EDITORIAL

Asthma gene

ADAM 33: just another asthma gene or a breakthrough in understanding the origins of bronchial hyperresponsiveness?

S T Holgate, D E Davies, G Murphy, R M Powell, J W Holloway

Southampton General Hospital, Southampton, UK

Correspondence to:
Correspondence to:
Professor S T Holgate, Southampton General Hospital, Southampton, UK;
s.holgate@soton.ac.uk

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ADAM 33, the latest of the ADAM proteins to be described, has been identified as a major susceptibility gene in asthma linked to bronchial hyperresponsiveness. It provides an important breakthrough in our understanding of this complex disorder and its variable clinical and physiological presentations.

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Keywords: ADAM 33; asthma; genetics

The first 150 words of the full text of this article appear below.

Asthma is a disorder of the conducting airways in which Th2 mediated inflammation interacts with structural changes to cause variable airflow obstruction. Fundamental to disordered function is the concept of bronchial hyperresponsiveness (BHR) in which the airways constrict too much and too easily. In chronic severe asthma the inflammation and structural changes both become more intense¹ and are paralleled by an increase in BHR that is only partially or non-responsive to treatment with corticosteroids.² Explanations for BHR include mucosal and adventitial swelling causing a disproportionate reduction in airway calibre for a given degree of airways smooth muscle (ASM) shortening,³ excessive ASM shortening,⁴ an increase in ASM mass causing greater force generation,⁵ and an excessive velocity of contraction linked to altered crossbridge cycling.⁶ Morphometric studies have shown a graded increase in ASM mass in proportion to disease severity, and computer modelling has revealed that this and altered contractility are . . . [Full text of this article]

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This article has been cited by other articles:

• Haitchi, H. M., Powell, R. M., Shaw, T. J., Howarth, P. H., Wilson, S. J., Wilson, D. I., Holgate, S. T., Davies, D. E. (2005). ADAM33 Expression in Asthmatic Airways and Human Embryonic Lungs. Am. J. Respir. Crit. Care Med. 171: 958-965 [Abstract] [Full Text]  
• Raby, B. A., Weiss, S. T. (2004). ADAM33: Where Are We Now?. Am. J. Respir. Cell Mol. Bio. 31: 1-2 [Full Text]  
• Powell, R. M., Wicks, J., Holloway, J. W., Holgate, S. T., Davies, D. E. (2004). The Splicing and Fate of ADAM33 Transcripts in Primary Human Airways Fibroblasts. Am. J. Respir. Cell Mol. Bio. 31: 13-21 [Abstract] [Full Text]  

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