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https://www.readbyqxmd.com/read/29923706/development-of-anti-cd74-antibody-drug-conjugates-to-target-glucocorticoids-to-immune-cells
#1
Philip Brandish, Anthony Palmieri, Svetlana Antonenko, Maribel Beaumont, Lia Benso, Mark Cancilla, Mangeng Cheng, Laurence Fayadat-Dilman, Guo Feng, Isabel Figueroa, Juhi Firdos, Robert M Garbaccio, Laura Garvin-Queen, Dennis Gately, Prasanthi Geda, Christopher Haines, SuChun Hseih, Douglas Hodges, Jeffrey C Kern, Nick Knudsen, Kristen Kwasnjuk, Linda Liang, Huiping Ma, Anthony Manibusan, Paul Miller, Lily Moy, Yujie Qu, Sanjiv Shah, John Shin, Peter Stivers, Ying Sun, Daniela Tomazela, Hyun Chong Woo, Dennis Zaller, Shuli Zhang, Yiwei Zhang, Mark Zielstorff
Glucocorticoids (GCs) are excellent anti-inflammatories but are dose-limited by on-target toxicity. We sought to solve this 13 problem by delivering GCs to immune cells with antibody drug conjugates (ADCs) using antibodies containing site-specific 14 incorporation of a non-natural amino acid, novel linker chemistry for in vitro and in vivo stability, and existing and novel 15 glucocorticoid receptor (GR) agonists as payloads. We directed fluticasone to human antigen-presenting immune cells to 16 afford GR activation that was dependent on the targeted antigen...
June 20, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29922045/patient-considerations-in-the-treatment-of-copd-focus-on-the-new-combination-inhaler-fluticasone-furoate-umeclidinium-vilanterol
#2
REVIEW
Antonio Molino, Giovanna Calabrese, Mauro Maniscalco
The pharmacological treatment for stable COPD is based on the use of inhaled bronchodilators (long-acting muscarinic receptor antagonists and long-acting beta-2 adrenoceptor agonists) and inhaled corticosteroids. The use of triple inhaled therapy is recommended to selected patients with COPD. Among the various inhaler combinations in triple therapy, a new combination by fluticasone furoate, umeclidinium, and vilanterol is available for COPD patients. Recently, a large clinical trial using this combination has been published, resulting in a reduction in exacerbation rate in COPD patients...
2018: Patient Preference and Adherence
https://www.readbyqxmd.com/read/29906501/repurposing-drugs-as-inhaled-therapies-in-asthma
#3
Sandra D Anderson
For the first 40 years of the 20th century treatment for asthma occurred in response to an asthma attack. The treatments were given by injection or orally and included the adrenergic agonists adrenalin/epinephrine and ephedrine and a phosphodiesterase inhibitor theophylline. Epinephrine became available as an aerosol in 1930. After 1945, isoprenaline, a non-selective beta agonist, became available for oral use but it was most widely used by inhalation. Isoprenaline was short-acting with unwanted cardiac effects...
June 12, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29884817/corticosteroid-suppression-of-antiviral-immunity-increases-bacterial-loads-and-mucus-production-in-copd-exacerbations
#4
Aran Singanayagam, Nicholas Glanville, Jason L Girkin, Yee Man Ching, Andrea Marcellini, James D Porter, Marie Toussaint, Ross P Walton, Lydia J Finney, Julia Aniscenko, Jie Zhu, Maria-Belen Trujillo-Torralbo, Maria Adelaide Calderazzo, Chris Grainge, Su-Ling Loo, Punnam Chander Veerati, Prabuddha S Pathinayake, Kristy S Nichol, Andrew T Reid, Phillip L James, Roberto Solari, Peter A B Wark, Darryl A Knight, Miriam F Moffatt, William O Cookson, Michael R Edwards, Patrick Mallia, Nathan W Bartlett, Sebastian L Johnston
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations...
