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Sensitized BALB\/c mice were exposed to aerosolized ovalbumin, either as chronic low-level challenge (mass concentration \u2248 3 mg\/m3) for 4 wk, a single moderate-level challenge (\u2248 30 mg\/m3), or chronic low-level followed by single moderate-level challenge (the acute exacerbation group). Compared with animals receiving chronic challenge alone, mice in the acute exacerbation group exhibited a more marked inflammatory response, with involvement of intrapulmonary airways and lung parenchyma, and increased numbers of lymphocytes and eosinophils in bronchoalveolar lavage fluid. They also developed airway hyperreactivity (AHR) to methacholine, demonstrable as increased transpulmonary resistance and decreased compliance. This pattern of AHR was absent in chronically challenged animals, but was also present in animals given single moderate-level challenge. However, compared with animals receiving a single moderate-level challenge, inflammation and AHR were induced more rapidly in the acute exacerbation group. Eosinophil-deficient GATA1 \u0394dbl mice exhibited undiminished AHR in the acute exacerbation model. We conclude that in mice with pre-existing airway lesions resembling mild chronic asthma, exposure to a moderately high concentration of inhaled antigen induces features of an acute exacerbation. The inflammatory response involves distal airways and is associated with a distinct pattern of AHR, which develops independent of the enhanced eosinophilic inflammation.<\/jats:p>","DOI":"10.1165\/rcmb.2006-0135oc","type":"journal-article","created":{"date-parts":[[2006,6,22]],"date-time":"2006-06-22T21:03:44Z","timestamp":1151010224000},"page":"565-570","source":"Crossref","is-referenced-by-count":37,"title":["Airway Hyperreactivity in Exacerbation of Chronic Asthma Is Independent of Eosinophilic Inflammation"],"prefix":"10.1093","volume":"35","author":[{"given":"Jessica S.","family":"Siegle","sequence":"first","affiliation":[{"name":"Department of Pathology, University of New South Wales, Sydney; School of Biomedical Sciences, University of Newcastle, Newcastle; and Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University, Canberra, 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Wales, Sydney; School of Biomedical Sciences, University of Newcastle, Newcastle; and Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University, Canberra, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul S.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New South Wales, Sydney; School of Biomedical Sciences, University of Newcastle, Newcastle; and Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University, Canberra, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh K.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of New South Wales, Sydney; School of Biomedical Sciences, University of Newcastle, Newcastle; and Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University, 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