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Allergen asthma challenge study

Lorenzo Cecchi, Gennaro D'Amato, Isabella Annesi-Maesano
Allergies are complex diseases that result from interactions between multiple genetic and environmental factors. However, the increase in allergies observed in the past decades is explained exclusively by environmental changes occurring in the same period. Presently, the exposome, the totality of specific and nonspecific external environmental exposures (external exposome) to which a subject is exposed from preconception onward and their consequences at the organ and cell levels (internal exposome), is being considered to explain the inception, development, and exacerbations of allergic diseases...
March 2018: Journal of Allergy and Clinical Immunology
Caitlin L Maikawa, Naomi Zimmerman, Manuel Ramos, Mittal Shah, James S Wallace, Krystal J Godri Pollitt
Diesel exhaust has been associated with asthma, but its response to other engine emissions is not clear. The increasing prevalence of vehicles with gasoline direct injection (GDI) engines motivated this study, and the objective was to evaluate pulmonary responses induced by acute exposure to GDI engine exhaust in an allergic asthma murine model. Mice were sensitized with an allergen to induce airway hyperresponsiveness or treated with saline (non-allergic group). Animals were challenged for 2-h to exhaust from a laboratory GDI engine operated at conditions equivalent to a highway cruise...
March 1, 2018: International Journal of Environmental Research and Public Health
Stephane Debelleix, Valérie Siao-Him Fa, Hugues Begueret, Patrick Berger, Roger Marthan, Michael Fayon
Asthma is characterized by airway hyperresponsiveness (AHR) and inflammation leading to airway remodeling (AR). In children, AR may occur very early prior to the age of 6 years. Treatments to prevent or reverse AR are unknown. AIM: We sought to determine (i) whether short allergenic sensitization at a young age in a mouse model may induce enhanced AR and inflammation compared to adults; (ii) the effect of Montelukast on such AR. METHODS: Immature and adult Balb/c mice were sensitized and challenged with ovalbumin...
March 1, 2018: Pediatric Pulmonology
Tara L Croston, Angela R Lemons, Donald H Beezhold, Brett J Green
Fungal bioaerosols are ubiquitous in the environment and human exposure can result in a variety of health effects ranging from systemic, subcutaneous, and cutaneous infections to respiratory morbidity including allergy, asthma, and hypersensitivity pneumonitis. Recent research has focused on the role of microRNAs (miRNAs) following fungal exposure and is overlooked, yet important, group of regulators capable of influencing fungal immune responses through a variety of cellular mechanisms. These small non-coding ribose nucleic acids function to regulate gene expression at the post-transcriptional level and have been shown to participate in multiple disease pathways including cancer, heart disease, apoptosis, as well as immune responses to microbial hazards and occupational allergens...
2018: Frontiers in Immunology
Wei Tang, Steven G Smith, Wei Du, Akash Gugilla, Juan Du, John Paul Oliveria, Karen Howie, Brittany M Salter, Gail M Gauvreau, Paul M O'Byrne, Roma Sehmi
Background: Eosinophil-lineage committed progenitor cells (EoP) migrate from the bone marrow and differentiate locally to provide an ongoing source of mature eosinophils in asthmatic inflammatory responses in the airways. Sputum levels of EoP are increased in asthmatics compared to normal controls suggesting an exaggerated eosinophilopoietic environment in the airways. Understanding what factors promote EoP traffic to the airways is important to understand the diathesis of asthma pathology...
2018: Clinical and Translational Allergy
Peter Korošec, Bernhard F Gibbs, Matija Rijavec PhD, Adnan Custovic, Paul J Turner
IgE-mediated allergic reactions involve the activation of effector cells, predominantly through the high-affinity IgE receptor (FcεRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis, and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response...
February 12, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
G M Gauvreau, J M FitzGerald, L P Boulet, R M Watson, L Hui, H Villineuve, T X Scime, A R Schlatman, C Obminski, J Kum, S Boehme, T W Ly, K B Bacon, P M O'Byrne
BACKGROUND: CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. OBJECTIVE: This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. METHODS: Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo...
February 9, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Yun-Duan Song, Xiao-Zong Li, Ya-Xian Wu, Yao Shen, Fang-Fang Liu, Pei-Pei Gao, Lei Sun, Feng Qian
Alternatively activated macrophages (AAMs) are not only associated with asthma but also lead to asthmatic airway inflammation and remodeling. Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. In this study we investigated whether emodin (1,3,8-trihydroxy-6-methylanthraquinone), isolated from the rhizome of Rheum palmatum, alleviated asthmatic airway inflammation and reduced AAM polarization in a murine asthma model. Mice were sensitized with a triple allergen mix containing dust mite, ragweed and aspergillus (DRA)...
February 8, 2018: Acta Pharmacologica Sinica
Everett K Henry, Juan M Inclan-Rico, Mark C Siracusa
Purpose of Review: It is well established that T helper type 2 (TH 2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH 2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH 2 cell polarization...
December 2017: Current Pharmacology Reports
Chi Liu, Lin Yuan, Yizhou Zou, Ming Yang, Yu Chen, Xiangping Qu, Huijun Liu, Jianxin Jiang, Yang Xiang, Xiaoqun Qin
Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy-induced airway inflammation and airway hyper-responsiveness (AHR) in mice...
February 2, 2018: Journal of Leukocyte Biology
Youming Zhang, Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Martin S Taylor, Lauren Chessum, Jackie Harrison, Loukia Tsaprouni, Ian M Adcock, Clare M Lloyd, William O Cookson, Miriam F Moffatt, Charlotte H Dean
We previously identified dipeptidyl-peptidase 10 (DPP10) on chromosome 2 as a human asthma susceptibility gene, through positional cloning. Initial association results were confirmed in many subsequent association studies but the functional role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N-nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that caused an amino acid change from valine to aspartic acid in the β propeller region of the protein. Mice carrying this point mutation were recovered and a congenic line was established (Dpp10145D )...
