Eur Respir J 2007; 29:834-860
Copyright ©ERS Journals Ltd 2007
Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma
S. S. An1,
T. R. Bai2,
J. H. T. Bates3,
J. L. Black4,
R. H. Brown5,
V. Brusasco6,
P. Chitano7,
L. Deng8,9,
M. Dowell10,
D. H. Eidelman11,
B. Fabry12,
N. J. Fairbank13,
L. E. Ford14,
J. J. Fredberg8,
W. T. Gerthoffer15,
S. H. Gilbert14,
R. Gosens16,
S. J. Gunst17,
A. J. Halayko16,
R. H. Ingram18,
C. G. Irvin3,
A. L. James19,
L. J. Janssen20,
G. G. King21,
D. A. Knight2,
A. M. Lauzon11,
O. J. Lakser22,
M. S. Ludwig11,
K. R. Lutchen23,
G. N. Maksym13,
J. G. Martin11,
T. Mauad24,
B. E. McParland4,
S. M. Mijailovich8,
H. W. Mitchell25,
R. W. Mitchell10,
W. Mitzner1,
T. M. Murphy7,
P. D. Paré2,
R. Pellegrino26,
M. J. Sanderson27,
R. R. Schellenberg2,
C. Y. Seow2,
P. S. P. Silveira24,
P. G. Smith28,
J. Solway10,
N. L. Stephens16,
P. J. Sterk29,
A. G. Stewart30,
D. D. Tang31,
R. S. Tepper32,
T. Tran16 and
L. Wang7
1 Division of Physiology, Dept of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health; 5 Dept of Anesthesiology and Critical Care medicine, Johns Hopkins Medical Institutions, Baltimore, MD; 3 Vermont Lung Center, University of Vermont College of Medicine, Burlington, VT; 7 Dept of Paediatrics, Duke University Medical Center, Durham, NC; 8 Program in Molecular and Integrative Physiological Sciences, Dept of Environmental Health, Harvard School of Public Health; 23 Dept of Biomedical Engineering, Boston University, Boston; 27 Dept of Physiology, University of Massachusetts Medical School, Worcester, MA; 10 Section of Pulmonary and Critical Care Medicine; 22 Section of Paediatric Pulmonary Medicine, University of Chicago, Chicago, IL; 14 Krannert Institute of Cardiology; Depts of 17 Physiology, and 32 Paediatrics, Indiana University School of Medicine, Indianapolis, IN; 15 Dept of Pharmacology, University of Nevada School of Medicine, Reno, NV; 18 Dept of Medicine, Emory University School of Medicine, Atlanta, GA; 28 Dept of Paediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH; 31 Center for Cardiovascular Sciences, Albany Medical College, Albany, NY, USA. 2 James Hogg iCAPTURE Centre, University of British Columbia, Vancouver; 11 Meakins-Christie Laboratories, Dept of Medicine, McGill University, Montreal; 13 School of Biomedical Engineering, Dalhousie University, Halifax; 16 Dept of Physiology, University of Manitoba, Winnipeg; 20 Dept of Medicine, McMaster University, Hamilton, Canada. 4 Dept of Pharmacology, University of Sydney, Sydney; 19 West Australian Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Nedlands; 21 Woolcock Institute of Medical Research, Camperdown; 25 Discipline of Physiology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth; 30 Dept of Pharmacology, University of Melbourne, Parkville, Australia. 6 Dept of Internal Medicine, University of Genoa, Genoa; 26 Dept of Respiratory Physiopathology, S. Croce e Carle Hospital, Cuneo, Italy. 9 Bioengineering College, Chongqing University, Chongqing, China. 12 Center for Medical Physics and Technology, Erlangen, Germany. 24 Dept of Pathology, Sao Paulo University Medical School, Sao Paulo, Brazil. 29 Dept of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
CORRESPONDENCE: C. Y. Seow, James Hogg iCAPTURE Centre, University of British Columbia, 1081 Burrard Street, Room 166, Vancouver, BC, V6Z 1Y6, Canada. Fax: 1 6048069274. E-mail: cseow{at}mrl.ubc.ca
Keywords: Airway mechanics, interdependence, lung function, muscle adaptation, muscle contraction, parenchyma
Received: August 28, 2006
Accepted October 10, 2007
Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma.
As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling.
Anti-inflammatory therapy, however, does not "cure" asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM.
In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.
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Copyright © 2007 by the European Respiratory Society.
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