asthma

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...
October 18, 2016: Cellular and Molecular Life Sciences: CMLS
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 paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4...
October 13, 2016: Journal of Allergy and Clinical Immunology
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...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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
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
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
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
Richard Y Kim, Brittany Rae, Rachel Neal, Chantal Donovan, James Pinkerton, Lohis Balachandran, Malcolm R Starkey, Darryl A Knight, Jay C Horvat, Philip M Hansbro
Corticosteroids are broadly active and potent anti-inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose-limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure...
July 2016: Clinical & Translational Immunology
Jeffrey R Stokes, Thomas B Casale
OBJECTIVE: To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers. DATA SOURCES: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (TH2)-low and TH2-high asthma. STUDY SELECTIONS: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic...
August 2016: Annals of Allergy, Asthma & Immunology
Ibrahim Sulaiman, Jonathan Chee Woei Lim, Hon Liong Soo, Johnson Stanslas
Extensive research into the therapeutics of asthma has yielded numerous effective interventions over the past few decades. However, adverse effects and ineffectiveness of most of these medications especially in the management of steroid resistant severe asthma necessitate the development of better medications. Numerous drug targets with inherent airway smooth muscle tone modulatory role have been identified for asthma therapy. This article reviews the latest understanding of underlying molecular aetiology of asthma towards design and development of better antiasthma drugs...
October 2016: Pulmonary Pharmacology & Therapeutics
Izabela Kupryś-Lipińska, Katarzyna Molińska, Piotr Kuna
Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically...
2016: Pneumonologia i Alergologia Polska
A C Gavino, K Nahmod, U Bharadwaj, G Makedonas, D J Tweardy
BACKGROUND: STAT3 drives development of Th17 cells and cytokine production by Th2 and Th17 cells, which contribute to asthma. Alternative asthma treatments are needed, especially for the Th17 phenotype. We sought to determine whether C188-9, a small-molecule STAT3 inhibitor, can block Th2 and Th17 cell expansion and cytokine production to prevent house dust mite (HDM)-induced airway inflammation and remodeling. METHODS: Three groups of C57BL/6 mice were treated intranasally (IN) and intraperitoneally (IP) daily for 3 weeks with the following: (i) vehicle 1 IN and vehicle 2 IP, (ii) HDM IN and vehicle 2 IP, or (iii) HDM IN and C188-9 IP...
May 26, 2016: Allergy
Zhonghua Zhang, Jocelyn M Biagini Myers, Eric B Brandt, Patrick H Ryan, Mark Lindsey, Rachael A Mintz-Cole, Tiina Reponen, Stephen J Vesper, Frank Forde, Brandy Ruff, Stacey A Bass, Grace K LeMasters, David I Bernstein, James Lockey, Alison L Budelsky, Gurjit K Khurana Hershey
BACKGROUND: Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. OBJECTIVE: We sought to determine the mechanism by which fungi affect asthma development and severity. METHODS: We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity...
April 20, 2016: Journal of Allergy and Clinical Immunology
José Eduardo Vargas, Bárbara Nery Porto, Renato Puga, Renato Tetelbom Stein, Paulo Márcio Pitrez
Corticosteroid resistance (CR) is a major barrier to the effective treatment of severe asthma. Hence, a better understanding of the molecular mechanisms involved in this condition is a priority. Network analysis is an emerging strategy to explore this complex heterogeneous disorder at system level to identify a small own network for CR in asthma. Gene expression profile of GSE7368 from bronchoalveolar lavage (BAL) of CR in subjects with asthma was downloaded from the gene expression omnibus (GEO) database and compared to BAL of corticosteroid-sensitive (CS) patients...
July 2016: Molecular Biology Reports
Wupeng Liao, W S Daniel Tan, W S Fred Wong
LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-γ-induced IL-27 production and AHR via its antioxidative property...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
William B Klaustermeyer, Soo H Choi
BACKGROUND: Systemic corticosteroids have been used in the treatment of asthma since 1950 and are still required for the treatment of acute severe asthma and corticosteroid dependent asthma. OBJECTIVE: To provide an updated overview of clinical considerations of systemic corticosteroids use in severe adult bronchial asthma. METHODS: PubMed searches were undertaken of studies published between 1950 and 2015. RESULTS: In this review the following concepts are discussed...
May 2016: Allergy and Asthma Proceedings:
Hongjuan Jiang, Xiangyu Chi, Xuan Zhang, Jing Wang
BACKGROUND: Asthmatic symptoms usually can be controlled with corticosteroids, but partly asthmatic patients do not respond to corticosteroids, steroid resistance (SR) play a significant role in the poorly responding. However, no approach can accurately predict steroid responsiveness in asthma patients, so prediction of SR with noninvasive means has become a critical issue. OBJECTIVE: The aim of this study was to evaluate the difference in serum proteomes between steroid-sensitive asthma (SSA) and steroid-resistant asthma (SRA) patients and identify potential biomarkers for the prediction of SR in asthma patients...
May 2016: Respiratory Medicine
Cara J Bossley, Louise Fleming, Nicola Ullmann, Atul Gupta, Alexandra Adams, Prasad Nagakumar, Andrew Bush, Sejal Saglani
BACKGROUND: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients. OBJECTIVE: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA. METHODS: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid...
August 2016: Journal of Allergy and Clinical Immunology
Thi Hiep Nguyen, Steven Maltby, Jodie L Simpson, Fiona Eyers, Katherine J Baines, Peter G Gibson, Paul S Foster, Ming Yang
Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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