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https://www.readbyqxmd.com/read/29134633/first-in-human-study-with-the-inhaled-tlr9-oligonucleotide-agonist-azd1419-results-in-interferon-responses-in-the-lung-and-is-safe-and-well-tolerated
#1
Sam Jackson, Albert F Candia, Stephen Delaney, Simone Floettmann, Clifford Wong, John D Campbell, Sariah Kell, Jeremy Lum, Edith Hessel, Paula Traquina, Mark McHale, Ian Robinson, John Bell, Rainard Fuhr, David Keeling, Robert L Coffman
Current asthma treatments address symptoms rather than the underlying disease pathophysiology, a better understanding of which has led to the identification of the Th2 high endotype. The activation of Toll-like receptors to induce Type I interferons directly in the lungs represents a novel therapeutic approach to reset this underlying Th2 pathophysiology with the potential to provide long-term disease modification. We present the nonclinical data and phase 1 clinical profile of an inhaled TLR9 agonist, AZD1419, a C-type CpG designed to induce interferon in the lung...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29122081/gender-specific-differences-in-serum-immunoglobulin-e-levels-and-prevalence-of-fungus-in-sinonasal-tissue-noted-in-patients-with-chronic-rhinosinusitis-who-underwent-endoscopic-sinus-surgery
#2
Antoine Azar, Matthew A Rank, Matthew A Zarka, Yu-Hui Chang, Devyani Lal
BACKGROUND: We previously presented that women with chronic rhinosinusitis (CRS) who elected endoscopic sinus surgery (ESS) have a higher symptom burden than men. Causes of these gender-based differences warranted further study. OBJECTIVES: To study gender differences in another cohort of adult patients with CRS who underwent ESS and to compare key histopathologic and serologic features Methods: Patients with CRS who underwent ESS (from 2011 to 2014) with structured histopathology reports on surgical samples were studied...
November 1, 2017: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29120932/an-update-on-preoperative-assessment-and-preparation-of-surgical-patients-with-obstructive-sleep-apnea
#3
Poorna Madhusudan, Jean Wong, Arun Prasad, Elena Sadeghian, Frances F Chung
PURPOSE OF REVIEW: There is a high prevalence of obstructive sleep apnea (OSA) in the surgical population, however, a significant proportion of patients are undiagnosed. The Society of Anesthesia and Sleep Medicine (SASM) has issued recent guidelines for preoperative assessment and preparation of patients with known or suspected OSA. The purpose of this review is to highlight key points in the new guidelines and explore the possibilities of different strategies in optimizing patients with OSA preoperatively...
November 7, 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/29119328/endoplasmic-reticulum-stress-and-allergic-diseases
#4
REVIEW
Jae Seok Jeong, So Ri Kim, Seong Ho Cho, Yong Chul Lee
PURPOSE OF REVIEW: In this review, we will integrate recent knowledge on endoplasmic reticulum (ER) stress and allergy, thereby highlighting the therapeutic potential of ER stress in the context of precision medicine for allergic diseases. RECENT FINDINGS: Emerging evidence suggests that allergic diseases are very heterogeneous having numerous endotypes. This leads to the new era of modern medicine, which assumes that a particular endotype-driven therapy, called precision medicine, would be more efficacious in a specific group of patients rather than in all patients...
November 8, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/29106996/chronic-rhinosinusitis-endotypes-biomarkers-and-treatment-response
#5
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 impacts prognosis and most importantly is necessary as the basis for making therapeutic decisions. The need for individualized defining of pathogenic mechanisms prior to initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics where, barring an influence from their off-target anti-inflammatory pharmacological effects, an understanding of the role of individual biome predicts likelihood of therapeutic benefit...
October 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29077521/new-approaches-for-identifying-and-testing-potential-new-anti-asthma-agents
#6
Amelia Licari, Riccardo Castagnoli, Ilaria Brambilla, Alessia Marseglia, Maria Angela Tosca, Gian Luigi Marseglia, Giorgio Ciprandi
Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities...
October 27, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29071712/the-role-of-the-microbiome-in-psoriasis-moving-from-disease-description-to-treatment-prediction
#7
REVIEW
E A Langan, C E M Griffiths, W Solbach, J K Knobloch, D Zillikens, D Thaçi
With several million microbes per cm(2) of skin, the task of mapping the physiological cutaneous microbiome is enormous. Indeed, the reliance on bacterial culture to identify cutaneous bacterial communities has led to a systematic under-appreciation of cutaneous microbial diversity, potentially limiting our understanding of common inflammatory skin diseases including psoriasis. However, based heavily on developments in molecular biology and bioinformatics, including next generation sequencing, the last decade has witnessed a marked increase in our understanding of the extent and composition of the cutaneous microbiome...
