Precision Medicine in Neonates: Future Perspectives for the Lung

Abstract

Bronchopulmonary dysplasia (BPD) is the most common complication of pre-term birth with long lasting sequelae. Since its first description more than 50 years ago, many large randomized controlled trials have been conducted, aiming to improve evidence-based knowledge on the optimal strategies to prevent and treat BPD. However, most of these intervention studies have been performed on a population level without regard for the variation in clinical and biological diversity (e.g., gestational age, ethnicity, gender, or disease progression) between patients that is driven by the complex interaction of genetic pre-disposition and environmental exposures. Nevertheless, clinicians provide daily care such as lung protective interventions on an individual basis every day despite the fact that research supporting individualized or precision medicine for monitoring or treating pre-term lungs is immature. This narrative review summarizes four potential developments in pulmonary research that might facilitate the process of individualizing lung protective interventions to prevent development of BPD. Electrical impedance tomography and electromyography of the diaphragm are bedside monitoring tools to assess regional changes in lung volume and ventilation and spontaneous breathing effort, respectively. These non-invasive tools allow a more individualized optimization of invasive and non-invasive respiratory support. Investigation of the genomic variation in caffeine metabolism in pre-term infants can be used to optimize and individualize caffeine dosing regimens. Finally, volatile organic compound analysis in exhaled breath might accurately predict BPD at an early stage of the disease, enabling clinicians to initiate preventive strategies for BPD on an individual basis. Before these suggested diagnostic or monitoring tools can be implemented in daily practice and improve individualized patient care, future research should address and overcome their technical difficulties, perform extensive external validation and show their additional value in preventing BPD.

Keywords: individualized medicine; neonatal intensive care; newborn; personalized medicine; targeted treatment.

Figure 1

Lung recruitment visualized by Electric Impedance Tomography. Change in functional electrical impedance tomography in end expiratory lung impedance during an oxygenation guided lung recruitment procedure in a high frequency ventilated pre-term infant (945 grams). The impedance changes are referenced to the starting pressure of 8 cm H₂O. Row (A) shows the inflation and row (B) the deflation limb of the recruitment procedure (39). All images have the same scale where red indicates a large change and blue a small change in impedance.

Figure 2

Effect of caffeine on the amplitude of the diaphragm measured by electromyography. The transcutaneous electromyographic (EMG) analysis of the diaphragm showed a significant increase in logarithm of the EMG Activity Ratio (logEMGAR) after a loading dose caffeine, compared to baseline. The logEMGAR described the relative changes in EMG activity, either increasing or decreasing symmetrical around unity.

Figure 3

Study design for developing BPD specific eNose. Volatile organic compounds (VOCs) are absorbed onto a stainless-steel tube containing Tenax GR 60/80 (Interscience, Breda, The Netherlands) for 5 min at a flow rate of 50 ml/min. The captured VOCs in the tubes are released by re-heating the tubes after which the fragment ions are detected using a quadrupole mass spectrometer (GCMS-GP2010; Shimadzu, Den Bosch, The Netherlands) with a scan range of 37–300 Da. Ion fragment peaks were used for statistical analysis. GC-MS analysis will be performed in all infants.