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Steroid dependant asthma

Chih-Ming Weng, Meng-Jung Lee, Jung-Re He, Ming-Wei Chao, Chun-Hua Wang, Han-Pin Kuo
IL-17A is implicated in many aspects of pathogenesis of severe asthma, including inducing neutrophilic inflammation, airway hyperresponsiveness, steroid insensitivity and airway remodeling. Diesel exhaust particles (DEP) emission from vehicles has been shown to expand Th17 cells to increase IL-17A release that contributes to DEP-mediated exacerbation of asthma severity. It is not known whether non-immune cells in airways may also release IL-17A in response to DEP exposure. In this study, We found IL-17A expression was upregulated in the epithelium of severe allergic asthma patients from high road traffic pollution areas compared to those in low...
February 27, 2018: Biochemical Pharmacology
Yuzo Suzuki, Takafumi Suda
Chronic eosinophilic pneumonia (CEP) is an inflammatory disease characterized by accumulations of eosinophils in the lung with unknown etiology. Although corticosteroid treatment dramatically resolves these inflammations, relapse is common during the course of the disease. Approximately 50% of patients with CEP experience relapse. Subsequent to persistent disease and repeated relapse, and in cases of combined severe asthma, some CEP patients are administered corticosteroids indefinitely. Similar to patients with severe asthma who are often steroid dependent, a number of CEP patients exhibit prolonged persistent impairment of pulmonary function...
January 23, 2018: Allergology International: Official Journal of the Japanese Society of Allergology
Eoin Hunt, Deirdre Flynn, Elaine MacHale, Richard W Costello, Desmond M Murphy
INTRODUCTION: Exhaled nitric oxide is believed be a useful surrogate for airways inflammation while non-adherence with therapy is known to be associated with worsening of asthma control. CASE: We present the case of a 49-year-old female with steroid-dependent asthma and an exacerbation rate of >20/year. She was enrolled in a 3-month-long prospective study using a validated diagnostic inhaler device that provided objective evidence of inhaler compliance. Fractional exhaled nitric oxide (FeNO), peak expiratory flow rates, asthma control questionnaires were measured throughout the study period...
December 26, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Partha Palit, Dhrubojyoti Mukherjee, Poulami Mahanta, Md Shadab, Nahid Ali, Shubhadeep Roychoudhury, Md Asad, Subhash C Mandal
The plant Euphorbia tirucalli Linn has been successfully used as a tribal folk medicine in India and Africa for the management of acute inflammatory, arthritic, nociceptive pain and asthmatic symptoms. The present study was conducted to assess the anti-inflammatory, analgesic, anti-asthmatic and anti-arthritic role of the total steroid and terpenoid rich fractions of the hydro-alcoholic extract of E. tirucalli root (STF-HAETR). STF-HAETR fraction demonstrated 71.25 ± 2.5 and 74.25 ± 5.1% protection against acetic acid-induced pain and central neuropathic pain at 75 and 100 mg/kg doses, respectively...
October 23, 2017: Inflammopharmacology
Emily Medlin Martin, Rebecca Louise Till, Mary Katherine Sheats, Samuel L Jones
In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed...
2017: Frontiers in Veterinary Science
Xue Zhang, Jocelyn M Biagini Myers, Veda K Yadagiri, Ashley Ulm, Xiaoting Chen, Matthew T Weirauch, Gurjit K Khurana Hershey, Hong Ji
BACKGROUND: Treatment response to systemic corticosteroid in asthmatic children is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to identify DNA methylation (DNAm) changes responsive to steroid, and DNAm biomarkers that distinguish treatment response. MATERIALS AND METHODS: We followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for asthma exacerbation. Based on whether they met discharge criteria in ≤24 hours, participants were grouped into good and poor responders to steroid treatment...
2017: PloS One
I-Anne Huang, Tang-Her Jaing, Chang-Teng Wu, Chee-Jen Chang, Shan-Hsuan Hsia, Nicole Huang
BACKGROUND: The quality of pediatric emergency care has been a major concern in health care. Following a series of health system reforms in China, it is important to do this assessment of pediatric emergency care, and to explore potential influences of health care system. This study aimed to compare practice differences in treating children with respiratory illnesses in two emergency department (ED) settings within different health care systems: China and Taiwan. METHODS: A pooled cross-sectional hospital-based study was conducted in two tertiary teaching hospitals in Xiamen, China and Keelung, Taiwan belong to the same hospital chain group...
September 11, 2017: BMC Health Services Research
Bryan C Husta, Suhail Raoof, Serpil Erzurum, Atul C Mehta
Inhaled corticosteroids (ICSs) have become the mainstay of asthma control. They are also recommended as an add-on therapy to long-acting beta agonists and anticholinergics in moderate to severe COPD with recurrent exacerbations. Ultimately this clinical practice has led to the widespread use of ICSs, which are supported by a more favorable side effect profile than that of systemic steroids.
December 2017: Chest
Manali Mukherjee, David C Bulir, Katherine Radford, Melanie Kjarsgaard, Chynna Margaret Huang, Elizabeth A Jacobsen, Sergei I Ochkur, Ana Catuneanu, Hanah Lamothe-Kipnes, James Mahony, James J Lee, Paige Lacy, Parameswaran K Nair
BACKGROUND: The persistence of eosinophils in sputum despite high doses of corticosteroids indicates disease severity in asthmatic patients. Chronic inflamed airways can lose tolerance over time to immunogenic entities released on frequent eosinophil degranulation, which further contributes to disease severity and necessitates an increase in maintenance corticosteroids. OBJECTIVES: We sought to investigate the possibility of a polyclonal autoimmune event in the airways of asthmatic patients and to identify associated clinical and molecular characteristics...
