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https://www.readbyqxmd.com/read/29685885/the-extracellular-camp-adenosine-pathway-in-airway-smooth-muscle
#1
Enio Setsuo Arakaki Pacini, Sarah Sanders-Silveira, Rosely Oliveira Godinho
In the respiratory tract, intracellular cAMP has a key role in the smooth muscle relaxation induced by β2 -adrenoceptors/Gs protein/adenylyl cyclase axis. In other tissues, cAMP also works as an extracellular messenger, after its efflux and interstitial conversion to adenosine by ectoenzymes. The aim of this study was to identify cAMP efflux and "extracellular cAMP-adenosine pathway" in the airway smooth muscle. Firstly, we tested the ability of β2 -adrenoceptor agonists formoterol or fenoterol to increase the extracellular cAMP in isolated tracheal rings from adult male Wistar rats...
April 23, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29660434/the-beclomethasone-anti-inflammatory-effect-occurs-in-cell-mediator-dependent-manner-and-is-additively-enhanced-by-formoterol-nfkb-p38-pka-analysis
#2
Silvana Cianchetti, Cristina Cardini, Alessandro Corti, Marta Menegazzi, Elena Darra, Eleonora Ingrassia, Alfonso Pompella, Pierluigi Paggiaro
AIMS: Beclomethasone/formoterol (BDP/FOR) has been reported to be more effective than its separate components in airway disease control and in airway inflammation improvement. However, BDP/FOR effects on cytokine-induced inflammation in structural cells have not been described and whether these effects occur in a cell- and mediator-dependent manner has not been fully elucidated. We sought to evaluate BDP and/or FOR effects on endothelial ICAM-1, E-selectin, IL-8 and on bronchial epithelial ICAM-1 and IL-8...
April 13, 2018: Life Sciences
https://www.readbyqxmd.com/read/29650006/beclomethasone-dipropionate-and-formoterol-fumarate-synergistically-interact-in-hyperresponsive-medium-bronchi-and-small-airways
#3
Luigino Calzetta, Maria Gabriella Matera, Francesco Facciolo, Mario Cazzola, Paola Rogliani
BACKGROUND: Corticosteroids increase the expression of β2 -adrenoceptors (β2 -ARs) and protect them against down-regulation. Conversely, β2 -AR agonists improve the anti-inflammatory action of corticosteroids. Nevertheless, it is still uncertain whether adding a long-acting β2 -AR agonist (LABA) to an inhaled corticosteroid (ICS) results in an additive effect, or there is true synergy. Therefore, the aim of this study was to pharmacologically characterize the interaction between the ICS beclomethasone diproprionate (BDP) and the LABA formoterol fumarate (FF) in a validated human ex vivo model of bronchial asthma...
April 12, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29629403/effectiveness-of-umeclidinium-vilanterol-for-protocolized-management-of-chronic-obstructive-pulmonary-disease-exacerbation-in-hospitalized-patients-a-sequential-period-analysis
#4
Todd W Chapin, Michael A Mann, Gary L Brown, Traci L Leitheiser, Becky Anderson, David D Leedahl
Background: Bronchodilator therapy is a foundation of chronic obstructive pulmonary disease (COPD) exacerbation treatment. Although international guidelines recommend short-acting formulations given multiple times per day, long-acting formulations have not been adequately evaluated. The objective of our study was to determine the effectiveness of umeclidinium-vilanterol (UME/VIL), long-acting beta2-agonist/long-acting muscarinic antagonist (LABA/LAMA) as a once-daily alternative for treating COPD exacerbations in hospitalized patients...
January 24, 2018: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
https://www.readbyqxmd.com/read/29625570/the-inhibition-of-human-lung-fibroblast-proliferation-and-differentiation-by-gs-coupled-receptors-is-not-predicted-by-the-magnitude-of-camp-response
#5
Maxine J Roberts, Rebecca E Broome, Toby C Kent, Steven J Charlton, Elizabeth M Rosethorne
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3', 5' cyclic adenosine monophosphate (cAMP) pathway is an important modulator in the development of fibrosis, with increasing levels of cAMP able to inhibit cellular processes associated with IPF...
