Division of Respiratory Disease, Department of Clinical and Biological Sciences, University of Torino, Orbassano (Torino), Italy.
Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):175-82. doi: 10.1177/039463201202500120.
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 < 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.
呼出气一氧化氮（FeNO）与支气管嗜酸性粒细胞增多和轻度稳定型哮喘的气道高反应性（AHR）有关。我们之前在一个大型项目中证明，过敏原暴露能够升高 FeNO 并加重缓激肽引起的 AHR。我们推测，过敏原引起的 FeNO 增加可能与特应性哮喘中气道嗜酸性粒细胞增多和缓激肽引起的 AHR 有关。我们对同一大型项目中先前获得的支气管活检标本进行了新的免疫组织化学分析，以评估在稀释剂和过敏原暴露后 48 小时时粘膜嗜酸性粒细胞（EG-2+细胞）和其他炎症细胞的数量。炎症细胞计数与 FeNO 和 BK 引起的 AHR（以 logPD20 缓激肽表示）有关。在 10 名特应性轻度哮喘患者中，我们发现与稀释剂后相比，支气管粘膜下 EG-2+和 CD4+细胞数量在过敏原后明显增加（p < 0.01）。只有在过敏原刺激后，支气管粘膜下的 EG-2+细胞与 logPD20 缓激肽呈负相关（rho = -0.709，p = 0.027）。我们还发现，在特应性哮喘患者中，在稀释剂（rho = 0.746，p = 0.017）和过敏原（rho = 0.644，p = 0.049）后 48 小时，EG-2+细胞与 FeNO 值之间存在强正相关。只有在过敏原刺激后，FeNO 值与缓激肽的反应性呈负相关（rho = -0.675，p = 0.039）。这项研究表明，在过敏原暴露后，呼出的 NO 水平升高可能反映了气道嗜酸性粒细胞炎症的增加和对缓激肽的气道反应性增加，表明哮喘控制的丧失。
