Read by QxMD icon Read

Anti IL5 treatment

Manali Mukherjee, Hui Fang Lim, Sruthi Thomas, Douglas Miller, Melanie Kjarsgaard, Bruce Tan, Roma Sehmi, Nader Khalidi, Parameswaran Nair
BACKGROUND: Anti-interleukin (IL)-5 monoclonal antibodies as an eosinophil-depleting strategy is well established, with Mepolizumab being the first biologic approved as an adjunct treatment for severe eosinophilic asthma. CASE PRESENTATION: A 62-year old woman diagnosed with severe eosinophilic asthma showed poor response to Mepolizumab therapy (100 mg subcutaneous dose/monthly) and subsequent worsening of symptoms. The treatment response to Mepolizumab was monitored using both blood and sputum eosinophil counts...
2017: Allergy, Asthma, and Clinical Immunology
Eóin N McNamee, Kathryn A Biette, Juliet Hammer, Rachel Harris, Heather Miyazawa, James J Lee, Glenn T Furuta, Joanne C Masterson
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting GM-CSF (an agonist cytokine linked with eosinophil survival and activation) would be protective in a pre-clinical model of EoE...
December 7, 2016: Allergy
Kristine A Smith, Luke Rudmik
PURPOSE OF REVIEW: The purpose of this review is to address the most recent advances in the medical therapy for chronic rhinosinusitis (CRS), define recalcitrant and refractory CRS, and discuss the productivity costs associated with CRS. RECENT FINDINGS: Recent studies evaluating anti-IL-4 receptor α antibodies and calcium channel blockers have demonstrated promising early results during management of CRS. Recent appropriateness criteria have been developed to assist clinicians with defining which patients have 'refractory' CRS and may be considered candidates for endoscopic sinus surgery...
February 2017: Current Opinion in Allergy and Clinical Immunology
Y Cabon, N Molinari, G Marin, I Vachier, A S Gamez, P Chanez, A Bourdin
Inconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCTs with anti-IL5 treatments for patients with asthma over the 1990-September 2015 period. RCTs were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV1 changes, ACQ-5 improvement, adverse events and serious adverse events...
January 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Lara Ravanetti, Annemiek Dijkhuis, Yanaika S Sabogal Pineros, Suzanne M Bal, Barbara S Dierdorp, Tamara Dekker, Adrian Logiantara, Ian M Adcock, Navin L Rao, Louis Boon, Gino Villetti, Peter J Sterk, Fabrizio Facchinetti, René Lutter
BACKGROUND: Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics. AIM: We developed and characterized a robust, consistent and reproducible mouse model of severe exacerbation of chronic allergic asthma. METHODS: Chronic allergic airway inflammation was induced following a house dust mite (HDM)-sensitization protocol...
October 3, 2016: Allergy
Vanessa Popp, Katharina Gerlach, Stefanie Mott, Agnieszka Turowska, Holger Garn, Raja Atreya, Hans-Anton Lehr, I-Cheng Ho, Harald Renz, Benno Weigmann, Markus F Neurath
BACKGROUND & AIMS: GATA3 is a transcription factor that regulates T-cell production of cytokines. We investigated the role of GATA3 in development of colitis in mice. METHODS: We performed quantitative polymerase chain reaction and immunofluorescence analyses of colon tissues from patients with Crohn's disease (n = 61) or ulcerative colitis (UC, n = 74) or from patients without inflammatory bowel diseases (n = 22), to measure levels of GATA3. Colitis was induced by administration of oxazolone or 2,4,6-trinitrobenzenesulfonic acid to control mice, mice with T-cell-specific deletion of GATA3, and mice with deletion of tumor necrosis factor receptor (TNFR) 1 and TNFR2 (TNFR double knockouts); some mice were given a GATA3-specific DNAzyme (hgd40) or a control DNAzyme via intrarectal administration, or systemic injections of an antibody to TNF before or during sensitization and challenge phase of colitis induction...