December 28, 2017: Disease Models & Mechanisms
Yolanda van Wijck, Stan de Kleijn, Gerrit John-Schuster, Tinne C J Mertens, Pieter S Hiemstra, Anne Müller, Hermelijn H Smits, Christian Taube
Epidemiological and experimental studies have shown that exposure to the gastric bacterium Helicobacter pylori, especially in early life, prevents the development of asthma. Recent mouse studies have shown that this protective effect does not require live bacteria and that treatment with an extract of H. pylori in neonates prevents the development of airway inflammation and goblet cell metaplasia. In the current study, the effect of administration of an extract of H. pylori was assessed in a therapeutic study design with application of the extract just prior to allergen challenge...
January 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Damian L Turner, Monica Goldklang, Filip Cvetkovski, Daniel Paik, Jordis Trischler, Josselyn Barahona, Minwei Cao, Ronak Dave, Nicole Tanna, Jeanine M D'Armiento, Donna L Farber
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal house dust mite (HDM) extract to dissect how lung TRMs are generated and function in the persistence and pathogenesis of allergic airway disease...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Shinji Toki, Kasia Goleniewska, Sara Reiss, Jian Zhang, Melissa H Bloodworth, Matthew T Stier, Weisong Zhou, Dawn C Newcomb, Lorraine B Ware, Gregg D Stanwood, Aurelio Galli, Kelli L Boyd, Kevin D Niswender, R Stokes Peebles
BACKGROUND: IL-33 is one of the most consistently associated gene candidates for asthma identified by GWAS. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type-2 cytokine production from both group 2 innate lymphoid cells (ILC2) and Th2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells. OBJECTIVE: To determine the effect of glucagon like peptide receptor-1 GLP-1R signaling on aeroallergen-induced airway IL-33 production and release and on innate type-2 airway inflammation...
January 10, 2018: Journal of Allergy and Clinical Immunology
Seung-Hyung Kim, Evelyn Saba, Bok-Kyu Kim, Won-Kyung Yang, Yang-Chun Park, Han Jae Shin, Chang Kyun Han, Young Cheol Lee, Man Hee Rhee
Regulatory T cells play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+ CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR)...
February 5, 2018: European Journal of Pharmacology
Laura Farioli, Laura Michelina Losappio, Maria Gabriella Giuffrida, Valerio Pravettoni, Gianluigi Micarelli, Michele Nichelatti, Joseph Scibilia, Corrado Mirone, Laura Cavallarin, Cristina Lamberti, Luca Giuseppe Balossi, Elide Anna Pastorello
BACKGROUND: Shrimp sensitization is common in the general population, but the presence of symptoms is only moderately related to sensitization. A point still at issue is which in vivo and/or in vitro tests (food challenge, component-resolved diagnosis, house dust mite [HDM] sensitization) can help in distinguishing shrimp-allergic subjects from subjects that are sensitized but tolerant. METHODS: The aim of this study was to evaluate the role of IgE to the different shrimp and mite allergens in distinguishing shrimp challenge-positive from challenge-negative patients...
2017: International Archives of Allergy and Immunology
Marcelo Vivolo Aun, Rafael Bonamichi-Santos, Fernanda Magalhães Arantes-Costa, Jorge Kalil, Pedro Giavina-Bianchi
Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease...
2017: Journal of Asthma and Allergy
Li Yu, Qi Liu, Brendan J Canning
Mast cells play an essential role in immediate type hypersensitivity reactions and in chronic allergic diseases of the airways, including asthma. Mast cell mediator release can be modulated by locally released autacoids and circulating hormones, but surprisingly little is known about the autocrine effects of mediators released upon mast cell activation. We thus set out to characterize the autocrine and paracrine effects of mast cell mediators on mast cell activation in the guinea pig airways. By direct measures of histamine, cysteinyl-leukotriene and thromboxane release and with studies of allergen-evoked contractions of airway smooth muscle, we describe a complex interplay amongst these autacoids...
November 17, 2017: European Journal of Pharmacology
Anne K Ellis, Mark W Tenn
OBJECTIVE: To summarize studies highlighting recent advances in rhinitis-related research in the past 2 years. DATA SOURCES: Original research articles were procured and examined from the Rhinitis and Upper Airway Disease section of the 2015 to 2017 Annals of Allergy, Asthma & Immunology issues. Additional original research articles were identified from PubMed and Google Scholar using the following search terms: allergic rhinitis, rhinitis, chronic rhinosinusitis, environmental exposure unit, and nasal allergen challenge...
November 18, 2017: Annals of Allergy, Asthma & Immunology
Fei Shi, Yarui Zhang, Chen Qiu, Yi Xiong, Manhui Li, Aijun Shan, Ying Yang, Binbin Li
BACKGROUND: The tumor necrosis factor superfamily member LIGHT (the official gene symbol approved by NCBI Gene Database), an inflammatory factor secreted by T cells after allergen exposure, recently discovered to play crucial roles in asthmatic airway remodeling. However, it is unclear whether LIGHT could be controlled by inhaled corticosteroids, a key component of asthma management. This study was to investigate the effects and potential mechanisms of inhaled budesonide on the expressions of LIGHT and its receptors (LTβR and HVEM) of lung tissues in ovalbumin-sensitized mice...
October 2017: Experimental Lung Research
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