Unravelling the role of Pneumocystis jirovecii in utero infection in early and late pulmonary diseases of very preterm infants.

Descripción del proyecto

Predicción de neumopatías en niños prematuros

«Pneumocystis jirovecii» es un microhongo que causa neumonía grave en personas inmunodeprimidas y que, además, podría afectar hasta al 25 % de los niños prematuros, aumentando así el riesgo de síndrome de dificultad respiratoria y displasia broncopulmonar. El proyecto JIROborn, financiado por las acciones Marie Skłodowska-Curie, tiene por objeto investigar el efecto de «P. jirovecii» en los pulmones de niños prematuros y el posterior desarrollo de enfermedades. Sus investigadores examinarán los parámetros clínicos, las respuestas inmunitarias y la microbiota de una amplia cohorte de niños prematuros. La combinación de estos datos con información genética permitirá crear un modelo de predicción del riesgo de complicaciones pulmonares en niños prematuros.

Objetivo

Very preterm birth represent about 1% of livebirths in Europe each year and is associated with 58% of neonatal deaths and substantial lifetime health problems. Pneumocystis jirovecii is an ubiquitous microfungus commonly known for causing a severe interstitial
pneumonia in immunosuppressed subjects. However, this could be the tip of the iceberg and compelling new evidences suggest that
this infection may be pathogenic to certain groups of infants.
In utero transmission of P. jirovecii in humans has been recently proven. The fungus has been found in the lungs of 14-25%
preterm newborns, associated with an increased risk of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia. The
ability of P. jirovecii to change the pulmonary environment has been demonstrated in other contexts, inducing a modification of the
host immune response, pulmonary dysbiosis and thickening of pulmonary alveoli. Genetic polymorphisms have also been
independently implicated in both an increased risk of preterm bi or neonatal RDS and a susceptibility to P. jirovecii.
Hence, JIROborn aims to address the impact of P. jirovecii in utero infection on the preterm infants’ lungs alteration and on the
development of subsequent early or late diseases, constructing a predictive model for monitoring preterm infants’ related
pulmonary complications.
JIROborn is a nested case control study using a prospective cohort of 596 infected and uninfected preterm infants and their mothers.
First, the clinical impact of P. jirovecii infection will be evaluated for early and later lung complications. Then, biological effects of the
infection will be studied focusing on the immune parameters, the microbiota and on surfactant and mucus production. Genetic and
epigenetic susceptibilities to P. jirovecii colonization and/or to the development of pulmonary diseases will be evaluated. Finally, all
data will be analysed to build a predictive model for the monitoring of preterm infants’ pulmonary complications.