Nasal and bronchial airway reactivity in allergic and non allergic airway inflammation

Sammanfattning: In allergic or asthmatic airways disease, upper and lower airways show a uniform eosinophilic inflammation of the mucosa, and bronchial hyperreactivity is a common finding. To study the co- variation of mucosal reactivity in upper and lower airways, histamine challenges of both sites were performed in a group of patients with allergic rhinitis during non-season. Upper airways were monitored during challenge by the use of rhinostereometry, an optical technique that non-invasively measures nasal mucosa swelling. An increased histamine response was found in both nose and bronchi, and a subgroup of patients with non-specific nasal complaints reacted more strongly to histamine than patients without such problems, indicating that some patients with allergic rhinitis develop a permanent nasal hyperreactivity. By contrast, in patients with nasal polyposis, the nasal mucosa was non-reactive to histamine and thus did not differ from healthy volunteers in that respect, even though asthma and bronchial hyperreactivity was a common finding. Hence, although upper and lower airways mostly seem to react uniformly in allergic or asthmatic airway disease, non-specific reactivity may differ between the two sites. However, airway hyperreactivity was not restricted to the eosinophilic type of inflammation. Also in healthy volunteers exposed to swine dust by weighing pigs for 3 hours in a swine confinement building, a procedure known to induce an intense neutrophilic airway inflammation (organic dust toxic syndrome), both nasal and bronchial histamine reactivity were found to increase. In swine dust induced inflammation, neutrophils were found to rapidly migrate into the upper airways as detected by nasal lavage. Hence, there was reason to believe that the endothelial cells might be activated in this condition, and that endothelial cells, known controllers of leukocyte subset migration, also might influence the induction of airway hyperreactivity. Additional studies on swine dust exposed subjects revealed signs of activation of neutrophil/endothelial cell responses, i.e. changes of soluble adhesion levels, IL-8 and nitrate in peripheral blood. To further elucidate the role of endothelial cells in this type of inflammation, in vitro experiments were performed. Human umbilical vein endothelial cells were cultured and subsequently incubated with a swine dust extract. Cytokine secretion, expression of surface adhesion molecules and neutrophil adherence increased following swine dust stimulation, indicating that this dust directly induces neutrophil/endothelial cell interactions of importance for neutrophil accumulation in the airways.