In our study，it was found that LISA method was not superiot to InSurE method in reducing mortality or incidence of BPD. To the best of our knowledge, it was the largest Chinese single-center observational study. The main population of our retrospective study was infants at 29 weeks gestation age (mean), who were relatively older than those included in two previous multi-center studies conducted by Kribs et al. and Dargaville et al.
No mortality in either group was observed in our study. The result was consistent with that of Kribs et al, who found that the use of LISA was not associated with mortality. However, the result was in contrast with that of a systemic review conducted by Aldana-Aguirre et al., which showed that LISA could significantly reduce mortality compared with the traditional method. We speculate that the small sample size of our study and the relatively lower mortality rate of infants with gestational ages >28 weeks would be the main reason.
We did not find significant differences in the incidence of BPD between the two groups, consistent with the results of our previous study . This could again be attributed to the gestational age of our population.We speculated that LISA’s effects may depend on the population’s gestational age. Mohammadizadeh et al. conducted a study including 38 neonates with an average gestational age of 30 and 31 weeks in the LISA and control groups, respectively, and found that LISA had the same effect on BPD as traditional surfactant administration. A recent study involving 40 neonates with an average gestational age of 31 weeks also reported no effects of LISA on reducing BPD, as compared to InSurE . This could possibly be associated with the lower incidence of BPD in infants with gestation age >28 weeks. A study by Ramos-Navarro et al.  concluded that LISA significantly decreased the incidence of BPD among neonates with gestational age 26+0-28+6 weeks, while no effect was observed among neonates with gestational ages 29+0-31+6 weeks.
It is well known that infants with severe BPD are at a higher risk of mortality after discharge , and there is increasing interest in identifying the relationship between LISA and BPD severity. However, there were still no consensus for the relationship from previous studies. Buyuktiryaki et al.[ 18] found a significant reduction in BPD severity at 36 weeks PMA in the LISA group, compared with that in the InSurE group. Recently, Dargaville et al. conducted a multi-center study in infants with gestational ages between 25 to 28 weeks. They did not find a clear association between BPD severity and LISA. We speculate that many risk factors, such as gestational age, birth body weight, prenatal/perinatal/postnatal infecton and optimal managements after birth,affected the incidence of BPD, and each factor has various effects on the incidence of BPD among centers.
MV is a significant risk factor for BPD in preterm infants, specifically those with very low birth weights [19,20]. We found no significant difference in the incidence of MV within the first 72 h of birth, which was similar to the results of the study conducted by Kruczek et al. In contrast, Gopel et al.[22,23] found that LISA could reduce MV treatment within 72 h of birth for neonates with gestational ages of 26–28 weeks, as well as his following study. A study by Kribs et al. also showed that LISA could reduce the rate of tracheal intubation within the first 72 h after birth even for neonates with gestational ages <25 weeks who were at risk of nCPAP failure due to severe apnea or respiratory fatigue. We speculated the diffence may mainly caused by gestational age, and may be partley associated with policies of MV.
Adverse events have been noted during surfactant administration . However, there were no significant differences in the incidence of adverse events between the two groups in our study. Ambulkar et al. reported that approximately 5-40% of neonates undergoing LISA had adverse reactions, including apnea, transcutaneous oxygen desaturation, bradycardia, and choking. Surfactant reflux was also widespread during surfactant administration, especially in LISA. Furthermore, when compared with the InSurE group, the incidence of surfactant reflux was significantly higher in the LISA group. However, there was no difference in the effects of surfactant replacement, such as reduction in FiO2, PEEP, and the number of additional surfactant doses. Thus, further studies should focus on the issue of the optimal surfactant dose for LISA.
In our restropective study, the number of infants in the InSurE group was relatively higher than that in the LISA group. As shown in previous surveis，the doctors’ attitude may affect the clinical application of LISA[6,26]. Half of our cooperators were still hesitant to try this method, despite it being in use for nearly 10 years. Further reaserches needed to realease their concerns.
Further studies may focus on twoissues, one is which population could take most advantage from the method of LISA, although it has been proven to be safe for neonates with a gestational age <26 weeks  . The other is follow-up data of survivors, who received LISA methods.
There were some limitations in our study. Firstly, our study was a single-center retrospective study, the cohort was relatively small. Secondly, the mean gestational age in our study population was about 29 weeks, which is not the population at the highest risk for mortality and BPD. Finally, we did not perform follow-up in survivors. Our further stratified comparison studies would focus on these issues.
In our study, compared with the traditional application of surfactant administration, the LISA technique was an alternative method to delivery surfactant, but did not significantly reduce the mortality and incidence of BPD. whether it has potential effects on late improved pulmonary outcomes or neurodevelopment in survivors require further researches.