Division of Pediatrics and Neonatal Critical Care, "A.Béclère" Medical Centre, Paris Saclay University Hospitals, APHP, Paris, France.
Neonatology and Pulmonary Rare Disease Unit, Pharmacology & Toxicology Department Corporate Preclinical R&D, Chiesi, Parma, Italy.
J Appl Physiol (1985). 2021 Sep 1;131(3):895-904. doi: 10.1152/japplphysiol.00300.2021. Epub 2021 Jul 22.
Evolving bronchopulmonary dysplasia (BPD) is characterized by impaired alveolarization leading to lung aeration inhomogeneities. Hyperoxia-exposed preterm rabbits have been proposed to mimic evolving BPD; therefore, we aimed to verify if this model has the same lung ultrasound and mechanical features of evolving BPD in human neonates. Semiquantitative lung ultrasound and lung mechanics measurement was performed in 25 preterm rabbits (28 days of gestation) and 25 neonates (mean gestational age ≈ 26 wk) with evolving BPD. A modified rabbit lung ultrasound score (rLUS) and a validated neonatal lung ultrasound score (LUS) were used. Lung ultrasound images were recorded and evaluated by two independent observers blinded to each other's evaluation. Lung ultrasound findings were equally heterogeneous both in rabbits as in human neonates and encompassed all the classical lung ultrasound semiology. Lung ultrasound and histology examination were also performed in 13 term rabbits kept under normoxia as further control and showed the absence of ultrasound and histology abnormalities compared with hyperoxia-exposed preterm rabbits. The interrater absolute agreement for the evaluation of lung ultrasound images in rabbits was very high [ICC: 0.989 (95%CI: 0.975-0.995); < 0.0001], and there was no difference between the two observers. Lung mechanics parameters were similarly altered in both rabbits and human neonates. There were moderately significant correlations between airway resistances and lung ultrasound scores in rabbits ( = 0.519; = 0.008) and in neonates ( = 0.409; = 0.042). In conclusion, the preterm rabbit model fairly reproduces the lung ultrasound and mechanical characteristics of preterm neonates with evolving BPD. We have reported that hyperoxia-exposed preterm rabbits and human preterm neonates with evolving BPD have the same lung ultrasound appearance, and that lung ultrasound can be fruitfully applied on this model with a brief training. The animal model and human neonates also presented the same relationship between semiquantitative ultrasound-assessed lung aeration and airway resistances. In conclusion, this animal model fairly reproduce evolving BPD as it is seen in clinical practice.
进展性支气管肺发育不良(BPD)的特征是肺泡化受损,导致肺通气不均。先前有研究提出,高氧暴露的早产兔可模拟进展性 BPD;因此,我们旨在验证该模型是否与患有进展性 BPD 的人类新生儿具有相同的肺部超声和机械特征。对 25 只早产兔(28 天孕龄)和 25 名患有进展性 BPD 的新生儿(平均胎龄约 26 周)进行半定量肺部超声和肺力学测量。使用改良的兔肺超声评分(rLUS)和经过验证的新生儿肺超声评分(LUS)。记录肺部超声图像并由两位独立的观察者进行评估,观察者彼此之间的评估结果是盲法的。兔和人类新生儿的肺部超声表现同样不均一,包括所有经典的肺部超声半定量特征。还对 13 只在常氧下饲养的足月兔进行了肺部超声和组织学检查,作为进一步的对照,与高氧暴露的早产兔相比,这些兔没有出现超声和组织学异常。兔肺部超声图像评估的观察者间绝对一致性非常高[ICC:0.989(95%CI:0.975-0.995);<0.0001],并且两位观察者之间没有差异。兔和人类新生儿的肺力学参数也同样发生改变。兔( = 0.519; = 0.008)和新生儿( = 0.409; = 0.042)的气道阻力与肺超声评分之间存在中度显著相关性。总之,早产兔模型很好地再现了患有进展性 BPD 的早产儿的肺部超声和力学特征。我们已经报道,高氧暴露的早产兔和患有进展性 BPD 的早产儿的肺部超声表现相同,并且经过短暂的培训后,肺部超声可以成功地应用于该模型。该动物模型和人类新生儿之间的半定量超声评估肺充气与气道阻力之间也存在相同的关系。总之,该动物模型很好地模拟了临床实践中所见的进展性 BPD。