Asthma is recognized as an inflammatory disease; among children and young adults sensitization to allergens found in houses is the most consistent risk factor for chronic bronchial hyperreactivity. Furthermore, experimental exposure to these allergens can reduce characteristic eosinophil rich inflammation in the lungs. However, the severity of asthma symptoms is influenced by many factors other than allergen exposure. The overall purpose of this project is to study the relationship between exposure to foreign antigens, inflammation and asthma. These studies will use simple markers such as eosinophils in nasal secretions; nasal eosinophil cationic protein (ECP] and expired nitric oxide gas [NO.] as well as analyses of secretions for cells and cytokines to evaluate inflammation. Studies in children will focus on the interaction between exposure to allergens and intercurrent viral infections. In population based studies the relevance of exposure and sensitization to different allergens will be related to symptoms. Children with asthma in Virginia and Atlanta, whose allergen exposure is known, will be followed to identify markers of inflammation and PCR evidence of rhinovirus infection which correlate with increase in symptoms. Among adults with intrinsic asthma, inflammation as judged by sinusitis, eosinophilia, and cytokine production is also characteristic of the disease. However, in most of these cases the etiology of inflammation is not known. Furthermore, adults presenting with asthma do not all have evidence of inflammation. One hundred adults with moderate to severe asthma, 50 presenting to the clinic and 50 presenting to the ER, will be evaluated by lung function; quantitative sinus CT scan; IgE and serology; fungal and bacterial cultures; as well as markers of inflammation. In addition, thirty post-operative sinusitis patients whose maxillary sinuses can be sampled for NO. and secretions, and cultured repeatedly, will be used to the study the metabolism of NO. focussing on the role of nitrosothiols. On the basis of these studies we will identify sources of foreign antigens, e.g. fungi or bacteria that are associated with persistent sinusitis/asthma, and can be targeted for immunochemical and immunological investigation. The objective is to define the factors that contribute to ongoing inflammation and exacerbations of asthma, and to identify aspects of this process that are suitable for antigen specific intervention.
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