Overall, the results of the present review demonstrate that there was no difference between the use of HFNC and CPAP in the risk of BPD. In addition, no significant difference was found between the use of HFNC and CPAP related to the development of the air leak syndrome (pneumothorax) and nasal injury.
Most studies eligible for the current systematic review had as main objective to assess the incidence of extubation failure with the use of HFNC10,11,19,21,24−26, while other studies have evaluated the effectiveness of using HFNC as the primary treatment for the acute respiratory distress syndrome22,24, 28 and 4 studies had the primary objective of assessing the effectiveness and safety of HFNC18,20,21,27. Only one study assessed the relationship between the use of HFNC and the incidence of BDP28 and another one describes the use of HFNC with the greatest need for oxygen therapy29.
BPD was first described 50 years ago and still lacks effective treatment and a comprehensive definition. Differently from the original description, BPD is currently characterized by chronic respiratory failure mainly in extreme neonates, together with changes in non-invasive respiratory support and the severity of long-term lung damage, which makes it more difficult to define the current condition. Limitations related to definitions include the inability to classify neonates who die before 36 weeks and possibly the use of HFNC with room air (21%) or very low flow with 100% oxygen makes some neonates not included in these definitions2,7. However, keeping the criteria for defining the disease in just one specification can exclude relevant studies, restricting the results.
Even with the significant increase in the use of these non-invasive ventilation devices in the past two decades, there is evidence that incidence rates of BPD30 remained unchanged. Studies suggest that these results may occur due to the excessive use of interventions associated with other risk factors for BPD, such as infections in the peri and postnatal period, contributing to premature lung injuries30,31.
CPAP is recommended worldwide, by the World Health Organization, as first-line therapy for the treatment of premature newborns with respiratory disorders since birth, significantly improving oxygenation, when compared to HFNC, which may justify its greater popularity19,32,33. The HFNC application systems, currently available, do not measure pressure in the airways, which can lead to the release of excessive pressure, contributing to the appearance of lung lesions and consequently contributing to the development of BPD33. Therefore, the clinical use of lower flow rates and adequate control of it leads to a reduction in this risk34. The results of the present study are in accordance with the present one, since there was no greater risk for the development of BPD with the use of HFNC.
The literature points out that nasal injury is a common complication in premature infants using CPAP, with a prevalence of 20 to 60%34,35. Alternatives to prevent nasal trauma when using CPAP include the use of appropriately sized interfaces and dressings as protection for the skin29,35,36. Evidence indicates that the lower prevalence of injury to the nasal septum with the use of HFNC is due to the humidified and heated flow offered by the device, which reduces the inflammation of the upper airway epithelial cells34,37 and the injury to the nasal mucosa, in addition to fact that the HFNC interface is lighter and easier to install compared to CPAP36–38.
The high heterogeneity presented in the results for the nasal lesion outcome can be justified by the fact that most of the studies included in the meta-analysis did not present a standardized metric for assessing the outcome, as described in the GRADE table (see Additional file 6), as well as different forms administration of ventilatory support and the lack of explanation of the sizes and types of interfaces used.
There is a concern about the use of HFNC and the risk of air leak syndrome due to high flows, as the pressure within the circuit cannot be measured, allowing the supply of high flows to the lower airways18–38. A recent systematic review published in 2019 demonstrated a reduction in the prevalence of air leak syndrome with HFNC use compared to CPAP, in premature neonates, as a post-extubation conduct39. Our results observed no difference in relation to the air leak syndrome, specifically the pneumothorax, in accordance with the results of a recent published network meta-analysis comparing both interventions14.
The quality of the included studies determines the quality of the systematic review, which is why we conducted a review using strict quality assessment criteria in randomized clinical trial studies15. There was a high risk of bias and risk of uncertain bias in most studies. Another consideration in this sense is that is a lack of blindness in the participants and personnel due to the nature of the application of the intervention and the evaluator, factors that increase the chance of bias related to the included studies. Another limiting factor in the present study was the fact that we included preterm infants regardless of classification. It is known that one of the risk factors for BPD is extreme prematurity or very premature, that is, premature infants born with less than 32 weeks of gestational age. However, we chose to include all preterm infants since in the literature, RCTs that sampled only extremely preterm infants, or very preterm infants are scarce. The studies showed great variability in the protocols for the application of CPAP and HFNC, and there was also great variability in the BPD definitions. Regarding the criteria for the diagnosis of air leak syndrome and nasal injury, many studies did not present the metrics for diagnosis of the presented outcomes, which led to a higher level of observed indirect evidence, a factor that contributed to decrease the quality of the evidence. Thus, the evidence based on the included RCTs was of very low quality.
According our results, the effective prevention of BPD still remains a challenge, since the results found cannot be generalized for clinical application. Therefore, the choice between non-invasive ventilation devices, HFNC or CPAP, remains a matter of clinical judgment by the team, which must analyze what outcomes it intends to use with the device of choice.