Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Dec 23;118(7):439-50.
doi: 10.1042/CS20090474.

A new look at the pathogenesis of asthma

Affiliations
Review

A new look at the pathogenesis of asthma

Stephen T Holgate et al. Clin Sci (Lond). .

Abstract

Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Schematic representation of asthma over the life course
The arrows indicate exacerbations of asthma.
Figure 2
Figure 2. Chronic asthma is characterized by enhanced epithelial–mesenchymal communication with the release of a range of different growth factors linked to remodelling
Ar, amphiregulin; EGF, epidermal growth factor; ET-1, endothelin-1; FGF, fibroblast growth factor; IGF, insulin-like growth factor; KGF, keratinocyte growth factor; PDGF, platelet-derived growth factor; NGF, nerve growth factor; VEGF, vascular endothelial growth factor.
Figure 3
Figure 3. Defect in asthmatic epithelium to eliminate common respiratory viruses leading to cytotoxicity, mediator release and enhanced virus shedding associated with the asthma exacerbation
BEC, bronchial endothelial cell; LRT, lower respiratory tract; URT, upper respiratory tract.
Figure 4
Figure 4. Two or multiple ‘hit’ theory of the induction of new asthma through an interaction between virus infection and allergic sensitization
Figure 5
Figure 5. Potential role of TSLP in connecting epithelial activation to Th-2-type inflammation
GM-CSF, granulocyte/macrophage colony-stimulating factor; TLR, Toll-like receptor.

Similar articles

Cited by

References

    1. Holgate S., Bisgaard H., Bjermer L., Haahtela T., Haughney J., Horne R., McIvor A., Palkonen S., Price D. B., Thomas M., et al. The Brussels Declaration: the need for change in asthma management. Eur. Respir. J. 2008;32:1433–1442. - PubMed
    1. Editorial. Still more questions than answers. Lancet. 2008;372:1009. - PubMed
    1. Sly P. D., Boner A. L., Björksten B., Bush A., Custovic A., Eigenmann P. A., Gern J. E., Gerritsen J., Hamelmann E., Helms P. J., et al. Early identification of atopy in the prediction of persistent asthma in children. Lancet. 2008;372:1100–1106. - PMC - PubMed
    1. Sears M. R., Greene J. M., Willan A. R., Wiecek E. M., Taylor D. R., Flannery E. M., Cowan J. O., Herbison G. P., Silva P. A., Poulton R. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N. Engl. J. Med. 2003;349:1414–1422. - PubMed
    1. Horne R., Price D., Cleland J., Costa R., Covey D., Gruffydd-Jones K., Haughney J., Henrichsen S. H., Kaplan A., Langhammer A., et al. Can asthma control be improved by understanding the patient's perspective? BMC Pulm. Med. 2007;7:8. - PMC - PubMed

Publication types