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https://www.readbyqxmd.com/read/28099820/new-and-developing-non-adrenoreceptor-small-molecule-drugs-for-the-treatment-of-asthma
#1
Neil C Thomson
Introduction Inhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas covered New and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA...
January 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28092287/current-and-future-management-of-the-young-child-with-early-onset-wheezing
#2
Allison J Burbank, Stanley J Szefler
PURPOSE OF REVIEW: In this review, we discuss current thinking in relation to available guidelines for the care of preschool-aged children with recurrent wheezing, while highlighting the gaps in our knowledge and discussing changes that could occur over the next 5 years. RECENT FINDINGS: The Asthma Predictive Index as well as allergen-specific IgE, peripheral eosinophil count and exhaled nitric oxide are perhaps underutilized sources of information that can assist in predicting progression to asthma and response to therapies...
January 13, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28089872/identification-of-airway-mucosal-type-2-inflammation-by-clinical-biomarkers-in-asthma
#3
Philip E Silkoff, Michel Laviolette, Dave Singh, J Mark FitzGerald, Steven Kelsen, Vibeke Backer, Celeste M Porsbjerg, Pierre-Olivier Girodet, Patrick Berger, Joel N Kline, Geoffrey Chupp, Vedrana S Susulic, Elliot S Barnathan, Frédéric Baribaud, Matthew J Loza
BACKGROUND AND OBJECTIVE: The Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study profiled mild, moderate and severe asthma, and non-atopic healthy controls. We explored this dataset to define Type-2 inflammation based on airway-mucosal IL-13-driven gene expression and how this related to clinically-accessible biomarkers. METHODS: IL-13-driven gene expression was evaluated in several human cell lines. We then defined Type-2 status in 25 healthy subjects, 28 mild, 29 moderate, and 26 severe asthmatics, based on airway-mucosal expression of 1) CC-motif chemokine ligand (CCL)-26, (the most differentially expressed gene), 2) periostin, or 3) a multi-gene IL-13 in-vitro signature (IVS)...
January 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28076986/utilising-exhaled-nitric-oxide-information-to-enhance-diagnosis-and-therapy-of-respiratory-disease-current-evidence-for-clinical-practice-and-proposals-to-improve-the-methodology
#4
Marieann Högman, Lauri Lehtimäki, Anh Tuan Dinh-Xuan
A non-invasive tool to diagnose respiratory diseases and to follow treatment has long been looked-for. Exhaled nitric oxide (NO) is a promising marker of inflammation in asthma but nearly 25-years of research has shown that it works in only certain endotypes of asthma. The modelling of NO dynamics of the lung can give more information than a single FENO value. Areas covered: The estimation of the NO production in the conducting airways and in the gas exchange area has given new insight of the NO production in diseases beyond asthma...
January 11, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28065276/using-imaging-as-a-biomarker-for-asthma
#5
REVIEW
Abhaya Trivedi, Chase Hall, Eric A Hoffman, Jason C Woods, David S Gierada, Mario Castro
There have been significant advancements in the various imaging techniques being used for the evaluation of asthmatic patients, both from a clinical and research perspective. Imaging characteristics can be used to identify specific asthmatic phenotypes and provide a more detailed understanding of endotypes contributing to the pathophysiology of the disease. Computed tomography, magnetic resonance imaging, and positron emission tomography can be used to assess pulmonary structure and function. It has been shown that specific airway and lung density measurements using computed tomography correlate with clinical parameters, including severity of disease and pathology, but also provide unique phenotypes...
January 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28042687/unsupervised-network-mapping-of-commercially-available-immunoassay-yields-three-distinct-chronic-rhinosinusitis-endotypes
#6
Rohit Divekar, Matthew Rank, Diane Squillace, Hirohito Kita, Devyani Lal
BACKGROUND: Endotyping chronic rhinosinusitis (CRS) through simplified cytokine assays may help direct individualized therapy such as corticosteroids, antibiotics, or biologics. We performed an unsupervised network analysis to endotype CRS and control subjects using a commercially available cytokine-chemokine immunoassay. METHODS: A 41-plex cytokine-chemokine array along with major basic protein (MBP) assay was performed on sinonasal surgical tissue of 32 adults...
