The outer wall of small airways is a major site of remodeling in fatal asthma

Dolhnikoff, Marisa; Silva, Luiz F F da; Araujo, Bianca; Gomes, H.A.P.; Fernezlian, Sandra; Mulder, Adri; Lindeman, J.; Mauad, Thaís

doi:10.1016/j.jaci.2009.02.032

Cited by 111 publications

(99 citation statements)

References 42 publications

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“…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]. Indeed, increased production and altered composition of extracellular matrix in the small airways is characteristic of fatal asthma [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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“…Airway wall thickening with increase in smooth muscle mass and inflammatory cell infiltration by T lymphocytes and eosinophils were also present in large and small airways [7]. Post mortem studies have shown that the outer wall of the small airways was a major site of inflammation (especially with eosinophils) [8]. Inflammation in fatal asthma extended to the adjacent alveoli [9] and to the perivascular areas [10].…”

Section: Pathology Of Small Airways In Asthma and Copdmentioning

confidence: 99%

The role of small airways in obstructive airway diseases

Burgel¹

2011

European Respiratory Review

187

137

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This review article is a summary of a seminar organised by the European Respiratory Society on ''The role of small airways in obstructive airway diseases'' which was held in October 2010 in Amsterdam, the Netherlands.The aims of the seminar were to identify important questions related to small airways involvement in asthma and chronic obstructive pulmonary disease (COPD), and to discuss future approaches based on current and evolving knowledge. Data obtained by pathological and physiological measurements in small airways and their relevance to clinical manifestations and therapeutics in asthma and COPD were reviewed.It was concluded that our knowledge on the roles of small airways in asthma and COPD is limited. Studies of large numbers of well-characterised subjects using multiple methods (genetic characterisation, cell biology and physiology, imaging) and integration of the data using mathematical models are suggested to be of interest. The availability of these techniques coupled with our ability to better target inhaled molecules to small airways provide a unique opportunity for a reappraisal of the relevance of small airways in chronic airway diseases.

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“…combinations of inhaled corticosteroids and long-acting b 2 -agonists, are effective for most asthmatic individuals, 5-10% of patients have severe disease that responds poorly [115]. MMPs might contribute to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma, because MMP expression is increased at the outer region of the small airways and in the peribronchiolar parenchyma in asthmatic patients [116]. Moreover, the broad-spectrum MMP inhibitor R-94138 reduced the development of allergic airway inflammation in mice [56] and marimastat (another broad-spectrum MMP inhibitor) reduced bronchial hyperresponsiveness to inhaled allergen in atopic asthmatic subjects [57].…”

Section: Dysregulation Of Mmps In Different Lung Disorders and Its Thmentioning

confidence: 99%

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

Vandenbroucke¹,

Dejonckheere²,

Libert³

2011

European Respiratory Journal

107

104

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Disruption of the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors is considered a key event in the development of pulmonary diseases such as chronic obstructive pulmonary disease, asthma, interstitial lung diseases and lung cancer. This imbalance often results in elevated net MMP activity, making MMP inhibition an attractive therapeutic strategy. Although promising results have been obtained, the lack of selective MMP inhibitors, together with limited knowledge regarding the exact functions of a particular MMP, hampers clinical application. This review discusses the involvement of different MMPs in lung disorders and future opportunities and limitations of therapeutic MMP inhibition.

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The outer wall of small airways is a major site of remodeling in fatal asthma

Cited by 111 publications

References 42 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

The role of small airways in obstructive airway diseases

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

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