Allergen inhalation challenge: a human model of asthma exacerbation.
Allergen challenge by inhalation is a very useful clinical and research tool for evaluating allergic airway disease. Inhalation of allergen leads to cross-linking of allergen-specific IgE bound to IgE receptors on mast cells and basophils. This is followed by activation of secretory pathways to release preformed and newly generated mediators of bronchoconstriction and vascular permeability. The onset of bronchoconstriction, representing the early phase of the asthmatic response, can be detected within 10 min of the inhalation, reaches a maximum within 30 min, and resolves within 3 h. The late-phase asthmatic response starts between 4 and 8 h, and is characterized by cellular inflammation of the airway, increased bronchiovascular permeability, and mucus secretion. The late-phase asthmatic response is also associated with increased airway responsiveness to nonallergic stimuli. Approximately half of the allergic asthmatic patients develop a late-phase response after allergen inhalation challenge. There has been a tremendous interest in trying to understand the differences between the pathways leading to the dual response and those leading to the early response alone. The current hypotheses are discussed in this chapter. Our understanding of the allergen inhalation challenge model and the complex interplay between leukocytes, tissue and inflammatory mediators will doubtlessly help to define novel and relevant targets for new drugs for the treatment of allergic asthma.
Gauvreau
Gail M
GM
Department of Medicine, McMaster University, Hamilton, Ont., Canada.
Evans
Michelle Y
MY
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000175:diagnosis / Q000276:immunology*; D001985:Bronchial Provocation Tests / Q000379:methods*; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology
D000485:Allergens; D007073:Immunoglobulin E