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https://www.readbyqxmd.com/read/29332144/long-acting-%C3%AE-2-agonists-in-asthma-enantioselective-safety-studies-are-needed
#1
Glenn A Jacobson, Sharanne Raidal, Morten Hostrup, Luigino Calzetta, Richard Wood-Baker, Mark O Farber, Clive P Page, E Haydn Walters
Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection...
January 13, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29282192/mast-cell-activation-syndrome
#2
Owen N Kramer, Marla S Barkoff, Claudia Hernandez
A 51-year-old woman with a history of asthma and Hashimoto's thyroiditis presented to the dermatology service with a chief complaint of "itchy bumpy rashes" that persisted beyond 24 hours. She noted that, 3 days prior to the onset of urticaria, a pyrroloquinoline quinone supplement had been started. The urticaria was accompanied by variable episodes of transient facial swelling and difficulty breathing. The patient noted that exposure to fish, nuts, and nonsteroidal anti-inflammatory drugs triggered facial swelling...
2017: Skinmed
https://www.readbyqxmd.com/read/29274305/treatment-adherence-and-level-of-control-in-moderate-persistent-asthma-in-children-and-adolescents-treated-with-fluticasone-and-salmeterol
#3
Nulma S Jentzsch, Gabriela C G Silva, Guilherme M S Mendes, Paul L P Brand, Paulo Camargos
OBJECTIVE: There is a scarcity of studies that assessed the association between adherence to combination therapy and asthma control in pediatric patients. The authors investigated the association between adherence to fluticasone propionate/salmeterol xinafoate combination-metered aerosol and the level of asthma control in children. METHODS: This was a prospective observational study of 84 patients aged 5-16 years with moderate persistent asthma, who remained uncontrolled despite the use of 1000μg/day of inhaled nonextrafine-hydrofluoric alkane-beclomethasone dipropionate in the three months prior to study enrollment...
December 20, 2017: Jornal de Pediatria
https://www.readbyqxmd.com/read/29247741/investigations-on-the-mechanism-of-magnesium-stearate-to-modify-aerosol-performance-in-dry-powder-inhaled-formulations
#4
Martin Jetzer, Marcel Schneider, Bradley Morrical, Georgios Imanidis
The potential of the force control agent (FCA) magnesium stearate (MgSt) to enhance the aerosol performance of lactose-based dry powder inhaled (DPI) formulations was investigated in this study. The excipient blends were investigated with analytical techniques including time-of-flight secondary ion mass spectrometry (ToF-SIMS) and Single Particle Aerosol Mass Spectrometry (SPAMS) and particle size, morphology and surface properties were evaluated. Excipient-blends were manufactured either by high-shear or low-shear blending lactose carrier with different amounts of MgSt in the range from 0-10% (w/w)...
December 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29228950/indacaterol-glycopyrronium-is-cost-effective-compared-to-salmeterol-fluticasone-in-copd-flame-based-modelling-in-a-swedish-population
#5
Leif Bjermer, Job F M van Boven, Madlaina Costa-Scharplatz, Dorothy L Keininger, Florian S Gutzwiller, Karin Lisspers, Ronan Mahon, Petter Olsson, Nicolas Roche
BACKGROUND: This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. METHODS: A previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer's perspective and were discounted at 3% annually...
December 11, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29202304/development-and-validation-of-an-uhplc-ms-ms-method-for-%C3%AE-2-agonists-quantification-in-human-urine-and-application-to-clinical-samples
#6
Cristina Bozzolino, Marta Leporati, Federica Gani, Cinzia Ferrero, Marco Vincenti
A fast analytical method for the simultaneous detection of 24 β2-agonists in human urine was developed and validated. The method covers the therapeutic drugs most commonly administered, but also potentially abused β2-agonists. The procedure is based on enzymatic deconjugation with β-glucuronidase followed by SPE clean up using mixed-phase cartridges with both ion-exchange and lipophilic properties. Instrumental analysis conducted by UHPLC-MS/MS allowed high peak resolution and rapid chromatographic separation, with reduced time and costs...
December 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29193247/randomized-double-blind-crossover-clinical-end-point-pilot-study-to-examine-the-use-of-exhaled-nitric-oxide-as-a-bioassay-for-dose-separation-of-inhaled-fluticasone-propionate
#7
John M Weiler, Christine A Sorkness, Leslie Hendeles, Sara Nichols, Yaping Zhu
This was a randomized, double-blind, crossover, clinical-end-point pilot study examining the hypothesis that inhaled fluticasone propionate decreases exhaled nitric oxide (eNO) concentrations within a week of beginning treatment and shows evidence of dose separation across the marketed dose range. Subjects had a ≥6-month history of asthma and screening eNO ≥60 parts per billion. At the start of each treatment period, eNO was ≥55 parts per billion, and forced expiratory volume in 1 second was ≥50% predicted...
