To the Editor:
With interest we have read the letter by Lau等。[[1]关于在澳大利亚童年预防哮喘研究中循环不对称二甲基精氨酸(ADMA)。
ADMA, a product of protein degradation, is an endogenous nitric oxide synthase inhibitor that has been shown to be increased in mouse models of allergic airway inflammation and to be associated with airways hyperresponsiveness in these animals [2]。据报道,ADMA在痰样品中增加了[2] and exhaled breath condensates [3] from paediatric patients with asthma. Increased ADMA in serum has recently been found to be associated with the severity of symptoms in late-onset asthma and obesity [4]。
Lau等。[[1] found no difference in serum ADMA between clinically stable children with or without wheezing in the previous 12 months in their cohort of 8-year-old children. However, there was also no difference in post-bronchodilator spirometry (forced vital capacity (FVC) or the per cent predicted (% pred) forced expiratory volume in 1 s (FEV1)或FEV1/fvc)两组之间,也没有证据表明呼出的一氧化氮部分增加(F埃诺) in current asthma, as the meanF埃诺, although statistically different, was well within the normal range and very similar between the groups (mean±sd8.9±9.3相对11.1±7.7 ppb)。血清ADMA与(对数转换)无关F埃诺。
关于结果与以前报告之间差异的一种解释可能是l- 轻度哮喘和正常肺功能的稳定患者的血液中,气道中的精氨酸/一氧化氮稳态可能不会改变。该论点与H的发现一致olguin等。[[4], who reported that ADMA levels in peripheral plasma samples from patients with severe, late-onset asthma correlated with worsening of the FEV1%PREP,FVC%PREP和症状评分。这些数据和严重哮喘的成年人的数据[5]表明,循环ADMA的变化与特定定义明确的表型特征有关,这些特征可能与温和的疾病表型表现出来。
我们想提供其他支持证据,证明ADMA在气道反应性中的潜在作用:我们从10名患有轻度,嗜酸性嗜酸性哮喘的成年受试者(5名男性,5名雌性;中位女性; 36岁,范围18-61岁)获得了诱导的示例样品。;正常基线FEV1of 100.4±4.7% pred) at baseline and 7 and 24 hours following a controlled inhaled allergen challenge, as previously described [6,7]。在过敏原挑战后,在7和24小时时,基线痰嗜酸性粒细胞(1.6±0.9%)增加到7.6±3.1%和12.5±6.0%(弗里德曼测试p <0.05)。痰中的中性粒细胞计数为基线时为39.0±6.4%(最大69%)。肺功能测试的变化与气道高反应性和气流限制一致(i.e.reduction in the provocative concentration causing a 20% fall in FEV1(PC20),FEV下降1在这些受试者中观察到百分比),挑战后痰ADMA显着增加(通过重复测量方差分析的p <0.05)(p <0.05)(p <0.05)(fig. 1)。因此,在这些患有轻度过敏性哮喘的成年受试者中,在过敏原挑战后,一氧化氮合酶抑制剂ADMA的浓度显着增加,这与气道阻塞的发作伴随着。这些数据表明,ADMA参与哮喘反应,并且气道中ADMA的变化发生在急性加重中。看到哪些未来的研究比较不同隔室之间生物标志物的实用性的研究将告诉我们ADMA在哮喘中的作用。
脚注
Conflict of interest: None declared.
- 已收到2013年5月8日。
- AcceptedMay 17, 2013.
- ©ERS 2014