This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0135OCv1 35/5/565    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siegle, J. S. Articles by Kumar, R. K. Search for Related Content PubMed PubMed Citation Articles by Siegle, J. S. Articles by Kumar, R. K.

Airway Hyperreactivity in Exacerbation of Chronic Asthma Is Independent of Eosinophilic Inflammation

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

Correspondence and requests for reprints should be addressed to R. K. Kumar, Department of Pathology, University of New South Wales, Sydney, Australia 2052. E-mail: R.Kumar{at}unsw.edu.au

We have developed an animal model to investigate the mechanisms underlying an acute exacerbation of chronic asthma. Sensitized BALB/c mice were exposed to aerosolized ovalbumin, either as chronic low-level challenge (mass concentration 3 mg/m³) for 4 wk, a single moderate-level challenge ( 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 dbl 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.

Key Words: airway inflammation • bronchial hyperreactivity • eosinophils • severe asthma • small airways disease

This article has been cited by other articles:

				R. K. Kumar, M. P. Hitchins, and P. S. Foster Epigenetic changes in childhood asthma Dis. Model. Mech., November 1, 2009; 2(11-12): 549 - 553. [Abstract] [Full Text] [PDF]

				A. S. McKee, M. W. Munks, M. K. L. MacLeod, C. J. Fleenor, N. Van Rooijen, J. W. Kappler, and P. Marrack Alum Induces Innate Immune Responses through Macrophage and Mast Cell Sensors, But These Sensors Are Not Required for Alum to Act As an Adjuvant for Specific Immunity J. Immunol., October 1, 2009; 183(7): 4403 - 4414. [Abstract] [Full Text] [PDF]

				J. Kearley, K. F. Buckland, S. A. Mathie, and C. M. Lloyd Resolution of Allergic Inflammation and Airway Hyperreactivity Is Dependent upon Disruption of the T1/ST2-IL-33 Pathway Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 772 - 781. [Abstract] [Full Text] [PDF]

				J. Zhou, C. R. Wolf, C. J. Henderson, Y. Cai, P. G. Board, P. S. Foster, and D. C. Webb Glutathione Transferase P1: An Endogenous Inhibitor of Allergic Responses in a Mouse Model of Asthma Am. J. Respir. Crit. Care Med., December 15, 2008; 178(12): 1202 - 1210. [Abstract] [Full Text] [PDF]

				A. T. Nials and S. Uddin Mouse models of allergic asthma: acute and chronic allergen challenge Dis. Model. Mech., November 1, 2008; 1(4-5): 213 - 220. [Abstract] [Full Text] [PDF]

				K. Ito, C. Herbert, J. S. Siegle, C. Vuppusetty, N. Hansbro, P. S. Thomas, P. S. Foster, P. J. Barnes, and R. K. Kumar Steroid-Resistant Neutrophilic Inflammation in a Mouse Model of an Acute Exacerbation of Asthma Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 543 - 550. [Abstract] [Full Text] [PDF]

				Y.-C. Su, M. S. Rolph, N. G. Hansbro, C. R. Mackay, and W. A. Sewell Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation J. Immunol., February 15, 2008; 180(4): 2600 - 2607. [Abstract] [Full Text] [PDF]

				K. L. Asquith, H. S. Ramshaw, P. M. Hansbro, K. W. Beagley, A. F. Lopez, and P. S. Foster The IL-3/IL-5/GM-CSF Common Receptor Plays a Pivotal Role in the Regulation of Th2 Immunity and Allergic Airway Inflammation J. Immunol., January 15, 2008; 180(2): 1199 - 1206. [Abstract] [Full Text] [PDF]

				C. G. McVicker, S.-Y. Leung, V. Kanabar, L. M. Moir, K. Mahn, K. F. Chung, and S. J. Hirst Repeated Allergen Inhalation Induces Cytoskeletal Remodeling in Smooth Muscle from Rat Bronchioles Am. J. Respir. Cell Mol. Biol., June 1, 2007; 36(6): 721 - 727. [Abstract] [Full Text] [PDF]

				H. H. Kariyawasam, M. Aizen, J. Barkans, D. S. Robinson, and A. B. Kay Remodeling and Airway Hyperresponsiveness but Not Cellular Inflammation Persist after Allergen Challenge in Asthma Am. J. Respir. Crit. Care Med., May 1, 2007; 175(9): 896 - 904. [Abstract] [Full Text] [PDF]