the survival rates of preterm babies , particularly those at 2426 weeks of gestational age ( ga ) , have improved due to antenatal corticosteroid therapy , postnatal surfactant replacement therapy , and ventilator care . however , the incidence of bronchopulmonary dysplasia ( bpd ) in preterm babies has not declined over the last decade , with rates of 22% in western countries1 ) and 18% in korea2 ) . these results may be due to improved survival of very preterm infants with " new " bpd , which is caused by " arrested " development of alveoli and capillaries at early stages of lung development34 ) . this is in contrast to the " classic " or " old " bpd that was described by northway et al.5 ) in relatively mature newborn babies receiving ventilator care . many studies have described ways to reduce the rate of bpd , starting from resuscitation at birth with noninvasive ventilator ( niv ) and avoiding hyperoxia67 ) . the most important way to prevent bpd is to wean the patient from the ventilator as soon as possible to reduce ventilator - induced lung injury causing bpd ; and , using niv procedures have been increasingly adopted to reduce the use of invasive ventilators and the incidence of bpd . frequently used nivs in neonatal intensive care units ( nicus ) are nasal continuous positive airway pressure ( ncpap ) , which is the most commonly used ventilator , nasal intermittent positive pressure ventilation ( nippv ) , bi - level ncpap ( bipap ) , sigh cpap ( sipap ) , and a heated , humidified high flow nasal cannula ( hhhfnc)8 ) . sealing to the upper airway is critical in other niv modes except hhhfnc , so the use of a skilled sealing technique with proper nursing care is essential , although nasal breakdown due to fitted nasal prongs occurs frequently9 ) . abdominal distension , called " cpap belly , " is common in patients using ncpap , nippv , bipap , or sipap , which use fitted nasal prongs to deliver positive airway - distending pressure . hhhfnc is the most recently introduced mode of niv for respiratory support in preterm infants , and does not require sealing to the upper airway with fitted nasal prongs . despite the lack of evidence supporting the efficacy and safety of hhhfnc in randomized controlled trials , it is commonly used in many nicus due to the technical ease of use and the attending physician 's preference for hhhfnc over other standard nivs . here , the mechanisms of action , efficacy , and safety of hhhfnc are described in comparison to ncpap and nippv . low flow nasal cannulas ( flow rate less than 1 l / min ) are used to deliver oxygen to preterm infants with bpd . the term " high flow nasal cannula " was described by sreenan et al.10 ) . hfnc , which is used to treat apnea of prematurity , can deliver airway - distending pressure comparable to that of ncpap , and is as effective as ncpap . however , flow rates > 2 l / min cause mucosal dryness , airway dryness , and nosocomial infections , resulting in airway mucosal injury and airway obstruction due to mucous plugs1112 ) . thus , a heated humidified gas delivery system was developed to overcome these shortcomings , and gas is delivered through a hfnc system , called a heated humidified high flow nasal cannula13 ) . the precision flow ( vapotherm , exeter , nh , usa ) and the optiflow junior ( fisher & paykel , auckland , new zealand ) devices deliver gas temperatures up to 34 and 33 , respectively , and humidity up to 99% and 96% , respectively , at flow rates less than 4 l / min . as the flow rate increases , the temperature of the gas delivered is similar to that of a low flow rate ; however , humidity decreases ( up to 81.2% vs. 88.8% , respectively ) , when using the precision flow and optiflow junior devices at a flow rate of 8 l / min14 ) . the temperature of gas delivered by the precision flow device at a flow rate of 08 l / min is lower than that of ncpap ( 34.0 vs. 34.5 ) ; however , humidity is significantly higher than that of ncpap ( 83% vs. 76%)15 ) . a hhhfnc can deliver positive airway - distending pressure to the lungs just as ncpap does , if flow rate is greater than 2 l / min . however , unlike ncpap , the pressure delivered by the hhhfnc is not constant or fixed , and varies widely according to the size of the nasal prongs , gas flow rate , size of the patient 's airway , and airflow leakage through