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https://www.readbyqxmd.com/read/28775071/the-acute-effects-of-long-acting-bronchodilators-on-small-airways-detected-in-copd-patients-by-single-breath-n2-test-and-lung-p-v-curve
#1
Matteo M Pecchiari, Pierachille Santus, Dejan Radovanovic, Edgardo Giacomo D'Angelo
Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence, the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (mean age (SD): 70±7 years; 82% males) with moderate to very severe COPD. Patients underwent body-plethysmography, arterial blood gas-analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single breath nitrogen test (SBN) and transpulmonary pressure-volume curve (PL-V), before and one hour after drug administration...
August 3, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28768531/the-effect-of-glycopyrronium-and-indacaterol-as-monotherapy-and-in-combination-on-the-methacholine-dose-response-curve-of-mild-asthmatics-a-randomized-three-way-crossover-study
#2
Christianne M Blais, Beth E Davis, Donald W Cockcroft
BACKGROUND: Methacholine dose-response curves illustrate pharmacologic bronchoprotection against methacholine-induced airway hyperresponsiveness and can be used to quantitate changes in airway sensitivity (position), reactivity (slope), and maximal responsiveness following drug administration. Our objective was to determine the influence of single-dose glycopyrronium (long-acting muscarinic antagonist) and indacaterol (ultra-long acting β2 agonist), as monotherapy and in combination, on the methacholine dose-response curve of mild asthmatics and to compare these findings with a non-asthmatic control curve...
August 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28754132/interactions-between-glycopyrronium-and-indacaterol-on-cholinergic-neurotransmission-and-contractile-response-in-bovine-trachealis
#3
Michele Baroffio, Giovanni Barisione, Vito Brusasco
BACKGROUND: Muscarinic-receptor antagonists and β-adrenoceptor agonists are used, alone or in combination, as first-line treatment for chronic obstructive pulmonary disease. Both drugs decrease airway smooth muscle tone by post-junctional mechanisms but they may have opposing effects on pre-junctional acetylcholine (ACh)-release. METHODS: We studied the effects of the muscarinic-receptor antagonist glycopyrronium (GLY), the β-adrenoceptor agonist indacaterol (IND) and their combination on electrically-induced ACh-release and contractile response in isolated bovine trachealis...
July 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28729041/pharmacological-preclinical-characterization-of-las190792-a-novel-inhaled-bifunctional-muscarinic-receptor-antagonist-%C3%AE-2-adrenoceptor-agonist-maba-molecule
#4
Mònica Aparici, Carla Carcasona, Israel Ramos, José Luís Montero, José Luís Ortiz, Julio Cortijo, Carlos Puig, Dolors Vilella, Chris Doe, Amadeu Gavaldà, Montserrat Miralpeix
LAS190792 is a novel muscarinic antagonist and β2-adrenoceptor agonist in development for chronic respiratory diseases. This study investigated the pharmacological profile of LAS190792 in comparison to batefenterol, tiotropium, indacaterol and olodaterol. LAS190792 is potent at the human M3 receptor (pIC50: 8.8 in binding assays). It is selective for the β2-adrenoceptor over the β1-and β3-adrenoceptor, and shows a functional potency in a similar range to batefenterol and LABA compounds (pEC50 in spontaneous tone isolated trachea: 9...
July 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28720132/efficacy-and-safety-of-direct-switch-to-indacaterol-glycopyrronium-in-patients-with-moderate-copd-the-crystal-open-label-randomised-trial
#5
Claus F Vogelmeier, Mina Gaga, Maryam Aalamian-Mattheis, Timm Greulich, Jose M Marin, Walter Castellani, Vincent Ninane, Stephen Lane, Xavier Nunez, Francesco Patalano, Andreas Clemens, Konstantinos Kostikas
BACKGROUND: Dual bronchodilation combining a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q...
July 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28703592/interactions-between-%C3%AE-2-adrenoceptor-ligands-and-membrane-atomic-level-insights-from-magic-angle-spinning-nmr
#6
Si Yan, Duncan E Shaw, Linhong Yang, David A Sandham, Mark P Healy, John Reilly, Bing Wang
To understand the relationship between structural properties of the β2-adrenoceptor ligands and their interactions with membranes, we have investigated the location and distribution of five β2 agonists with distinct clinical durations and onsets of action (indacaterol, two indacaterol analogues, salmeterol and formoterol) in monounsaturated model membranes using magic angle spinning NMR to measure these interactions through both (1)H nuclear Overhauser enhancement (NOE) and paramagnetic relaxation enhancement (PRE) techniques...
August 4, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28696794/the-effects-of-asthma-medications-on-reactive-oxygen-species-production-in-human-monocytes
#7
Ming-Kai Tsai, Yi-Ching Lin, Ming-Yii Huang, Min-Sheng Lee, Chang-Hung Kuo, Po-Lin Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
OBJECTIVE: Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol)...