January 2017: Gastroenterology
Ramakrishna Edukulla, Kira Lee Rehn, Bo Liu, Jaclyn W McAlees, Gurjit K Hershey, Yui Hsi Wang, Ian Lewkowich, Andrew W Lindsley
INTRODUCTION: Ceramide is the central substrate of sphingolipid metabolism and plays a key role in cellular signal transduction pathways, regulating apoptosis, differentiation, and chemotaxis. Alterations in airway ceramide levels are observed in multiple pulmonary diseases and recent human genetic association studies have linked dysregulation of sphingolipid regulatory genes with asthma pathogenesis. METHODS: Utilizing myriocin, a potent inhibitor of sphingolipid synthesis, we evaluated the immune regulatory role of de novo ceramide generation in vitro and in vivo...
September 2016: Immunity, Inflammation and Disease
Gretchen M Oakley, Richard J Harvey
Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition with heterogeneous pathophysiology. A cornerstone of the management of this condition is the use of anti-inflammatory agents. Corticosteroids are very effective and the most commonly used, but other drugs with immunodulatory activity such as anti-IL5, doxycycline (Th2), and macrolides (anti-neutrophilic/IL8) have been shown to have efficacy. Although systemic corticosteroids have shown benefit in managing this condition, the frequency of use often required in this condition is associated with significant adverse effects...
2016: Advances in Oto-rhino-laryngology
Naohiro Tsukamoto, Naoki Takahashi, Hiroshi Itoh, Isabelle Pouliquen
Interleukin 5 (IL-5) and eosinophils are thought to play an important role in the pathology of asthma. This study evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of mepolizumab, a humanized anti-IL5 IgG1 monoclonal antibody, in development for the treatment of severe eosinophilic asthma. This single-blind study randomized 35 healthy Japanese male subjects (3:1) to receive either a single mepolizumab intravenous dose (10, 75, 250, or 750 mg) or placebo. Subjects were observed for up to 151 days postdose, depending on the dose administered...
March 2016: Clinical Pharmacology in Drug Development
Bram D van Rhijn, Joanne Verheij, Marius A van den Bergh Weerman, Caroline Verseijden, René M J G J van den Wijngaard, Wouter J de Jonge, Andreas J P M Smout, Albert J Bredenoord
OBJECTIVES: The esophageal mucosal integrity is impaired in patients with eosinophilic esophagitis (EoE). We aimed to evaluate the effect of fluticasone propionate on inflammation and functional and structural markers of esophageal mucosal barrier integrity in adult patients with EoE. METHODS: In this prospective study, we included 15 EoE patients (median age (IQR), 43 (30-45) years). Patients underwent upper endoscopy before and after an 8-week course of swallowed fluticasone propionate 500 μg BID...
September 2015: American Journal of Gastroenterology
Qi Yang, Moyar Q Ge, Blerina Kokalari, Imre G Redai, Xinxin Wang, David M Kemeny, Avinash Bhandoola, Angela Haczku
BACKGROUND: Asthmatic patients are highly susceptible to air pollution and in particular to the effects of ozone (O3) inhalation, but the underlying mechanisms remain unclear. OBJECTIVE: Using mouse models of O3-induced airway inflammation and airway hyperresponsiveness (AHR), we sought to investigate the role of the recently discovered group 2 innate lymphoid cells (ILC2s). METHODS: C57BL/6 and BALB/c mice were exposed to Aspergillus fumigatus, O3, or both (3 ppm for 2 hours)...
February 2016: Journal of Allergy and Clinical Immunology
J Lemale, L Dainese, P Tounian
Eosinophilic gastrointestinal disorders are a heterogeneous group of disorders characterized by no specific digestive symptoms associated with dense eosinophilic inflammation of the gastrointestinal tract in the absence of known causes for such tissue eosinophilia. Among these diseases, eosinophilic gastroenteritis (EGE) and colitis (EC) are less common than esophagitis, but their incidence and prevalence have been increasing over the past decade due in part to increased disease recognition. The exact pathophysiology is not clear: EGE and EC are immune-mediated diseases implicating adaptive T-helper cell type 2 immunity...
July 2015: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Manali Mukherjee, Roma Sehmi, Parameswaran Nair
Airway inflammation is considered to be the primary component contributing to the heterogeneity and severity of airway disorders. Therapeutic efficacies of diverse novel biologics targeting the inflammatory pathways are under investigation. One such target is IL-5, a type-1 cytokine that is central to the initiation and sustenance of eosinophilic airway inflammation. Over the past decade, anti-IL5 molecules have been documented to have mixed therapeutic benefits in asthmatics. Post hoc analyses of the trials reiterate the importance of identifying the IL-5-responsive patient endotypes...
