title: Exhaled nitric oxide is related to bronchial eosinophilia and airway hyperresponsiveness to bradykinin in allergen-induced asthma exacerbation.
abstract: Exhaled nitric oxide (FeNO) has been associated with bronchial eosinophilia  and with airway hyperresponsiveness  (AHR) in mild stable asthma. We previously demonstrated in a large  project that allergen exposure is able to raise FeNO and to worsen AHR to bradykinin. We postulated that allergen-induced increase in FeNO could be related to heightened mucosal eosinophils and AHR to bradykinin in atopic asthma. We performed a new immunohistochemical analysis on bronchial biopsy specimens, previously obtained from the same large project, in order to assess the number of mucosal eosinophils (EG-2+ cell) and other inflammatory cells at 48 hours after diluent and allergen exposures. Inflammatory cell counts were related to FeNO and AHR to BK (expressed as logPD20 bradykinin). In 10 atopic mild asthmatics, we found that the numbers of EG-2+ and CD4+ cells in bronchial submucosa were significantly increased after allergen compared to the respective counts after diluent (p &#x003C; 0.01). EG-2+ cells in the bronchial submucosa were negatively correlated with logPD20 bradykinin only after allergen challenge (rho = -0.709, p = 0.027). We also found a positive strong correlation between EG-2+ cells and FeNO values in atopic asthmatics at 48 hours after both diluent (rho = 0.746, p = 0.017) and allergen (rho = 0.644, p = 0.049) challenge. FeNO values negatively correlated with responsiveness to bradykinin only after allergen challenge (rho = -0.675, p = 0.039). This study indicates that after allergen exposure heightened level of exhaled NO may reflect augmented airway eosinophilic inflammation and  airway responsiveness to bradykinin indicating loss of asthma control.
authors.affiliation: Division of Respiratory Disease, Department of Clinical and Biological Sciences, University of Torino, Orbassano (Torino), Italy. fabioluigimassimo.ricciardolo@unito.it
authors.forename: F L M
authors.initials: FL
authors.lastname: Ricciardolo
authors.forename: A
authors.initials: A
authors.lastname: Di Stefano
authors.forename: M
authors.initials: M
authors.lastname: Silvestri
authors.forename: A M
authors.initials: AM
authors.lastname: Van Schadewijk
authors.forename: M
authors.initials: M
authors.lastname: Malerba
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D001944:Breath Tests; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D018592:Cross-Over Studies; D047091:Eosinophil Granule Proteins / Q000032:analysis; D004802:Eosinophilia / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D000485:Allergens; D047091:Eosinophil Granule Proteins; D009569:Nitric Oxide; D001920:Bradykinin