April 7, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29616842/the-discovery-and-development-of-aclidinium-bromide-for-the-treatment-of-chronic-obstructive-pulmonary-disease
#6
Mario Malerba, Alessandro Radaeli, Giuseppe Santini, Jaymin Morjaria, Nadia Mores, Chiara Mondino, Giuseppe Macis, Paolo Montuschi
Bronchodilators, including long-acting muscarinic receptor antagonists (LAMAs), are a mainstay of the pharmacological treatment of chronic obstructive pulmonary disease (COPD). LAMAs act as bronchodilators principally by antagonizing airway smooth muscle cells M3 muscarinic receptors. Aclidinium bromide is a twice-daily LAMA which was developed to improve on the efficacy and/or safety of previous LAMAs. Area covered: Herein, the authors present the pharmacotherapeutic role of aclidinium in COPD and point out unmet need in this research area...
April 4, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29606861/pharmacokinetics-of-glycopyrronium-formoterol-fumarate-dihydrate-delivered-via-metered-dose-inhaler-using-co-suspension-delivery-technology-in-patients-with-moderate-to-very-severe-copd
#7
Gary T Ferguson, Roberto Rodriguez-Roisin, Colin Reisner, Andrea Maes, Shahid Siddiqui, Ubaldo J Martin
Purpose: The efficacy and tolerability of GFF MDI (Bevespi Aerosphere® ), a fixed-dose combination of glycopyrronium (GP)/formoterol fumarate dihydrate (FF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg) delivered by metered dose inhaler (MDI) using innovative co-suspension delivery technology, has been investigated in a Phase III clinical trial program (NCT01854645, NCT01854658, NCT01970878) in patients with COPD. Here, we present findings from a pharmacokinetic (PK) sub-study of NCT01854645 (PINNACLE-1)...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29567116/cardiovascular-safety-profile-of-a-fixed-dose-combination-of-glycopyrrolate-and-formoterol-fumarate-delivered-via-metered-dose-inhaler-using-co-suspension-delivery-technology
#8
Gary T Ferguson, Colin Reisner, James Pearle, Paolo DePetrillo, Andrea Maes, Ubaldo J Martin
BACKGROUND: Glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI) is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA), glycopyrrolate (GP), and the long-acting β2 -agonist (LABA), formoterol fumarate (FF), delivered via metered dose inhaler using innovative co-suspension delivery technology. Here we report the results of two studies that examined the cardiovascular safety of GFF MDI. METHODS: The thorough QT (TQT) study was a Phase I, randomized, double-blind, single-dose, crossover study to assess GFF MDI 18/9...
April 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29554195/association-of-inhaled-corticosteroids-and-long-acting-%C3%AE-agonists-as-controller-and-quick-relief-therapy-with-exacerbations-and-symptom-control-in-persistent-asthma-a-systematic-review-and-meta-analysis
#9
Diana M Sobieraj, Erin R Weeda, Elaine Nguyen, Craig I Coleman, C Michael White, Stephen C Lazarus, Kathryn V Blake, Jason E Lang, William L Baker
Importance: Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma. Objective: To conduct a systematic review and meta-analysis of the effects of SMART in patients with persistent asthma. Data Sources and Study Selection: The databases of MEDLINE via OVID, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched from database inception through August 2016 and updated through November 28, 2017...
March 19, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29552299/tulobuterol-patch-alleviates-allergic-asthmic-inflammation-by-blockade-of-syk-and-nf-%C3%AE%C2%BAb-activation-in-mice
#10
Lixia Fu, Jing Guan, Yujia Zhang, Pei Ma, Yuanyuan Zhuang, Jinye Bai, Yasi Ding, Qi Hou, Wan Gong, Mingbao Lin, Wensheng Zheng, Jianmin Zhang
Background: Tulobuterol patch, one of strongest bronchodilators, was recently shown to improve bronchial hyperresponsiveness and significantly decrease the sputum eosinophil counts by combining with nonspecific anti-inflammatory drugs on patients with asthma. However, there is limited study on the anti-inflammatory activities of tulobuterol patch and its potential machenism. Results: The tulobuterol patch significantly ameliorated inflammatory cell infiltration in the lung tissue, reduced the number of total leukocytes and its differential count, markedly reduced the production of IL-1β, TNF-α, IL-6, CCL-11 and IL-4 in bronchial alveolar lavage fluid, as well as a reduction in IL-4/IFN-γ ratio...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29545018/-persistence-to-treatment-and-resources-use-with-inhaled-fixed-dose-combinations-of-corticosteroids-and-long-acting-%C3%AE-adrenergic-agonists-for-the-treatment-of-asthma-a-population-based-retrospective-study
#11
A Sicras-Mainar, S Traseira-Lugilde, T Fernández-Sánchez, R Navarro-Artieda
OBJECTIVE: To determine the persistence, exacerbations, and use of resources in patients who use inhaler treatment with fluticasone propionate/formoterol (PF/Form) in relation with other combinations of inhaled corticosteroid/long-acting β-adrenergic (ICS/LABA) at fixed doses, for the treatment of asthma in real-life practice. MATERIAL AND METHODS: Observational study conducted by reviewing medical records. The study included subjects ≥18 years of age who started treatment with ICS/LABA and who met certain inclusion/exclusion criteria...
