呼出气一氧化氮水平与极低／超低出生体重儿支气管肺发育不良的关系

Relationship between fractional exhaled nitric oxide and bronchopulmonary dysplasia in extremely/very low birth weight infants

目的探讨呼出气一氧化氮（fractional exhaled nitric oxide，FeNO）水平与极低／超低出生体重儿支气管肺发育不良（bronchopulmonary dysplasia，BPD）的相关性。方法选择2014年10月至2015年3月，北京大学第三医院新生儿重症监护病房收治的35例以呼吸困难为主诉人院、经诊治存活的出生胎龄〈34周且出生体重〈1500g的极低／超低出生体重儿，其中11例诊断BPD，另24例为非BPD。出院前使用Exhalyzer D肺功能仪检测FeNO水平。采用Fisher精确概率法和独立样本t检验比较BPD组和非BPD组FeNO和一氧化氮产量的差异，绘制受试者工作特性曲线评估FeNO诊断BPD的价值。结果BPD组出生胎龄小于非BPD组[（29．7±1．9）与（32．0±1．5）周，t=4．005，P=0．000]；有创通气时间[（53．0±91．3）与（15．0±30．2）h，t=1．598，P=0．002]和需要氧气吸入时间均长于非BPD组[（42．1±7．8）与（8．2±6．4）d，t=13．567，P=0．000]。BPD组患儿使用肺表面活性物质治疗（10／11）、产前应用激素促肺成熟（11／11）和住院期间应用雾化吸入激素和支气管扩张剂的比例（11／11）高于非BPD组[分别为38％（9／24）、58％（14／24）和21％（5／24）]（Fisher精确概率法，P值均〈0．05）。BPD组检测FeNO的日龄[（46．4±16．3）与（20．9±11．7）d，t=5．278，P=0．000]和体重大于非BPD组[（2090±164）与（1892±153）g，t=3．498，P=0．001]，但校正胎龄相似[（36.3±3．1）与（35．0±2．3）周，t=1．407，P=0．169]。BPD组FeNO水平[（13．6±6．9）与（8．0±3．6）ppb（1ppb=1×10^-9mol／L），t=2．967，P=0．006]和一氧化氮产量[（25．6±10．1）与（18．1±9．0）nl／min，t=2．478，P=0．018]显著高于非BPD组。FeNO诊断BPD的受试者工作特性曲线下面积为O．749（P=0．021），95％CI为0．539～0．953，FeNO对于BPD的诊断具有中等准确性，约登指数最大值为0．477，诊断BPD的FeNO最佳阈值为11．55ppb，灵敏度为72．7％，特异度为75．0％。结论BPD患儿FeNO和一氧化氮产量显著高于非BPD患儿。对极低／超低出生体重儿出院前通过面罩进行FeNO和一氧化氮产量测定，是一项简单、无创的操作，可相对客观地评价生后早期肺功能。

Objective To investigate the relationship between fractional exhaled nitric oxide （FeNO） and bronchopulmonary dysplasia （BPD） in extremely/very low birth weight infant （ELBWI/VLBWI）. Methods Thirty-five ELBWI/VLBWI （gestational age 〈34 weeks at birth and birth weight 〈1 500 g）, who were admitted to neonatal intensive care unit of Peking University Third Hospital from October 2014 to March 2015 with respiratory distress soon after birth, were enrolled into the study, and divided into BPD group （n=l 1） and non-BPD group 1 （n=24） according to the diagnosis at discharge. One day before they left the hospital, FeNO level was determined with Exhalyzer D, an equipment for pulmonary function test. Difference of FeNO and nitric oxide （NO） production between the two groups was compared with t-test or Fisher exact test, and the value of FeNO in predicting BPD was tested by receiver-operating characteristic （ROC） curve. Results The mean gestational age at birth in BPD group was significantly less than that in non-BPD group [（29.7± 1.9） vs （32.0± 1.5） weeks, t=4.005, P=0.000], and the duration of invasive ventilation [（53.0±91.3） vs （15.0±30.2） h, t=1.598, P=0.002] and oxygenation was longer [（42.1±7.8） vs （8.2±6.4） d, t=13.567, P=0.000]. There were more babies required surfactant treatment, prenatal cortisone administration, and inhalation of cortisone and bronchodilator during hospital stay in BPD group than in non-BPD group[10/11 vs 38%（9/24）, 11/11 v s 58%（14/24） and 11/11 vs 21%（5/24）, Fisher exact test, all P〈0.05]. The age and body weight of the babies at the time of FeNO determination in BPD group were older or higher than those in non-BPD group [（46.4± 16.3） vs （20.9±11.7） d, t=5.278, P=0.000; （2 090± 164） vs （1 892±153） g, t=3.498, P=0.001], but the corrected gestational age was similar [（36.3±3.1） vs （35.0±2.3） weeks, t=1.407, P=0.169]. Both the mean FeNO level and NO production in BPD group were significantly higher than those in non-BPD group [（13.6±6.9） vs （8.0±3.6） ppb （1 ppb=1× 10^- mol/L）, （25.6± 10.1） vs （18.1 ±9.0） nl/min, t=2.967 and 2.478, P=0.006 and 0.018]. The area under the ROC curve was 0.749 （P=0.021, 95%CI： 0.539-0.953） which implied that FeNO provided medium power for discrimination of ELBWI/VLBWI with BPD from those without, with a sensitivity of 72.7% and specificity of 75.0% at the cut-off value of 11.55 ppb. Conclusions FeNO and NO production in BPD infants are significantly higher than non-BPD infants. Measurement of FeNO for ELBWI/VLBWI through mask before discharge is a simple, safe and invasive procedure to objectively evaluate pulmonary function early after birth.