June 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29882826/a-muscarinic-antagonist-reduces-airway-inflammation-and-bronchoconstriction-induced-by-ambient-particulate-matter-in-a-mouse-model-of-asthma
#5
Jun Kurai, Masanari Watanabe, Hiroyuki Sano, Kyoko Iwata, Degejirihu Hantan, Eiji Shimizu
Ambient particulate matter (PM) can increase airway inflammation and induce bronchoconstriction in asthma. This study aimed to investigate the effect of tiotropium bromide, a long-acting muscarinic antagonist, on airway inflammation and bronchoconstriction induced by ambient PM in a mouse model of asthma. We compared the effect of tiotropium bromide to that of fluticasone propionate and formoterol fumarate. BALB/c mice were sensitized to ovalbumin (OVA) via the airways and then administered tiotropium bromide, fluticasone propionate, or formoterol fumarate...
June 6, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29881320/low-dose-fluticasone-propionate-in-combination-with-salmeterol-in-patients-with-chronic-obstructive-pulmonary-disease
#6
Hideki Yasui, Naoki Inui, Tomoyuki Fujisawa, Masato Karayama, Noriyuki Enomoto, Yutaro Nakamura, Shigeki Kuroishi, Hisano Ohba, Koshi Yokomura, Jun Sato, Masaki Sato, Naoki Koshimizu, Mikio Toyoshima, Takashi Yamada, Masafumi Masuda, Toshihiro Shirai, Takafumi Suda
Inhaled corticosteroids are widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, their use has been questioned for appropriate dose and a possible increased risk of pneumonia. Here, we reviewed patients with COPD who had received fluticasone-salmeterol combination treatment using data from a linked electronic medical record database. A total of 180 patients received salmeterol with 250 µg fluticasone propionate twice daily and 78 received salmeterol and 100 µg fluticasone propionate twice daily...
2018: Clinical Medicine Insights. Circulatory, Respiratory and Pulmonary Medicine
https://www.readbyqxmd.com/read/29857783/efficacy-and-safety-of-fluticasone-propionate-formoterol-fumarate-in-pediatric-asthma-patients-a-randomized-controlled-trial
#7
Anna Płoszczuk, Miroslava Bosheva, Kay Spooner, Tammy McIver, Sanjeeva Dissanayake
BACKGROUND: The efficacy and safety of fluticasone propionate/formoterol fumarate pressurized metered-dose inhaler (pMDI) (fluticasone/formoterol; Flutiform® ; 100/10 µg b.i.d.) was compared with fluticasone propionate (Flixotide® Evohaler® pMDI; 100 µg b.i.d.) and fluticasone/salmeterol (Seretide® Evohaler® pMDI; 100/50 µg b.i.d.) in a pediatric asthma population (EudraCT number: 2010-024635-16). METHODS: A double-blind, double-dummy, parallel group, multicenter study...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29794744/post-radiotherapy-maintenance-treatment-with-fluticasone-propionate-and-salmeterol-for-lung-cancer-patients-with-grade-iii-radiation-pneumonitis-a-case-report
#8
Pingping Zhang, Hongxia Yan, Sheng Wang, Jindan Kai, Guoliang Pi, Yi Peng, Xiyou Liu, Junwei Sun
RATIONALE: This combination of fluticasone propionate (FP) and the long-acting β2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29792288/tralokinumab-for-severe-uncontrolled-asthma-stratos-1-and-stratos-2-two-randomised-double-blind-placebo-controlled-phase-3-clinical-trials
#9
Reynold A Panettieri, Ulf Sjöbring, AnnaMaria Péterffy, Peter Wessman, Karin Bowen, Edward Piper, Gene Colice, Christopher E Brightling
BACKGROUND: Tralokinumab is an anti-interleukin-13 human monoclonal antibody developed for the treatment of severe, uncontrolled asthma. These clinical trials aimed to assess the efficacy and safety of tralokinumab in this population. METHODS: STRATOS 1 and STRATOS 2 were randomised, double-blind, parallel-group, placebo-controlled, phase 3 clinical trials that enrolled participants aged 12-75 years with severe asthma that was inadequately controlled despite use of inhaled corticosteroids (≥500 μg per day fluticasone or equivalent) and a long-acting β2 agonist (but not oral corticosteroids)...
