Efectos en el desarrollo pulmonar de la oclusión traqueal precoz como terapia fetal de la hipoplasia pulmonar en la hernia diafragmática congénita del feto ovino

Abstract

Introduction:_x000D_ _x000D_ Fetal tracheal occlusion by the endoscopic introduction of an endotracheal balloon at 26 – 29 weeks of gestation represents the standard of care of patients suffering from severe congenital diaphragmatic hernia (CDH) diagnosed prenatally. However, some patients present prenatal indicators of extreme pulmonary hypoplasia and the survival rate, despite the standard fetoscopic treatment, approaches the 0%. Clinical reports advocate for an early tracheal occlusion, in an early pulmonary developmental stage, to allow the lungs to grow more and be adequate for a better gas exchange after birth. The aim of the present study is to evaluate the anatomical, morphological and morphometrical effects of an early tracheal occlusion of the lungs in lambs with CDH and to compare them among those with standard tracheal occlusion and those with normal lungs. _x000D_ _x000D_ Methods:_x000D_ _x000D_ 24 at term fetal lambs were analyzed after distribution in groups of 4 members each: normal lung line: A) Sham; B) Late tracheal occlusion (LTO); C) Early tracheal occlusion (ETO). Line with lungs with CDH created at 65 days of gestation (DOG): D) CDH; E) CDH + LTO; F) CDH + ETO. LTO was created at 105 DOG and ETO at 85 DOG. C-section was carried out at term (130-145 DOG) and lungs and intrapulmonary fluid, among other samples, were extracted. Lungs were preserved by tracheal infusion of formaldehyde and fixed in paraffin. Histologic sections were obtained from the peripheral areas of the left lower lobe. Anatomical, volumetric, histologic morphology and morphometric parameters were used as study variables. Results were statistically analyzed by the following tests: Kruskal-Wallis for comparison among lines and U-Mann-Whitney test for comparison between two groups. Morphometric variables were analyzed by lineal regression model. _x000D_ _x000D_ Results:_x000D_ _x000D_ Presence of CDH caused less pulmonary volume, with less parenchyma and intra-pulmonary fluid compared to normal lungs. Tracheal occlusion increased the size of the lungs, parenchyma, intrapulmonary fluid and air space in both lines, with or without CDH. These parameters were also higher in the ETO compared with LTO. Histology showed a bigger size of the alveoli and alveolar surface proportional to the time of occlusion (LTO or ETO) in both lines of the study. Interstitial tissue by field diminished proportionally with the time of tracheal occlusion. In CDH groups, tracheal occlusion improved maturation in relation with controls. Pneumocyte II population was decreased related to the time of tracheal occlusion._x000D_ _x000D_ Conclusion:_x000D_ _x000D_ Tracheal occlusion increases the size of the air space and pulmonary parenchyma, improving the maturation state, proportionally to the time of occlusion in the animals with CDH. Human patients with extreme pulmonary hypoplasia due to CDH could beneficiate from an early fetoscopic tracheal occlusion, in early stages of pulmonary development, followed by an elective dis-occlusion to improve the pneumocyte II population and optimize the conditions for a sufficient gas exchange after birth.

Date of Award	18 Jul 2017
Original language	Spanish
Awarding Institution	Vall d'Hebron University Hospital (HUVH)
Supervisor	Eloy Espin-Basany (Director) & Mario Marotta Baleriola (Director)