Novel High Resolution Mass Spectrometry Applications for the Study of Lung Diseases

Respiratory Distress Syndrome (RDS) is a respiratory disorder that can affect preterm newborns. It is due to lung immaturity and a deficiency of lung surfactant, a thin lipoprotein layer which allows lung expansion and prevents alveolar collapse during expiration. In these babies, nasal Continuous Positive Airway Pressure (nCPAP) provides non-invasive respiratory support by alveolar recruitment and improves functional residual capacity during spontaneous breathing. In case nCPAP fails, the next step is treatment with exogenous surfactant, which improves gas exchange and survival, reducing the need for mechanical ventilation and then the incidence of chronic lung disease. Although surfactant replacement therapy remains the gold standard for the treatment of RDS, failure rate ranges from 9% to 50%. The possibility of tracing the fate of the administered drug and estimate in vivo the amount of drug reaching the lung could help in improving the therapy and allow the premise to test different delivery systems. RDS is a disorder related to prematurity. Among the factors responsible for premature birth, intrauterine infection (chorioamnionitis) is one of the main causes and it has been reported to have effects on the development of fetal organs. In particular, it has been reported that infants exposed to chorioamnionitis had a reduced risk to develop RDS but an increased risk for chronic lung diseases. Since the function of lung surfactant strictly depends on its composition, a better knowledge on surfactant metabolite and lipid changes would elucidate the effects of the exposition of the foetus to maternal intrauterine infection on RDS. The PhD project focused on 2 objectives: 1. To validate natural abundance stable isotopes approach as a reliable method to quantify the contribution of exogenous surfactant to the alveolar surfactant pool in a rabbit model of RDS treated with a porcine exogenous surfactant; 2. To assess the effect of maternal intrauterine infection on the surfactant composition of newborns affected by RDS by liquid chromatography-mass spectrometry (LC-MS/MS) based metabolomics .