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Involvement of distal airways in a chronic model of experimental asthma.
Clin Exp Allergy. 2005 Oct; 35(10):1263-71.CE

Abstract

BACKGROUND

Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation.

OBJECTIVE

This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype.

METHODS

For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks.

RESULTS

In chronically challenged mice, tissue inflammation in proximal as well as distal airways was observed with a predominance of lymphocytes within the cellular infiltrate. In contrast, inflammation in the airway lumen decreased over time. These changes were associated by a shift in bronchoalveolar lavage-cytokine levels from IL-4, IL-5 and TNF-alpha production (during the acute phase) towards markedly increased levels of TGF-beta during the chronic phase. Goblet cell hyperplasia and subepithelial fibrosis occurred throughout the airway tree. In terms of lung function, chronically challenged mice developed persistent bronchial hyper-responsiveness and progressive airflow limitation. Six weeks after OVA aerosol discontinuation, airway inflammation still persisted although lung function was normalized.

CONCLUSION

These data indicate that our model of chronic aerosol allergen challenges leads to a phenotype of experimental asthma with participation of distal airways and persistence of inflammation thereby resembling many morphological and physiological aspects of human bronchial asthma.

Authors+Show Affiliations

Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps-University, Marburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16238784

Citation

Wegmann, M, et al. "Involvement of Distal Airways in a Chronic Model of Experimental Asthma." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 35, no. 10, 2005, pp. 1263-71.
Wegmann M, Fehrenbach H, Fehrenbach A, et al. Involvement of distal airways in a chronic model of experimental asthma. Clin Exp Allergy. 2005;35(10):1263-71.
Wegmann, M., Fehrenbach, H., Fehrenbach, A., Held, T., Schramm, C., Garn, H., & Renz, H. (2005). Involvement of distal airways in a chronic model of experimental asthma. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 35(10), 1263-71.
Wegmann M, et al. Involvement of Distal Airways in a Chronic Model of Experimental Asthma. Clin Exp Allergy. 2005;35(10):1263-71. PubMed PMID: 16238784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of distal airways in a chronic model of experimental asthma. AU - Wegmann,M, AU - Fehrenbach,H, AU - Fehrenbach,A, AU - Held,T, AU - Schramm,C, AU - Garn,H, AU - Renz,H, PY - 2005/10/22/pubmed PY - 2006/2/10/medline PY - 2005/10/22/entrez SP - 1263 EP - 71 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin Exp Allergy VL - 35 IS - 10 N2 - BACKGROUND: Bronchial asthma is characterized by chronic airway inflammation and airway remodelling which occurs in both proximal and distal airways. These changes are associated with development of airway hyper-responsiveness and airflow limitation. OBJECTIVE: This study was aimed to analyse whether chronic inhalative allergen challenges in mice lead to morphological and physiological changes comparable with this phenotype. METHODS: For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed by aerosol allergen challenges on 2 consecutive days per week for 12 weeks. RESULTS: In chronically challenged mice, tissue inflammation in proximal as well as distal airways was observed with a predominance of lymphocytes within the cellular infiltrate. In contrast, inflammation in the airway lumen decreased over time. These changes were associated by a shift in bronchoalveolar lavage-cytokine levels from IL-4, IL-5 and TNF-alpha production (during the acute phase) towards markedly increased levels of TGF-beta during the chronic phase. Goblet cell hyperplasia and subepithelial fibrosis occurred throughout the airway tree. In terms of lung function, chronically challenged mice developed persistent bronchial hyper-responsiveness and progressive airflow limitation. Six weeks after OVA aerosol discontinuation, airway inflammation still persisted although lung function was normalized. CONCLUSION: These data indicate that our model of chronic aerosol allergen challenges leads to a phenotype of experimental asthma with participation of distal airways and persistence of inflammation thereby resembling many morphological and physiological aspects of human bronchial asthma. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/16238784/Involvement_of_distal_airways_in_a_chronic_model_of_experimental_asthma_ DB - PRIME DP - Unbound Medicine ER -