the nares or mouth1617 ) . therefore , it is difficult to predict the pressure generated by a hhhfnc . more pressure can be generated if airflow leakage is decreased with nasal prongs , and if the flow rate is high . sealing to the upper airway is critical for delivering positive airway - distending pressure during ncpap . a chinstrap or pacifier is used to decrease airflow leakage through the mouth during ncpap . however , unlike ncpap , sealing the nasal prongs to nares is not necessary when using hhhfnc . thus , the airway - distending pressure generated by hhhfnc is changed dynamically according to the infant 's respiratory cycle , which is more physiological but is also a shortcoming18 ) . several studies have reported positive airway - distending pressure according to the flow rate of a hhhfnc . a flow rate of 2.5 l / min is equivalent to a positive airway pressure of 6 cmh2o , and a flow rate of 1.6 l / min ( preterm infants with body weight of 1,000 g ) or 1.3 l / min ( preterm infants with body weight of 500 g ) is equivalent to positive airway pressure of 6 cmh2o10 ) . although information on the mechanisms of action of a hhhfnc is limited , there are several proposed mechanisms19 ) . ( 1 ) a hhhfnc delivers positive airway - distending pressure comparable to that of ncpap . a linear relationship is observed between the flow rate of a hfnc and tracheal pressure in a neonatal piglet model . tracheal pressure is higher with a low - leak double prong ( cannula fully occludes both nares ) than with a high - leak single prong ( cannula occludes only half the area of the nares ) . ( 2 ) a hhhfnc decreases airway resistance and improves gas exchange by washing out anatomic dead space in the upper airways due to the high gas flow . anatomic dead space is relatively higher in infants , particularly in preterm infants ( greater than 3 ml / kg in early infancy ) compared to adults , but decreases with age20 ) . washing hypoxic and hypercapnic gas out of the dead space with oxygenated fresh gas is effective , particularly in preterm infants who have a larger anatomic dead space . ( 4 ) a hhhfnc reduces metabolic demands and reduces the burden of breathing due to the highly humidified heated gas . oxygenation has been shown to improve in a neonatal piglet model fitted with a hhhfnc , which may be due to increased flow rate , regardless of airflow leakage . arterial oxygen tension ( pao2 ) increases in a flow - dependent manner in a hhhfnc device as flow rate is increased to 28 l / min . a double prong with low leakage ( cannula fully occludes both nares ) improves oxygenation , while a single prong with high leakage ( cannula occludes only half the area of the nares ) improves co2 excretion or ventilation . however , pao2 did not increase with a cpap device when it was 400 mmhg , as cpap pressure was increased19 ) . holleman - duray et al.21 ) reported that the rate of reintubation after extubation failure is not different between hhhfnc and ncpap groups in preterm infants 2529 weeks of ga . intraventricular hemorrhage ( ivh ) , periventricular leukomalacia , necrotizing enterocolitis ( nec ) , retinopathy of prematurity , bpd , and mortality rates were also not different between the 2 groups . ventilator duration was relatively shorter , and the rate of ventilator - associated pneumonia rather decreased in the hhhfnc group . weight gain was greater in the hhhfnc group ( p=0.016 ) , which may have been due to reduced metabolic demands and burden of breathing because of the availability of highly humidified heated gas through the hfnc system21 ) . collins et al.22 ) applied hhhfnc at a flow rate of 8 l / min and ncpap at a pressure of 8 cmh2o , and reported that extubation failure and weaning of invasive ventilator in patients with a hhhfnc was lower than that of ncpap , but no difference was found in preterm ( less than 28 weeks of ga ) infants ( 22% in hhhfnc group vs. 34% in ncpap group ; odds ratio , 0.56 , 95% confidence interval [ ci ] , 0.261.22 ) . similar results were observed for extubation failure in relatively older infants who needed respiratory support after extubation ( ga28 weeks ; 15.1% in hhhfnc group and 11.4% in the ncpap group ; p=0.252 ) ; in this case , the investigators applied hhhfnc at a flow rate of 3 to 5 l / min and ncpap at a pressure of 5 to 6 cmh2o . again , no