May 18, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29792141/molecular-docking-for-prediction-and-interpretation-of-adverse-drug-reactions
#10
Heng Luo, Achille Fokoue-Nkoutche, Nalini Singh, Lun Yang, Jianying Hu, Ping Zhang
Adverse drug reactions (ADRs) present a major burden for patients and the healthcare industry. Various computational methods have been developed to predict ADRs for drug molecules. However, many of these methods require experimental or surveillance data and cannot be used when only structural information is available. We collected 1,231 small molecule drugs and 600 human proteins and utilized molecular docking to generate binding features among them. We developed machine learning models that use these docking features to make predictions for 1,533 ADRs...
May 23, 2018: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29781748/pediatric-sloughing-esophagitis-a-case-report-and-discussion
#11
Lulu Sun, Christina A Hickey, Brendan R Harris, Horacio M Maluf, Mai He
BACKGROUND: Sloughing esophagitis is an uncommon entity with an unclear pathogenesis characterized by desquamating sheets of squamous mucosa. It has been associated with bullous dermatologic disorders, other autoimmune diseases and has been most commonly reported in elderly, debilitated individuals on multiple medications. CASE REPORT: We report sloughing esophagitis in a previously healthy 17 year-old girl. While the initial trigger of her esophagitis is unclear, she improved with proton pump inhibitor therapy and swallowed fluticasone, with complete resolution after 6 months...
May 21, 2018: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/29779416/long-term-triple-therapy-de-escalation-to-indacaterol-glycopyrronium-in-copd-patients-sunset-a-randomized-double-blind-triple-dummy-clinical-trial
#12
Kenneth R Chapman, John R Hurst, Stefan-Marian Frent, Michael Larbig, Robert Fogel, Tadhg Guerin, Donald Banerji, Francesco Patalano, Pankaj Goyal, Pascal Pfister, Konstantinos Kostikas, Jadwiga A Wedzicha
RATIONALE: There are no studies on ICS withdrawal in patients on long-term triple therapy in the absence of frequent exacerbations. OBJECTIVE: To evaluate the efficacy and safety of the direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in non-frequently exacerbating COPD patients. METHODS: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50μg once daily) or continuation of triple therapy (tiotropium 18μg once daily plus combination of salmeterol/fluticasone propionate [50/500μg] twice daily) in non-frequently exacerbating patients with moderate-to-severe COPD...
May 20, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29762864/population-pharmacokinetic-analysis-of-fluticasone-furoate-umeclidinium-vilanterol-via-a-single-inhaler-in-patients-with-copd
#13
Rashmi Mehta, Eleni Pefani, Misba Beerahee, Noushin Brealey, Helen Barnacle, Ruby Birk, Chang-Qing Zhu, David A Lipson
A population pharmacokinetic analysis was conducted from a subset of samples obtained from the Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy trial to characterize the pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol in patients with symptomatic COPD following treatment with fluticason furoate-umeclidinium-vilanterol combined in a single inhaler. This was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticason furoate-umeclidinium-vilanterol, 100 μg/62...
May 15, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29750142/single-inhaler-triple-therapy-in-symptomatic-copd-patients-fulfil-subgroup-analyses
#14
David M G Halpin, Ruby Birk, Noushin Brealey, Gerard J Criner, Mark T Dransfield, Emma Hilton, David A Lomas, Chang-Qing Zhu, David A Lipson
Triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β2 -agonist (LABA) therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD) and at risk of exacerbations. However, the benefits versus side-effects of triple inhaled therapy for COPD, based on distinct patient clinical profiles, are unclear. FULFIL, a phase III, randomised, double-blind study, compared 24 weeks of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62...