July 11, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28695328/study-of-the-emitted-dose-after-two-separate-inhalations-at-different-inhalation-flow-rates-and-volumes-and-an-assessment-of-aerodynamic-characteristics-of-indacaterol-onbrez-breezhaler-%C3%A2-150-and-300%C3%A2-%C3%AE-g
#8
Mohamad Abadelah, Henry Chrystyn, Golshan Bagherisadeghi, Gaballa Abdalla, Hassan Larhrib
Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin...
July 10, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28665534/bronchoprotective-tolerance-with-indacaterol-is-not-modified-by-concomitant-tiotropium-in-persistent-asthma
#9
Sunny Jabbal, Arvind Manoharan, Brian Lipworth
BACKGROUND: Tiotropium is a long acting antimuscarinic (LAMA), licenced as triple therapy with inhaled corticosteroid and long acting beta-agonist (ICS/LABA). There may be a synergistic benefit between LAMA and LABA as a consequence of receptor cross-talk, which in turn could modify beta-2 receptor down-regulation and associated tolerance induced by LABA. OBJECTIVE: We hypothesise this mechanism may result in a reduction of airway hyperresponsiveness (AHR) when using triple therapy...
June 30, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28615931/inhaled-indacaterol-for-the-treatment-of-copd-patients-with-destroyed-lung-by-tuberculosis-and-moderate-to-severe-airflow-limitation-results-from-the-randomized-infinity-study
#10
Cheong-Ju Kim, Hyoung-Kyu Yoon, Myung-Jae Park, Kwang-Ha Yoo, Ki-Suck Jung, Jeong-Woong Park, Seong Yong Lim, Jae Jeong Shim, Yong Chul Lee, Young-Sam Kim, Yeon-Mok Oh, Song Kim, Chul-Gyu Yoo
BACKGROUND AND OBJECTIVE: Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28594587/response-to-indacaterol-glycopyrronium-ind-gly-by-sex-in-patients-with-copd-a-pooled-analysis-from-the-ignite-program
#11
Ioanna Tsiligianni, Karen Mezzi, Sebastian Fucile, Konstantinos Kostikas, Steven Shen, Donald Banerji, Robert Fogel
In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment...
June 8, 2017: COPD
https://www.readbyqxmd.com/read/28566230/efficacy-and-safety-of-indacaterol-in-patients-with-chronic-obstructive-pulmonary-disease-aged-over-65-years-a-pooled-analysis
#12
Pierre-Olivier Girodet, Jean-Yves Jasnot, Vincent Le Gros, Laurent Decuypère, Weihua Cao, Gilles Devouassoux
BACKGROUND: Although the prevalence of chronic obstructive pulmonary disease (COPD) increases with age, no specific therapeutic approaches are available till date for the elderly population. AIM: To assess the efficacy and safety of once-daily indacaterol 150 and 300 μg in elderly patients with moderate to severe COPD. METHODS: Data were pooled from 11 randomized, double-blind, placebo- and active-controlled studies (8445 patients with COPD)...
May 24, 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28496316/the-effect-of-indacaterol-glycopyrronium-versus-tiotropium-or-salmeterol-fluticasone-on-the-prevention-of-clinically-important-deterioration-in-copd
#13
Antonio R Anzueto, Claus F Vogelmeier, Konstantinos Kostikas, Karen Mezzi, Sebastian Fucile, Giovanni Bader, Steven Shen, Donald Banerji, Robert Fogel
BACKGROUND: Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients. METHODS: Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28389258/role-of-dual-bronchodilators-in-copd-a-review-of-the-current-evidence-for-indacaterol-glycopyrronium
#14
REVIEW
Joachim H Ficker, Klaus F Rabe, Tobias Welte
In this review, we summarize the rationale for combining long-acting bronchodilators in the management of chronic obstructive pulmonary disease (COPD), and the evidence for the long-acting bronchodilator combination indacaterol/glycopyrronium (IND/GLY). Clinical practice guidelines generally recommend the use of long-acting bronchodilators in the treatment of patients with all severities of COPD, either as a first-choice or alternative-choice therapy. Combining classes of long-acting bronchodilators can result in superior improvements in lung function and clinical outcomes compared with bronchodilator monotherapy, as observed in studies of free combinations of long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs)...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28383836/-study-of-the-month-flame-study-in-chronic-obstructive-pulmonary-disease
#15
REVIEW
J-L Corhay
The place of combinations of bronchodilators (longacting beta-agonist / muscarinic agonist or LABA / LAMA) in the prevention of the exacerbations of the chronic obstructive pulmonary disease (COPD) is not still clearly established, and need a comparison with combination of LABA/ inhaled steroids. FLAME was a randomized non-inferiority phase 3 study comparing indacaterol/glycopyrronium 110/50 μg (IND/GLY) once daily with salmeterol/proprionate of fluticasone 50/500 μg (SAL/FC) twice daily. The primary objective of the study was to demonstrate that IND/GLY was non-inferior to SAL/FC in terms of reduction of all COPD exacerbations (mild/moderate/severe) during 52 weeks of treatment in patients having had at least 1 exacerbation in previous 12 months...
