Pathogenesis of Asthma

Abstract

While asthma is considered an inflammatory disorder of the conducting airways, it is becoming increasingly apparent that the disease is heterogeneous with respect to immunopathology, clinical phenotypes, response to therapies, and natural history. Once considered purely an allergic disorder dominated by Th2-type lymphocytes, IgE, mast cells, eosinophils, macrophages, and cytokines, the disease also involves local epithelial, mesenchymal, vascular and neurologic events that are involved in directing the Th2 phenotype to the lung and through aberrant injury-repair mechanisms to remodeling of the airway wall. Structural cells provide the necessary "soil" upon which the "seeds" of the inflammatory response are able to take root and maintain a chronic phenotype and upon which are superimposed acute and subacute episodes usually driven by environmental factors such as exposure to allergens, microorganisms, pollutants or caused by inadequate antiinflammatory treatment. Greater consideration of additional immunologic and inflammatory pathways are revealing new ways of intervening in the prevention and treatment of the disease. Thus increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions.

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

“…22,23 In humans, lung macrophages are increased in the CF, 24 as well as in adult-but not pediatric-patients with severe eosinophilic asthma, 25,26 and in individuals with severe COPD. 27 Their role in asthma is largely unknown, 28 but an impairment of phagocytic and antimicrobial functions in CF and COPD suggest that lung macrophages may have a key role in these two pathologies. 29,30 Interstitial lung macrophages are difficult to obtain, and isolation of alveolar macrophages from bronchoalveolar lavage requires an invasive clinical procedure that limits their access for research.…”

The Morphological Effects of Asthma, As Well As Conventional and Alternative Asthma Therapies on Parietal and Chief Cells in the Stomach of BALB/c Mice

“…The untreated asthmatic mice of this study showed a five-fold increase in eosinophil number, a clear indication that asthma was indeed induced amongst these mice. The collected BAL results for this study were theoretically expected as untreated asthmatics have been reported to show an increase in BAL fluid eosinophil levels while the use of corticosteroids, such as Hydrocortisone, have been shown to reduce the infiltration of eosinophils amongst asthmatics (Gwinn et al;Holgate, 2008;Venge, 1988).…”

Étude d'association entre l'asthme et les gènes associés à ce phénotype et à la pollution de l'air, dans un échantillon d'asthme provenant d'un environnement régional caractérisé par différentes industries /

“…Celle-ci est présente chez tous les sujets atteints d'asthme, qu'ils soient atteints d'asthme léger ou sévère. C'est un processus qui implique plusieurs cellules comme les lymphocytes T CD4+, les neutrophiles, les mastocytes ainsi que les éosinophiles dont l'infiltration au niveau des voies respiratoires constitue une des caractéristiques les plus importantes de ce mécanisme (19). De plus, les médiateurs inflammatoires reliés à ces différents types cellulaires (cytokines, chimiokines, leucotriènes, etc.)…”