J Appl Physiol 103: 1461, 2007;
doi:10.1152/japplphysiol.00665.2007
8750-7587/07 $8.00
LETTER TO THE EDITOR
Commentary on "The role of the large airways on smooth muscle contraction in asthma"
TO THE EDITOR: Dr. Permutt (6) puts the focus back on large airways as culprits in asthma. Large airways present a greater challenge to physiologists than small airways since they are more complex and do not necessarily behave isotropically when ASM is stimulated (4). A central role for ASM in asthma has been recently highlighted (1), but Permutt's hypothesis questions the role since correlations between airway narrowing and lung function at TLC were not found. However, as noted (3), airway dimensions under normal breathing conditions and TLC are subject to elastic properties of the activated airway under their different conditions of tone, so a conclusive case against airway narrowing is not yet made.
Permutt's hypothesis rests on a series of correlations, but cause and effect remains to be confirmed. How do the structural changes described actually alter lung volume—for example, the thicker wall in relaxed large airways (but not other airways) on RV? The animal studies cited by Dr. Permutt showed large airways can close, but only with maximal pharmacological stimulation unlikely to exist physiologically, whereas lower levels of stimulation left airways patent (2).
If large airways are the problem in asthma, presumably the capacity of deep inspiration (DI) to improve the FEV1 also rests at that level. We recently showed in an animal model that cartilaginous airways with high ASM tone and increased stiffness become insensitive to DI (5). Large toned asthmatic airways may be similarly unresponsive to DI, explaining why asthmatics show little improvement in lung function with DI.
FOOTNOTES
Address for reprint requests and other correspondence: H. Mitchell, 35 Stirling Highway, Crawley, Perth, Western Australia, Australia 6009 (e-mail: mitchell{at}cyllene.uwa.edu.au)
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- Brown RH, Mitzner W. The myth of maximal airway responsiveness in vivo. J Appl Physiol 85: 2012–2017, 1998.[Abstract/Free Full Text]
- Brown RH, Pearse DB, Pyrgos G, Liu MC, Togias A, Permutt S. The structural basis of airways hyperresponsiveness in asthma. J Appl Physiol 101: 30–39, 2006.[Abstract/Free Full Text]
- Mitchell HW, Gray PR. Assessment of the dynamic relationship between external diameter and lumen flow in isolated bronchi. Respir Physiol 116: 67–76, 1999.[CrossRef][Web of Science][Medline]
- Noble PB, McFawn PK, Mitchell HW. Responsiveness of the isolated airway during simulated deep inspirations: effect of airway smooth muscle stiffness and strain. J Appl Physiol; doi:10.1152/japplphysiol.00314.2007.
- Permutt S. The role of the large airways on smooth muscle contraction in asthma. J Appl Physiol; doi:10.1152/japplphysiol.00568.2007.
Howard Mitchell
Peter Noble
Peter McFawn
Department of Physiology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia
Copyright © 2007 by the American Physiological Society.