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Review
, 29 (5), 834-60

Airway Smooth Muscle Dynamics: A Common Pathway of Airway Obstruction in Asthma

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Review

Airway Smooth Muscle Dynamics: A Common Pathway of Airway Obstruction in Asthma

S S An et al. Eur Respir J.

Abstract

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.

Figures

FIGURE 1
FIGURE 1
Maximal (M)/partial (P) ratio measured during spontaneous asthma (●), following treatment (○) and following acutely induced bronchoconstriction (□; induced by either dry air or histamine). To calculate the M/P ratio, the maximal mid-expiratory flow on a P and complete M expiratory flow volume curve are compared. An M/P ratio of 1 indicates that the deep inspiration accompanying the complete flow–volume manoeuvre causes neither an increase nor a decrease in mid-expiratory flow. An M/P ratio of <1 means that the deep inspiration decreased mid-expiratory flow; while an M/P ratio of >1 indicates that the deep inspiration increased mid-expiratory flow. During spontaneous asthma, a deep inspiration causes further airway narrowing. This paradoxical bronchoconstriction declines with effective treatment and, when comparable airway narrowing is induced by inhalation of histamine or dry air, a bronchodilating effect of deep inspiration is apparent. FEV1: forced expiratory volume in one second; % pred: % predicted. Modified from [41] with permission.
FIGURE 2
FIGURE 2
Shift in the length–force relationship of airway smooth muscle due to length adaptation. The solid curve (———) represents the length–force relationship of a muscle adapted at an arbitrarily chosen reference length (Lref). Upon shortening by an amount (X), the actively developed force decreases from A to B. After adaptation at the new length (Lref - X), usually through repeated activation and relaxation, the maximal active force for the muscle at the new length recovers to the level before the length change (C), and the muscle now possesses a new length–force relationship (- - - - -).
FIGURE 3
FIGURE 3
a) Airway smooth muscle cells being stretched in circular dishes by oscillating negative pressure below the flexible membrane. b) The strain field is anisotropic with nearly constant strain in the radial strain (–––––––) but gradually decreasing stretch in the circumferential strain (-------), which results in nearly uniaxial strain near the edge where the membrane is held. c, d, e) Cells are shown in Hoffmann contrast microscopy after 7 days of continuous cyclic stretching in culture. Cells do not align in the biaxial strain region, where strain is the same in every direction in the plane (arrows, as shown in c), but near the edge become almost completely aligned transverse to the applied strain direction (e). c, d, e) Microscopy shows the strain profile near radial positions 0, 0.5. and 1.0, respectively. As indicated by the normalised radial position in (b). Reproduced from [246] with permission.

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