Global and regional heterogeneity of lung aeration in neonates with different respiratory disorders: a physiological, observational study

Background.: Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). We hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support.

Methods.: Observational, prospective study. Neonates with respiratory distress syndrome (RDS), transient tachypnea (TTN), evolving bronchopulmonary dysplasia (BPD) and neonatal ARDS (NARDS) were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and inter-patient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes.

Results.: 230 (50 RDS, TTN or evolving BPD and 80 NARDS) patients were studied. Intra-patient aeration heterogeneity was higher in TTN (mean: 61% [standard deviation: 33%]) and evolving BPD (mean: 57% [standard deviation: 20%], p<0.001), with distinctive aeration distributions. Inter-patient aeration heterogeneity was high for all disorders (Gini-Simpson index: between 0.6 and 0.72) except RDS (Gini-Simpson index: 0.5) whose heterogeneity was significantly lower than all others (p<0.001). NARDS and evolving BPD had the most diffuse injury and worst gas exchange metrics. Regional aeration heterogeneity was mostly localized in upper anterior and posterior zones. Aeration heterogeneity and total lung aeration had an exponential relationship (p<0.001; adj-R 2=0.62). Aeration heterogeneity is associated with greater total lung aeration (i.e., higher heterogeneity means a relatively higher proportion of normally aerated lung zones, thus greater aeration; p<0.001; adj-R 2=0.83) and better oxygenation metrics upon multivariable analyses.

Conclusions.: Global aeration heterogeneity and regional aeration heterogeneity differ amongst neonatal respiratory disorders. TTN and evolving BPD have the highest intra-patient aeration heterogeneity. TTN, evolving BPD and NARDS have the highest inter-patient aeration heterogeneity, but the latter two have the most diffuse injury and worst gas exchange. Higher aeration heterogeneity is associated with better total lung aeration and oxygenation.