Non-invasive respiratory support is nowadays a mainstay of treatment in neonates with respiratory failure. Established treatment options such as nasal continuous positive airway pressure (CPAP) have been refined over the years. More innovative strategies of non-invasive respiratory support are evolving, but quite often there is a paucity of evidence to support their use. The present habilitation thesis applied different methodologies to address specific research questions relating to the efficacy and safety of these new approaches. In a meta-analysis of randomized controlled trials, we showed that non-invasive respiratory support strategies to avoid endotracheal mechanical ventilation reduced the incidence of death or bronchopulmonary dysplasia without increasing intraventricular hemorrhage in preterm infants of <30 weeks’ gestational age. In a clinical crossover study, we investigated the impact of experimental leak reduction in 32 neonates on nasopharyngeal CPAP but detected only minor beneficial effects on oxygenation. In an international survey, we gained insights about the current clinical use of nasal high-frequency oscillatory ventilation (nHFOV) in tertiary neonatal units. We encountered a great variety of clinical practices and identified upper airway obstruction due to highly viscous secretions as a specific adverse effect of nHFOV. In a dedicated neonatal bench model, we further investigated the determinants of oropharyngeal gas conditions during non-invasive respiratory support. A bench study during nasal CPAP showed that mouth opening reduced oropharyngeal temperature and absolute humidity, even during heated humidification. A second bench study showed that nHFOV additionally impaired oropharyngeal gas conditions and that the magnitude of this effect depended on the ventilatory settings of nHFOV. The implications of the study results on current clinical care and on future research are discussed.
