Published online before print December 12, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: ajpath.2009.071151v1 174/1/3    most recent Purchase Article View Shopping Cart 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 Google Scholar Google Scholar Articles by Bogaert, P. Articles by Grooten, J. Search for Related Content PubMed PubMed Citation Articles by Bogaert, P. Articles by Grooten, J.

(American Journal of Pathology. 2009;174:3-13.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.071151

Review

Where Asthma and Hypersensitivity Pneumonitis Meet and Differ

Noneosinophilic Severe Asthma

Pieter Bogaert^*, Kurt G. Tournoy, Thomas Naessens and Johan Grooten

From the Departments of Molecular Biomedical Research, Molecular Signaling and Cell Death,^* Flanders Institute for Biotechnology, and the Department of Molecular Biology, Laboratory of Molecular Immunology, Ghent University, Ghent; and the Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium

Abstract

Asthma is a type-I allergic airway disease characterized by Th₂ cells and IgE. Episodes of bronchial inflammation, eosinophilic in nature and promoting bronchoconstriction, may become chronic and lead to persistent respiratory symptoms and irreversible structural airway changes. Representative mostly of mild to moderate asthma, this clinical definition fails to account for the atypical and often more severe phenotype found in a considerable proportion of asthmatics who have increased neutrophil cell counts in the airways as a distinguishing trait. Neutrophilic inflammation is a hallmark of another type of allergic airway pathology, hypersensitivity pneumonitis. Considered as an immune counterpart of asthma, hypersensitivity pneumonitis is a prototypical type-III allergic inflammatory reaction involving the alveoli and lung interstitium, steered by Th₁ cells and IgG and, in its chronic form, accompanied by fibrosis. Although pathologically very different and commonly approached as separate disorders, as discussed in this review, clinical studies as well as data from animal models reveal undeniable parallels between both airway diseases. Danger signaling elicited by the allergenic agent or by accompanying microbial patterns emerges as critical in enabling immune sensitization and in determining the type of sensitization and ensuing allergic disease. On this basis, we propose that asthma allergens cause severe noneosinophilic asthma because of sensitization in the presence of hypersensitivity pneumonitis-promoting danger signaling.