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Pulmonary Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/28729042/effects-of-%C3%AE-blockers-on-house-dust-mite-driven-murine-models-pre-and-post-development-of-an-asthma-phenotype
#1
Radhika Joshi, Daniel Valdez, Hosu Kim, Douglas C Eikenburg, Brian J Knoll, Richard A Bond
BACKGROUND: Our previous studies suggested certain β-adrenoceptor blockers (β-blockers) attenuate the asthma phenotype in ovalbumin driven murine models of asthma. However, the ovalbumin model has been criticized for lack of clinical relevance. METHODS: We tested the non-selective β-blockers, carvedilol and nadolol, in house dust mite (HDM) driven murine asthma models where drugs were administered both pre- and post-development of the asthma phenotype. We measured inflammation, mucous metaplasia, and airway hyper-responsiveness (AHR)...
July 17, 2017: Pulmonary Pharmacology & Therapeutics
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
#2
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/28689020/ferulic-acid-supresses-th2-immune-response-and-prevents-remodeling-in-ovalbumin-induced-pulmonary-allergy-associated-with-inhibition-of-epithelial-derived-cytokines
#3
Alessa Sin Singer Brugiolo, Ana Cláudia Carvalho Gouveia, Caio César de Souza Alves, Flávia Márcia de Castro E Silva, Érick Esteves de Oliveira, Ana Paula Ferreira
Asthma is characterized by intermittent airway obstruction and chronic inflammation, orchestrated primarily by Th2 cytokines. There is a strong rationale for developing new asthma therapies, since current treatment protocols present side effects and may not be effective in cases of difficult-to-control asthma. The purpose of this study was to evaluate the effect of ferulic acid, a phenolic acid commonly present in plants, in the ovalbumin-induced pulmonary allergy murine model. METHODS: BALB/c mice were sensitized and challenged with ovalbumin, and treatments were provided by gavage...
July 5, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28687463/non-asthmatic-eosinophilic-bronchitis-and-its-relationship-with-asthma
#4
REVIEW
Kefang Lai, Ruchong Chen, Wen Peng, Wenzhi Zhan
Non-asthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough. The patients with NAEB present irritable cough as a sole or major symptom. They share similar features with asthmatic patients: sputum eosinophilia and responds well to glucocorticosteroids. However, compared with asthma, NAEB subjects have a normal spirometry and absence of airway hyperresponsiveness. The inflammatory cells and airway remodeling might result in the difference of mechanism between NAEB and asthma. On the prognosis of NAEB, only a few studies have been conducted in the last two decades...
July 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28687462/the-effect-of-tiotropium-in-combination-with-olodaterol-on-house-dust-mite-induced-allergic-airway-disease
#5
Gerrit John-Schuster, Stan de Kleijn, Yolanda van Wijck, Veerle Kremer, Hermelijn H Smits, Michael P Pieper, Pieter S Hiemstra, Christian Taube
One of the major goals of asthma therapy is to maintain asthma control and prevent acute exacerbations. Long-acting bronchodilators are regularly used for the treatment of asthma patients and in clinical studies the anti-cholinergic tiotropium has recently been shown to reduce exacerbations in patients with asthma. So far it is unclear how tiotropium exerts this effect. For this purpose, we designed an allergen-driven rechallenge model of allergic airway inflammation in mice, to assess the effectiveness of tiotropium and the long-acting β-2 adrenoceptor agonist olodaterol on allergen-induced exacerbations of airway disease...
July 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28669932/cough-and-airway-disease-the-role-of-ion-channels
#6
REVIEW
Sara J Bonvini, Maria G Belvisi
Cough is the most common reason for patients to visit a primary care physician, yet it remains an unmet medical need. It can be idiopathic in nature but can also be a troublesome symptom across chronic lung diseases such as asthma, COPD and idiopathic pulmonary fibrosis (IPF). Chronic cough affects up to 12% of the population and yet there are no safe and effective therapies. The cough reflex is regulated by vagal, sensory afferent nerves which innervate the airway. The Transient Receptor Potential (TRP) family of ion channels are expressed on sensory nerve terminals, and when activated can evoke cough...
June 29, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28666965/individualizing-duration-of-antibiotic-therapy-in-community-acquired-pneumonia
#7
Stefano Aliberti, Julio Ramirez, Fabio Giuliani, Timothy Wiemken, Giovanni Sotgiu, Sara Tedeschi, Manuela Carugati, Vincenzo Valenti, Marco Marchioni, Marco Camera, Roberto Piro, Manuela Del Forno, Giuseppe Milani, Paola Faverio, Luca Richeldi, Martina Deotto, Massimiliano Villani, Antonio Voza, Eleonora Tobaldini, Mauro Bernardi, Andrea Bellone, Matteo Bassetti, Francesco Blasi
International experts suggest tailoring antibiotic duration in community-acquired pneumonia (CAP) according to patients' characteristics. We aimed to assess the effectiveness of an individualized approach to antibiotic duration based on time in which CAP patients reach clinical stability during hospitalization. In a multicenter, non-inferiority, randomized, controlled trial hospitalized adult patients with CAP reaching clinical stability within 5 days after hospitalization were randomized to a standard vs. individualized antibiotic duration...
