Eggenkemper Lisa, Schlegtendal Anne, Maier Christoph, Lücke Thomas, Brinkmann Folke, Beckmann Bibiana, Tsikas Dimitrios, Koerner-Rettberg Cordula
University Children's Hospital, Ruhr-University Bochum, 44791 Bochum, Germany.
Department of Internal Medicine and Gastroenterology, Christophorus-Kliniken Coesfeld, Teaching Hospital of University Münster, 48653 Coesfeld, Germany.
J Clin Med. 2023 Sep 16;12(18):6010. doi: 10.3390/jcm12186010.
Low nasal nitric oxide (nNO) is a typical feature of Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases, such as cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma, and urine using validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, < 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, < 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, = 0.023; nitrate 12.86 vs. 40.33, = 0.008), but higher in CF (nitrite 16.28, < 0.001; nitrate 56.83, = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.
低鼻一氧化氮（nNO）是原发性纤毛运动障碍（PCD）的典型特征。由于nNO对其他肺部疾病（如囊性纤维化（CF））具有鉴别能力，因此它是PCD诊断算法的一部分。然而，其潜在的病理机制尚不清楚。为了更好地理解PCD中NO的失调情况，我们研究了PCD患者（pwPCD）、CF患者（pwCF）和健康对照（HC）受试者的L-精氨酸/NO（Arg/NO）途径。在一项前瞻性对照研究中，我们使用经过验证的方法，测量了24例pwPCD、25例年龄匹配的pwCF和14例HC患者痰液、血浆和尿液中NO前体精氨酸（Arg）和高精氨酸（hArg）、精氨酸酶代谢产物鸟氨酸（Orn）、NO抑制剂不对称二甲基精氨酸（ADMA）以及主要NO代谢产物（硝酸盐、亚硝酸盐）的浓度。与HC相比，PCD患者痰液中L-Arg的含量（以µmol/mg计）（PCD为18.43，CF为329.46，HC为9.86，<0.001）和ADMA的含量（PCD为0.055，CF为0.015，HC为0.010，<0.001）更高。相比之下，与HC相比，PCD患者痰液中硝酸盐和亚硝酸盐的含量（以µmol/mg计）较低（亚硝酸盐为4.54对9.26，=0.023；硝酸盐为12.86对40.33，=0.008），但CF患者痰液中硝酸盐和亚硝酸盐的含量更高（亚硝酸盐为16.28，<0.001；硝酸盐为56.83，=0.002）。所有组尿液和血浆中的代谢产物浓度相似。我们的研究结果表明，与CF不同，PCD与肺部NO合成受损有关，可能是由于机械化学解偶联所致。
