Lung aeration and gas exchange in preterm infants developing moderate-to-severe bronchopulmonary dysplasia: a multicentre prospective study from the PATH-BPD cohort

Background We lack data about the early evolution of lung pathophysiology in infants developing moderate-to-severe broncho-pulmonary dysplasia (msBPD). We aimed to describe lung aeration and gas exchange during the early phase of msBPD development and identify the critical moments at which they change. Methods Prospective, multicentre, cohort study performed in three European centres enrolling preterm (≤30 weeks' gestation) infants evaluated at 10, 21, 28 days (D) of life and 34 and 36 weeks (W) post-menstrual age, while receiving as little invasive ventilation as possible. Lung aeration was assessed with quantitative lung ultrasound. Pulse oximetry and transcutaneous blood gas measurements were used to calculate the SpO 2 /FiO 2 and PtcO 2 /FiO 2 ratios. msBPD was defined using NIH-2001, NICHD-2018 and Jensen definitions. Findings 347 infants were studied, of which 80, 79 and 89 had msBPD, using the three definitions, respectively. Lung aeration and oxygenation were always poorer, since D10, in patients with msBPD than in those without it. The difference in lung aeration (β ranging from +0.009 (95% CI: 0; 0.01) to +0.012 (95% CI: 0.01; 0.02), depending on the used definition, p < 0.001) and carbon dioxide (β ranging from +0.01 (95% CI: 0; 0.02) to +0.014 (95% CI: 0.01; 0.02), depending on the used definition, p < 0.001) between patients with and without msBPD increased overtime. Results were similar regardless of the BPD definition. The strongest discrimination was obtained by the lung aeration evolution (β(t) = 0.227 (95% CI: 0.152, 0.302), p < 0.001) with a peak at 26 days. Interpretation Patients who develop msBPD consistently demonstrate early and typical pathophysiological phenotypes regardless of the BPD definition. These data highlight critical moments in the development of msBPD and are not captured by currently available BPD definitions. Funding Only institutional funding to support the author's working time was used.