July 24, 2017: Journal of Allergy and Clinical Immunology
Jessica Roos, Marcus Peters, Isabelle V Maucher, Benjamin Kühn, Jasmin Fettel, Nadine Hellmuth, Camilla Brat, Benita Sommer, Anja Urbschat, Matthias Piesche, Anja Vogel, Ewgenij Proschak, René Blöcher, Estel la Buscató, Ann-Kathrin Häfner, Carmela Matrone, Oliver Werz, Juliana Heidler, Ilka Wittig, Carlo Angioni, Gerd Geisslinger, Michael J Parnham, Kai Zacharowski, Dieter Steinhilber, Thorsten J Maier
AIMS: 5-Lipoxygenase (5-LO) is the key enzyme of leukotriene (LT) biosynthesis and is critically involved in a number of inflammatory diseases such as arthritis, gout, bronchial asthma, atherosclerosis, and cancer. Because 5-LO contains critical nucleophilic amino acids, which are sensitive to electrophilic modifications, we determined the consequences of a drug-mediated intracellular release of nitric oxide (NO) on 5-LO product formation by human granulocytes and on 5-LO-dependent pulmonary inflammation in vivo...
September 8, 2017: Antioxidants & Redox Signaling
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
L E Barry, J Sweeney, C O'Neill, D Price, L G Heaney
BACKGROUND: Treatment of severe asthma may include high dose systemic-steroid therapy which is associated with substantial additional morbidity. This study estimates the additional healthcare costs associated with steroid-induced morbidity by comparing three patients groups: those with severe asthma, moderate asthma and no asthma. METHODS: Patients with severe asthma (n = 808, GINA step 5 treatment) were matched by age and gender with patients with mild/moderate asthma (n = 3,975, GINA step 2 and 3 treatment) and a non-asthma control cohort (with a diagnosis of rhinitis; n = 2,412) from the Optimum Patient Care Research Database (OPCRD), a nationally representative primary care database...
June 26, 2017: Respiratory Research
Caroline Sanden, Michiko Mori, Prajakta Jogdand, Jimmie Jönsson, Ravi Krishnan, Xiangdong Wang, Jonas S Erjefält
BACKGROUND: Th2 cytokines like interleukin-4, -5, and -13 are regarded as important drivers of the immunopathology underlying allergic rhinitis (AR) and asthma. The present study explores the capacity of pentosan polysulfate sodium (PPS), a semi-synthetic heparin-like macromolecular carbohydrate, to bind Th2 cytokines and exert biological neutralization in vitro, as well as anti-inflammatory actions in vivo. METHODOLOGY: The capacity of PPS to bind recombinant Th2 cytokines was tested with surface plasmon resonance (SPR) technology and biological Th2 neutralization was assessed by Th2-dependent proliferation assays...
September 2017: Immunity, Inflammation and Disease
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
Kayleigh M Kew, Robin Carr, Iain Crossingham
BACKGROUND: Adolescents with asthma are at high risk of poor adherence with treatment. This may be compounded by activities that worsen asthma, in particular smoking. Additional support above and beyond routine care has the potential to encourage good self-management. We wanted to find out whether sessions led by their peers or by lay leaders help to reduce these risks and improve asthma outcomes among adolescents. OBJECTIVES: To assess the safety and efficacy of lay-led and peer support interventions for adolescents with asthma...
April 19, 2017: Cochrane Database of Systematic Reviews
Katie Baker, Kristof Raemdonck, Robert J Snelgrove, Maria G Belvisi, Mark A Birrell
BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the current available therapies are effective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In the search to understand disease pathogenesis and find effective therapies hypotheses are often tested in animal models before progressing into clinical studies. However, current dogma is that animal model data is often not predictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challenge induced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal model systems...
April 11, 2017: Respiratory Research
Stacey N Reinke, Héctor Gallart-Ayala, Cristina Gómez, Antonio Checa, Alexander Fauland, Shama Naz, Muhammad Anas Kamleh, Ratko Djukanović, Timothy S C Hinks, Craig E Wheelock
In this study, we sought to determine whether asthma has a metabolic profile and whether this profile is related to disease severity.We characterised the serum from 22 healthy individuals and 54 asthmatics (12 mild, 20 moderate, 22 severe) using liquid chromatography-high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted mass spectrometry assays of eicosanoids, sphingolipids and free fatty acids.We conclusively identified 66 metabolites; 15 were significantly altered with asthma (p≤0...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Johanna Melin, Susanne Prothon, Charlotte Kloft, Adriaan Cleton, Carl Amilon, Carin Jorup, Per Bäckman, Bo Olsson, Ulrika Wählby Hamrén
AZD5423 is a non-steroidal glucocorticoid receptor modulator, with low aqueous solubility, developed for treatment of asthma and COPD. In this work, we aim to evaluate and compare the absorption pharmacokinetics (PK) of AZD5423 after inhalation via four devices, (Spira®, I-neb®, Turbuhaler® and a new dry powder inhaler (new DPI)) with two formulations using differently sized primary particles, and to compare the pulmonary bioavailability with the predicted lung deposited dose. Plasma concentration-time data after intravenous, oral and inhaled administration via four devices were available from two clinical studies in healthy and asthmatic subjects...
May 2017: AAPS Journal
Richard Y Kim, James W Pinkerton, Ama T Essilfie, Avril A B Robertson, Katherine J Baines, Alexandra C Brown, Jemma R Mayall, M 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 nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, 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...
August 1, 2017: American Journal of Respiratory and Critical Care Medicine
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
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