Specificity of basement membrane thickening in severe asthma

Bourdin, Arnaud; Neveu, Dorine; Vachier, Isabelle; Paganin, F.; Godard, P.; Chanez, Pascal

doi:10.1016/j.jaci.2007.01.055

Cited by 120 publications

(98 citation statements)

References 31 publications

(37 reference statements)

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“…Subepithelial thickening of the bronchial reticular layer is an early feature of severe asthma in children, and appears to be a characteristic of the eosinophilic phenotype [18,112,113]. Patients with severe asthma also have increased expression of transforming growth factor-b isoforms and collagen deposition as compared to mild asthmatics, again in association with eosinophilic asthma, with evidence for remodelling in the peripheral airways as well [18,114].…”

Section: Structural Abnormalitiesmentioning

confidence: 99%

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

et al. 2013

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Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults.A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations.When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided.Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

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Section: Structural Abnormalitiesmentioning

confidence: 99%

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

et al. 2013

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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

121

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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“…Some studies fi nd a normal RBM, [6][7][8] while others report it to be thickened, [9][10][11][12][13] but generally to a smaller extent than in asthma. 9,10,12,14,15 The differences in observations may be due to the fact that some studies have included only a few COPD patients 7 or COPD patients with only mild 10 or more severe 9 airway obstruction.…”

Section: Introductionmentioning

confidence: 99%

Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition

Liesker

Hacken

Zeinstra-Smith³

et al. 2009

COPD

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Background: Reticular basement membrane (RBM) thickening has been variably associated with asthma and chronic obstructive pulmonary disease (COPD). Even if RBM thickness is similar in both diseases, its composition might still differ. Objective: To assess whether RBM thickness and composition differ between asthma and COPD. Methods: We investigated 24 allergic asthmatics (forced expiratory volume in one second [FEV 1 ] 92% predicted), and 17 nonallergic COPD patients (FEV 1 60% predicted), and for each group a control group of similar age and smoking habits (12 and 10 persons, respectively). Snapfrozen sections of bronchial biopsies were stained with hematoxylin/eosin and for collagen I, III, IV, V, laminin and tenascin. RBM thickening was assessed by digital image analysis. Relative staining intensity of each matrix component was determined. Results: Mean (SD) RBM thickness was not signifi cantly different between asthma and COPD 5.5 (1.3) vs 6.0 (1.8) μm, but signifi cantly larger than in their healthy counterparts, ie, 4.7 (0.9) and 4.8 (1.2) μm, respectively. Collagen I and laminin stained signifi cantly stronger in asthma than in COPD. Tenascin stained stronger in asthma than in healthy controls of similar age, and stronger in COPD controls than in asthma controls (p Ͻ 0.05). Conclusion: RBM thickening occurs both in asthma and COPD. We provide supportive evidence that its composition differs in asthma and COPD.

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Specificity of basement membrane thickening in severe asthma

Cited by 120 publications

References 31 publications

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

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

Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition

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