Mucosal Inflammation in Asthma

Abstract

Over the past decade, it has become increasingly recognized that airways inflammation is one of the major components of asthma. Until recently, measurements of bronchial responsiveness and mediators of allergic reactions were the only methods of studying pathogenetic mechanisms in asthma. With improved diagnostic procedures such as fiberoptic bronchoscopy, it has become possible to investigate these mechanisms and the resulting inflammatory changes in situ. BAL has highlighted the presence of mast cells and eosinophils and has given proof of their mediator participation in airways inflammation and hyperresponsiveness. Endobronchial biopsies have so far yielded results that are similar to those obtained from postmortem studies, although it appears that there are varying degrees of inflammation in living asthmatics. Even in mild disease, the histopathologic features of bronchial asthma are consistent with chronic inflammation. Indirect evidence obtained from allergen challenge leading to increased bronchial hyperresponsiveness during LAR, and direct evidence of inflammatory cells and their mediators in the airway mucosa and lumen after allergen challenge argue for an active role of cells in bringing about inflammatory changes. At present, however, it is not possible to relate precisely the findings obtained by bronchoscopy to the clinical presentation and progression of asthma. Cell activation with production of potent mediators of inflammation may be more relevant to inflammation than the simple presence of these cells in the airways. Almost all the inflammatory cells present in the bronchial wall and lumen have been implicated in the pathogenesis of mucosal inflammation in asthma, but with our current state of knowledge, none can be singled out as the most important contributor. The mast cell was the first to be investigated in depth, and despite the accumulation of large amounts of data concerning its ultrastructure and function, it remains uncertain to what extent this cell is involved in inflammatory responses. Thus, while its main role appears to be that of initiator of allergen-induced responses, the eosinophil has attracted more attention as a proinflammatory cell rather than as an antiinflammatory cell with a capacity to be selectively recruited from the circulation in response to IgE-dependent signals. The eosinophil secretes potent mediators that cause damage to the bronchial epithelium and lead to bronchoconstriction. The role of other cells is at present not as well defined.(ABSTRACT TRUNCATED AT 400 WORDS)

Bronchial angiogenesis in severe glucocorticoid-dependent asthma

“…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].…”

“…The pathophysiological implications of these changes as components of airway remodelling of living patients with chronic severe asthma are not fully understood. Plasma exudation and vascular congestion are induced by various mediators, such as histamine and sulfidopeptide leukotrienes, known to be released in asthma, and may contribute to the acute airway obstruction observed in asthmatic subjects following allergen exposition [1,4].…”

Relationship between house dust mite (HDM) allergen exposure level and inhaled corticosteroid dosage in HDM-sensitive asthma patients on a self management program

“…Inflammation of the airways is a major underlying pathophysiological mechanism of asthma [1]. This inflammation leads to bronchoconstriction, which causes symptoms.…”

Elevation of serum soluble tumour necrosis factor (TNF) receptor and IL-1 receptor antagonist levels in bronchial asthma

“…The pathogenesis of allergic inflammation is complex and involves multiple inflammatory cells and mediators [2,3]. The involvement of macrophages and macrophage-derived cytokines such as TNF-and IL-1 in the production of allergic inflammation has been described [4,5].…”