November 28, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29183838/abediterol-las100977-an-inhaled-long-acting-%C3%AE-2-adrenoceptor-agonist-has-a-fast-association-rate-and-long-residence-time-at-receptor
#8
Israel Ramos, Mònica Aparici, Maria Letosa, Carlos Puig, Amadeu Gavaldà, Josep Maria Huerta, Sonia Espinosa, Dolors Vilella, Montserrat Miralpeix
This study describes the association rate and residence time of abediterol, a novel long-acting β2-adrenoceptor agonist (LABA) in Phase II development for treatment of asthma and COPD, in comparison with indacaterol, olodaterol, vilanterol and salmeterol, for both human β1- and β2-adrenoceptors. Abediterol association and dissociation rates were monitored directly by using its tritiated form. Moreover, association was determined indirectly using experimental Ki and koff obtained from assays performed with unlabelled compound...
November 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29174062/tiotropium-respimat-add-on-is-efficacious-in-symptomatic-asthma-independent-of-t2-phenotype
#9
Thomas B Casale, Eric D Bateman, Mark Vandewalker, J Christian Virchow, Hendrik Schmidt, Michael Engel, Petra Moroni-Zentgraf, Huib A M Kerstjens
BACKGROUND: Adding tiotropium to existing inhaled corticosteroid (ICS) maintenance therapy with or without a long-acting β2-agonist (LABA) has been shown to be beneficial in patients with symptomatic asthma. OBJECTIVE: To assess whether responses to tiotropium Respimat add-on therapy were influenced by patients' T2 status. METHODS: In this exploratory study, data from 4 phase III trials were analyzed: once-daily tiotropium 5 μg or placebo as add-on to ICS + LABA (PrimoTinA-asthma; 2 replicate trials; NCT00772538/NCT00776984; n = 912); once-daily tiotropium 5 μg or 2...
November 22, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29162108/reduced-suppressive-effect-of-%C3%AE-2-adrenoceptor-agonist-on-fibrocyte-function-in-severe-asthma
#10
Chun-Yu Lo, Charalambos Michaeloudes, Pankaj K Bhavsar, Chien-Da Huang, Po-Jui Chang, Chun-Hua Wang, Han-Pin Kuo, Kian Fan Chung
BACKGROUND: Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. METHODS: Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone...
November 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29073309/thinking-outside-the-checkbox
#11
Maki Kanamori, Gurpreet Dhaliwal, Masami Matsumura, Bradley Monash
A 34-year-old, previously healthy Japanese man developed a dry cough. He did not have dyspnea, nasal discharge, sore throat, facial pain, nasal congestion, or postnasal drip. His symptoms persisted despite several courses of antibiotics (from different physicians), including clarithromycin, minocycline, and levofl oxacin. A chest x-ray after 2 months of symptoms and a noncontrast chest computed tomography (CT) after 4 months of symptoms were normal, and bacterial and mycobacterial sputum cultures were sterile...
October 18, 2017: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/28982774/long-term-effects-of-inhaled-corticosteroids-on-sputum-bacterial-and-viral-loads-in-copd
#12
Marco Contoli, Alessia Pauletti, Maria Rita Rossi, Antonio Spanevello, Paolo Casolari, Andrea Marcellini, Giacomo Forini, Giulia Gnesini, Brunilda Marku, Neil Barnes, Andrea Rizzi, Giacomo Curradi, Gaetano Caramori, Paolo Morelli, Alberto Papi
Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections. The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months...
October 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28961020/once-daily-fluticasone-furoate-vilanterol-versus-twice-daily-fluticasone-propionate-salmeterol-in-patients-with-asthma-well-controlled-on-ics-laba
#13
David Bernstein, Leslie Andersen, Richard Forth, Loretta Jacques, Louisa Yates
OBJECTIVE: We aimed to demonstrate non-inferiority of once-daily fluticasone furoate/vilanterol 100/25 μg (FF/VI) to twice-daily fluticasone propionate/salmeterol 250/50 μg (FP/SAL) in adults/adolescents with asthma well controlled on inhaled corticosteroid/long-acting β2 agonist (ICS/LABA). METHODS: This was a randomized, double-blind, double-dummy, parallel-group, 24-week study (NCT02301975/GSK study 201378). Patients whose asthma met study-defined criteria for control were randomized 1:1:1 to receive FF/VI, FP/SAL or twice-daily FP 250 μg for 24 weeks...
September 29, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28933971/the-pharmacokinetics-safety-and-tolerability-of-single-high-strength-doses-of-fluticasone-propionate-and-fluticasone-propionate-salmeterol-delivered-via-a-novel-multidose-dry-powder-inhaler-in-adolescents-and-adults-with-persistent-asthma
#14
Courtney Nugent, Gloria Yiu, Sharon Song, Cynthia Caracta
OBJECTIVE: Characterize fluticasone propionate (Fp) and combination fluticasone propionate and salmeterol (FS) pharmacokinetic and safety profiles, delivered via a novel, inhalation-driven, multidose dry powder inhaler (MDPI). METHODS: This multicenter, open-label, four-period crossover, single-dose study randomized patients aged ≥12 years with persistent asthma to Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, Fp dry powder inhaler (DPI) 500 mcg (250 mcg × 2 inhalations), or FS DPI 500/50 mcg...