April 2018: ERJ Open Research
https://www.readbyqxmd.com/read/29733738/case-study-a-combination-of-mepolizumab-and-omaluzimab-injections-for-severe-asthma
#15
Rejmon Dedaj, Lindie Unsel
A Combination of Mepolizumab and Omaluzimab injections for severe asthma. INTRODUCTION: Patients with severe persistent asthma account for a large proportion of asthma morbidity and health care expenditures. In this case report we describe the use of a combination of omalizumab and mepolizumab in severe asthma with elevated IgE levels and eosinophilic phenotype. CASE STUDY: We are treating a 55 year old woman with severe persistent eosinophilic asthma and elevated IgE levels...
May 7, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29724381/pulmonary-deposition-of-fluticasone-propionate-formoterol-in-healthy-volunteers-asthmatics-and-copd-patients-with-a-novel-breath-triggered-inhaler
#16
Dominik Kappeler, Knut Sommerer, Claudius Kietzig, Bärbel Huber, Jo Woodward, Mark Lomax, Prashant Dalvi
INTRODUCTION: A combination of fluticasone propionate/formoterol fumarate (FP/FORM) has been incorporated within a novel, breath-triggered device, named K-haler® . This low resistance device requires a gentle inspiratory effort to actuate it, triggering at an inspiratory flow rate of approximately 30 L/min; thus avoiding the need for coordination of inhalation with manual canister depression. The aim of the study was to evaluate total and regional pulmonary deposition of FP/FORM when administered via the K-haler device...
May 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29719507/breathomics-for-assessing-the-effects-of-treatment-and-withdrawal-with-inhaled-beclomethasone-formoterol-in-patients-with-copd
#17
Paolo Montuschi, Giuseppe Santini, Nadia Mores, Alessia Vignoli, Francesco Macagno, Rugia Shoreh, Leonardo Tenori, Gina Zini, Leonello Fuso, Chiara Mondino, Corrado Di Natale, Arnaldo D'Amico, Claudio Luchinat, Peter J Barnes, Tim Higenbottam
Background: Prospective pharmacological studies on breathomics profiles in COPD patients have not been previously reported. We assessed the effects of treatment and withdrawal of an extrafine inhaled corticosteroid (ICS)-long-acting β2 -agonist (LABA) fixed dose combination (FDC) using a multidimensional classification model including breathomics. Methods: A pilot, proof-of-concept, pharmacological study was undertaken in 14 COPD patients on maintenance treatment with inhaled fluticasone propionate/salmeterol (500/50 μg b...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29705779/when-two-drugs-are-better-than-three-re-modulating-the-therapeutic-plan-of-a-chronic-obstructive-pulmonary-disease-patient
#18
Antonella Ielpo, Ernesto Crisafulli
We present the case of a 77-year-old man diagnosed with chronic obstructive pulmonary disease (COPD) stage D with emphysema phenotype and treated with triple therapy (salmeterol, fluticasone propionate, and tiotropium) for 1 year without relevant improvements in exertional dyspnea and disease impact. After switching to combination therapy with a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (indacaterol/glycopyrronium), we observed, in a 3-month period, a substantial reduction of the modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT) scores...
2018: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/29692607/exacerbation-heterogeneity-in-copd-subgroup-analyses-from-the-flame-study
#19
Claus F Vogelmeier, Kenneth R Chapman, Marc Miravitlles, Nicolas Roche, Jørgen Vestbo, Chau Thach, Donald Banerji, Robert Fogel, Francesco Patalano, Petter Olsson, Konstantinos Kostikas, Jadwiga A Wedzicha
Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg with twice-daily salmeterol/fluticasone (SFC) 50/500 μg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29692212/use-of-glucocorticoids-in-patients-with-copd-exacerbations-in-china-a-retrospective-observational-study
#20
Jing Zhang, Jinping Zheng, Kewu Huang, Yahong Chen, Jingping Yang, Wanzhen Yao
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common in patients with underlying moderate to severe COPD and are associated with increased health and economic burden. International and Chinese guidelines recommend using glucocorticoids for the management of AECOPD because glucocorticoid therapy has been shown to benefit clinical outcomes. However, only scant data are available for current status of glucocorticoid therapy in hospitalized AECOPD patients in China...
January 2018: Therapeutic Advances in Respiratory Disease
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