Relating maximum airway dilation and subsequent reconstriction to reactivity in human lungs

Black, Lauren D.; Henderson, A. Cortney; Atileh, Haytham; Israel, Elliot; Ingenito, Edward P.; Lutchen, Kenneth R.

doi:10.1152/japplphysiol.01170.2003

Cited by 38 publications

(39 citation statements)

References 17 publications

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“…Such behaviour is consistent with observations from studies in isolated nonasthmatic ASM or in situ in human asthmatics [21,27,58,60,61]. Such an outcome becomes all the more likely when the ASM mass is increased, when the muscle becomes uncoupled from the lung parenchyma, when expansion of the chest wall is restricted, or when large lung inflations are prohibited during a bronchial challenge [18,62,63], all of which are factors that reduce the stretch experienced by the smooth muscle and circumstances relevant to AHR [49,64]. That being the case, this musclebased molecular mechanism explains not only how the airways can become refractory to the effects of a deep inspiration, but also how it can exhibit a bronchoconstrictor response.…”

Section: Evidence Of Asm Involvement In Asthmasupporting

confidence: 88%

“…This problem is amplified by bronchoprovocation with inhaled methacholine (or similar bronchoconstrictors). Even if baseline Raw increases in healthy subjects to that of symptomatic asthmatics, the asthmatics have a lesser decrease in Raw with a deep inspiration [63]. The implication is that the tracheobronchial tree is inherently stiffer in asthma [125].…”

Section: Removal Of Smooth Muscle From Asthmatic Airwaysmentioning

confidence: 99%

“…An advantage of this approach is that it explicitly captures the functional impact of the deep inspiration on the net change in airway diameters averaged over the entire airway tree. Also, one can track the dynamics of airway reconstriction [21,63,141], which may be sensitive to altered ASM function in situ. A disadvantage is that one cannot distinguish airway dilation from either airway or alveolar recruitment.…”

Section: Removal Of Smooth Muscle From Asthmatic Airwaysmentioning

confidence: 99%

See 2 more Smart Citations

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

An¹,

Bai²,

Bates³

et al. 2007

Eur Respir J

344

298

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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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Section: Evidence Of Asm Involvement In Asthmasupporting

confidence: 88%

Section: Removal Of Smooth Muscle From Asthmatic Airwaysmentioning

confidence: 99%

Section: Removal Of Smooth Muscle From Asthmatic Airwaysmentioning

confidence: 99%

See 1 more Smart Citation

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

An¹,

Bai²,

Bates³

et al. 2007

Eur Respir J

344

298

View full text Add to dashboard Cite

show abstract

“…7). It is well known that asthmatics' airways respond differently to those of nonasthmatics to the stretch that accompanies deep inspiration [25,[39][40][41][42]. In vivo, the effects of deep inspiration can be assessed by taking big breaths before or after the administration of a bronchoconstricting stimulus.…”

Section: Discussionmentioning

confidence: 99%

Mechanical properties of asthmatic airway smooth muscle

Chin

Bossé²,

Pascoe³

et al. 2012

Eur Respir J

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Airway smooth muscle (ASM) is the major effector of excessive airway narrowing in asthma. Changes in some of the mechanical properties of ASM could contribute to excessive narrowing and have not been systematically studied in human ASM from nonasthmatic and asthmatic subjects.Human ASM strips (eight asthmatic and six nonasthmatic) were studied at in situ length and force was normalised to maximal force induced by electric field stimulation (EFS). Measurements included: passive and active force versus length before and after length adaptation, the forcevelocity relationship, maximal shortening and force recovery after length oscillation. Force was converted to stress by dividing by cross-sectional area of muscle.The only functional differences were that the asthmatic tissue was stiffer at longer lengths (p,0.05) and oscillatory strain reduced isometric force in response to EFS by 19% as opposed to 36% in nonasthmatics (p,0.01).The mechanical properties of human ASM from asthmatic and nonasthmatic subjects are comparable except for increased passive stiffness and attenuated decline in force generation after an oscillatory perturbation. These data may relate to reduced bronchodilation induced by a deep inspiration in asthmatic subjects.KEYWORDS: Airway hyperresponsiveness, airway mechanics, asthma, force-velocity relationships, length-tension relationships, smooth muscle A sthma is characterised by exaggerated airway narrowing caused by airway smooth muscle (ASM) shortening. However, it is unclear whether there is a fundamental phenotypic change in the ASM itself or if the nonmuscle components of the airway wall or surrounding lung parenchyma are primary contributors to this airway hyperresponsiveness (AHR) [1,2]. A major hurdle to a clear understanding of ASM contractile function in disease has been the limited data. Of the 12 studies in which ASM mechanical properties have been compared in asthmatic and nonasthmatic tissue, seven have demonstrated no differences [3][4][5][6][7][8][9], while five have shown increases in force, shortening or agonist sensitivity [10][11][12][13][14].We have previously demonstrated that ASM cell bundles carefully dissected from the tracheas of nonasthmatic subjects whose lungs were donated for medical research provide a valuable, high quality tissue preparation for study of the mechanical properties of ASM [15].We showed that the mechanical properties of nonasthmatic ASM were similar to those measured in other mammalian models. This is in contrast to previous studies which suggested that human ASM produced less force per unit area and shortened less than the ASM of other mammals [16].The purpose of this study was to re-evaluate a series of hypotheses related to ASM mechanics that have been suggested as possible defects in asthmatic ASM function and potential contributors to AHR. These include determining whether asthmatic ASM produces more stress (force per unit cross-sectional area of muscle) than nonasthmatic ASM [17,18]; whether the length-tension relationship of asthmat...

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“…This force of airway-parenchymal interdependence mediates the transmission of transpulmonary pressure across the airway wall and thus is tied directly to lung volume. Indeed, airways responsiveness is exquisitely sensitive to lung volume (25)(26)(27), which explains why a deep lung inflation is the most potent means of reversing established bronchoconstriction (25,28,29), at least in normal lungs. By the same token, reducing lung volume below normal levels is a potent means of inducing AHR (30), which has obvious implications for obesity in which mass loading of the chest wall may compress the lungs and reduce the functional residual capacity (FRC).…”

Section: Mechanistic Bases Of Ahrmentioning

confidence: 99%

Physiological Mechanisms of Airway Hyperresponsiveness in Obese Asthma

Bates

2016

Am J Respir Cell Mol Biol

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Obesity affects the incidence and severity of asthma in at least two major phenotypes: an early-onset allergic (EOA) form that is complicated by obesity and a late-onset nonallergic (LONA) form that occurs only in the setting of obesity. Both groups exhibit airway hyperresponsiveness to methacholine challenge but exhibit differential effects of weight loss. Measurements of lung function in patients with LONA obese asthma suggest that this group of individuals may simply be those unlucky enough to have airways that are more compliant than average, and that this leads to airway hyperresponsiveness at the reduced lung volumes caused by excess adipose tissue around the chest wall. In contrast, the frequent exacerbations in those with EOA obese asthma can potentially be explained by episodic inflammatory thickening of the airway wall synergizing with obesity-induced reductions in lung volume. These testable hypotheses are based on the strong likelihood that LONA and EOA obese asthma are distinct diseases. Both, however, may benefit from targeted therapeutics that impose elevations in lung volume.

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Relating maximum airway dilation and subsequent reconstriction to reactivity in human lungs

Cited by 38 publications

References 17 publications

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

Mechanical properties of asthmatic airway smooth muscle

Physiological Mechanisms of Airway Hyperresponsiveness in Obese Asthma

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