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Asthma small airway disease

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https://www.readbyqxmd.com/read/28626064/monitoring-c3ar-expression-using-a-floxed-tdtomato-c3ar-reporter-knock-in-mouse
#1
Katharina M Quell, Christian M Karsten, Anna Kordowski, Larissa Nogueira Almeida, Daria Briukhovetska, Anna V Wiese, Jing Sun, Fanny Ender, Konstantina Antoniou, Torsten Schröder, Inken Schmudde, Johann L Berger, Peter König, Tillman Vollbrandt, Yves Laumonnier, Jörg Köhl
C3a exerts multiple biologic functions through activation of its cognate C3a receptor. C3(-/-) and C3aR(-/-) mice have been instrumental in defining important roles of the C3a/C3aR axis in the regulation of acute and chronic inflammatory diseases, including ischemia/reperfusion injury, allergic asthma, autoimmune nephritis, and rheumatoid arthritis. Surprisingly little is known about C3aR expression and function in immune and stromal cells. To close this gap, we generated a floxed tandem-dye Tomato (tdTomato)-C3aR reporter knock-in mouse, which we used to monitor C3aR expression in cells residing in the lung, airways, lamina propria (LP) of the small intestine, brain, visceral adipose tissue, bone marrow (BM), spleen, and the circulation...
June 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28601047/role-of-epigenetics-in-the-pathogenesis-of-asthma
#2
Zahra Alizadeh, Esmaeil Mortaz, Ian Adcock, Mostafa Moin
Asthma is a complex, heterogeneous and chronic airway inflammatory disease with different clinical phenotypes caused by diverse triggers and pathophysiological mechanisms. Asthma heritability has been established in many genetic studies but it is evident that only genetic elements are not responsible for the development of asthma. Increasing rate of asthma incidence during past decades has implicated the role of epigenetics in development of asthma. Environmental factors perform as initiator signals through epigenetic mechanisms...
April 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28596268/application-of-euclidean-distance-mapping-for-assessment-of-basement-membrane-thickness-distribution-in-asthma
#3
Leila B Mostaco-Guidolin, Soheil M Hajimohammadi, Dragos Mihai Vasilescu, Tillie-Louise Hackett
Abnormal thickening of the airway basement membrane is one of the hallmarks of airway remodeling in asthma. Current protocols for measuring the basement membrane involve the use of stained tissue sections and measurements of the basement membrane thickness at certain intervals, followed by the calculation of the geometric mean thickness for each airway. This report describes an automated, unbiased approach which uses colour segmentation to identify structures of interest on stained sections and euclidean distance mapping to measure the thickness distribution of airway structures...
June 8, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28583618/new-anti-eosinophil-drugs-for-asthma-and-copd-targeting-the-trait
#4
REVIEW
Elisabeth H Bel, Anneke Ten Brinke
Asthma and chronic obstructive airways disease (COPD) are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade several monoclonal antibodies and small molecule therapies have been developed to target this trait...
June 2, 2017: Chest
https://www.readbyqxmd.com/read/28511478/recognition-of-small-airways-obstruction-in-asthma-and-copd-the-road-less-travelled
#5
REVIEW
Desh Deepak, Akhila Prasad, Swapndeep Singh Atwal, Kshitij Agarwal
The small airways, once regarded as the silent zone in the air conducting system of the lungs are now known to be one of the initial sites of involvement in diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD). Identification of the involvement of distal airways in these diseases is often difficult to assess, clinically as well as by conventional pulmonary function tests and therefore, usually remains undiscovered in early stages. Early recognition of their involvement in asthma and COPD and timely management may reduce long term morbidity in these conditions...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28493293/responsiveness-to-oral-prednisolone-in-severe-asthma-is-related-to-the-degree-of-eosinophilic-airway-inflammation
#6
Ana R Sousa, Richard P Marshall, Linda C Warnock, Sarah Bolton, Annette Hastie, Fiona Symon, Beverley Hargadon, Hilary Marshall, Matthew Richardson, Christopher E Brightling, Pranab Haldar, Roberta Milone, Peter Chalk, Rick Williamson, Reynold Panettieri, Richard Knowles, Eugene R Bleecker, Andrew J Wardlaw
BACKGROUND: Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear. OBJECTIVE: To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation...
May 10, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28442577/association-between-exposure-in-the-cement-production-industry-and-non-malignant-respiratory-effects-a-systematic-review
#7
Anne Kristin Møller Fell, Karl Christian Nordby
OBJECTIVES: Based on findings from a systematic literature search, we present and discuss the evidence for an association between exposure to cement dust and non-malignant respiratory effects in cement production workers. DESIGN AND SETTING: Systematic literature searches (MEDLINE and Embase) were performed. Outcomes were restricted to respiratory symptoms, lung function indices, asthma, chronic bronchitis, chronic obstructive pulmonary disease, pneumoconiosis, induced sputum or fraction of exhaled nitric oxide (FeNO) measurements...
April 24, 2017: BMJ Open
https://www.readbyqxmd.com/read/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#8
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28295526/pharmacological-treatments-in-asthma-affected-horses-a-pair-wise-and-network-meta-analysis
#9
L Calzetta, P Roncada, D di Cave, L Bonizzi, A Urbani, E Pistocchini, P Rogliani, M G Matera
BACKGROUND: Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyperresponsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma results from several small studies, and no head-to-head clinical trials have been conducted among the available medications...