January 2, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28036144/revisiting-type-2-high-and-type-2-low-airway-inflammation-in-asthma-current-knowledge-and-therapeutic-implications
#7
Douglas Robinson, Marc Humbert, Roland Buhl, Alvaro A Cruz, Hiromasa Inoue, Stephan Korom, Nicola A Hanania, Parameswaran Nair
Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. Type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems...
December 30, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27989587/cellular-and-humoral-biomarkers-of-bronchopulmonary-dysplasia
#8
Charitharth Vivek Lal, Namasivayam Ambalavanan
The pathogenesis of Bronchopulmonary Dysplasia (BPD) is multifactorial and the clinical phenotype of BPD is extremely variable. Predicting BPD is difficult, as it is a disease with a clinical operational definition but many clinical phenotypes and endotypes. Most biomarkers studied over the years have low predictive accuracy, and none are currently used in routine clinical care or shown to be useful for predicting longer-term respiratory outcome. Targeted cellular and humoral biomarkers and novel systems biology 'omic' based approaches including genomic and microbiomic analyses are described in this review...
December 15, 2016: Early Human Development
https://www.readbyqxmd.com/read/27978840/validated-and-longitudinally-stable-asthma-phenotypes-based-on-cluster-analysis-of-the-adept-study
#9
Matthew J Loza, Ratko Djukanovic, Kian Fan Chung, Daniel Horowitz, Keying Ma, Patrick Branigan, Elliot S Barnathan, Vedrana S Susulic, Philip E Silkoff, Peter J Sterk, Frédéric Baribaud
BACKGROUND: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. METHODS: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available...
December 15, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27942592/dna-methylation-in-lung-cells-is-associated-with-asthma-endotypes-and-genetic-risk
#10
Jessie Nicodemus-Johnson, Rachel A Myers, Noburu J Sakabe, Debora R Sobreira, Douglas K Hogarth, Edward T Naureckas, Anne I Sperling, Julian Solway, Steven R White, Marcelo A Nobrega, Dan L Nicolae, Yoav Gilad, Carole Ober
The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults...
December 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27942351/therapeutic-interventions-in-severe-asthma
#11
REVIEW
Giorgio Walter Canonica, Gianenrico Senna, Patrick D Mitchell, Paul M O'Byrne, Giovanni Passalacqua, Gilda Varricchi
The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy...
2016: World Allergy Organization Journal
https://www.readbyqxmd.com/read/27942210/airflow-obstruction-is-it-asthma-or-is-it-copd
#12
REVIEW
Paola Rogliani, Josuel Ora, Ermanno Puxeddu, Mario Cazzola
Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction. However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction. Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27931975/identification-of-il-17f-frequent-exacerbator-endotype-in-asthma
#13
Fabio L M Ricciardolo, Valentina Sorbello, Anna Folino, Fabio Gallo, Gian Mario Massaglia, Gabriella Favatà, Salvatore Conticello, Davide Vallese, Federica Gani, Mario Malerba, Gert Folkerts, Giovanni Rolla, Mirella Profita, Thais Mauad, Antonino Di Stefano, Giorgio Ciprandi
BACKGROUND: Severe asthma might be associated with overexpression of Th17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways. OBJECTIVE: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate. METHODS: Inflammatory cells and IL-17A(+), IL-17F(+), IL-21(+), IL-22(+), and IL-23(+) cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls...