differences were observed between the 2 groups on supplemental oxygen , incidence of bpd ( 20% in hhhfnc group vs. 16% in ncpap group ) , or discharge from the hospital with oxygen23 ) . in a noninferiority trial in australia , manley et al.24 ) reported that hhhfnc is not inferior to ncpap , while applying hhhfnc at a flow rate of 5 to 6 l / min and ncpap at a pressure of 7 cmh2o . the rate of extubation failure in patients with a hhhfnc is not inferior to that of ncpap ( 34.2% in hhhfnc group vs. 25.8% in ncpap group ; risk difference , 8.4% ; 95% ci , 1.9 to 18.7 ) . here , manley et al.24 ) found no differences were observed in bpd , pneumothorax , ventilator duration , or discharge from the hospital with oxygen . however , about half of the infants with hhhfnc treatment failure were successfully treated with ncpap without reintubation24 ) . after that study , the same authors reported results from follow - up studies , and concluded that hhhfnc is comparable to ncpap for respiratory support after extubation in preterm infants . on the other hand , campbell et al.26 ) reported that the rate of reintubation due to extubation failure , apnea , and bradycardia , were higher in the hfnc group ( flow rate of 1.6 l / min ) than in the cpap group ( pressure of 5 to 6 cmh2o ) . however , the flow rate of hfnc was lower than that of other hhhfncs , and they did not use the heated humidified gas . futhermore , abdel - hady et al.27 ) reported that the hhhfnc group ( flow rate of 2 l / min ) showed longer duration of oxygen therapy and respiratory support compared to the ncpap group ( pressure of 5 cmh2o ) . hhhfnc was not different from ncpap or nippv in respiratory support after extubation in a cochrane meta - analysis28 ) . only a few randomized controlled trials have been conducted to compare hhhfnc to ncpap or nippv as initial respiratory support systems , particularly in extremely preterm infants . shoemaker et al.29 ) reported that hhhfnc is superior to ncpap as initial respiratory support in preterm infants less than 30 weeks of ga . the rate of intubation due to treatment failure was significantly less in the hhhfnc group ( 18% in hhhfnc group vs. 40% in ncpap group ) . no differences in mortality rate , ventilator duration , bpd , or sepsis were observed between the hhhfnc and ncpap groups29 ) . however , the authors noted that ventilator duration decreased after introduction of the hhhfnc to the nicu ( 19.4 to 9.9 days ) . the use of hhhfnc increased to 64% , and use of ncpap decreased to 4% after introduction of the hhhfnc , particularly in 95% and 12% of infants yoder et al.23 ) applied hhhfnc at a flow rate of 3 l / min to infants with a body weight 1,000 to < 2,000 g , 4 l / min for those 2,000 to < 3,000 g , and 5 l / min for those 3,000 g , and reported that treatment failure requiring intubation within 72 hours as a primary mode of respiratory support in infants greater than 28 weeks ga was not different between hhhfnc and ncpap groups ( 10.8% in hhhfnc group vs. 8.2% in ncpap group , p=0.344 ) . however , the duration of respiratory support was longer in the hhhfnc group than in the ncpap group . ciuffini et al.30 ) reported preliminary results indicating that the incidence of treatment failure requiring intubation within 72 hours as a primary mode of respiratory support in 29- to 36-week ga infants were slightly higher in the hhhfnc group than that in the ncpap group , although the differences were not statistically significant ( 12.9% in hfnc group vs. 5.4% in ncpap group , p= 0.11 ) . kugelman et al.31 ) compared hhhfnc to nippv , and found that treatment failure as a primary mode of respiratory support for respiratory distress syndrome at birth was not different between the hhhfnc and nippv groups ( 28.9% in hhhfnc group vs. 34.2% in nippv group ) in preterm infants ( less than 35 weeks ga , and birth weight greater than 1,000 g ) . however , the failure rate was about 30% , which is much higher than that reported in other studies , although the mean ga was not significantly different ( ga : 31.82.3 weeks vs. 32.02.3 weeks in hhhfnc and nippv groups , respectively ) . in the insure study , " intubation , surfactant administration , and rapid extubation ( insure ) " ( or extubated to ncpap in cases of respiratory difficulty ) did not decrease mortality or bpd in comparison with