Airway Structural Alterations Selectively Associated with Severe Asthma

Benayoun, Laurent; Druilhe, Anne; Dombret, Marie-Christine; Aubier, Michel; Pretolani, Marina

doi:10.1164/rccm.200209-1030oc

Cited by 720 publications

(704 citation statements)

References 59 publications

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“…Vessels within the submucosa plexus have since 13 then been reported extensively to be increased in the asthmatic airway. The subepithelial space is shortened in asthmatics and this correlates to disease severity [76], bringing the increased ASM bundles into close proximity to the submucosa plexus. Thickening of the airway wall in asthma also includes increased vessel calibre as a result of dilatation of capillary vessels, angiogenesis, oedema from microvascular leakage, increased capillary permeability and engorgement of lymphatic and blood capillaries.…”

Section: Vascular Inflammation and Remodelling Processes In Asthmamentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.

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Section: Vascular Inflammation and Remodelling Processes In Asthmamentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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“…Many of these patients are labelled as corticosteroid-dependent, in that reduction in either maintenance ICS or oral CS leads to a deterioration of asthma control. Studies have reported that there is persistent neutrophilic and eosinophilic inflammation [78,79] in the airways, together with increased subbasement membrane thickness and airway smooth-muscle mass [80,81]. There is altered expression of markers of epithelial proliferation such as an increased expression of the proliferation marker, Ki67, and reduced expression of Bcl-2, a negative regulator of epithelial cell death [82].…”

Section: Corticosteroid Insensitivity In Airways Diseasementioning

confidence: 99%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

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International audienceInhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV and the rate of exacerbations. A reduction in the rate of decline in FEV of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases

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“…The airways of patients with asthma typically display a number of structural changes, including goblet cell metaplasia and excessive mucus production, thickening of the lamina reticularis, angiogenesis, and increased smooth muscle mass with a reduced distance between muscle cells and the airway epithelium as asthma severity increases (1,2). These changes, collectively termed airway remodeling, lead to a thickening of the airway wall.…”

Section: Introductionmentioning

confidence: 99%

Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration

Shariff

Shelfoon

Holden

et al. 2017

Am J Respir Cell Mol Biol

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Rationale: Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell mass with a greater proximity of the airway smooth muscle cells (ASMC) to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMC.Methods: ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer. Multiplex bead analysis was used to measure HRVinduced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8 and CXCL10 were also examined.Results: Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMC with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8 and CXCL10 were used at levels found in epithelial supernatants they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration and treatment of supernatant from HRVinfected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. Conclusion:These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis, and thus may contribute to the pathogenesis of airway remodeling in asthmatic patients.3

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Airway Structural Alterations Selectively Associated with Severe Asthma

Cited by 720 publications

References 59 publications

Pulmonary vascular changes in asthma and COPD

Pulmonary vascular changes in asthma and COPD

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration

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