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Asthma

  • Chapter
Molecular Pathology of Lung Diseases

Part of the book series: Molecular Pathology Library ((MPLB,volume 1))

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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.1–3

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.

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Authors and Affiliations

  1. Department of Medicine and Immunology, Baylor College of Medicine, Houston, TX, USA

    David B. Corry MD (Associate Professor) & Farrah Kheradmand MD (Associate Professor)

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  1. David B. Corry MD
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  2. Farrah Kheradmand MD
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Editor information

Editors and Affiliations

  1. Department of Pathology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA

    Dani S. Zander MD

  2. Institute of Pathology, Laboratories for Molecular Cytogenetics, Medical University of Graz, Graz, Austria

    Helmut H. Popper MD

  3. Department of Pathology, University of Texas Health Science Center, San Antonio, TX, USA

    Jaishree Jagirdar MD

  4. Weill Medical College of Cornell University, New York, NY

    Abida K. Haque MD

  5. Department of Pathology, San Jacinto Methodist Hospital, Baytown, TX, USA

    Abida K. Haque MD

  6. Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY

    Philip T. Cagle MD  & Roberto Barrios MD  & 

  7. The Methodist Hospital, Houston, TX, USA

    Philip T. Cagle MD  & Roberto Barrios MD  & 

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Corry, D.B., Kheradmand, F. (2008). Asthma. In: Zander, D.S., Popper, H.H., Jagirdar, J., Haque, A.K., Cagle, P.T., Barrios, R. (eds) Molecular Pathology of Lung Diseases. Molecular Pathology Library, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72430-0_51

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  • DOI: https://doi.org/10.1007/978-0-387-72430-0_51

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