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Asthma

  • David B. Corry
  • Farrah Kheradmand
Part of the Molecular Pathology Library book series (MPLB, volume 1)

Abstract

Asthma is an inflammatory disease of the airways in which patients suffer from episodic dyspnea, cough, and related symptoms accompanied by characteristic abnormalities of the airways that include the presence of eosinophil-predominant allergic inflammation and airway hyperresponsiveness to provocative challenge. The latter abnormality reflects the exaggerated tendency of the asthmatic airway to constrict in response to a broad range of provocative stimuli. Enhanced constrictive responses to especially histamine and cholinergic agonists are used in the bronchial provocation test as a diagnostic aid where disease status remains uncertain based on clinical grounds alone. Additional highly characteristic histologic features of asthma include a metaplastic response of the airway epithelium involving the appearance of mucous-secreting goblet cells with enhanced secretion into the airway of mucin gene products and subepithelial airway fibrosis (Figure 51.1). Both of these abnormalities contribute to airway obstruction acutely and chronically, with airway mucous impaction strongly linked to asphyxiation and death in severe asthma.1, 2, 3
Figure 51.1

The major immune mechanisms underlying asthma pathogenesis. Two major mechanisms, type I hypersensitivity and type IV hypersensitivity, are thought to contribute to the major structural and physiologic changes associated with asthma, including airway hyperresponsiveness, goblet cell metaplasia with mucous hypersecretion, subepithelial airway fibrosis, and recruitment to the lungs of diverse inflammatory cells. During type I hypersensitivity, immunoglobulin (Ig) E secreted by B cells is captured by high-affinity receptors (FcεRI) present on mast cells and eosinophils. Cross-linking of surface-associated IgE induced by exposure to cognate antigen results in activation of FcεRI-bearing cells and the release of a large number of potentially toxic molecules that together contribute to the asthma phenotype. In contrast, type I hypersensitivity involves predominantly T lymphocytes and is immunoglobulin independent. The cytokines interleukin (IL)-4 and IL-13, secreted predominantly by Th2 cells, act directly on target tissues of the airway to elicit the asthma phenotype. Note that Th2 cells, through the cytokines that they secrete, are critical mediators of both disease mechanisms and provide the factors necessary for the growth and differentiation of asthma-associated inflammatory cells. STAT, signal transducer and activator of transcription.

Keywords

Allergy Clin Immunol Respir Crit Airway Hyperresponsiveness Atopic Asthma Airway Hyperreactivity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • David B. Corry
    • 1
  • Farrah Kheradmand
    • 1
  1. 1.Department of Medicine and ImmunologyBaylor College of MedicineHoustonUSA

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