March 10, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28288272/interventions-to-improve-inhaler-technique-for-people-with-asthma
#10
REVIEW
Rebecca Normansell, Kayleigh M Kew, Alexander G Mathioudakis
BACKGROUND: Asthma is a common chronic disease worldwide. Inhalers are often prescribed to help control asthma symptoms, improve quality of life and reduce the risk of exacerbations or flare-ups. However, evidence suggests that many people with asthma do not use their inhaler correctly. It is therefore important to evaluate whether interventions aimed specifically at improving technique are effective and safe, and whether use of these interventions translates into improved clinical outcomes...
March 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28262277/-the-interactions-between-microorganisms-and-the-small-airways-a-paediatric-focus
#11
REVIEW
J de Blic, J Brouard, A Vabret, A Deschildre
The spectrum of respiratory viruses is expanding and emerging diseases have been described regularly over the last fifteen years. The origin of these emerging respiratory viruses may be zoonotic (by crossing species barrier, after changes to RNA viruses such as avian influenza virus type A or coronaviruses), or related to the use of new identification techniques (metapneumovirus, bocavirus). The relationship between bronchiolitis and asthma is now better understood thanks to prospective follow up of birth cohorts...
February 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28236369/patients-hospitalized-with-an-infective-exacerbation-of-bronchiectasis-unrelated-to-cystic-fibrosis-clinical-physiological-and-sputum-characteristics
#12
Victoria Venning, James Bartlett, Lata Jayaram
BACKGROUND AND OBJECTIVE: Bronchiectasis is a growing health burden both globally and in Australasia. Associated with repeated respiratory infections, the disease often results in hospital admission, impaired quality of life, reduced lung function and shortened life expectancy. We describe the local clinical, physiological and sputum characteristics in patients hospitalized with an infective exacerbation of bronchiectasis. METHODS: This study examined the medical records of all 61 adults admitted to a metropolitan Australian hospital with an infective exacerbation of bronchiectasis in a calendar year...
February 24, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#13
Caini Liu, Liang Zhu, Koichi Fukuda, Suidong Ouyang, Xing Chen, Chenhui Wang, Cun-Jin Zhang, Bradley Martin, Chunfang Gu, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li
Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#14
K D Quinn, M Schedel, Y Nkrumah-Elie, A Joetham, M Armstrong, C Cruickshank-Quinn, R Reisdorph, E W Gelfand, N Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28106744/oligonucleotide-therapy-for-obstructive-and-restrictive-respiratory-diseases
#15
REVIEW
Wupeng Liao, Jinrui Dong, Hong Yong Peh, Lay Hong Tan, Kah Suan Lim, Li Li, Wai-Shiu Fred Wong
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28102056/asthma-related-outcomes-in-patients-initiating-extrafine-ciclesonide-or-fine-particle-inhaled-corticosteroids
#16
Dirkje S Postma, Richard Dekhuijzen, Thys van der Molen, Richard J Martin, Wim van Aalderen, Nicolas Roche, Theresa W Guilbert, Elliot Israel, Daniela van Eickels, Javaria Mona Khalid, Ron M C Herings, Jetty A Overbeek, Cristiana Miglio, Victoria Thomas, Catherine Hutton, Elizabeth V Hillyer, David B Price
PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year...
March 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28087917/-reasearch-progress-on-the-role-of-neutrophils-in-asthma
#17
Tingting Li, Yuehai Ke, Hongqiang Cheng
Asthma is a phenotypically heterogeneous chronic disease of the airways. Studies have found that neutrophils are crucial to airway inflammation in acute asthma, persistent asthma, particularly in asthma of poor response to glucocorticoid treatment. The role of neutrophils in development of bronchial asthma is complex, as they can release a potent source of cytokines and inflammatory mediators participating in asthma. Differing from eosinophilic inflammatory asthma, neutrophilic inflammatory asthma is not depend on helper T (Th)2 cells, but may be related to Th1 and Th17 cells...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28079597/histologic-findings-of-severe-therapy-resistant-asthma-from-video-assisted-thoracoscopic-surgery-biopsies
#18
Humberto E Trejo Bittar, Daniel Doberer, Mitra Mehrad, Diane C Strollo, Joseph K Leader, Sally Wenzel, Samuel A Yousem
The histologic changes occurring in severe/therapy-resistant asthma (SA) as defined by the European Respiratory Society/American Thoracic Society guidelines, particularly at the level of the distal airways are unknown. This study describes the clinical, radiologic, and histologic characteristics of 29 SA patients who underwent video-assisted thoracoscopic surgery lung biopsy. Pathologic observations were correlated with clinical features, especially the presence of autoimmune disease (AID) (15/29, 51.7%). Ten biopsies (10/29, 34...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28065276/using-imaging-as-a-biomarker-for-asthma
#19
REVIEW
Abhaya Trivedi, Chase Hall, Eric A Hoffman, Jason C Woods, David S Gierada, Mario Castro
There have been significant advancements in the various imaging techniques being used for the evaluation of asthmatic patients, both from a clinical and research perspective. Imaging characteristics can be used to identify specific asthmatic phenotypes and provide a more detailed understanding of endotypes contributing to the pathophysiology of the disease. Computed tomography, magnetic resonance imaging, and positron emission tomography can be used to assess pulmonary structure and function. It has been shown that specific airway and lung density measurements using computed tomography correlate with clinical parameters, including severity of disease and pathology, but also provide unique phenotypes...
January 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28045928/altered-epithelial-gene-expression-in-peripheral-airways-of-severe-asthma
#20
Akul Singhania, Hitasha Rupani, Nivenka Jayasekera, Simon Lumb, Paul Hales, Neil Gozzard, Donna E Davies, Christopher H Woelk, Peter H Howarth
Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2...
2017: PloS One
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