October 26, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29059087/controversies-and-opportunities-in-severe-asthma
#8
Marc Humbert, William Busse, Nicola A Hanania
PURPOSE OF REVIEW: Despite currently available treatments, many asthma patients remain inadequately controlled, but identifying distinct patient populations (phenotypes/endotypes) may optimize their management. This review discusses some of the controversies and opportunities for improved disease control in severe asthma. RECENT FINDINGS: Currently approved anti-immunoglobulin E and anti-interleukin 5 biologics, which target specific pathways instead of using a 'one size fits all' strategy, are efficacious and well tolerated therapies for severe asthma...
October 20, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29051276/precision-medicine-in-airway-diseases-moving-to-clinical-practice
#9
Alvar Agustí, Mona Bafadhel, Richard Beasley, Elisabeth H Bel, Rosa Faner, Peter G Gibson, Renaud Louis, Vanessa M McDonald, Peter J Sterk, Mike Thomas, Claus Vogelmeier, Ian D Pavord
On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often overlap and that both require individualised assessment and treatment. This paper summarises the presentations and discussions that took place during the seminar. Specifically, we discussed the need for a new taxonomy of human diseases, the role of different players in this scenario (exposome, genes, endotypes, phenotypes, biomarkers and treatable traits) and a number of unanswered key questions in the field...
October 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29049049/treatable-traits-of-chronic-airways-disease
#10
James Fingleton, Jo Hardy, Richard Beasley
PURPOSE OF REVIEW: To describe the rationale on which the treatable traits approach to the management of airways disease is based and the issues that need to be considered for its implementation in clinical practice. RECENT FINDINGS: In clinical practice, treatable traits can be classified according to both endotypes and phenotypes, broadly grouped within pulmonary, extrapulmonary, environmental and behavioural factors. Specific investigations and treatments are undertaken for each of the traits rather than a 'one size fits all' stepwise approach to pharmacological treatment which currently represents the core of asthma and chronic obstructive pulmonary disease (COPD) guidelines...
October 18, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29046192/management-of-adverse-reactions-to-biologic-agents
#11
Ghislaine Annie C Isabwe, Leticia de Las Vecillas Sanchez, Mariana Castells
Hypersensitivity reactions (HSR) to targeted biologic agents present as immediate reactions during infusion or as delayed reactions (after one or more exposures). The new classification includes phenotypes, endotypes, and biomarkers. Phenotypes include immediate type I (immunoglobulin E [IgE] or non-IgE mediated), cytokine release, mixed (type I/cytokine), and immune complexes type III (IgG mediated) reactions as well as delayed type IV reactions. Endotypes include IgE or non-IgE mediated mast cells/basophils activation with elevated serum tryptase and T cells values as well as macrophages, which lead to cytokine production, e...
November 1, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/29040053/periostin-as-a-biomarker-for-nasal-polyps-in-chronic-rhinosinusitis
#12
Alice Z Maxfield, Lukas D Landegger, Christopher D Brook, Ashton E Lehmann, Adam P Campbell, Regan W Bergmark, Konstantina M Stankovic, Ralph Metson
Objective Periostin is an extracellular matrix protein that is elevated in the sinonasal tissues of patients with chronic rhinosinusitis (CRS). The purpose of this study was to determine whether serum periostin could serve as a molecular biomarker of nasal polyp burden in sinonasal disease. Study Design Prospective cohort study. Setting Academic medical center. Subjects and Methods Serum periostin levels were measured by ELISA on blood samples collected from patients undergoing sinus surgery for CRS (n = 71), further stratified by phenotype as defined by nasal polyps and asthma...
October 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29036019/targeting-the-interleukin-4-and-interleukin-13-pathways-in-severe-asthma-current-knowledge-and-future-needs
#13
Amit D Parulekar, Christina C Kao, Zuzana Diamant, Nicola A Hanania
PURPOSE OF REVIEW: Severe asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) asthma. This article reviews the signaling pathway of IL-4 and IL-13 and highlights its targeted therapy in severe asthma. RECENT FINDINGS: Several clinical trials of biologics targeting the IL-4/IL-13 pathway have recently been completed. In patients with severe, uncontrolled asthma, targeting IL-13 alone with biologics including lebrikizumab and tralokinumab has not shown consistent reduction in asthma exacerbations...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29036018/precision-medicine-in-asthma-linking-phenotypes-to-targeted-treatments
#14
Kian F Chung
PURPOSE OF REVIEW: Asthma is a heterogeneous disease consisting of different phenotypes that are driven by different mechanistic pathways. The purpose of this review is to emphasize the important role of precision medicine in asthma management. RECENT FINDINGS: Despite asthma heterogeneity, the approach to management has been on the basis of disease severity, with the most severe patients reserved for the maximum treatments with corticosteroids and bronchodilators...
