Proliferative aspects of airway smooth muscle

Hirst, Stuart J John; Martin, James G.; Bonacci, John V; Chan, Vivien W.; Fixman, Elizabeth D.; Hamid, Qutayba; Herszberg, Bérénice; Lavoie, Jean‐Pierre; McVicker, Clare G.; Moir, Lyn M.; Nguyen, Trang T-B; Peng, Qi; Ramos-Barbón, David; Stewart, Alastair G.

doi:10.1016/j.jaci.2004.04.039

Cited by 200 publications

(174 citation statements)

References 113 publications

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“…In humans with asthma, increased airway smooth muscle mass also is seen. 18,19 Glucocorticoids and b 2 agonists can attenuate the proliferative response of airway smooth muscle. Use of glucocorticoids arrests cell cycle progression but results in an increase in airway smooth muscle cell size.…”

Section: Discussionmentioning

confidence: 99%

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Lung Function and Airway Cytologic Profiles in Horses with Recurrent Airway Obstruction Maintained in Low‐Dust Environments

Miskovic

Couëtil

Thompson

2007

Veterinary Internal Medicne

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Background: The effects of long-term environmental management on airway obstruction and inflammation in horses with recurrent airway obstruction (RAO) are unknown.Hypothesis: Horses with RAO maintained in low-dust environments have persistent airway obstruction and neutrophilic inflammation.Animals: Study horses were treated for RAO and then maintained in low-dust environments with no medical management. Horses were classified into 3 groups by years after diagnosis: 1 year (time 1, n 5 9), 2-3 years (time 2, n 5 7), and 5-6 years (time 3, n 5 8). The comparison groups were age-matched healthy horses.Methods: In this cross-sectional study, a clinical examination was performed, and the clinical score was calculated. Standard lung function, forced expiratory maneuvers, and the cytology of bronchoalveolar lavage fluid (BALF) were evaluated.Results: The clinical scores of the RAO horses were higher than those of the non-RAO horses at time 2 (P 5 .018). Standard lung function data were not different between the groups at any time point. The forced expiratory flow between 75-95% of exhaled vital capacity was lower in RAO horses than in non-RAO horses at all time points (P , .02), indicating persistent peripheral airway obstruction. Cytologic evaluation of BALF revealed no difference in total nucleated cell numbers or differential cell counts between RAO and non-RAO horses at any time point.Conclusions and Clinical Importance: The peripheral airway obstruction detected in horses with RAO maintained in lowdust environments likely is due to irreversible airway remodeling but is not associated with cytologic evidence of airway inflammation.

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Section: Discussionmentioning

confidence: 99%

“…18 b 2 agonists decrease airway smooth muscle DNA synthesis and smooth muscle cell numbers. 18,19 Prolonged treatment with glucocorticoids and b 2 agonists in combination may decrease the extent of airway smooth muscle remodeling.…”

Section: Discussionmentioning

confidence: 99%

Lung Function and Airway Cytologic Profiles in Horses with Recurrent Airway Obstruction Maintained in Low‐Dust Environments

Miskovic

Couëtil

Thompson

2007

Veterinary Internal Medicne

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“…Proliferation has been extensively explored in smooth muscle cultures from post mortem tissue, resections, lung transplants and biopsies. There are a number of recent studies that identify the diversity of growth stimuli that range from growth factors (fibroblast growth factor (FGF)-b), spasmogens (cysteinyl leukotrienes), cytokines (TNF-a), and the ECM components (monomeric type I collagen) through to physical influences, such as stretch (supra-tidal breathing volumes) and stasis, when smooth muscle is cultured on flexible supports that can be subjected to pressure cycles that simulate the impact of different breathing patterns on the forces acting on smooth muscle [104][105][106]. Furthermore, signal transduction pathways have been extensively examined, leading to identification of roles for extracellular signal-related kinase 1 and 2, phosphoinositide-3 kinase and p38MAPK in the initial signalling followed by activation of cyclin-dependent kinases and diminished levels of cyclin-dependent kinase inhibitors, including p27 kip 1 andp21 cip1 , which culminate in retinoblastoma phosphorylation to allow cells to continue through the final stages of G1 and onto S-phase.…”

Section: Asm Growth Responsesmentioning

confidence: 99%

“…This has promoted understanding of the functional properties of ASM cells that contribute to airway remodelling, including myocyte proliferation, secretion of pro-inflammatory bio-molecules, and synthesis of ECM components [232][233][234]. Nonetheless, key ultrastructural changes are evident when smooth muscle cells are plated as a monolayer in culture dishes, and this underpins a need for careful assessment of the effects of external mechanical strain on myocyte function.…”

Section: Chronic Oscillatory Length Change In Cultured Asm Cellsmentioning

confidence: 99%

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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“…As the disease becomes more progressive and persistent, other factors such as edema, mucus hyper-secretion, inflammation, mucus plugs and structural changes such as hypertrophy and hyperplasia of the airway smooth muscle further limit the bronchial air flow (Hirst et al, 2004). Due to augmentation of goblet cells in the airway epithelium, it leads to mucus hyper-secretion and increased size of sub-mucosal glands.…”

Section: Pathophysiologymentioning

confidence: 99%