March 12, 2018: Semergen
https://www.readbyqxmd.com/read/29544728/the-pharmacokinetics-of-three-doses-of-budesonide-glycopyrronium-formoterol-fumarate-dihydrate-metered-dose-inhaler-compared-with-active-controls-a-phase-i-randomized-single-dose-crossover-study-in-healthy-adults
#12
Patrick Darken, Paolo DePetrillo, Colin Reisner, Earl St Rose, Paul Dorinsky
The budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) is an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2 -agonist fixed-dose combination formulated with innovative co-suspension delivery technology that is in clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, Phase I, single-dose, six-treatment, four-period, crossover study (NCT01980615) examined the pharmacokinetic (PK) and safety profile of three doses of BGF MDI (320/14...
March 12, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29518847/-trends-of-asthma-control-disease-management-and-perception-in-china
#13
J T Lin, W Q Wang, X Zhou, K S Yin, C T Liu, C Z Wang, M Huang, P Chen, Y D Yuan, S X Cai, C G Wu, J Li, Q C Lin, J Y Zhou, H G Liu, Y H Gu, X G Huang, D J Sun, X H Yang, L Yang, J M Huo, Z C Chen, W Zhou, P Jiang, H P Tang, R Y Liu, W Zhang, Y Q Chen, Y J Huang, X J Liu, L M Dai, X W Ye, C P Hu, J Zhang, J Y Xu
Objective: To evaluate the changes of asthma control, disease management and perception in recent years in China. Methods: We conducted 2 multi-center, cross-sectional surveys. Outpatient asthmatic patients from 10 cities in mainland China (2007-2008) and 30 central cities from 30 provinces in China (except Tibet)(2015-2016) were recruited respectively. Data of asthma control, disease management and perception from the 2 surveys were compared for 10 cities which took part in both of the 2 surveys. Chi-square test was used for comparison between groups...
March 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29517976/notes-on-test-and-estimation-in-comparison-of-three-treatments-under-a-simple-carry-over-three-period-model
#14
Kung-Jong Lui
Under the three-treatment three-period crossover design with simple carry-over effects, we derive the least-squares estimators for period effects, treatment effects and carry-over effects, as well as their covariance matrix in closed and explicit expressions. Using Monte Carlo simulation, we compare the test procedure adjusting carry-over with that ignoring carry-over with respect to Type I error and power. We further compare interval estimators adjusting carry-over with those ignoring carry-over with respect to the coverage probability and the average length...
March 7, 2018: International Journal of Biostatistics
https://www.readbyqxmd.com/read/29506504/a-phase-iib-randomized-chronic-dosing-incomplete-block-cross-over-study-of-glycopyrronium-delivered-via-metered-dose-inhaler-compared-with-a-placebo-and-an-active-control-in-patients-with-moderate-to-severe-copd
#15
Edward M Kerwin, Selwyn Spangenthal, Christine Kollar, Earl St Rose, Colin Reisner
BACKGROUND: Long-acting muscarinic antagonist (LAMA) and long-acting β2 -agonist (LABA) bronchodilators are key to the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). This Phase IIb study investigated the safety and efficacy of four doses of the LAMA glycopyrronium (GP) delivered using co-suspension delivery technology via metered dose inhaler (MDI). The study was part of a wider clinical trial program performed to determine the optimal dose of GP MDI, the LABA formoterol fumarate dihydrate (FF) MDI, and glycopyrronium/formoterol fumarate dihydrate (GFF) MDI fixed-dose combination to be taken forward into Phase III studies...
