| New perspectives on the mechanical basis for airway hyperreactivity and airway hypersensitivity in asthma. | |
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MedLine Citation:
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PMID: 16902064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We revisit the airway wall model of Lambert et. al. (Lambert RK, Wiggs BR, Kuwano K, Hogg JC, and Pare PD. J Appl Physiol 74: 2771-2781, 1993). We examine in detail the notion of a general airway bistability such that the airway lumen can suddenly decrease from a relatively open to a relatively closed condition without needing additional increase in active airway smooth muscle (ASM) tension during the stimulation. The onset of this bistability is an emergent consequence of the balance of forces associated with airway wall properties, parenchymal tissue properties, maximum lung elastic recoil, and the maximum stress that the ASM can generate. In healthy lungs, we find that all these properties reside in conditions that largely prevent the emergence of the bistability even during maximum ASM stimulation. In asthmatic airways, however, the airway wall and ASM remodeling conditions can tip the balance so as to promote the onset of the bistability at a lower dose of ASM stimulation (enhanced sensitivity) and then work to amplify the maximum constriction reached by each airway (enhanced reactivity). Hence, a larger fraction of asthmatic airways can display overall airway hyperreactivity. Simulations studies examine the role of increasing ASM maximum tension, airway wall stiffening, reduced lung volume, and decreased parenchymal tethering. Results predict that the single most important factor causing this airway hyperreactivity is amplified maximum ASM tension and not a thickening of the airway wall per se. |
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Authors:
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Derek A Affonce; Kenneth R Lutchen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-08-10 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 101 ISSN: 8750-7587 ISO Abbreviation: J. Appl. Physiol. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-11-19 Completed Date: 2007-01-04 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 1710-9 Citation Subset: IM |
Affiliation:
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Biomedical Engineering Department, Boston University, 44 Cummington St., Boston, MA 02215, USA. daffonce@bu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Asthma
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physiopathology* Bronchial Hyperreactivity / physiopathology* Computer Simulation Elasticity Humans Lung / physiopathology* Mechanotransduction, Cellular* Models, Biological* Muscle, Smooth / physiopathology* Shear Strength Stress, Mechanical |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL-076778/HL/NHLBI NIH HHS |
| Comments/Corrections | |
Erratum In:
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J Appl Physiol. 2007 Mar;102(3):1296 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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