surfactant and mechanical ventilation32 ) . of those who had been successfully extubated or changed to ncpap after insure due to respiratory difficulty , 41.7% required reintubation . however , ovalle et al . reported that 30% of infants who received a hhhfnc after insure required reintubation , leading the authors to suggest that a hhhfnc could be comparable to ncpap to prevent reintubation in patients treated with insure . further randomized controlled trials are needed3334 ) . holleman - duray et al.21 ) reported that the rate of reintubation after extubation failure is not different between hhhfnc and ncpap groups in preterm infants 2529 weeks of ga . intraventricular hemorrhage ( ivh ) , periventricular leukomalacia , necrotizing enterocolitis ( nec ) , retinopathy of prematurity , bpd , and mortality rates were also not different between the 2 groups . ventilator duration was relatively shorter , and the rate of ventilator - associated pneumonia rather decreased in the hhhfnc group . weight gain was greater in the hhhfnc group ( p=0.016 ) , which may have been due to reduced metabolic demands and burden of breathing because of the availability of highly humidified heated gas through the hfnc system21 ) . collins et al.22 ) applied hhhfnc at a flow rate of 8 l / min and ncpap at a pressure of 8 cmh2o , and reported that extubation failure and weaning of invasive ventilator in patients with a hhhfnc was lower than that of ncpap , but no difference was found in preterm ( less than 28 weeks of ga ) infants ( 22% in hhhfnc group vs. 34% in ncpap group ; odds ratio , 0.56 , 95% confidence interval [ ci ] , 0.261.22 ) . similar results were observed for extubation failure in relatively older infants who needed respiratory support after extubation ( ga28 weeks ; 15.1% in hhhfnc group and 11.4% in the ncpap group ; p=0.252 ) ; in this case , the investigators applied hhhfnc at a flow rate of 3 to 5 l / min and ncpap at a pressure of 5 to 6 cmh2o . again , no differences were observed between the 2 groups on supplemental oxygen , incidence of bpd ( 20% in hhhfnc group vs. 16% in ncpap group ) , or discharge from the hospital with oxygen23 ) . in a noninferiority trial in australia , manley et al.24 ) reported that hhhfnc is not inferior to ncpap , while applying hhhfnc at a flow rate of 5 to 6 l / min and ncpap at a pressure of 7 cmh2o . the rate of extubation failure in patients with a hhhfnc is not inferior to that of ncpap ( 34.2% in hhhfnc group vs. 25.8% in ncpap group ; risk difference , 8.4% ; 95% ci , 1.9 to 18.7 ) . here , manley et al.24 ) found no differences were observed in bpd , pneumothorax , ventilator duration , or discharge from the hospital with oxygen . however , about half of the infants with hhhfnc treatment failure were successfully treated with ncpap without reintubation24 ) . after that study , the same authors reported results from follow - up studies , and concluded that hhhfnc is comparable to ncpap for respiratory support after extubation in preterm infants . on the other hand , campbell et al.26 ) reported that the rate of reintubation due to extubation failure , apnea , and bradycardia , were higher in the hfnc group ( flow rate of 1.6 l / min ) than in the cpap group ( pressure of 5 to 6 cmh2o ) . however , the flow rate of hfnc was lower than that of other hhhfncs , and they did not use the heated humidified gas . futhermore , abdel - hady et al.27 ) reported that the hhhfnc group ( flow rate of 2 l / min ) showed longer duration of oxygen therapy and respiratory support compared to the ncpap group ( pressure of 5 cmh2o ) . hhhfnc was not different from ncpap or nippv in respiratory support after extubation in a cochrane meta - analysis28 ) . only a few randomized controlled trials have been conducted to compare hhhfnc to ncpap or nippv as initial respiratory support systems , particularly in extremely preterm infants . shoemaker et al.29 ) reported that hhhfnc is superior to ncpap as initial respiratory support in preterm infants less than 30 weeks of ga . the rate of intubation due to treatment failure was significantly less in the hhhfnc group ( 18% in hhhfnc group vs. 40% in ncpap group ) . no differences in mortality rate , ventilator duration , bpd , or sepsis were observed between the hhhfnc and ncpap groups29 ) . however , the authors noted that ventilator duration