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Copd lung challenge model

Piotr Kuna, Magnus Aurivillius, Carin Jorup, Susanne Prothon, Ziad Taib, Staffan Edsbäcker
AZD5423 is a novel, inhaled, selective glucocorticoid receptor modulator (SGRM), which in an allergen challenge model in asthmatics improved lung function and airway hyper-reactivity. In the current trial, AZD5423 was for the first time tested in patients with chronic obstructive pulmonary disease (COPD). In this double-blind, randomised and parallel group study, we examined airway and systemic effects of two doses of AZD5423, inhaled via Turbuhaler for 12 weeks, in 353 symptomatic COPD patients (average pre-bronchodilator forced expiratory volume in one second (FEV1) at screening was 50-52% of predicted normal)...
February 17, 2017: Basic & Clinical Pharmacology & Toxicology
Fumin Guo, Sarah Svenningsen, Miranda Kirby, Dante P I Capaldi, Khadija Sheikh, Aaron Fenster, Grace Parraga
PURPOSE: Recent pulmonary imaging research has revealed that in patients with chronic obstructive pulmonary disease (COPD) and asthma, structural and functional abnormalities are spatially heterogeneous. This novel information may help optimize treatment in individual patients, monitor interventional efficacy and develop new treatments. Moreover, by automating the measurement of regional biomarkers for the 19 different anatomical lung segments, there is an opportunity to embed imaging biomarkers into clinically-acceptable clinical workflows and improve lung disease clinical care...
February 16, 2017: Medical Physics
Peng-Jiu Yu, Li-Mei Wan, Shan-He Wan, Wen-Ying Chen, Hui Xie, Dong-Mei Meng, Jia-Jie Zhang, Xiang-Lin Xiao
CONTEXT: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD). OBJECTIVE: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). MATERIALS AND METHODS: Male BALB/c mice were treated with standardized myrtol for 1.5 h prior to exposure of atomized LPS...
December 2016: Pharmaceutical Biology
Vaibhav Shrirang Dhawale, Venkateswara Rao Amara, Pinakin Arun Karpe, Vajir Malek, Deep Patel, Kulbhushan Tikoo
Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2weeks...
September 1, 2016: Toxicology and Applied Pharmacology
Katsuyuki Takeda, Nobuaki Miyahara, Shigeki Matsubara, Christian Taube, Kenichi Kitamura, Astushi Hirano, Mitsune Tanimoto, Erwin W Gelfand
Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge...
June 2016: Immune Network
Aran Singanayagam, Sebastian L Johnston
Inhaled β2-adrenoceptor agonists are a mainstay of therapy for airways diseases and are almost universally prescribed for patients with asthma or chronic obstructive pulmonary disease (COPD). Very few studies have evaluated the efficacy of these commonly used therapies during acute disease exacerbations which are frequently triggered by viral infection. In this edition of Clinical Science, Donovan et al. assess the ex vivo effects of the most commonly used short-acting β2-agonist salbutamol on small airway reactivity using precision cut lung slices (PCLS) from a mouse model of virus-induced exacerbation of COPD...
May 1, 2016: Clinical Science (1979-)
W S Daniel Tan, Hong Yong Peh, Wupeng Liao, Chu Hui Pang, Tze Khee Chan, Suk Hiang Lau, Vincent T Chow, W S Fred Wong
Cigarette smoke (CS) is associated with many maladies, one of which is chronic obstructive pulmonary disease (COPD). As the disease progresses, patients are more prone to develop COPD exacerbation episodes by bacterial infection, particularly to nontypeable Haemophilus influenza (NTHi) infection. The present study aimed to develop a CS-exposed mouse model that increases inflammation induced by NTHi challenge and investigate the protective effects of andrographolide, a bioactive molecule with anti-inflammatory and antioxidant properties isolated from the plant Andrographis paniculata...
May 27, 2016: Journal of Natural Products
S W Kim, J H Kim, C K Park, T J Kim, S Y Lee, Y K Kim, S S Kwon, C K Rhee, H K Yoon
BACKGROUND: Airway remodelling is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Roflumilast is a selective phosphodiesterase-4 inhibitor that has an anti-inflammatory effect in chronic obstructive pulmonary disease (COPD). OBJECTIVE: The objective of this study was to study the effect of roflumilast on airway inflammation and remodelling in a murine model of chronic asthma...