June 27, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28648907/sulfated-dehydropolymer-of-caffeic-acid-in-vitro-anti-lung-cell-death-activity-and-in-vivo-intervention-in-emphysema-induced-by-vegf-receptor-blockade
#8
Tien M Truong, Hua Li, Sneha Dhapare, Umesh R Desai, Nobert F Voelkel, Masahiro Sakagami
Induced lung cell death and impaired hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) signaling are proposed as a pathobiologic mechanism for alveolar structural destruction and loss in emphysema. We hypothesized that our sulfated dehydropolymer of caffeic acid, CDSO3, exerts anti-cell death activities and therapeutic interventions in emphysema by virtue of Fe(2+) chelation-based HIF-1α/VEGF stabilization and elevation. The Fe(2+) chelating activity was determined in the chromogenic ferrozine-Fe(2+) chelation inhibitory assay...
June 22, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28645584/effects-of-intranasal-treatment-with-slow-gyy4137-and-rapid-nahs-donors-of-hydrogen-sulfide-in-lipopolysaccharide-induced-airway-inflammation-in-mice
#9
Yesim Kaya-Yasar, Yasemin Karaman, Turgut Emrah Bozkurt, Sevgen Celik Onder, Inci Sahin-Erdemli
We have investigated the effects of slow (GYY4137) and rapid (NaHS) hydrogen sulfide (H2S) releasing donors in lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS (0.1 mg/ml) in 60 μl PBS was administered by the intranasal (i.n.) route and control group received vehicle, whereas the subgroups of mice were treated with i.n. GYY4137 or NaHS. The tracheal reactivity, inflammatory cell count in bronchoalveolar lavage (BAL) fluid and lung histopathology were evaluated in all groups 48 h after LPS/PBS applications...
June 20, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28642014/acute-hemodynamic-effects-of-intravenous-adenosine-in-patients-with-associated-pulmonary-arterial-hypertension-comparison-with-intravenous-epoprostenol
#10
Rosario Rossi, Francesca Coppi, Fabio Sgura, Daniel Monopoli, Giuseppe Boriani
Exogenous intravenous (IV) adenosine and epoprostenol are effective vasodilator agents, causing a substantial reduction in pulmonary vascular resistance in patients affected by idiopathic pulmonary arteriolar hypertension (PAH). Their action, in patients with PAH associated with other pathological conditions, is not well defined. In the present paper the authors retrospectively analyzed the acute hemodynamic effects of intravenous adenosine and epoprostenol in 30 consecutive patients (mean age: 58 ± 15 years; 21 females, and 9 males) affected by PAH associated with other pathological conditions, as determined by changes from baseline in systemic and pulmonary hemodynamic parameters...
June 19, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28627376/inhaled-salbutamol-dose-delivered-by-jet-nebulizer-vibrating-mesh-nebulizer-and-metered-dose-inhaler-with-spacer-during-invasive-mechanical-ventilation
#11
Muhammad E ElHansy, Marina Emad, Assem Fouad Mohamed El Essawy, Mohamed Bakry Al-Kholy, Maha M Abdelrahman, Amira S A Said, Raghda R S Hussein, Mohamed E Abdelrahim
BACKGROUND: Patient receiving invasive mechanical ventilation (IMV) may benefit from medical aerosol, but guidance on dosing with different aerosol devices is limited to in-vitro studies. The study was designed to compare aerosol delivery with five different types of aerosol generators during IMV. METHOD: In randomized design, 60 (30 female) mechanically ventilated chronic obstructive pulmonary disease (COPD) patients were assigned to one of 5 groups. Groups 1-4 received 5000 μg salbutamol using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO vibrating mesh and jet nebulizers (JN), respectively, while group 5 received 800 μg (8 puffs) of salbutamol via metered dose inhaler with AeroChamber-MV (MDI-AC)...
June 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28619646/time-dependent-effects-of-hjp272-an-endothelin-receptor-antagonist-in-bleomycin-induced-pulmonary-fibrosis
#12
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
Using a lipopolysaccharide (LPS) model of acute lung injury, we have previously shown that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. To further investigate the potential of ET-1 to limit the progression of lung injury, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of bleomycin (BLM) or 24 h afterwards. Lung injury and repair were examined by measuring the following parameters: 1) histopathological changes; 2) neutrophil content in bronchoalveolar lavage fluid (BALF); 3) lung collagen content; 4) tumor necrosis factor receptor 1 (TNFR1) expression by BALF macrophages; 5) BALF levels of: a) transforming growth factor beta-1 (TGF-β1), b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and c) platelet-derived growth factor BB (PDGF-BB); 6) alveolar septal cell apoptosis (as measured by the TUNEL assay)...
