Subepithelial Fibrosis in the Bronchi of Asthmatics

Roche, William R.; Williams, James; Beasley, Richard; Holgate, S. T.

doi:10.1016/s0140-6736(89)90067-6

Cited by 1,037 publications

(671 citation statements)

References 13 publications

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“…In postmortem studies in cases of asthma death, the majority of patients were characterized by a long history of symptomatic asthma, frequent hospitalizations, persistent airflow obstruction, and had previously been treated with glucocorticoids [14]. This typical profile of severe asthma was found to be associated with an increase in smooth muscle, mucous gland hyperplasia, and basement membrane thickening, all probably a result of chronic airway inflammation [1,2]. Adding to the complexity of this remodelling process, increases in submucosal vessel density and vascular volume have been described [4±6].…”

Section: Discussionmentioning

confidence: 99%

“…There is increasing evidence that angiogenesis occurs in asthmatic airways early in the process of airway remodelling [2,12]. XUN and WILSON [12] found significantly higher numbers of vessels in bronchial biopsies from mild asthmatics ((mean SD) 738 150 .…”

Section: Discussionmentioning

confidence: 99%

“…The immunopathology of asthma is characterized by accumulation of eosinophils and mononuclear cells in the submucosa, and is associated with sloughing of epithelial cells, smooth muscle hypertrophy and hyperplasia, goblet cell metaplasia, and subepithelial collagen deposition, which can result in permanent thickening and remod elling of the airways [1,2]. This may give rise to an irreversible component of bronchial obstruction and ex plain the persistent airflow limitation observed in patients with poorly-controlled asthma [3].…”

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confidence: 99%

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Bronchial angiogenesis in severe glucocorticoid-dependent asthma

Vrugt¹,

Wilson²,

Bron³

et al. 2000

Eur Respir J

131

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To examine the role of the bronchial microvasculature and adhesion molecule expression in severe asthma, the authors have performed an immunohistochemical study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15 mild asthmatics and eight control subjects.Serially cut glycol methacrylate-embedded sections were stained with monoclonal antibodies identifying the vessel marker EN-4, intercellular adhesion molecule (I-CAM)-1, vascular cell adhesion molecule (VCAM)-1, E-and P-selectin. Sections were also stained for lymphocyte function associated antigen (LFA)-1 and very late antigen (VLA)-4.By comparison with mild asthma and nonasthma, severe asthma was characterized by increased numbers of submucosal vessels (p=0.009) which was associated with increased numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation was found between the total number of EN-4+ vessels and the vessels expressing ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe as compared with mild asthma (p=0.01) but not different from normal. No differences were found between the three groups in the expression of VCAM-1 and Pselectin nor in numbers of LFA-1+ and VLA-4+ cells.The results of this study support the notion that mucosal neovascularization is an important feature of airways remodelling in severe asthma. This is associated with a relatively higher density of vessels expressing intercellular adhesion molecule-1, although the expression of this adhesion molecule per vessel was not raised.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Bronchial angiogenesis in severe glucocorticoid-dependent asthma

Vrugt¹,

Wilson²,

Bron³

et al. 2000

Eur Respir J

131

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“…One of the consequences of chronic airway inflammation in asthma is remodelling of the airways, which consists of increases in airway smooth muscle (ASM) mass (Dunnill et al, 1969), goblet cell hyperplasia (Laitinen et al, 1985;Aikawa, 2001) and subepithelial fibrosis (Roche et al, 1989). ASM thickening in chronic asthma involves both hyperplasia and hypertrophy of ASM cells (Ebina et al, 1993) and compared with other structural abnormalities in the airways of asthmatics, increased ASM mass is a most important determinant of excessive airway lumen narrowing (James et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Eynott

Nath

Leung

et al. 2003

British J Pharmacology

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1 Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N-terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)-1. 2 We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9-cd] pyrazole-6 (2 H)-one), in a model of chronic allergic inflammation in the rat. 3 Rats sensitised to ovalbumin (OA) were exposed to OA-aerosol every third day on six occasions and were treated with SP600125 (30 mg kg À1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T-cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine. 4 SP600125 significantly reduced the number of eosinophils (Po0.05) and lymphocytes (Po0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (Po0.05) and CD 2 þ T-cell (Po0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (Po0.05) and epithelial cell incorporation (Po0.05). 5 SP600125 did not alter bronchial hyper-responsiveness observed after chronic allergen exposure. 6 Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

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“…In patients with chronic obstructive pulmonary disease (COPD) a patchy alveolar wall fibrosis develops whereas in chronic asthmatics, a fibrotic response occurs predominantly in the lamina reticularis, leading to a thickening of the basement membrane (4,5). In both cases the ongoing inflammation-repair cycle leads to permanent structural changes in the airway wall (remodeling) of which fibrosis is a major constituent (6,7).…”

mentioning

confidence: 99%

Bleomycin‐induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI

Karmouty‐Quintana

Cannet

Zurbruegg

et al. 2007

Magnetic Resonance Imaging

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Purpose:To apply proton magnetic resonance imaging (MRI) techniques to assess noninvasively and in spontaneously breathing rats, structural changes following a single intratracheal administration of bleomycin (BLM). Materials and Methods:Rats were scanned by MRI prior to BLM or vehicle administration and at six hours, 24 hours, week 1, and at weeks 2, 3, 6, and 8 after treatment. Bronchoalveolar lavage (BAL) fluid and histological analyses were performed at 24 hours, and at weeks 1 and 8 (histology only).Results: Prominent MRI fluid signals were detected in the lungs of BLM-treated rats one week after challenge. These signals correlated with increased inflammatory parameters in BAL fluid and with marked perivascular and parenchymal infiltration with inflammatory cells in histological slices. At week 2 the MRI signals due to edema resolved, but nevertheless an increase in MRI signal intensity from the lung parenchyma was apparent. In some areas of the right lung the MRI signal intensity in the parenchyma decreased between weeks 2 and 8. These observations were in line with histology demonstrating collagen deposition and atelectasis (hallmarks of fibrosis) at week 1 and a partial recovery of the lung parenchyma at week 8. Conclusion:The data demonstrate the ability of proton MRI to detect BLM-induced lung fibrosis as well as the acute inflammatory response caused by the agent.

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Subepithelial Fibrosis in the Bronchi of Asthmatics

Cited by 1,037 publications

References 13 publications

Bronchial angiogenesis in severe glucocorticoid-dependent asthma

Bronchial angiogenesis in severe glucocorticoid-dependent asthma

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

Bleomycin‐induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI

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