Collagen Deposition in Large Airways May Not Differentiate Severe Asthma from Milder Forms of the Disease

Chu, Hong Wei; Halliday, Janet L.; Martin, Richard J.; Leung, Donald Y.M.; Szefler, Stanley J.; Wenzel, Sally E.

doi:10.1164/ajrccm.158.6.9712073

Cited by 214 publications

(168 citation statements)

References 30 publications

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“…The lack of an association of past RBM thickness with wheeze persisting at age 5 yrs and lung function is in agreement with studies in older children and adults with asthma that were unable to demonstrate a relationship between RBM thickness, duration and severity of asthma [18,19] and lung function [18,20]. Indeed, it has been proposed that RBM thickening may be protective rather than deleterious [5,6].…”

Section: Discussionsupporting

confidence: 81%

Relationship between past airway pathology and current lung function in preschool wheezers

Sonnappa¹,

Bastardo²,

Saglani³

et al. 2011

Eur Respir J

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The functional outcome in preschool severe wheezers with eosinophilic airway inflammation and increased reticular basement membrane (RBM) thickness is unknown. We investigated the relationship between airway pathology at age 2 yrs and lung function at age 4-6 yrs in previous severe wheezers.Severe wheezers previously investigated by endobronchial biopsy and healthy children aged 4-6 yrs were recruited. Lung clearance index (LCI), conducting zone ventilation inhomogeneity (Scond), acinar ventilation inhomogeneity by multiple-breath washout, plethysmographic-specific airway resistance and exhaled nitric oxide fraction (FeNO) were measured. Lung function was compared between wheezers and healthy controls, and in wheezers correlated with past RBM thickness and mucosal eosinophilia (EG2+ cells).72 healthy controls and 28 previous severe wheezers were tested. Wheezers had significantly higher median LCI (6.8 versus 6.6; p50.001) and Scond (0.046 versus 0.016; p,0.0005) than healthy controls. Past RBM thickness (r50.474, p50.047) and EG2+ cells (r50.552, p50.041) showed significant correlations with current FeNO, but no correlations were seen between past RBM thickness and current lung function.RBM thickness and EG2+ cells at age 2 yrs show a significant positive association with FeNO at age 5 yrs. Although lung function was abnormal at age 5 yrs in severe wheezers, this did not correlate with past RBM thickness.

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Section: Discussionsupporting

confidence: 81%

Relationship between past airway pathology and current lung function in preschool wheezers

Sonnappa¹,

Bastardo²,

Saglani³

et al. 2011

Eur Respir J

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“…CHAKIR et al [45] described an association between disease severity and collagen deposition. In contrast, CHU et al [24] found no identifiable differences in collagen deposition or TGF-b expressing cells in the large airways of mild when compared with severe asthmatics.…”

Section: Is Remodelling Positively Correlated To Disease Severity?mentioning

confidence: 83%

“…This region, which is composed of collagen I, collagen III, collagen V, fibronectin and tenascin, and is situated just below the basement membrane, has an overall thickness of ,3-4 mm in nonasthmatics, while in asthma this is increased two-to three-fold [22,23]. Although increased collagen deposition in the lamina reticularis is a characteristic of asthma, it may not explain the differences in severity of asthma [24]. Functionally, thickening of the lamina reticularis has been linked to reduced airway distensibility and increased airflow limitation in asthma [25], suggesting that this altered structure has a negative impact on lung function.…”

Section: Thickening Of the Lamina Reticularismentioning

confidence: 99%

The contribution of transforming growth factor- and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

European Respiratory Journal

225

187

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Asthma is increasing in prevalence in the developing world, affecting ,10% of the world's population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-b is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-b in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-b and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-b, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.

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“…The effect on structural airway changes, the so-called airway remodelling, is less clear. These changes that include goblet cell hyperplasia (GCH), smooth muscle hypertrophy/hyperplasia, airway wall thickening and increased deposition of extracellular matrix proteins are present even in patients with mild asthma [2] and early in the disease process [3,4]. Most [5][6][7][8][9], but not all [10,11], biopsy studies show a limited effect of ICS on remodelling of asthmatic airways, possibly attributable to an effect on growth factor expression [8] or on the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 [9].…”

mentioning

confidence: 99%

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

Vanacker¹,

Palmans²,

Pauwels³

et al. 2002

European Respiratory Journal

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To examine whether fluticasone propionate (FP) dose-dependently inhibits inflammatory as well as structural changes, Brown Norway rats were sensitised to ovalbumin (OA) on day 0 and 7. From day 14-28, rats were exposed to aerosolised OA (1%) or phosphate buffered saline every 2 days. Thirty minutes before each allergen exposure, animals were pre-treated with aerosolised placebo or FP (0.1, 1 or 10 mg) or prednisolone 3 mg?kg -1 i.p.At day 29, 0.1 mg FP had no measurable effect, either on inflammatory or structural changes, such as goblet cell hyperplasia and airway wall thickening. The allergeninduced increase in eosinophilic inflammation in bronchoalveolar lavage fluid and in the airway mucosa, as well as increased fibronectin deposition, were inhibited by treatment with FP from a dose of 1 mg onwards. Inhibition of goblet cell hyperplasia and thickening of the airway wall required 10 mg inhaled FP. At this dose, systemic effects were observed. However, for a comparable degree of systemic activity, prednisolone was far less effective at preventing airway changes.The dose of inhaled fluticasone propionate required to inhibit allergen-induced structural alterations was higher than to prevent eosinophil influx, and caused systemic side-effects. However, for a similar systemic activity, prednisolone was ineffective in preventing airway remodelling.

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Collagen Deposition in Large Airways May Not Differentiate Severe Asthma from Milder Forms of the Disease

Cited by 214 publications

References 30 publications

Relationship between past airway pathology and current lung function in preschool wheezers

Relationship between past airway pathology and current lung function in preschool wheezers

The contribution of transforming growth factor- and epidermal growth factor signalling to airway remodelling in chronic asthma

Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats

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