Kim Yoon Hee, Sol In Suk, Yoon Seo Hee, Kim Min Jung, Kim Kyung Won, Sohn Myung Hyun, Kim Kyu-Earn
Department of Pediatrics, Gangnam Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
J Breath Res. 2017 Sep 13;11(4):046003. doi: 10.1088/1752-7163/aa7c1f.
Theoretical non-linear modeling of exhaled nitric oxide has revealed extended flow-independent parameters that could explain where or how nitric oxide is produced in the lung and transferred to the airway gas stream. We aimed to evaluate the associations of bronchial hyperresponsiveness and bronchodilator response with extended flow-independent nitric oxide parameters. Nitric oxide (30, 50, 100, 200 ml s) was measured in 432 children with asthma on the same day with either a methacholine challenge test (n = 156) or spirometry with bronchodilator (n = 276; 96 previously diagnosed with asthma and treated with inhaled corticosteroid, 37 with acute exacerbation treated with systemic corticosteroid). We additionally included 107 healthy controls for evaluation of the suitability of the non-linear model of exhaled nitric oxide. In asthmatic children, the response-dose ratio of the methacholine challenge test was correlated positively with bronchial nitric oxide (JawNO) and airway tissue nitric oxide (CawNO) (r = 0.367 and r = 0.299, respectively; both p < 0.001), while the change in forced expiratory volume in 1 s, representing bronchodilator response, was associated positively with only JawNO (r = 0. 216, p < 0.001). On multiple regression, JawNO, CawNO, and the diffusing capacity of NO (DawNO) were significantly associated with the response-dose ratio. JawNO was significantly associated with change in forced expiratory volume in children with stable asthma but not those with acute exacerbation. Our findings suggest that bronchial hyperresponsiveness is associated with CawNO while factors other than airway tissue inflammation could affect bronchodilator response in children with mild asthma. Systemic corticosteroid use during asthma exacerbation could affect the association of bronchodilator response with extended nitric oxide parameters.
呼出一氧化氮的理论非线性模型揭示了一些与流量无关的扩展参数，这些参数可以解释一氧化氮在肺部的产生位置或方式以及如何转移到气道气流中。我们旨在评估支气管高反应性和支气管扩张剂反应与扩展的与流量无关的一氧化氮参数之间的关联。在同一天，对432名哮喘儿童进行了一氧化氮（30、50、100、200 ml/s）测量，其中156名儿童进行了乙酰甲胆碱激发试验，276名儿童进行了支气管扩张剂肺量计检查（96名先前诊断为哮喘并接受吸入性糖皮质激素治疗，37名急性加重期接受全身性糖皮质激素治疗）。我们还纳入了107名健康对照者，以评估呼出一氧化氮非线性模型的适用性。在哮喘儿童中，乙酰甲胆碱激发试验的反应剂量比与支气管一氧化氮（JawNO）和气道组织一氧化氮（CawNO）呈正相关（分别为r = 0.367和r = 0.299；均p < 0.001），而代表支气管扩张剂反应的1秒用力呼气量变化仅与JawNO呈正相关（r = 0.216，p < 0.001）。在多元回归分析中，JawNO、CawNO和一氧化氮弥散能力（DawNO）与反应剂量比显著相关。JawNO与稳定期哮喘儿童的1秒用力呼气量变化显著相关，但与急性加重期儿童无关。我们的研究结果表明，支气管高反应性与CawNO相关，而气道组织炎症以外的因素可能影响轻度哮喘儿童的支气管扩张剂反应。哮喘加重期使用全身性糖皮质激素可能会影响支气管扩张剂反应与扩展的一氧化氮参数之间的关联。