June 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28606478/withdrawal-of-inhaled-corticosteroids-in-copd-a-meta-analysis
#13
Luigino Calzetta, Maria Gabriella Matera, Fulvio Braido, Marco Contoli, Angelo Corsico, Fabiano Di Marco, Pierachille Santus, Nicola Scichilone, Mario Cazzola, Paola Rogliani
BACKGROUND: Conflicting findings exist on the benefit of withdrawal of inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD). We performed a quantitative synthesis in order to assess real impact of ICS discontinuation in COPD patients. METHODS: We carried out a meta-analysis via random-effects model on the available clinical evidence to evaluate the effect of ICS discontinuation in COPD. Randomized clinical trials and observational real-life studies investigating the effects of ICS withdrawal on the risk of COPD exacerbation, lung function (forced expiratory volume in 1 s [FEV1]) and quality of life (St...
June 9, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28602999/cough-and-bronchiectasis
#14
REVIEW
Paul McCallion, Anthony De Soyza
Bronchiectasis is a chronic lung disease with permanent airway dilatation, mucus retention and recurrent lower respiratory tract infections. Bronchiectasis is increasing in prevalence and has a significant morbidity and an excess mortality rate over age matched controls. It is increasingly identified during investigations into chronic cough and is evident high resolution CT scanning. There remain significant knowledge gaps in our understanding of the epidemiology, pathophysiology, prognosis and optimal treatments in bronchiectasis...
June 7, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28587842/sustained-sensitizing-effects-of-tumor-necrosis-factor-alpha-on-sensory-nerves-in-lung-and-airways
#15
REVIEW
Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee
Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 h later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and cytokines in the lung and airways...
June 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28571757/hmgb1-promotes-hlf-1-proliferation-and-ecm-production-through-activating-hif1-%C3%AE-regulated-aerobic-glycolysis
#16
JianNing Xu, JingYing Li, ZhiHong Yu, HaiWei Rao, Shu Wang, HaiBing Lan
Aerobic glycolysis is a crucial event in fibroblast differentiation, and extracellular matrix (ECM) production in the progression of pulmonary fibrosis (PF). Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of PF. However, whether aerobic glycolysis contributes to HMGB1-induced fibroblast proliferation and ECM production in PF has not yet been determined. In this study, we investigated the effects of HMGB1 on human embryonic lung fibroblast (HLF-1) proliferation, ECM production, and aerobic glycolysis...
May 29, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28564586/a-57-year-old-chronic-cougher-with-somatically-evoked-cough
#17
Federico Lavorini, Giovanni A Fontana
No abstract text is available yet for this article.
May 28, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28552795/rhukgf-ameliorates-protease-anti-protease-imbalance-in-emphysematous-mice
#18
Sudhir Kotnala, Amit Tyagi, Jai Prakash Muyal
We attempted to elucidate the beneficial role of rHuKGF supplementation in the amelioration of protease/antiprotease imbalance and TGF-β1 signalling pathway leading to alveolar tissue maintenance in elastase induced emphysematous mice. Thirty two male C57BL mice were divided into four groups i.e. control, emphysema, therapy and rHuKGF only and were oropharyngeally instilled with saline/porcine pancreatic elastase/rHuKGF. Subsequently, lungs from mice were collected for histopathology and molecular biology studies...
May 25, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28549850/effects-of-the-cxcr2-antagonist-azd5069-on-lung-neutrophil-recruitment-in-asthma
#19
LETTER
Henrik Watz, Mohib Uddin, Frauke Pedersen, Anne Kirsten, Torsten Goldmann, Florian Stellmacher, Espen Groth, Bengt Larsson, Gerhard Böttcher, Anna Malmgren, Maarten Kraan, Klaus F Rabe
No abstract text is available yet for this article.
May 23, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28527922/bronchodilator-therapy-for-chronic-cough
#20
REVIEW
Maria Gabriella Matera, Paola Rogliani, Alessandro Zanasi, Mario Cazzola
Experimental studies indicate that airway calibre increases the sensitivity of the afferents involved in the cough reflex but it has proved difficult to demonstrate that airway calibre increases the sensitivity of the afferents involved in the cough reflex. Therefore, bronchodilators might have a role, although rather minor, in the treatment of cough. However, although bronchodilators represent the standard of care in the treatment of airway obstruction associated with asthma or COPD, controversy persists regarding the mechanism(s) by which these agents alleviate cough...
May 17, 2017: Pulmonary Pharmacology & Therapeutics
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