September 21, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28929816/which-inhaled-corticosteroid-and-long-acting-%C3%AE-agonist-combination-is-better-in-patients-with-moderate-to-severe-asthma-a-dry-powder-inhaler-or-a-pressurized-metered-dose-inhaler
#15
Masato Muraki, Kyuya Gose, Soichiro Hanada, Hirochiyo Sawaguchi, Yuji Tohda
Two main types of devices are used to facilitate the administration of inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) in combination, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). There are few reports comparing the effects of the two devices, and it is unknown which should be recommended for asthma patients with given sets of characteristics. In the current study, the beneficial effects and side effects associated with DPIs and pMDIs were compared, and the question of which device should be recommended for asthma patients was investigated...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28926855/a-comparison-of-the-efficacy-of-once-daily-fluticasone-furoate-vilanterole-with-twice-daily-fluticasone-propionate-salmeterol-in-elderly-asthmatics
#16
Yoshihisa Ishiura, Masaki Fujimura, Yasutaka Shiba, Noriyuki Ohkura, Johsuke Hara, Miki Abo, Kazuo Kasahara
Background Asthma in the elderly population has been focused because it affects quality of life and results in a higher hospitalization rate and mortality. Fluticasone furoate (FF)/vilanterole (VI) is a novel inhaled corticosteroids (ICS)/long-acting β2 agonist (LABA) combination being developed for once-daily administration for asthma with greater anti-inflammatory activity and longer duration of bronchidilation. The ElliptaTM dry powder inhaler (DPI) has also been available as a new device with high levels of satisfaction and preference...
September 19, 2017: Drug Research
https://www.readbyqxmd.com/read/28864391/particle-interactions-of-fluticasone-propionate-and-salmeterol-xinafoate-detected-with-single-particle-aerosol-mass-spectrometry-spams
#17
Martin W Jetzer, Bradley D Morrical, David P Fergenson, Georgios Imanidis
Particle co-associations between the active pharmaceutical ingredients fluticasone propionate and salmeterol xinafoate were examined in dry powder inhaled (DPI) and metered dose inhaled (MDI) combination products. Single Particle Aerosol Mass Spectrometry was used to investigate the particle interactions in Advair Diskus(®) (500/50 mcg) and Seretide(®) (125/25 mcg). A simple rules tree was used to identify each compound, either alone or co-associated at the level of the individual particle, using unique marker peaks in the mass spectra for the identification of each drug...
August 31, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28860742/severe-exacerbation-and-pneumonia-in-copd-patients-treated-with-fixed-combinations-of-inhaled-corticosteroid-and-long-acting-beta2-agonist
#18
Hsi-Hsing Yang, Chih-Cheng Lai, Ya-Hui Wang, Wei-Chih Yang, Cheng-Yi Wang, Hao-Chien Wang, Likwang Chen, Chong-Jen Yu
BACKGROUND: It remains unclear whether severe exacerbation and pneumonia of COPD differs between patients treated with budesonide/formoterol and those treated with fluticasone/salmeterol. Therefore, we conducted a comparative study of those who used budesonide/formoterol and those treated with fluticasone/salmeterol for COPD. METHODS: Subjects in this population-based cohort study comprised patients with COPD who were treated with a fixed combination of budesonide/formoterol or fluticasone/salmeterol...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28860739/the-comparative-effectiveness-of-initiating-fluticasone-salmeterol-combination-therapy-via-pmdi-versus-dpi-in-reducing-exacerbations-and-treatment-escalation-in-copd-a-uk-database-study
#19
Rupert Jones, Jessica Martin, Vicky Thomas, Derek Skinner, Jonathan Marshall, Martina Stagno d'Alcontres, David Price
Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28833774/corticosteroid-and-long-acting-%C3%A3-agonist-therapy-reduces-epithelial-goblet-cell-metaplasia
#20
M E Lachowicz-Scroggins, W E Finkbeiner, E D Gordon, S Yuan, L Zlock, N R Bhakta, P G Woodruff, J V Fahy, H A Boushey
BACKGROUND: Bronchial epithelial goblet cell metaplasia (GCM) with hyperplasia is a prominent feature of asthma, but the effects of treatment with corticosteroids, alone or in combination with a long-acting β2 -adrenergic receptor agonist (LABA) on GCM in the bronchial epithelium are unknown. OBJECTIVES: To determine if corticosteroid alone or in combination with a LABA alter protein and gene expression pathways associated with IL-13-induced goblet cell metaplasia...
August 22, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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