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Steroid dependant asthma

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https://www.readbyqxmd.com/read/28751233/sputum-autoantibodies-in-severe-eosinophilic-asthma
#1
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 asthma. Chronic inflamed airways over time may lose tolerance to immunogenic entities released upon frequent eosinophil degranulation, which further contributes to disease severity and necessitates increase in maintenance corticosteroids. OBJECTIVES: To investigate the possibility of a polyclonal autoimmune event in asthmatic airways, and identify associated clinical and molecular characteristics...
July 24, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28699354/drug-mediated-intracellular-donation-of-nitric-oxide-potently-inhibits-5-lipoxygenase-a-possible-key-to-future-anti-leukotriene-therapy
#2
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 Buscato, Ann-Kathrin Häfner, Carmela Matrone, Oliver Werz, Juliana Heidler, Ilka Wittig, Carlo Angioni, Gerd Geisslinger, Michael J Parnham, Kai Zacharowski, Dieter Steinhilber, Thorsten Jürgen Maier
AIMS: 5-lipoxygenase (5-LO) is the key enzyme of leukotriene 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...
July 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28658543/modeling-th-2-responses-and-airway-inflammation-to-understand-fundamental-mechanisms-regulating-the-pathogenesis-of-asthma
#3
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/28651591/the-cost-of-systemic-corticosteroid-induced-morbidity-in-severe-asthma-a-health-economic-analysis
#4
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
https://www.readbyqxmd.com/read/28497614/broad-th2-neutralization-and-anti-inflammatory-action-of-pentosan-polysulfate-sodium-in-experimental-allergic-rhinitis
#5
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...
May 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-from-patients-with-severe-asthma-the-role-of-thymic-stromal-lymphopoietin
#6
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
https://www.readbyqxmd.com/read/28421600/lay-led-and-peer-support-interventions-for-adolescents-with-asthma
#7
REVIEW
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
https://www.readbyqxmd.com/read/28399855/characterisation-of-a-murine-model-of-the-late-asthmatic-response
#8
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
https://www.readbyqxmd.com/read/28356371/metabolomics-analysis-identifies-different-metabotypes-of-asthma-severity
#9
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
https://www.readbyqxmd.com/read/28281196/pharmacokinetics-of-the-inhaled-selective-glucocorticoid-receptor-modulator-azd5423-following-inhalation-using-different-devices
#10
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...
March 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28252317/role-for-nlrp3-inflammasome-mediated-il-1%C3%AE-dependent-responses-in-severe-steroid-resistant-asthma
#11
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
https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#12
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
https://www.readbyqxmd.com/read/28176948/theophylline-action-on-primary-human-bronchial-epithelial-cells-under-proinflammatory-stimuli-and-steroidal-drugs-a-therapeutic-rationale-approach
#13
Luca Gallelli, Daniela Falcone, Roberto Cannataro, Mariarita Perri, Raffaele Serra, Girolamo Pelaia, Rosario Maselli, Rocco Savino, Giuseppe Spaziano, Bruno D'Agostino
Theophylline is a natural compound present in tea. Because of its property to relax smooth muscle it is used in pharmacology for the treatment of airway diseases (ie, chronic obstructive pulmonary disease, asthma). However, this effect on smooth muscle is dose dependent and it is related to the development of side effects. Recently, an increasing body of evidence suggests that theophylline, at low concentrations, also has anti-inflammatory effects related to the activation of histone deacetylases. In this study, we evaluated the effects of theophylline alone and in combination with corticosteroids on human bronchial epithelial cells under inflammatory stimuli...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28089919/an-orally-active-geranyl-acetophenone-attenuates-airway-remodeling-in-a-murine-model-of-chronic-asthma
#14
Yu Zhao Lee, Khozirah Shaari, Manraj Singh Cheema, Chau Ling Tham, Mohd Roslan Sulaiman, Daud Ahmad Israf
2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a synthetic compound that is naturally found in Melicope ptelefolia. We had previously demonstrated that parenteral administration of tHGA reduces pulmonary inflammation in OVA-sensitized mice. In this study, we evaluated the effect of orally administered tHGA upon airway remodeling in a murine model of chronic asthma. Female BALB/C mice were sensitized intraperitoneally with ovalbumin (OVA) on day 0, 7 and 14, followed by aerosolized 1% OVA 3 times per week for 6 weeks...
February 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27852250/impaired-anti-inflammatory-action-of-glucocorticoid-in-neutrophil-from-patients-with-steroid-resistant-asthma
#15
Meijia Wang, Pengfei Gao, Xiaojie Wu, Yuetao Chen, Yikuan Feng, Qun Yang, Yongjian Xu, Jianping Zhao, Jungang Xie
BACKGROUND: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared to SR asthmatics. METHODS: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following a one-month inhaled corticosteroid (ICS) treatment...
November 16, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27815425/stat6-regulates-the-development-of-eosinophilic-versus-neutrophilic-asthma-in-response-to-alternaria-alternata
#16
COMPARATIVE STUDY
Andrea C Valladao, Charles W Frevert, Lisa K Koch, Daniel J Campbell, Steven F Ziegler
Human asthma is a heterogeneous disease characterized by the expression of both Th2 and Th17 cytokines. In vitro and in vivo studies have shown a reciprocal regulation between Th2 and Th17 pathways, suggesting a potential induction of neutrophil-promoting Th17 inflammation in the absence of a Th2 response. Alternaria alternata is a clinically relevant allergen that is associated with severe and fatal asthma exacerbations. Exposure to A. alternata is characterized by a predominant Th2 response, but can also induce the production of factors associated with Th17 responses (e...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27742828/cytokine-induced-glucocorticoid-resistance-from-eosinophil-activation-protein-phosphatase-5-modulation-of-glucocorticoid-receptor-phosphorylation-and-signaling
#17
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...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27719658/aspirin-intolerance-experimental-models-for-bed-to-bench
#18
Masamichi Yamashita
Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms...
2016: Current Drug Targets
https://www.readbyqxmd.com/read/27649894/cognitive-behavioural-therapy-cbt-for-adults-and-adolescents-with-asthma
#19
Kayleigh M Kew, Marina Nashed, Valdeep Dulay, Janelle Yorke
BACKGROUND: People with asthma have a higher prevalence of anxiety and depression than the general population. This is associated with poorer asthma control, medication adherence, and health outcomes. Cognitive behavioural therapy (CBT) may be a way to improve the quality of life of people with asthma by addressing associated psychological issues, which may lead to a lower risk of exacerbations and better asthma control. OBJECTIVES: To assess the efficacy of CBT for asthma compared with usual care...
September 21, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27582398/eicosanoid-mediators-in-the-airway-inflammation-of-asthmatic-patients-what-is-new
#20
REVIEW
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
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