Elmasri Mary, Romero Karina M, Gilman Robert H, Hansel Nadia N, Robinson Colin L, Baumann Lauren M, Cabrera Lilia, Hamilton Robert G, Checkley William
Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, 1800 Orleans Ave Suite 9121, Baltimore, MD, 21205, USA.
Lung. 2014 Apr;192(2):305-12. doi: 10.1007/s00408-013-9551-8. Epub 2014 Jan 12.
Fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker.
We identified 19 children aged 13-15 years at baseline with a significant elevation in FeNO ≥ 80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79 ppb) and normal-to-low FeNO (<40 ppb). Between November 2010 and July 2011, three additional study visits were conducted.
Ninety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5 years of follow-up, mean FeNO levels were 82.6 ppb (standard deviation [SD] = 65.9) for atopic asthmatics, 50.6 ppb (SD = 42.6) for nonasthmatic atopics, 17.0 ppb (SD = 10.8) for nonatopic asthmatics, and 17.8 ppb (SD = 13.9) for nonatopic nonasthmatics (p < 0.001). FeNO levels remained stable: 63 % of the high FeNO group had a FeNO ≥ 80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of <40 across all 4 measurements. The high FeNO group also was found to have an elevation in IL-5 (p = 0.04), IL-6 (p = 0.003), IL-10 (p = 0.002), and total serum IgE (p < 0.001), after adjustment by age, sex, height, body mass index, and atopy and asthma status.
An elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis, clinical symptoms, or corticosteroid use. An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines.
呼出一氧化氮分数（FeNO）已成为哮喘的一项重要生物标志物。越来越多的证据表明特应性是影响对FeNO升高进行解读的一个混杂因素。我们开展了一项纵向研究，以了解FeNO作为一种炎症生物标志物的临床意义。
我们确定了19名13 - 15岁基线时FeNO显著升高（≥80十亿分之一[ppb]）的儿童，并随机选择了一组年龄相仿、FeNO中度升高（40 - 79 ppb）以及FeNO正常至偏低（<40 ppb）的儿童。在2010年11月至2011年7月期间，又进行了三次研究随访。
93名儿童参与了该研究。FeNO高、中、低组分别有16名、24名和53名参与者。在1.5年的随访期间，特应性哮喘患者的平均FeNO水平为82.6 ppb（标准差[SD]=65.9），非哮喘特应性患者为50.6 ppb（SD = 42.6），非特应性哮喘患者为17.0 ppb（SD = 10.8），非特应性非哮喘患者为17.8 ppb（SD = 13.9）（p < 0.001）。FeNO水平保持稳定：高FeNO组63%的患者在所有4次测量中FeNO≥80，正常至偏低FeNO组87%的患者在所有4次测量中FeNO<40。在按年龄、性别、身高、体重指数、特应性和哮喘状态进行调整后，还发现高FeNO组的白细胞介素-5（IL-5）（p = 0.04）、白细胞介素-6（IL-6）（p = 0.003）、白细胞介素-10（IL-10）（p = 0.002）和总血清免疫球蛋白E（IgE）（p < 0.001）升高。
无论哮喘诊断、临床症状或皮质类固醇使用情况如何，FeNO升高似乎表明一种特应性表型。FeNO升高还与炎症细胞因子的全身升高有关。