December 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27917403/a-review-of-classification-schemes-for-chronic-rhinosinusitis-with-nasal-polyposis-endotypes
#14
REVIEW
Steven K Dennis, Kent Lam, Amber Luong
OBJECTIVE: The recent development of endotypes to categorize disease variants of chronic rhinosinusitis (CRS) reflects an evolving understanding of the various pathophysiologic and pathogenetic mechanisms that contribute to the clinical heterogeneity of CRS manifestations. This review highlights popular endotype-based criteria used to define different CRS with nasal polyposis (CRSwNP) subtypes and further discusses the emerging therapeutic advances for each classificatory approach. DATA SOURCES: PubMed literature review...
October 2016: Laryngoscope Investigative Otolaryngology
https://www.readbyqxmd.com/read/27879060/evidence-of-microbiota-dysbiosis-in-chronic-rhinosinusitis
#15
Michael Hoggard, Kristi Biswas, Melissa Zoing, Brett Wagner Mackenzie, Michael W Taylor, Richard G Douglas
BACKGROUND: Despite considerable research, the pathogenesis of chronic rhinosinusitis (CRS) remains poorly understood. Potential microbial roles in the etiology or progression of CRS have long been hypothesized, yet few specific associations have been identified. In this study we investigate associations between patterns in resident bacterial communities and clinical variants of CRS. METHODS: Bacterial communities were assessed in 94 patients with extensive bilateral CRS undergoing endoscopic sinus surgery (ESS) and 29 controls undergoing ESS for indications other than CRS...
November 23, 2016: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/27871878/large-scale-gene-expression-profiling-reveals-distinct-type-2-inflammatory-patterns-in-chronic-rhinosinusitis-subtypes
#16
Matthew A Tyler, Chris B Russell, Dirk E Smith, James B Rottman, Caroline J Padro Dietz, Xuguang Hu, Martin J Citardi, Samer Fakhri, Shervin Assassi, Amber Luong
No abstract text is available yet for this article.
November 18, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27867084/new-concepts-in-asthma-clinical-phenotypes-and-pathophysiological-mechanisms
#17
REVIEW
Andreas R Koczulla, Claus F Vogelmeier, Holger Garn, Harald Renz
Asthma is among the most common chronic inflammatory diseases worldwide. Recent evidence indicates that the pathogenesis shows a high degree of heterogeneity. Patient subsets have been identified that exhibit different cellular and molecular patterns of dysregulation. A prominent example is eosinophilic Th2-driven asthma. These unique and molecular patterns are termed endotypes. Characterization of endotypes has broad implications for therapeutic interventions. Although ∼80% of asthmatic patients respond well to standard anti-inflammatory therapies, the remaining subset particularly consisting of severe patients requires a more specialized endotype-specific approach...
November 17, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27864676/anti-ige-and-biologic-approaches-for-the-treatment-of-asthma
#18
Patrick D Mitchell, Amani I El-Gammal, Paul M O'Byrne
Current asthma treatments are effective for the majority of patients with mild-to-moderate disease. However, in those with more severe refractory asthma, agents other than inhaled corticosteroids and beta-agonists are needed both to better manage this group of patients and to avoid the side effects of high-dose corticosteroids and the social and personal hardship endured. Several biological pathways have been targeted over the last 20 years, and this research has resulted in pharmacological approaches to attempt to better treat patients with severe refractory asthma...
November 19, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27861433/understanding-phenotypes-of-obstructive-sleep-apnea-applications-in-anesthesia-surgery-and-perioperative-medicine
#19
Yamini Subramani, Mandeep Singh, Jean Wong, Clete A Kushida, Atul Malhotra, Frances Chung
Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing with potential long-term major neurocognitive and cardiovascular sequelae. The pathophysiology of OSA varies between individuals and is composed of different underlying mechanisms. Several components including the upper airway anatomy, effectiveness of the upper airway dilator muscles such as the genioglossus, arousal threshold of the individual, and inherent stability of the respiratory control system determine the pathogenesis of OSA...
January 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27850966/1330-sepsis-endotypes-and-their-physiologic-characterization-using-vital-signs
#20
Li Ang Zhang, Robert Parker, Ipsita Banerjee, Gilles Clermont
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
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