Pulmonary periarterial inflammation in fatal asthma

Shiang, Christina; Mauad, Thaís; Senhorini, José Augusto; Araujo, Bianca; Ferreira, Diogenes S.; Silva, L F F da; Dolhnikoff, Marisa; Tsokos, Michael; Rabe, Klaus F.; Pabst, Reinhard

doi:10.1111/j.1365-2222.2009.03281.x

Cited by 30 publications

(28 citation statements)

References 56 publications

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“…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]. Studies have also shown loss of alveolar attachments in fatal asthma [11], which positively correlated with both mast cell and eosinophilic inflammation, suggesting roles for these inflammatory cells in alveolar disruption.…”

Section: Pathology Of Small Airways In Asthma and Copdmentioning

confidence: 99%

The role of small airways in obstructive airway diseases: Figure 1.

Burgel¹

2011

Eur Respir Rev

196

139

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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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Section: Pathology Of Small Airways In Asthma and Copdmentioning

confidence: 99%

The role of small airways in obstructive airway diseases: Figure 1.

Burgel¹

2011

Eur Respir Rev

196

139

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“…Emerging evidence suggests that pulmonary inflammation associated with Th2-mediated inflammation could represent a novel pathway for the pathogenesis of pulmonary arterial remodeling. While the pathology seen in asthma is often described as limited to the airways, pulmonary artery pathology is also found in those with fatal asthma (39). A recent study of asthma patients showed that bronchial arteries exhibited an increase in intimal area, associated with smooth muscle proliferation and calcification of the elastica, and a corresponding decrease in luminal area (16).…”

Section: Discussionmentioning

confidence: 99%

“…A study of asthma patients showed that bronchial arteries exhibited an increase in the intimal area, associated with smooth muscle proliferation and calcification of the elastica, and a corresponding decrease in the luminal area (16). In addition, pulmonary artery pathology has also been found in those with fatal asthma (39). While the pathophysiology of pulmonary arterial remodeling remains largely unclear, recent advances implicate a role for inflammation in the process that results in an imbalance between cellular proliferation and apoptosis, the presence of inflammatory cells in the remodeled artery microenvironment, and an association with increased levels of inflammatory mediators, including various chemokines and cytokines (12,19).…”

mentioning

confidence: 99%

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

et al. 2012

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Pulmonary arterial remodeling is a pathological process seen in a number of clinical disease states, driven by inflammatory cells and mediators in the remodeled artery microenvironment. In murine models, Th2 cell-mediated immune responses to inhaled antigens, such as purified Aspergillus allergen, have been reported to induce remodeling of pulmonary arteries. We have previously shown that repeated intranasal exposure of healthy C57BL/6 mice to viable, resting Aspergillus fumigatus conidia leads to the development of chronic pulmonary inflammation and the coevolution of Th1, Th2, and Th17 responses in the lungs. Our objective was to determine whether repeated intranasal exposure to Aspergillus conidia would induce pulmonary arterial remodeling in this mixed Th inflammatory microenvironment. Using weekly intranasal conidial challenges, mice developed robust pulmonary arterial remodeling after eight exposures (but not after two or four). The process was partially mediated by CD4 ؉ T cells and by interleukin-4 (IL-4) production, did not require eosinophils, and was independent of gamma interferon (IFN-␥) and IL-17. Furthermore, remodeling could occur even in the presence of strong Th1 and Th17 responses. Rather than serving an antiinflammatory function, IL-10 was required for the development of the Th2 response to A. fumigatus conidia. However, in contrast to previous studies of pulmonary arterial remodeling driven by the A. fumigatus allergen, viable conidia also stimulated pulmonary arterial remodeling in the absence of CD4 ؉ T cells. Remodeling was completely abrogated in IL-10 ؊/؊ mice, suggesting that a second, CD4 ؉ T cell-independent, IL-10-dependent pathway was also driving pulmonary arterial remodeling in response to repeated conidial exposure.

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“…In addition, the degree of neutro philic inflammation strongly relates to worsening lung function [201,202]. Finally, in patients who died soon after the onset of a severe asthma exacerbation, autopsies have shown the presence of neutrophils [203][204][205].…”

Section: Neutrophilic Asthmamentioning

confidence: 97%

Asthma phenotypes in adults and clinical implications

Fajt¹,

Wenzel²

2009

Expert Review of Respiratory Medicine

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It is becoming increasingly recognized that asthma is a heterogeneous disease, whether based on clinical factors, including the patient's age at diagnosis, symptom spectrum and treatment response, triggering factors, or the level and type of inflammation. Attempts to analyze the importance of these characteristics to the clinical presentation of asthma have led to the appreciation of numerous separate and overlapping asthma phenotypes. However, these approaches are 'biased' and based on the clinician/scientist's own experience. Recently, unbiased approaches have also been attempted using both molecular and statistical tools. Early results from these approaches have supported and expanded on the clinician's concepts. However, until specific biologic markers are identified for any of these proposed phenotypes, the definitive nature of any phenotype will remain speculative.

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Pulmonary periarterial inflammation in fatal asthma

Abstract: Our results show that the adventitial layer of the pulmonary artery participates in the inflammatory process in FA, demonstrating increased infiltration of mast cells, eosinophils, and neutrophils, but not of T and B lymphocytes.

Cited by 30 publications

References 56 publications

The role of small airways in obstructive airway diseases: Figure 1.

The role of small airways in obstructive airway diseases: Figure 1.

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Asthma phenotypes in adults and clinical implications

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Pulmonary periarterial inflammation in fatal asthma

Abstract: Our results show that the adventitial layer of the pulmonary artery participates in the inflammatory process in FA, demonstrating increased infiltration of mast cells, eosinophils, and neutrophils, but not of T and B lymphocytes.

Cited by 30 publications

References 56 publications

The role of small airways in obstructive airway diseases: Figure 1.

The role of small airways in obstructive airway diseases: Figure 1.

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4+T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10

Asthma phenotypes in adults and clinical implications

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Product

Resources

About

Repeated Exposure to Aspergillus fumigatus Conidia Results in CD4⁺T Cell-Dependent and -Independent Pulmonary Arterial Remodeling in a Mixed Th1/Th2/Th17 Microenvironment That Requires Interleukin-4 (IL-4) and IL-10