{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:56:28Z","timestamp":1791284188652,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T00:00:00Z","timestamp":1478736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T00:00:00Z","timestamp":1478736000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>We developed and characterized a robust, consistent, and reproducible mouse model of severe exacerbation of chronic allergic asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Chronic allergic airway inflammation was induced following a house dust mite (\n                      <jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>\n                      ) sensitization protocol.\n                      <jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>\n                      \u2010sensitized mice and controls were infected with influenza virus A\/X31 H3N2 and either or not treated with inhaled fluticasone propionate (\n                      <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content>\n                      ), systemic corticosteroids (Pred), or anti\u2010\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20105. Mice were killed at different time points after infection: Cellular accumulation and cytokines levels in the airways, PenH as a measure of airway hyper\u2010responsiveness (\n                      <jats:styled-content style=\"fixed-case\">AHR<\/jats:styled-content>\n                      ), and lung histology and viral replication were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Infection with low\u2010dose A\/X31 H3N2 led to prolonged deterioration of lung function, aggravated mucus production, peri\u2010vascular, peri\u2010bronchial, and allergic inflammation that was unresponsive to inhaled corticosteroids, but responsive to systemic corticosteroids. The exacerbation was preceded at 14 h after virus exposure by a marked innate, but no Th2 and Th1 response subsequently followed by enhanced numbers of eosinophils, neutrophils, dendritic, and T cells into the lung lumen, parenchyma, and draining lymph nodes in\n                      <jats:styled-content style=\"fixed-case\">HDM<\/jats:styled-content>\n                      \u2010sensitized mice. Anti\u2010\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20105 treatment attenuated eosinophils and prevented the X31\u2010induced exacerbation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, these findings indicate that an early innate response that involves eosinophils underlies the exacerbation. This model recapitulates all major features of severe asthma exacerbations and can serve to discern driving mechanisms and promote the development of novel therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.13057","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T11:37:02Z","timestamp":1475840222000},"page":"737-753","source":"Crossref","is-referenced-by-count":38,"title":["An early innate response underlies severe influenza\u2010induced exacerbations of asthma in a novel steroid\u2010insensitive and anti\u2010\n                    <scp>IL<\/scp>\n                    \u20105\u2010responsive mouse model"],"prefix":"10.1111","volume":"72","author":[{"given":"L.","family":"Ravanetti","sequence":"first","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"},{"name":"Department of Respiratory Medicine Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Dijkhuis","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"},{"name":"Department of Respiratory Medicine Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. S.","family":"Sabogal Pineros","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"},{"name":"Department of Respiratory Medicine Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. M.","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology Academic Medical Centre Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. S.","family":"Dierdorp","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Dekker","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Logiantara","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. M.","family":"Adcock","sequence":"additional","affiliation":[{"name":"Airway Disease Section National Heart &amp; Lung Institute Imperial College London Royal Brompton Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. L.","family":"Rao","sequence":"additional","affiliation":[{"name":"Immunology Discovery Janssen Research and Development LLC San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Boon","sequence":"additional","affiliation":[{"name":"Bioceros Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Villetti","sequence":"additional","affiliation":[{"name":"Pulmonary Pharmacology Unit Corporate Pre\u2010Clinical R&amp;D Chiesi Farmaceutici S.p.A. Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. J.","family":"Sterk","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Facchinetti","sequence":"additional","affiliation":[{"name":"Pulmonary Pharmacology Unit Corporate Pre\u2010Clinical R&amp;D Chiesi Farmaceutici S.p.A. Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Lutter","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Centre"},{"name":"Department of Respiratory Medicine Academic Medical Centre"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the U\u2010BIOPRED Study 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