Objective To compare the effect of heated, humidified, high-flow nasal cannula (HHHFNC) and nasal continuous positive airways pressure (NCPAP) on lung function and mechanics in preterm infants with respiratory distress syndrome (RDS) at the same level of retropharyngeal pressure (P_rp).

Design Randomised crossover trial.

Setting Neonatal intensive care unit, Ospedale Maggiore Policlinico, Milan, Italy.

Patients 20 preterm infants (gestational age: 31±1 wks) with mild-moderate RDS requiring non-invasive respiratory support within 96 h after birth.

Interventions Infants were exposed to a randomised sequence of NCPAP and HHHFNC at different settings (2, 4 and 6 cmH₂O for NCPAP and 2, 4, 6 L/min for HHHFNC) to enable comparison at the same level of P_rp.

Main outcome measures Tidal volume by respiratory inductance plethysmography, pleural pressure estimated by oesophageal pressure, and gas exchange were evaluated at each setting and used to compute breathing pattern parameters, lung mechanics and work of breathing (WOB).

Results A poor linear regression between flow and P_rp was found during HHHFNC (P_rp=0.3+0.7*flow; r²=0.37). Only in 15 out of 20 infants it was possible to compare HHHFNC and NCPAP at a P_rp of 2 and 4 cmH₂O. No statistically significant differences were found in breathing pattern, gas exchange, lung mechanics and total WOB. Resistive WOB in the upper airways was slightly but significantly higher during HHHFNC (0.65 (0.49;1.09) vs 1.57 (0.85;2.09) cmH₂O median (IQR)).

Conclusions Despite differing mechanisms for generating positive airway pressure, when compared at the same P_rp, NCPAP and HHHFNC provide similar effects on all the outcomes explored.