decreased after introduction of the hhhfnc to the nicu ( 19.4 to 9.9 days ) . the use of hhhfnc increased to 64% , and use of ncpap decreased to 4% after introduction of the hhhfnc , particularly in 95% and 12% of infants yoder et al.23 ) applied hhhfnc at a flow rate of 3 l / min to infants with a body weight 1,000 to < 2,000 g , 4 l / min for those 2,000 to < 3,000 g , and 5 l / min for those 3,000 g , and reported that treatment failure requiring intubation within 72 hours as a primary mode of respiratory support in infants greater than 28 weeks ga was not different between hhhfnc and ncpap groups ( 10.8% in hhhfnc group vs. 8.2% in ncpap group , p=0.344 ) . however , the duration of respiratory support was longer in the hhhfnc group than in the ncpap group . ciuffini et al.30 ) reported preliminary results indicating that the incidence of treatment failure requiring intubation within 72 hours as a primary mode of respiratory support in 29- to 36-week ga infants were slightly higher in the hhhfnc group than that in the ncpap group , although the differences were not statistically significant ( 12.9% in hfnc group vs. 5.4% in ncpap group , p= 0.11 ) . kugelman et al.31 ) compared hhhfnc to nippv , and found that treatment failure as a primary mode of respiratory support for respiratory distress syndrome at birth was not different between the hhhfnc and nippv groups ( 28.9% in hhhfnc group vs. 34.2% in nippv group ) in preterm infants ( less than 35 weeks ga , and birth weight greater than 1,000 g ) . however , the failure rate was about 30% , which is much higher than that reported in other studies , although the mean ga was not significantly different ( ga : 31.82.3 weeks vs. 32.02.3 weeks in hhhfnc and nippv groups , respectively ) . in the insure study , " intubation , surfactant administration , and rapid extubation ( insure ) " ( or extubated to ncpap in cases of respiratory difficulty ) did not decrease mortality or bpd in comparison with surfactant and mechanical ventilation32 ) . of those who had been successfully extubated or changed to ncpap after insure due to respiratory difficulty , reported that 30% of infants who received a hhhfnc after insure required reintubation , leading the authors to suggest that a hhhfnc could be comparable to ncpap to prevent reintubation in patients treated with insure . collins et al.22 ) reported that nasal trauma was significantly lower in the hhhfnc group than in the ncpap group in preterm infants less than 32 weeks of ga ( p<0.05 ) . in a similar study , collins et al.35 ) reported that nasal trauma ( scored by erythema , bleeding , or ulceration at 6 sites on the nose ; score of 2.8 in the hhhfnc group and 11.7 in the ncpap group ) in preterm infants less than 32 weeks ga was significantly lower in the hhhfnc group than in the ncpap group ( p<0.001 ) . nasal breakdown was significantly lower in the hhhfnc group than in the ncpap group ( 9% in hhhfnc group vs. 16% in ncpap group , p=0.047)23 ) . abdominal distension , which is common in patients receiving ncpap ( cpap belly ) , and full enteral feeding days ( > 120 ml / kg / day ) were not different , leading to the conclusion that a hhhfnc is comparable to ncpap , particularly from a safety perspective ( abdominal distension : 10% vs. 8% ; full enteral feeding days : 18 vs. 17 days in hhhfnc and ncpap groups , respectively ) . manley et al.24 ) reported a significant reduction in nasal trauma in the hhhfnc group compared to that in the ncpap group ( 39.5 % in hhhfnc group vs. 54.3% in ncpap group , p=0.01 ) in preterm infants less than 32 weeks ga ; however , the findings for neonatal outcomes such as mortality rate , pneumothorax , bpd , ivh , nec , and ventilator duration , were not different . nasal trauma decreased significantly in the hhhfnc group , but the incidence of nasal trauma in both groups was higher than that reported by other studies ; this may have been due to the subjective nature of the nasal trauma diagnosis , which is made by the attending physicians or nurses based on determination of mild erythema to severe ulceration of the nose . the incidence rates of nasal breakdown and neonatal complications , such as pneumothorax , bpd , ivh , nec , patent ductus arteriosus , and sepsis , are not different between the hhhfnc and nippv groups31 ) . the nippv set ( positive end expiratory