Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibumachi, Tochigi, Japan.
Tomishiro Central Hospital, Tomishiro, Okinawa, Japan.
Clin Exp Allergy. 2019 May;49(5):582-590. doi: 10.1111/cea.13344. Epub 2019 Feb 15.
Fractional exhaled nitric oxide concentration (FeNO) is widely used to support diagnosis and monitoring of bronchial asthma (BA). Tsoukias and George proposed a two-compartment model (2CM) for assessing the alveolar concentration of NO, referred to as CANO(2CM), while Condorelli et al proposed a model based on the trumpet shape of the airway tree and axial diffusion (TMAD), referred to as CANO(TMAD). In addition, Högman et al proposed non-linear model, referred to as CANO(non-linear).
We examined associations between the expression of inducible nitric oxide synthase (iNOS) mRNA in airway cells (ACs) by bronchoscopy and NO-parameters calculated by the three methods and identified which of them accurately reflected expression of iNOS mRNA from different airway portions.
We retrospectively analysed data of 18 patients with stable, mild-moderate asthma, including 10 steroid-naïve BA (snBA) patients. Samples were obtained from airway brushings and bronchoalveolar lavage (BAL). Expressions of iNOS protein in tissue samples were evaluated by immunostaining. The iNOS mRNA in ACs was measured by qPCR. NO-parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA in ACs derived from proximal (2nd carina), distal (10-15th) airways and alveolar regions.
Immunostaining revealed expression of iNOS proteins mainly in epithelial cells in the airways, while it was mainly expressed in macrophages in the alveolar region in the snBA group. The iNOS mRNA expression was increased in both proximal and distal ACs in the snBA group compared with steroid-treated BA group (stBA). CANO(2CM) negatively associated with FEV (%predicted) and also associated with iNOS mRNA in distal ACs significantly. However, CANO(TMAD) and CANO(non-linear) showed no correlation with lung function nor iNOS mRNA expression in any portions of ACs.
These results suggested that CANO(2CM) reflected distal airway inflammation in steroid-naïve asthma.
呼出气一氧化氮浓度（FeNO）广泛用于支持支气管哮喘（BA）的诊断和监测。Tsoukias 和 George 提出了一种用于评估肺泡中 NO 浓度的双室模型（2CM），称为 CANO（2CM），而 Condorelli 等人提出了一种基于气道树 trumpet 形状和轴向扩散的模型（TMAD），称为 CANO（TMAD）。此外，Högman 等人提出了一种非线性模型，称为 CANO（非线性）。
我们通过支气管镜检查检查气道细胞（AC）中诱导型一氧化氮合酶（iNOS）mRNA 的表达与三种方法计算的 NO 参数之间的关联，并确定它们中的哪一种能准确反映来自不同气道部位的 iNOS mRNA 的表达。
我们回顾性分析了 18 例稳定、轻度至中度哮喘患者的数据，包括 10 例未接受类固醇治疗的哮喘（snBA）患者。通过气道刷检和支气管肺泡灌洗（BAL）获得样本。通过免疫染色评估组织样本中 iNOS 蛋白的表达。通过 qPCR 测量 AC 中的 iNOS mRNA。通过上述三种方法计算 NO 参数，并评估它们是否与来自近端（第 2 气管隆突）、远端（第 10-15 气管隆突）气道和肺泡区域的 AC 中的 iNOS mRNA 相关。
免疫染色显示 iNOS 蛋白主要在气道上皮细胞中表达，而在 snBA 组中，肺泡区域中的巨噬细胞主要表达 iNOS。与接受类固醇治疗的哮喘组（stBA）相比，snBA 组中近端和远端 AC 中的 iNOS mRNA 表达均增加。CANO（2CM）与 FEV（%预测值）呈负相关，与远端 AC 中的 iNOS mRNA 也有显著相关性。然而，CANO（TMAD）和 CANO（非线性）与任何 AC 部位的肺功能或 iNOS mRNA 表达均无相关性。
这些结果表明，CANO（2CM）反映了类固醇-naïve 哮喘中的远端气道炎症。
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