Document Detail


The structural basis of airways hyperresponsiveness in asthma.
MedLine Citation:
PMID:  16469934     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We hypothesized that structural airway remodeling contributes to airways hyperresponsiveness (AHR) in asthma. Small, medium, and large airways were analyzed by computed tomography in 21 asthmatic volunteers under baseline conditions (FEV1 = 64% predicted) and after maximum response to albuterol (FEV1 = 76% predicted). The difference in pulmonary function between baseline and albuterol was an estimate of AHR to the baseline smooth muscle tone (BSMT). BSMT caused an increase in residual volume (RV) that was threefold greater than the decrease in forced vital capacity (FVC) because of a simultaneous increase in total lung capacity (TLC). The decrease in FVC with BSMT was the major determinant of the baseline FEV1 (P < 0.0001). The increase in RV correlated inversely with the relaxed luminal diameter of the medium airways (P = 0.009) and directly with the wall thickness of the large airways (P = 0.001). The effect of BSMT on functional residual capacity (FRC) controlled the change in TLC relative to the change in RV. When the FRC increased with RV, TLC increased and FVC was preserved. When the relaxed large airways were critically narrowed, FRC and TLC did not increase and FVC fell. With critical large airways narrowing, the FRC was already elevated from dynamic hyperinflation before BSMT and did not increase further with BSMT. FEV1/FVC in the absence of BSMT correlated directly with large airway luminal diameter and inversely with the fall in FVC with BSMT. These findings suggest that dynamic hyperinflation caused by narrowing of large airways is a major determinant of AHR in asthma.
Authors:
Robert H Brown; David B Pearse; George Pyrgos; Mark C Liu; Alkis Togias; Solbert Permutt
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-02-09
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  101     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-19     Completed Date:  2006-08-28     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  30-9     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. rbrown@jhsph.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology,  therapeutic use
Adult
Albuterol / pharmacology,  therapeutic use
Asthma / drug therapy,  pathology*,  physiopathology*
Bronchial Hyperreactivity / pathology*,  physiopathology*
Bronchoconstriction / drug effects,  physiology
Bronchoconstrictor Agents / pharmacology
Bronchodilator Agents / pharmacology,  therapeutic use
Female
Forced Expiratory Volume / drug effects,  physiology
Humans
Lung / innervation,  pathology*,  physiopathology*,  radiography
Male
Methacholine Chloride / pharmacology
Middle Aged
Muscle, Smooth / drug effects,  innervation,  pathology,  physiopathology
Residual Volume / drug effects,  physiology
Respiratory Muscles / innervation,  pathology,  physiopathology
Tomography, X-Ray Computed
Total Lung Capacity / drug effects,  physiology
Vital Capacity / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
HL-10342/HL/NHLBI NIH HHS; HL-61277/HL/NHLBI NIH HHS; R01 HL-62698/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Bronchoconstrictor Agents; 0/Bronchodilator Agents; 18559-94-9/Albuterol; 62-51-1/Methacholine Chloride
Comments/Corrections
Comment In:
J Appl Physiol (1985). 2006 Jul;101(1):7-9   [PMID:  16782831 ]
J Appl Physiol (1985). 2006 Dec;101(6):1812; author reply 1813   [PMID:  16931560 ]

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