Elastosis and Fragmentation of Fibers of the Elastic System in Fatal Asthma

Mauad, Thaís; Xavier, Ana C.; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa

doi:10.1164/ajrccm.160.3.9809088

Cited by 111 publications

(108 citation statements)

References 24 publications

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“…This is supported by in vitro studies showing increased responsiveness of human ASM after treatment with collagenase [131]. Loss of elastin may contribute to altered airway mechanics in asthma, possibly increasing deformability, with a tendency towards increased airway narrowing [63,65]. Thus, in some asthma cases the airways could be more collapsible, which will increase the tendency for airway closure.…”

Section: Airway Wall Collapsementioning

confidence: 87%

“…JAMES AND S. WENZEL I, III and IV [51][52][53][54]; decorin [55,56]; laminin [57,58]; tenascin [53,59,60]; versican [55,56,59]; biglycan [56,59,61]; perlecan [56,61]; hyaluranon [50,62]; and decreased lumican [55]. Reductions in elastin have been observed in a number of studies [63][64][65]. Increased collagen in the airway submucosa has also been observed in occupational asthma [66].…”

Section: Airway Remodelling In Airway Diseasesmentioning

confidence: 98%

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Clinical relevance of airway remodelling in airway diseases

James¹,

Wenzel²

2007

European Respiratory Journal

301

214

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Asthma and chronic obstructive pulmonary disease (COPD) are characterised by airflow obstruction, airway remodelling (measurable structural change) and inflammation. The present review will examine the relationship between airway remodelling in these two conditions with respect to symptoms, abnormal lung function, airway hyperresponsiveness and decline in lung function. The potential for remodelling to be a protective response will also be discussed.Asthma is associated with variable symptoms and changes in lung function and also fixed abnormalities of lung function and an increased rate of decline in lung function with age. There is a relative preservation of the relaxed airway lumen dimensions, prominent thickening of the smooth muscle layer and reduced airway distensibility. The severity of asthma is related to the degree of airway remodelling, which is most marked in cases of fatal asthma.In COPD, symptoms are persistent and predictable but also progressive and are related to fixed abnormalities of lung function. Remodelling is associated with narrowing of the airway lumen and an increased thickness of the airway wall, although not usually to the extent seen in asthma. COPD is most often due to smoking where there is also remodelling of the parenchyma that may contribute to symptoms.

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Section: Airway Wall Collapsementioning

confidence: 87%

Section: Airway Remodelling In Airway Diseasesmentioning

confidence: 98%

Clinical relevance of airway remodelling in airway diseases

James¹,

Wenzel²

2007

European Respiratory Journal

301

214

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“…Parallel observations have been made in the airways in severe asthma. MAUAD et al [28] performed morphometric studies on the central airways of subjects with fatal asthma, and found fragmentation of elastic fibres and a reduction in the content of elastic fibres in the subepithelial portion of the airway wall. In a subsequent study of fatal asthma, MAUAD et al [29] reported a reduction in the content of elastic fibres in the adventitial layer of the small airways, although they also noted a reduction in alveolar attachments to the small airways but without any evidence of changes in the elastic fibres elsewhere in the alveoli.…”

Section: Discussionmentioning

confidence: 99%

Changes in elastic fibres in the small airways and alveoli in COPD

Black¹,

Ching²,

Beaumont³

et al. 2008

European Respiratory Journal

137

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Small airways are the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD). This is attributed to loss of elastin in alveoli and fibrosis in small airways. In the present study, it was hypothesised that changes to elastic fibres in alveoli might be paralleled by a similar reduction in elastic fibres in small airways.Tissue blocks from patients who had lobectomy for bronchial carcinoma were studied. Patients were classified as COPD (forced expiratory volume in one second (FEV1) ,80% predicted, FEV1/ forced vital capacity (FVC) ,0.7) or controls (FEV1 o80% pred, FEV1/FVC o0.7). Elastic fibres were visualised using Elastic van Gieson staining and the volume fraction (v/f) of elastic fibres was determined as a percentage of tissue volume using point counting. Elastic fibre networks were also visualised by confocal microscopy.The v/f for elastic fibres in alveoli was 18.6% for COPD and 32.8% in controls. In the airways the v/f was 14.6% for COPD and 25.5% in controls. FEV1% predicted was correlated with v/f in both alveoli and small airways.The volume fraction of elastic fibres was reduced to a similar extent in small airways and alveoli in chronic obstructive pulmonary disease and both were correlated with the extent of airflow obstruction. Loss of elastic fibres in small airways may contribute to the development of airflow obstruction in chronic obstructive pulmonary disease.

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“…Although studies are limited, distal lung parenchyma or alveolar tissue appears to be nearly devoid of fibrosis. Rather, data suggest abnormal loss of ECM in the alveolar interstitium adjacent to small airways in the distal lung tissue of individuals with fatal asthma (7,8). The cellular mecha-nisms of such contrasting matrix patterns in proximal airways versus distal lung tissue of individuals with asthma remain to be determined.…”

mentioning

confidence: 99%

Regional Fibroblast Heterogeneity in the Lung

Kotaru

Schoonover²,

Trudeau³

et al. 2006

Am J Respir Crit Care Med

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Rationale: Excessive deposition of extracellular matrix occurs in proximal airways of individuals with asthma, but fibrosis in distal lung has not been observed. Whether differing fibrotic capacities of fibroblasts from these two regions contribute to this variability is unknown. Objectives: We compared morphologic and functional characteristics of fibroblasts isolated from proximal airways and distal lung parenchyma to determine phenotypic differences. Methods: Concurrent proximal airway and distal lung biopsies were obtained by bronchoscopy from subjects with asthma to isolate airway and distal lung fibroblasts, respectively. The following characteristics were compared: morphology, proliferation, ␣-smooth muscle actin expression, and synthesis of procollagen type I and eotaxin-1. Results: Airway fibroblasts (AFs) are morphologically distinct from distal lung fibroblasts (DLFs): they are larger (2.3-fold greater surface area vs. matched DLFs; p ϭ 0.02), stellate in appearance, and with more cytoplasmic projections compared with the spindleshaped DLFs. AFs synthesized more procollagen type I than did DLFs at baseline (twofold higher; p ϭ 0.003) and after transforming growth factor-␤ stimulation (1.4-fold higher; p ϭ 0.02). Similarly, AFs produced more eotaxin-1 than did DLFs at baseline (2.5-fold higher; p ϭ 0.004) and after interleukin-13 stimulation (13-fold higher; p ϭ 0.0001). In contrast, DLFs proliferate more than AFs with serum stimulation (about sixfold greater; p ϭ 0.03). Unstimulated DLFs also expressed more ␣-smooth muscle actin than did corresponding AFs (p ϭ 0.006). Conclusions: These studies suggest that at least two phenotypes of fibroblast exist in the lung. These phenotypic differences may partially explain the variable responses to injury and repair between proximal airways and distal lung/parenchyma in asthma and other respiratory diseases.

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Elastosis and Fragmentation of Fibers of the Elastic System in Fatal Asthma

Cited by 111 publications

References 24 publications

Clinical relevance of airway remodelling in airway diseases

Clinical relevance of airway remodelling in airway diseases

Changes in elastic fibres in the small airways and alveoli in COPD

Regional Fibroblast Heterogeneity in the Lung

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