Respiratory Medicine and Allergology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
National Heart & Lung Institute, Imperial College, London, UK.
Allergy. 2017 Apr;72(4):627-635. doi: 10.1111/all.13052. Epub 2016 Oct 14.
Increased exhaled nitric oxide (NO) levels in asthma are suggested to be through inducible NO synthase (iNOS). The aim of this study was to investigate the expression of iNOS in bronchoalveolar lavage (BAL) cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in patients with asthma vs a control group.
Thirty-two patients with asthma (defined as controlled or uncontrolled according to Asthma Control Test score cut-off: 20) and eight healthy controls were included. Exhaled NO was measured, and alveolar concentration and bronchial flux were calculated. iNOS was measured in central and peripheral lung biopsies, as well as BAL cells. Bronchoalveolar lavage macrophages were stimulated in vitro, and iNOS expression and NO production were investigated.
Expression of iNOS was increased in central airway tissue and the alveolar compartment in uncontrolled as compared to controlled asthmatics and healthy controls. There were no differences, however, in iNOS mRNA levels in total BAL cells in uncontrolled as compared to controlled asthma. Bronchoalveolar lavage cell mRNA levels of iNOS or iNOS expression in central and alveolar tissue did not relate to alveolar NO, nor to bronchial flux of NO. In vitro stimulation with leukotriene D increased iNOS mRNA levels and NO production in cultured BAL macrophages.
The levels of both bronchial and alveolar iNOS are increased in uncontrolled as compared to controlled asthma. However, levels of iNOS in BAL macrophages were not reflected by alveolar NO. Both central and distal iNOS levels may reflect responsiveness to steroid treatment.
哮喘患者呼出的一氧化氮（NO）水平升高被认为是诱导型一氧化氮合酶（iNOS）的作用。本研究旨在研究诱导型一氧化氮合酶在支气管肺泡灌洗液（BAL）细胞和中央及外周气道组织中的表达，并将其与哮喘患者与对照组的呼气支气管和肺泡 NO 水平进行比较。
纳入 32 例哮喘患者（根据哮喘控制测试评分的截止值定义为控制或未控制：20）和 8 例健康对照者。测量呼气一氧化氮，计算肺泡浓度和支气管通量。测量中央和外周肺活检以及 BAL 细胞中的 iNOS。体外刺激支气管肺泡灌洗中的巨噬细胞，研究 iNOS 表达和 NO 生成。
与健康对照组和控制组相比，未控制组的中央气道组织和肺泡部位 iNOS 的表达增加。然而，与控制组相比，未控制组的 BAL 细胞总 iNOS mRNA 水平并无差异。BAL 细胞中 iNOS 或中央和肺泡组织中 iNOS 表达的 mRNA 水平与肺泡 NO 或 NO 的支气管通量均无相关性。白细胞三烯 D 的体外刺激增加了培养的 BAL 巨噬细胞中的 iNOS mRNA 水平和 NO 生成。
与控制组相比，未控制组的支气管和肺泡 iNOS 水平均升高。然而，肺泡 NO 并未反映 BAL 巨噬细胞中的 iNOS 水平。中央和远端的 iNOS 水平可能反映对类固醇治疗的反应性。