October 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29035619/personalized-medicine-with-biologics-for-severe-type-2-asthma-current-status-and-future-prospects
#15
Marie Godar, Christophe Blanchetot, Hans de Haard, Bart N Lambrecht, Guy Brusselle
Asthma affects more than 300 million people worldwide and poses a large socioeconomic burden, particularly in the 5% to 10% of severe asthmatics. So far, each entry of new biologics in clinical trials has led to high expectations for treating all severe asthma forms, but the outcome has only been successful if the biologic, as add-on treatment, targeted specific patient subgroups. Indeed, we now realize that asthma is a heterogeneous disease with multiple phenotypes, based on distinct pathophysiological mechanisms, called endotypes...
October 16, 2017: MAbs
https://www.readbyqxmd.com/read/29018800/asthma-endotypes-and-an-overview-of-targeted-therapy-for-asthma
#16
REVIEW
Sarah Svenningsen, Parameswaran Nair
Guidelines for the management of severe asthma do not emphasize the measurement of the inflammatory component of airway disease to indicate appropriate treatments or to monitor response to treatment. Inflammation is a central component of asthma and contributes to symptoms, physiological, and structural abnormalities. It can be assessed by a number of endotyping strategies based on "omics" technology such as proteomics, transcriptomics, and metabolomics. It can also be assessed using simple cellular responses by quantitative cytometry in sputum...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28992358/role-of-galectin-3-in-the-pathophysiology-underlying-allergic-lung-inflammation-in-a-timp-1-knockout-model-of-murine-asthma
#17
Manoj J Mammen, Mark F Sands, Elaine Abou-Jaoude, Ravikumar Aalinkeel, Jessica L Reynolds, Neil U Parikh, Umesh Sharma, Stanley A Schwartz, Supriya D Mahajan
Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyper-responsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Utilizing a Tissue inhibitors of metalloproteinase-1 (TIMP-1) knockout murine allergic asthma model, we previously showed that Tissue inhibitors of metalloproteinase-1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation, and TH2 cytokine gene and protein expression following sensitization with ovalbumin...
October 9, 2017: Immunology
https://www.readbyqxmd.com/read/28991828/pediatric-sepsis-endotypes-among-adults-with-sepsis
#18
Hector R Wong, Timothy E Sweeney, Kimberly W Hart, Purvesh Khatri, Christopher J Lindsell
OBJECTIVES: Recent transcriptomic studies describe two subgroups of adults with sepsis differentiated by a sepsis response signature. The implied biology and related clinical associations are comparable with recently reported pediatric sepsis endotypes, labeled "A" and "B." We classified adults with sepsis using the pediatric endotyping strategy and the sepsis response signature and determined how endotype assignment, sepsis response signature membership, and age interact with respect to mortality...
December 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28987809/monitoring-the-inflammatory-heterogeneity-with-multiple-biomarkers-for-multidimensional-endotyping-of-asthma
#19
Ioana Agache, Daniel S Strasser, Gabin M Pierlot, Hervé Farine, Kenji Izuhara, Cezmi A Akdis
The complexity of type 2 and non-type 2 asthma requires monitoring with multiple biomarkers. We evaluated the potential of multidimensional endotyping to characterise physio-pathological clusters based on asthma severity and intensity of the blood eosinophilia.
October 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28976216/how-should-treatment-approaches-differ-depending-on-the-severity-of-asthma
#20
Maciej Kupczyk, Piotr Kuna
Asthma is nowadays regarded as a syndrome of various overlapping phenotypes with defined clinical characteristics, different underlying inflammatory mechanisms, identifiable genetic background, environmental risk factors and possible biomarkers. There are no doubts that due to the diversity of asthma, a 'one size fits all' management of the disease is no longer valid. Areas covered: Nowadays asthma management is based on the control of the disease, and the goals of asthma treatment are defined as good symptom control, decreased future risk of exacerbations, fixed airflow limitation, and side-effects of treatment...
October 16, 2017: Expert Review of Respiratory Medicine
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