2014: World Allergy Organization Journal
B Hilvering, I D Pavord
Asthma is a heterogeneous airway disease characterized by typical symptoms in combination with variable airway obstruction. Most patients with asthma have well controlled symptoms and a low risk of asthma attacks with inhaled corticosteroid (ICS) treatment. However, a clinically important subgroup (~ 10%) remains symptomatic and/or at risk of asthma attacks despite maximum inhaled therapy. Patients with severe asthma are responsible for a significant proportion of healthcare costs attributable to asthma and have a large unmet need for better treatments...
July 2015: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Teresa Hemmerle, Silvana Zgraggen, Mattia Matasci, Cornelia Halin, Michael Detmar, Dario Neri
BACKGROUND: The antibody-mediated delivery of cytokines ("immunocytokines") to sites of pathological angiogenesis represents an attractive strategy for the development of innovative biopharmaceuticals, capable of modulating the activity of the immune system in cancer and in chronic inflammatory conditions. OBJECTIVE: Recombinant IL4 has previously been shown to be therapeutically active in patients with psoriasis. The antibody-mediated delivery of this cytokine to sites of chronic skin inflammatory conditions should lead to an improved potency and selectivity, compared to non-targeted IL4...
November 2014: Journal of Dermatological Science
Ronen Bar Yoseph, Galit Livnat, Zeev Schnapp, Fahed Hakim, Husein Dabbah, Aviv Goldbart, Lea Bentur
BACKGROUND: Cross-sectional studies have reported an association of vitamin D deficiency with increased asthma prevalence and severity, and with allergies. The effect of vitamin D as sole therapy on airway hyper-reactivity (AHR) and airway inflammation has not been reported. AIM: To evaluate the effect of vitamin D therapy on AHR as assessed by methacholine concentration, causing a 20% reduction in FEV1 (PC20 -FEV1 ) and fractional exhaled nitric oxide (FeNO), systemic markers of allergy and inflammation, and exhaled breath condensate cytokines...
August 2015: Pediatric Pulmonology
C Persson
Primary lysis of eosinophils liberates free eosinophil granules (FEGs) releasing toxic proteins in association with bronchial epithelial injury repair. Eosinophil lysis may be significantly pathogenic. Bronchial mucosal FEGs are associated with uncontrolled asthma, severe asthma, aspirin-sensitive asthma, and lethal asthma. FEGs in the bronchial wall may characterize severe asthma without sputum eosinophilia. Excessive numbers of sputum FEGs occur in severe exacerbations of asthma and are reduced along with clinical improvement...
February 2014: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Wiparat Manuyakorn, Peter H Howarth, Stephen T Holgate
Asthma is an airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness (BHR) and airflow obstruction. Airway structural changes or airway remodelling consist of epithelial injury, goblet cell hyperplasia, subepithelial layer thickening, airway smooth muscle hyperplasia and angiogenesis. These changes were previously considered as a consequence of chronic airway inflammation. However, several studies have demonstrated that inflammation and remodelling can occur as separate but parallel aspects of the asthmatic process...
March 2013: Asian Pacific Journal of Allergy and Immunology
Joanne C Masterson, Eóin N McNamee, Lindsay Hosford, Kelley E Capocelli, Joseph Ruybal, Sophie A Fillon, Alfred D Doyle, Holger K Eltzschig, Anil K Rustgi, Cheryl A Protheroe, Nancy A Lee, James J Lee, Glenn T Furuta
OBJECTIVE: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia. DESIGN: We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia...
January 2014: Gut
Jonathan Corren
Elevated numbers of blood and tissue eosinophils are present in allergic diseases and experimental evidence suggests that eosinophils play an important pathogenic role in these conditions. Regulation of eosinophil maturation, recruitment, and survival is under the control of a small group of factors, including interleukin-5 (IL-5). Given the probable importance of eosinophils to allergy and other associated disorders, IL-5 has been proposed as a potential molecular target in the treatment of these diseases...
April 2012: Discovery Medicine
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"