pressure , 6 cmh2o ; peak inspiratory pressure , 1422 cmh2o ; and rate , 1230 breaths / min ) , and hhhfnc set ( flow rate started at 1 l / min and increased by 0.51 l / min according to the infant 's weight and respiratory status ) were similar to those in other studies . however , nasal trauma did not occur in both groups , which may have been related to the much shorter duration of noninvasive respiratory support than reported in other studies ( 4.0 days ; range , 1.015.0 days in hhhfnc group vs. 2.0 days ; range , 0.36.5 days in nippv group ) . according to rnnestad et al.36 ) , early - onset sepsis diagnosed at 27 days postnatally is mainly caused by nosocomial flora and is dominant in preterm infants ( less than 28 weeks ga , or birth weight less than 1,000 g ) receiving ncpap . those authors suggested that the increase in unexplained sepsis in patients receiving ncpap is related to nasal mucosal breakdown and nasal injury by ncpap . however , most studies considering safety of hhhfnc have reported that sepsis does not decrease in the hhhfnc group , and that there are no differences in sepsis between hhhfnc and other niv modes . further studies on nasal trauma and sepsis are therefore required . a cochrane meta - analysis significantly less nasal trauma and pneumothorax were reported in the hhhfnc group than those in the ncpap group28 ) . we do not have long - term experience with hhhfnc , the most recently introduced niv mode for respiratory support in preterm infants , and few randomized controlled trials have investigated the efficacy and safety of hhhfnc . however , use of hhhfnc is increasing rapidly in many nicus due to technical ease of use without sealing , and attending physicians prefer this mode of support due to its empirical efficacy compared to that of other niv modes . some researchers have concluded that the rate of extubation failure was higher26 ) , the duration of oxygen therapy was longer , and the duration of respiratory support was longer in the hhhfnc group compared to ncpap group27 ) . hhhfnc may deliver unpredictably high airway - distending pressure to the lungs , which can cause airway trauma or air leakage . nasal breakdown and neonatal complications are significantly lower when using a hhhfnc than those of ncpap or nippv . there were no significant differences in the rates of reintubation after extubation between hhhfnc and ncpap . however , evidence supporting hhhfnc as initial respiratory support , particularly in extremely preterm infants , is unclear . the size of the nasal prongs must be considered according to airway size and body weight to allow air leakage between the prongs and nares . in summary , although evidence supporting the use of hhhfnc as a respiratory support after extubation is strong , data from studies in extremely preterm infants is still limited . a large randomized controlled trial is therefore needed before considering hhhfnc as an niv standard , particularly in extremely preterm infants .
the incidence of bronchopulmonary dysplasia ( bpd ) has not decreased over the last decade . 
 the most important way to decrease bpd is by weaning the patient from the ventilator as soon as possible in order to reduce ventilator - induced lung injury that underlies bpd , and by using a noninvasive ventilator ( niv ) . 
 use of a heated , humidified , high flow nasal cannula ( hhhfnc ) , which is the most recently introduced niv mode for respiratory support in preterm infants , is rapidly increasing in many neonatal intensive care units due to the technical ease of use without sealing , and the attending physician 's preference compared to other niv modes . a number of studies have shown that nasal breakdown and neonatal complications were lower when using a hhhfnc than when using nasal continuous positive airway pressure ( ncpap ) , or nasal intermittent positive pressure ventilation . 
 the rates of extubation failure during respiratory support were not different between patients who used hhhfnc and ncpap . 
 however , data from the use of hhhfnc as the initial respiratory support " after birth " , particularly in extremely preterm infants , are lacking . 
 although the hhhfnc is efficacious and safe , large randomized controlled trials are needed before the hhhfnc can be considered an niv standard , particularly for extremely preterm infants .