Abstract
Ethical restrictions are limitations of in vivo inhalation studies, on humans and animal models. Thus, in vitro or ex vivo anatomical models offer an interesting alternative if limitations are clearly identified and if extrapolation to human is made with caution. This work aimed to develop an ex vivo infant-like respiratory model of bronchopulmonary dysplasia easy to use, reliable and relevant compared to in vivo infant data. This model is composed of a 3D-printed head connected to a sealed enclosure containing a leporine thorax. Physiological data and pleural-mimicking depressions were measured for chosen respiratory rates. Homogeneity of ventilation was assessed by 81mkrypton scintigraphies. Regional radioaerosol deposition was quantified with 99mtechnetium-diethylene triamine pentaacetic acid after jet nebulization. Tidal volumes values are ranged from 33.16 ± 7.37 to 37.44 ± 7.43 mL and compliance values from 1.78 ± 0.65 to 1.85 ± 0.99 mL/cmH2O. Ventilation scintigraphies showed a homogenous ventilation with asymmetric repartition: 56.94% ± 9.4% in right lung and 42.83% ± 9.36 in left lung. Regional aerosol deposition in lungs exerted 2.60% ± 2.24% of initial load of radioactivity. To conclude the anatomical model satisfactorily mimic a 3-months old BPD-suffering bronchopulmonary dysplasia and can be an interesting tool for aerosol regional deposition studies.
Highlights
Bronchopulmonary dysplasia (BPD) is one of the most common pathology of pre-term newborns[1,2,3,4]
Based on previous work of our laboratory[34,35], this chimeric model is composed of a 3D-printed upper airways replica of the Sophia Anatomical Infant Nose-Throat (SAINT) model connected to an ex vivo leporine respiratory thorax placed in a sealed instrumented enclosure designed for that purpose
Objectives of this work were to validate the likelihood of this innovative ex vivo respiratory model in comparison with infants’ respiratory physiology and existing alternative animal models used in literature
Summary
Bronchopulmonary dysplasia (BPD) is one of the most common pathology of pre-term newborns[1,2,3,4]. Inhaled corticotherapy could be use as a prophylactic treatment on very low birth weight preterms but failed to show significant efficacy[15,16] and as a symptomatic treatment[17] These approaches are known to impair neurologic development of newborn[18] and infants and to increase relative risk associated to death for extremely preterm newborns[19]. In vivo human studies of regional deposition assessed by radiolabeled aerosols are focused mainly on adults, infant/newborn features are addressed by mathematical modeling[30]. A greater pulmonary dose could be administered to infants due to architecture of airways, lung surface area or breathing pattern[33] This lack of data concerning inhalation studies focused on infants requires relevant and reliable respiratory models to perform inhalation studies. This study is divided into 3 main parts: i) breathing pattern and respiratory parameters, ii) assessment of ventilation and iii) regional aerosol deposition within respiratory tract
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