May 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
H Vignaud, C Cullin, M Bouchecareilh
Chronic obstructive pulmonary disease (COPD) is currently the ninth leading cause of death in France and is predicted to become the third leading cause of worldwide morbidity and mortality by 2020. Risk factors for COPD include exposure to tobacco, dusts and chemicals, asthma and alpha-1 antitrypsin deficiency. This genetic disease, significantly under-diagnosed and under-recognized, affects 1 in 2500 live births and is an important cause of lung and, occasionally, liver disease. Alpha-1 antitrypsin deficiency is a pathology of proteostasis-mediated protein folding and trafficking pathways...
December 2015: Revue des Maladies Respiratoires
Jinho Kim, John D O'Neill, N Valerio Dorrello, Matthew Bacchetta, Gordana Vunjak-Novakovic
The ability to deliver drugs to specific sites in the lung could radically improve therapeutic outcomes of a variety of lung diseases, including cystic fibrosis, severe bronchopneumonia, chronic obstructive pulmonary disease, and lung cancer. Using conventional methods for pulmonary drug administration, precise, localized delivery of exact doses of drugs to target regions remains challenging. Here we describe a more controlled delivery of soluble reagents (e.g., drugs, enzymes, and radionuclides) in microvolume liquid plugs to targeted branches of the pulmonary airway tree: upper airways, small airways (bronchioles), or the most distal alveoli...
September 15, 2015: Proceedings of the National Academy of Sciences of the United States of America
A Planagumà, T Domènech, M Pont, E Calama, V García-González, R López, M Aulí, M López, S Fonquerna, I Ramos, J de Alba, A Nueda, N Prats, V Segarra, M Miralpeix, M D Lehner
Neutrophil infiltration and activation in the lung are important pathophysiological features in COPD, severe asthma and bronchiectasis mostly mediated by CXCL8 and CXCL1 via CXCR1 and CXCR2. No thorough study to date has been performed to compare the anti-inflammatory effect profile of dual CXCR1/2 vs. selective CXCR2 antagonists in relevant human neutrophil assays and pulmonary inflammation models. Dual CXCR1/2 (SCH527123, diaminocyclobutandione-1) and selective CXCR2 (SB265610, thiopyrimidine-1) antagonist activity and receptor residence time were determined by [(35)S]GTPγS binding in human (h)- and guinea pig (gp)-CXCR1 and CXCR2 overexpressing membranes...
October 2015: Pulmonary Pharmacology & Therapeutics
Young-Bin Chen, Ying-Wei Lan, Lih-Geeng Chen, Tsung-Teng Huang, Kong-Bung Choo, Winston T K Cheng, Hsuan-Shu Lee, Kowit-Yu Chong
Chronic obstructive pulmonary disease (COPD) is a sustained blockage of the airways due to lung inflammation occurring with chronic bronchitis and/or emphysema. Progression of emphysema may be slowed by vascular endothelial growth factor A (VEGFA), which reduces apoptotic tissue depletion. Previously, authors of the present report demonstrated that cis-resveratrol (c-RSV)-induced heat-shock protein 70 (HSP70) promoter-regulated VEGFA expression promoted neovascularization of genetically modified mesenchymal stem cells (HSP-VEGFA-MSC) in a mouse model of ischemic disease...
November 2015: Cell Stress & Chaperones
Philippe Devillier, Eric Garrigue, Guillaume D'Auzers, Nicolas Monjotin, Thomas Similowski, Thierry Clerc
BACKGROUND: Long acting bronchodilators are the standard of care in the management of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the efficacy and safety of V0162, a novel anticholinergic agent with bronchodilator properties, in preclinical models and in patients with COPD. METHODS: Guinea pigs were used to evaluate the impact of V0162 on the acetylcholine or histamine-induced bronchoconstriction. V0162 was also investigated in an allergic asthma model on ovalbumin-sensitized guinea pig...
