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Guinea pigs share anatomical, pharmacological and physiological features with human airways and may enable the development of a pre\u2010clinical in vivo model that closely resembles asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To develop an asthma model in guinea pigs using the allergen house dust mite (HDM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Guinea pigs were intranasally sensitized to HDM which was followed by HDM challenges once weekly for five weeks. Antigen\u2010induced bronchoconstriction (AIB) was evaluated as alterations in <jats:italic>R<jats:sub>n<\/jats:sub><\/jats:italic> (Newtonian resistance), <jats:italic>G<\/jats:italic> (tissue damping) and <jats:italic>H<\/jats:italic> (tissue elastance) at the first challenge with forced oscillation technique (FOT), and changes in respiratory pattern upon each HDM challenge were assessed as enhanced pause (Penh) using whole\u2010body plethysmography. Airway responsiveness to methacholine was measured one day after the last challenge by FOT. Inflammatory cells and cytokines were quantified in bronchoalveolar lavage fluid, and HDM\u2010specific immunoglobulins were measured in serum by ELISA. Airway pathology was evaluated by conventional histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first HDM challenge after the sensitization generated a marked increase in <jats:italic>R<jats:sub>n<\/jats:sub><\/jats:italic> and <jats:italic>G<\/jats:italic>, which was abolished by pharmacological inhibition of histamine, leukotrienes and prostanoids. Repeated weekly challenges of HDM caused increase of Penh and a marked increase in airway hyperresponsiveness for all three lung parameters (<jats:italic>R<jats:sub>n<\/jats:sub><\/jats:italic>, <jats:italic>G<\/jats:italic> and <jats:italic>H<\/jats:italic>) and eosinophilia. Levels of IgE, IgG<jats:sub>1<\/jats:sub>, IgG<jats:sub>2<\/jats:sub> and IL\u201013 were elevated in HDM\u2010treated guinea pigs. HDM exposure induced infiltration of inflammatory cells into the airways with a pronounced increase of mast cells. Subepithelial collagen deposition, airway wall thickness and goblet cell hyperplasia were induced by repeated HDM challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Clinical Relevance<\/jats:title><jats:p>Repeated intranasal HDM administration induces mast cell activation and hyperplasia together with an asthma\u2010like pathophysiology in guinea pigs. This model may be suitable for mechanistic investigations of asthma, including evaluation of the role of mast cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13713","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T11:45:30Z","timestamp":1595331930000},"page":"1184-1195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A new house dust mite\u2013driven and mast cell\u2013activated model of asthma in the guinea pig"],"prefix":"10.1111","volume":"50","author":[{"given":"Patricia","family":"Ramos\u2010Ram\u00edrez","sequence":"first","affiliation":[{"name":"Experimental Asthma and Allergy Research Unit Institute of Environmental Medicine (IMM) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Noreby","sequence":"additional","affiliation":[{"name":"Experimental Asthma and Allergy Research Unit Institute of Environmental Medicine (IMM) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jielu","family":"Liu","sequence":"additional","affiliation":[{"name":"Experimental Asthma and Allergy Research Unit Institute of Environmental Medicine (IMM) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ji","sequence":"additional","affiliation":[{"name":"Bioscience COPD\/IPF, Research and Early Development Respiratory &amp; Immunology, BioPharmaceuticals R&amp;D, AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suado M.","family":"Abdillahi","sequence":"additional","affiliation":[{"name":"Bioscience COPD\/IPF, Research and Early Development Respiratory &amp; Immunology, BioPharmaceuticals R&amp;D, AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henric","family":"Olsson","sequence":"additional","affiliation":[{"name":"Translational Science and Experimental Medicine, Research and Early Development Respiratory, Inflammation and Autoimmune (RIA) AstraZeneca Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven\u2010Erik","family":"Dahl\u00e9n","sequence":"additional","affiliation":[{"name":"Experimental Asthma and Allergy Research Unit Institute of Environmental Medicine (IMM) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy Department of Medicine Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-4759","authenticated-orcid":false,"given":"Mikael","family":"Adner","sequence":"additional","affiliation":[{"name":"Experimental Asthma and Allergy Research Unit Institute of Environmental Medicine (IMM) Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,5]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Asthma GIf.Global Initiative for Asthma. 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