Lucca Francesca, Da Dalt Liviana, Ros Mirco, Gucciardi Antonina, Pirillo Paola, Naturale Mauro, Perilongo Giorgio, Giordano Giuseppe, Baraldi Eugenio
Women's and Children's Health Department, University of Padova, Padova, Italy.
Cystic Fibrosis Unit, Pediatric Department, Treviso Hospital, Treviso, Italy.
Clin Respir J. 2018 Jan;12(1):140-148. doi: 10.1111/crj.12502. Epub 2016 Jun 20.
Asymmetric dimethylarginine (ADMA) competitively inhibits nitric oxide synthase (NOS). Its levels in specimens from murine models and asthmatic patients are related to inflammation and oxidative stress. Patients with cystic fibrosis(CF) reportedly have higher arginase activity, lower NO production and NOS expression than healthy controls.
The objective was to assess the role of ADMA and related metabolites as disease biomarkers in exhaled breath condensate (EBC) of pediatric CF patients, compared with age-matched healthy controls (HC).
A longitudinal design was conceived and 34 CF patients (21 stable, 13 at the onset of exacerbation) and 16 HC were enrolled. All CF patients underwent clinical examination, spirometry and EBC collection at enrolment; the same tests were performed also after an antibiotic course in those patients with exacerbation. Metabolites levels in EBC were measured with an ultra-performance liquid chromatography and tandem mass spectrometry technique.
All CF patients had ADMA levels (expressed as ratio to tyrosine) similar to those in HC (median 0.0112, IQR 0.0103-0.0120 and median 0.0114, IQR 0.0090-0.0128, respectively; P = 0.983), while a significant increase in the citrulline/tyrosine ratio was found in CF patients (median 0.6419, IQR 0.5738-0.6899 in CF vs median 0.4176, IQR 0.2986-0.5082 in HC; P = 0.00003). No differences in ADMA levels emerged between stable patients and those with exacerbation.
ADMA and related aminoacids were measured simultaneously for the first time in EBC from CF patients. Higher citrulline/tyrosine ratios were found in CF children with normal ADMA levels, suggesting a dysregulated ADMA metabolism in these patients.
不对称二甲基精氨酸（ADMA）竞争性抑制一氧化氮合酶（NOS）。在小鼠模型和哮喘患者的样本中，其水平与炎症和氧化应激有关。据报道，囊性纤维化（CF）患者的精氨酸酶活性较高，一氧化氮生成量和NOS表达低于健康对照。
与年龄匹配的健康对照（HC）相比，评估ADMA及相关代谢产物作为小儿CF患者呼出气冷凝液（EBC）中疾病生物标志物的作用。
采用纵向设计，纳入34例CF患者（21例病情稳定，13例病情加重期）和16例HC。所有CF患者在入组时均接受临床检查、肺功能测定和EBC采集；病情加重的患者在接受抗生素治疗后也进行同样的检查。采用超高效液相色谱和串联质谱技术测定EBC中的代谢产物水平。
所有CF患者的ADMA水平（以与酪氨酸的比值表示）与HC相似（中位数分别为0.0112，四分位数间距0.0103 - 0.0120和中位数0.0114，四分位数间距0.0090 - 0.0128；P = 0.983），而CF患者的瓜氨酸/酪氨酸比值显著升高（CF患者中位数为0.6419，四分位数间距0.5738 - 0.6899，HC患者中位数为0.4176，四分位数间距0.2986 - 0.5082；P = 0.00003）。稳定患者和病情加重患者之间的ADMA水平无差异。
首次同时测定了CF患者EBC中的ADMA及相关氨基酸。ADMA水平正常的CF儿童中瓜氨酸/酪氨酸比值较高，提示这些患者的ADMA代谢失调。