March 5, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29504290/myoblast-mitochondrial-respiration-is-decreased-in-chronic-binge-alcohol-administered-simian-immunodeficiency-virus-infected-antiretroviral-treated-rhesus-macaques
#16
Anthony A Duplanty, Robert W Siggins, Timothy Allerton, Liz Simon, Patricia E Molina
Work from our group demonstrated that chronic binge alcohol (CBA)-induces mitochondrial gene dysregulation at end-stage disease of simian immunodeficiency virus (SIV) infection in antiretroviral therapy (ART) naïve rhesus macaques. Alterations in gene expression can disrupt mitochondrial homeostasis and in turn contribute to the risk of metabolic comorbidities characterized by loss of skeletal muscle (SKM) functional mass that are associated with CBA, human immunodeficiency virus (HIV) infection, and prolonged ART...
March 2018: Physiological Reports
https://www.readbyqxmd.com/read/29499614/use-of-functional-respiratory-imaging-to-characterize-the-effect-of-inhalation-profile-and-particle-size-on-lung-deposition-of-inhaled-corticosteroid-long-acting-%C3%AE-2-agonists-delivered-via-a-pressurized-metered-dose-inhaler
#17
Cedric Van Holsbeke, Jan De Backer, Wim Vos, Jonathan Marshall
BACKGROUND: Functional respiratory imaging (FRI) uses three-dimensional models of human lungs and computational fluid dynamics to simulate functional changes within airways and predict the deposition of inhaled drugs. This study used FRI to model the effects of different patient inhalation and drug formulation factors on lung deposition of an inhaled corticosteroid/long-acting β2 -agonist (ICS/LABA) combination, administered by a pressurized metered-dose inhaler. METHODS: Three-dimensional models of the lungs of six patients with asthma (mean forced expiratory volume in 1 s, 83%), treated with an ICS/LABA, were included...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29429593/extrafine-inhaled-triple-therapy-versus-dual-bronchodilator-therapy-in-chronic-obstructive-pulmonary-disease-tribute-a-double-blind-parallel-group-randomised-controlled-trial
#18
Alberto Papi, Jørgen Vestbo, Leonardo Fabbri, Massimo Corradi, Hélène Prunier, Géraldine Cohuet, Alessandro Guasconi, Isabella Montagna, Stefano Vezzoli, Stefano Petruzzelli, Mario Scuri, Nicolas Roche, Dave Singh
BACKGROUND: Evidence is scarce on the relative risk-benefit of inhaled triple therapy, consisting of inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2 -agonist, versus dual bronchodilation for chronic obstructive pulmonary disease (COPD). We aimed to compare a single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) versus a single-inhaler dual bronchodilator combination of indacaterol plus glycopyrronium (IND/GLY) in terms of the rate of moderate-to-severe COPD exacerbations over 52 weeks of treatment...
February 8, 2018: Lancet
https://www.readbyqxmd.com/read/29428600/contraction-dependent-tgf-%C3%AE-1-activation-is-required-for-thrombin-induced-remodeling-in-human-airway-smooth-muscle-cells
#19
Zhi-Hui Yao, Hao-Jun Xie, Ya-Lu Yuan, Ya-Ting Huo, Jing Cao, Wen-Yan Lai, Rui-Jun Cai, Yuan-Xiong Cheng
AIMS: Thrombin is a serine proteinase that is not only involved in coagulation cascade, but also mediates a number of biological responses relevant to tissues repair, and induces bronchoconstriction. TGF-β plays a pivotal role in airway remodeling due to its effects on airway smooth muscle proliferation and extracellular matrix (ECM) deposition. Recently, bronchoconstriction itself is found to constitute a form of strain and is highly relevant to asthmatic airway remodeling. However, the underlying mechanisms remain unknown...
March 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29400090/symbicort%C3%A2-maintenance-and-reliever-therapy-smart-and-the-evolution-of-asthma-management-within-the-gina-guidelines
#20
Jiangtao Lin, Xin Zhou, Changzheng Wang, Chuntao Liu, Shaoxi Cai, Mao Huang
The Global Initiative for Asthma (GINA) annual report summarizes the latest evidence for asthma management. GINA recommends stepwise pharmacological treatment, advocating inhaled corticosteroids (ICS) plus rapid, long-acting β2 -agonists (LABA) delivered in a single inhaler for maintenance and relief at Steps 3 (moderate persistent asthma requiring 1-2 controllers plus as-needed reliever), 4 (severe persistent asthma requiring ≥2 controllers plus as-needed reliever), and 5 (higher level care and/or add-on treatment)...
March 2018: Expert Review of Respiratory Medicine
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