哮喘患者气道不同部位诱导型一氧化氮合酶基因表达的比较及与一氧化氮参数的关系
2019/05/10
摘要
背景：呼出一氧化氮分数浓度（FENO）广泛应用于支气管哮喘（BA）的诊断和监测。Tsoukias和George提出了一个两室模型（2CM），用于评估NO的肺泡浓度，称为CANO（2cm），而Condorelli等人提出了一个基于气道树的喇叭形状和轴向扩散（TMAD）的模型，称为CANO（TMAD）。此外，Högman等人提出了非线性模型，称为CANO（非线性）。
目的：通过支气管镜检查测定气道细胞（ACs）中诱导型一氧化氮合酶（iNOS）mRNA的表达与通过三种方法非参数计算所得结果之间的关系，确定哪种方法能准确反映不同气道部位的iNOS的表达。
方法：回顾性分析18例稳定期轻中度哮喘患者的资料，其中10例为无激素治疗哮喘（snBA）。样本来自气道刷洗和支气管肺泡灌洗（BAL）。用免疫染色法检测组织样品中iNOS蛋白的表达。用qPCR测定ACs的iNOS mRNA。上述三种方法通过非参数计算，评估其是否与来自近端（2级隆突）、远端（10-15级）气道和肺泡区的ACs的iNOS mRNA相关。
结果：免疫染色显示iNOS蛋白主要在气道上皮细胞表达，同时在snBA组肺泡区的巨噬细胞上高表达。相较于激素治疗组（stBA），无激素治疗组哮喘患者iNOS mRNA在近端及远端气道上皮细胞均表达增加。CANO（2CM）与FEV1（%预测值）呈负相关，也与气道远端ACs的iNOS mRNA显著相关。然而，CANO（TMAD）和CANO（非线性）与肺功能及气道任何部位的ACs中iNOS的mRNA表达均无相关性。
结论：这些结果提示CANO（2CM）反映了无激素治疗哮喘患者的气道远端炎症。
Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma.
Sato Y, Chibana K, Horigane Y, Uchida N, Masawa M, Koike R, Nakamura Y, Watanabe T, Shiobara T, Arai R, Shimizu Y, Takemasa A, Ishii Y.
Abstract
BACKGROUND: 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).
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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 FEV1 (%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.
CONCLUSIONS: These results suggested that CANO(2CM) reflected distal airway inflammation in steroid-naive asthma.
背景：呼出一氧化氮分数浓度（FENO）广泛应用于支气管哮喘（BA）的诊断和监测。Tsoukias和George提出了一个两室模型（2CM），用于评估NO的肺泡浓度，称为CANO（2cm），而Condorelli等人提出了一个基于气道树的喇叭形状和轴向扩散（TMAD）的模型，称为CANO（TMAD）。此外，Högman等人提出了非线性模型，称为CANO（非线性）。
目的：通过支气管镜检查测定气道细胞（ACs）中诱导型一氧化氮合酶（iNOS）mRNA的表达与通过三种方法非参数计算所得结果之间的关系，确定哪种方法能准确反映不同气道部位的iNOS的表达。
方法：回顾性分析18例稳定期轻中度哮喘患者的资料，其中10例为无激素治疗哮喘（snBA）。样本来自气道刷洗和支气管肺泡灌洗（BAL）。用免疫染色法检测组织样品中iNOS蛋白的表达。用qPCR测定ACs的iNOS mRNA。上述三种方法通过非参数计算，评估其是否与来自近端（2级隆突）、远端（10-15级）气道和肺泡区的ACs的iNOS mRNA相关。
结果：免疫染色显示iNOS蛋白主要在气道上皮细胞表达，同时在snBA组肺泡区的巨噬细胞上高表达。相较于激素治疗组（stBA），无激素治疗组哮喘患者iNOS mRNA在近端及远端气道上皮细胞均表达增加。CANO（2CM）与FEV1（%预测值）呈负相关，也与气道远端ACs的iNOS mRNA显著相关。然而，CANO（TMAD）和CANO（非线性）与肺功能及气道任何部位的ACs中iNOS的mRNA表达均无相关性。
结论：这些结果提示CANO（2CM）反映了无激素治疗哮喘患者的气道远端炎症。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Clin Exp Allergy. 2019 Jan 22. doi: 10.1111/cea.13344.)
(Clin Exp Allergy. 2019 Jan 22. doi: 10.1111/cea.13344.)
Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma.
Sato Y, Chibana K, Horigane Y, Uchida N, Masawa M, Koike R, Nakamura Y, Watanabe T, Shiobara T, Arai R, Shimizu Y, Takemasa A, Ishii Y.
Abstract
BACKGROUND: 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).
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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 FEV1 (%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.
CONCLUSIONS: These results suggested that CANO(2CM) reflected distal airway inflammation in steroid-naive asthma.
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