Immunopathology of Atopic and Nonatopic Asthma
Atopy is a disorder characterized by sustained, inappropriate IgE responses to common environmental antigens (‘‘allergens’’) encountered at mucosal surfaces (1). Atopy is a very common feature in asthmatics: atopic asthma is characterized by in¢ltration of the bronchial mucosa with eosinophils and Th2-type cells, circulating speci¢c IgE antibodies and positive skin tests to common aeroallergens, and airway hyperresponsiveness (2).Stimulationof IgE synthesis by B cells andmobilization of eosinophils is believed to be driven by a complex network of cytokines and chemokines, including interleukin-4 (IL-4) and IL-5 (3). Since Rackeman’s clinical classi¢cation of asthma, it has been widely accepted that a subgroup of asthmatic patients are not demonstrably atopicthe ‘‘intrinsic’’ variant of the disease (4). Intrinsic asthmatics show negative skin tests and there is no history of allergy (4,5). Furthermore, serum total IgE concentrations arewithin the normal range and there is no evidence of speci¢c IgE antibodies directed against common allergens (5). These patients are usually older than their allergic counterparts and have onset of symptoms in later life, often with a more severe clinical course (4,5). There is a preponderance of females, and the association of nasal polyps and aspirin sensitivity occursmore frequently in the nonatopic formof the disease (4,5).Whereas some authors suggest that around 10% of asthmatics have the intrinsic form of the disease, the Swiss SAPALDIA survey (8357 adults, 18^60 years old) found that one-third of total asthmatics were nonallergic (intrinsic) (6).