September 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28284212/combination-of-glycopyrronium-and-indacaterol-inhibits-carbachol-induced-erk5-signal-in-fibrotic-processes
#16
Yukiko Namba, Shinsaku Togo, Miniwan Tulafu, Kotaro Kadoya, Kumi Yoneda Nagahama, Hikari Taka, Naoko Kaga, Akira Orimo, Xiangde Liu, Kazuhisa Takahashi
BACKGROUND: Airway fibrosis is one of the pathological features of chronic obstructive pulmonary disease (COPD), and recent studies revealed that acetylcholine plays an important role in the development of airway remodeling by stimulating proliferation and collagen synthesis of lung fibroblasts. This study was designed to examine the effects of a long-acting muscarinic receptor antagonist (LAMA) glycopyrronium and a long-acting β2 adrenergic receptor agonist (LABA) indacaterol on acetylcholine-mediated fibrotic responses in lung fibroblasts...
March 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28278391/blood-eosinophils-and-response-to-maintenance-chronic-obstructive-pulmonary-disease-treatment-data-from-the-flame-trial
#17
RANDOMIZED CONTROLLED TRIAL
Nicolas Roche, Kenneth R Chapman, Claus F Vogelmeier, Felix J F Herth, Chau Thach, Robert Fogel, Petter Olsson, Francesco Patalano, Donald Banerji, Jadwiga A Wedzicha
RATIONALE: Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD). OBJECTIVES: We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β2-agonist combination versus a long-acting β2-agonist/long-acting muscarinic antagonist combination for exacerbation prevention...
May 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28228952/assessment-of-the-expectancy-seriousness-and-severity-of-adverse-drug-reactions-reported-for-chronic-obstructive-pulmonary-disease-therapy
#18
Guenka Petrova, Assena Stoimenova, Maria Dimitrova, Maria Kamusheva, Daniela Petrova, Ognian Georgiev
INTRODUCTION: Adverse drug reactions can cause increased morbidity and mortality, and therefore information needs to be studied systematically. Little is known about the adverse drug reactions for chronic obstructive pulmonary disease therapy. The goal of this study is to assess the expectedness, seriousness and severity of adverse drug reactions during chronic obstructive pulmonary disease therapy based on their reporting in the national pharmacovigilance system. METHODS: This was a prospective, observational, 1-year, real-life study about the pharmacotherapy of a sample of 390 chronic obstructive pulmonary disease patients...
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/28228162/efficacy-and-safety-of-indacaterol-glycopyrronium-fixed-dose-combination-in-mild-to-moderate-copd-patients-symptomatic-on-tiotropium-in-korea-study-protocol-for-a-randomized-controlled-trial
#19
Chin Kook Rhee, Hye Yun Park, Jeong-Woong Park, Ji-Hyun Lee, Tae-Hyung Kim, Sei Won Lee, Ji Ye Jung, Song Kim, Yong Il Hwang, Ki-Suck Jung
BACKGROUND: Long-acting bronchodilator monotherapy (long-acting β2-agonist [LABA] or long-acting muscarinic antagonist [LAMA]) is extensively used for treatment of patients with chronic obstructive pulmonary disease (COPD) with mild-to-moderate airflow limitation. However, a substantial number of patients remain symptomatic despite treatment with a single bronchodilator, necessitating a change in therapy. METHODS: This 12-week, randomized, multicenter, open-label, phase IV study aims to show that the once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg fixed-dose LABA/LAMA combination results in an improved lung function in symptomatic patients with mild-to-moderate COPD who switch from once-daily tiotropium 18 μg...
February 22, 2017: Trials
https://www.readbyqxmd.com/read/28176893/indacaterol-glycopyrronium-versus-salmeterol-fluticasone-in-asian-patients-with-copd-at-a-high-risk-of-exacerbations-results-from-the-flame-study
#20
Jadwiga A Wedzicha, Nanshan Zhong, Masakazu Ichinose, Michael Humphries, Robert Fogel, Chau Thach, Francesco Patalano, Donald Banerji
BACKGROUND: The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β2-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study. PATIENTS AND METHODS: Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included...
2017: International Journal of Chronic Obstructive Pulmonary Disease
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