June 8, 2015: Respiratory Research
Jibing Yang, Zhenquan Jia
Chronic lung diseases are becoming a leading cause of death worldwide. There are few effective treatments for those patients and less choices to prevent the exacerbation or even reverse the progress of the diseases. Over the past decade, cell-based therapies using stem cells to regenerate lung tissue have experienced a rapid growth in a variety of animal models for distinct lung diseases. This novel approach offers great promise for the treatment of several devastating and incurable lung diseases, including emphysema, idiopathic pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome...
December 2014: Regenerative Medicine Research
Franziska E Uhl, Sarah Vierkotten, Darcy E Wagner, Gerald Burgstaller, Rita Costa, Ina Koch, Michael Lindner, Silke Meiners, Oliver Eickelberg, Melanie Königshoff
Chronic obstructive pulmonary disease (COPD) is characterised by a progressive loss of lung tissue. Inducing repair processes within the adult diseased lung is of major interest and Wnt/β-catenin signalling represents a promising target for lung repair. However, the translation of novel therapeutic targets from model systems into clinical use remains a major challenge.We generated murine and patient-derived three-dimensional (3D) ex vivo lung tissue cultures (LTCs), which closely mimic the 3D lung microenvironment in vivo...
October 2015: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Amanda R Lever, Hyoungshin Park, Thomas J Mulhern, George R Jackson, James C Comolli, Jeffrey T Borenstein, Patrick J Hayden, Rachelle Prantil-Baun
Respiratory viruses invade the upper airway of the lung, triggering a potent immune response that often exacerbates preexisting conditions such as asthma and COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the characteristic inflammatory response associated with viral infection, such as loss of epithelial integrity, and increased production of mucus and inflammatory cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well-defined primary normal human bronchial epithelial (NHBE) model that recapitulates in vivo functions and responses...
April 2015: Physiological Reports
Layal Chaker, Abby Falla, Sven J van der Lee, Taulant Muka, David Imo, Loes Jaspers, Veronica Colpani, Shanthi Mendis, Rajiv Chowdhury, Wichor M Bramer, Raha Pazoki, Oscar H Franco
Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions...
May 2015: European Journal of Epidemiology
Shung-Te Kao, Ching-Ju Liu, Chia-Chou Yeh
ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae japonicae has shown antibacterial, anti-inflammatory, antipyretic, antioxidant, antiviral, and protective effects in animal models of chronic obstructive pulmonary disease. AIM OF THE STUDY: To investigate the effects of Flos L. japonicae (FLJ), a traditional Chinese medicinal herb, on acute lung inflammation induced by lipopolysaccharide (LPS), in vivo, using a murine model. MATERIALS AND METHODS: Thirty 6-week-old female BALB/c mice were challenged with intratracheal LPS before treatment with FLJ or vehicle...
June 20, 2015: Journal of Ethnopharmacology
Stephanie Boue, Brett Fields, Julia Hoeng, Jennifer Park, Manuel C Peitsch, Walter K Schlage, Marja Talikka, Ilona Binenbaum, Vladimir Bondarenko, Oleg V Bulgakov, Vera Cherkasova, Norberto Diaz-Diaz, Larisa Fedorova, Svetlana Guryanova, Julia Guzova, Galina Igorevna Koroleva, Elena Kozhemyakina, Rahul Kumar, Noa Lavid, Qingxian Lu, Swapna Menon, Yael Ouliel, Samantha C Peterson, Alexander Prokhorov, Edward Sanders, Sarah Schrier, Golan Schwaitzer Neta, Irina Shvydchenko, Aravind Tallam, Gema Villa-Fombuena, John Wu, Ilya Yudkevich, Mariya Zelikman
The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks...
2015: F1000Research
Nicole Zehethofer, Saskia Bermbach, Stefanie Hagner, Holger Garn, Julia Müller, Torsten Goldmann, Buko Lindner, Dominik Schwudke, Peter König
Airway epithelial cells play an important role in the pathogenesis of inflammatory lung diseases such as asthma, cystic fibrosis and COPD. Studies concerning the function of the lipid metabolism of the airway epithelium are so far based only on the detection of lipids by immunohistochemistry but quantitative analyses have not been performed. Although recent advances in mass spectrometry have allowed to identify a variety of lipid classes simultaneously in isolated tissue samples, up until now, these methods were not suitable to analyze lipids in the airway epithelium...
2015: Chromatographia
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