Pulmonary Surfactant Replacement Therapy Research Articles

Prospective, non-blinded, randomized controlled trial on early administration of pulmonary surfactant guided by lung ultrasound scores in very preterm infants: study protocol.

Bedside lung ultrasonography has been widely used in neonatal intensive care units (NICUs). Lung ultrasound scores (LUS) may predict the need for pulmonary surfactant (PS) application. PS replacement therapy is the key intervention for managing moderate to severe neonatal respiratory distress syndrome (NRDS), with early PS administration playing a positive role in improving patient outcomes. Lung ultrasonography aids in the prompt diagnosis of NRDS, while LUS offers a semi-quantitative assessment of lung health. However, the specific methodologies for utilizing LUS in clinical practice remain controversial. This study hypothesizes that, in very preterm infants [<32 weeks gestational age (GA)] exhibiting respiratory distress symptoms, determining PS application through early postnatal LUS combined with clinical indicators, as opposed to relying solely on clinical signs and chest x-rays, can lead to more timely PS administration, reduce mechanical ventilation duration, improve patient outcomes, and lower the occurrence of bronchopulmonary dysplasia (BPD). This is a protocol for a prospective, non-blinded, randomized controlled trial that will be conducted in the NICU of a hospital in China. Eligible participants will include very preterm infants (< 32 weeks GA) exhibiting signs of respiratory distress. Infants will be randomly assigned in a 1:1 ratio to either the ultrasound or control group. In the ultrasonography group, the decision regarding PS administration will be based on a combination of lung ultrasonography and clinical manifestations, whereas in the control group, it will be determined solely by clinical signs and chest x-rays. The primary outcome measure will be the mechanical ventilation duration. Statistical analysis will employ independent sample t-tests with a significance level set at α = 0.05 and a power of 80%. The study requires 30 infants per group (in total 60 infants). This study aims to demonstrate that determining PS application based on a combination of LUS and clinical indicators is superior to traditional approaches. This approach may enhance the accuracy of NRDS diagnosis and facilitate early prediction of PS requirements, thereby reducing the duration of mechanical ventilation. The findings of this research may contribute valuable insights into the use of LUS to guide PS administration.

Excipient-free lyophilization of block copolymer micelles for potential lung surfactant therapy applications

Polymer lung surfactant (PLS) is a polyethylene glycol (PEG)-brushed block copolymer micelle designed for pulmonary surfactant replacement therapy. Saccharides (e.g., sucrose and (2-hydroxypropyl)-β-cyclodextrin) and water-soluble polymers (e.g., PEG), common excipients for lyophilization, were found to severely impair the surface activity of lyophilized PLS. To investigate the feasibility of excipient-free lyophilization of PLS, we studied the effects of both PLS material parameters and lyophilization operating parameters on the redispersibility and surface availability of reconstituted PLS, all without relying on excipients. We found that the redispersibility was improved by three factors; a faster cooling rate during the freezing stage reduced freezing stress; a higher PEG grafting density enhanced dissipating effects; and the absence of hydrophobic endgroups in the PEG block further prevented micelle aggregation. Consequently, the surface availability of PLS increased, enabling the micelle monolayer at the air/water interface to achieve a surface tension below 10 mN/m, which is a key pharmaceutical function of PLS. Moreover, the lyophilized micelles in powder form could be easily dispersed on water surfaces without the need for reconstitution, which opens up the possibility of inhalation delivery, a more patient-friendly administration method compared to instillation. The successful excipient-free lyophilization unlocks the potential of PLS for addressing acute respiratory distress syndrome (ARDS) and other pulmonary dysfunctions.

Application Value of a New Lung Ultrasound Scoring Method in Neonatal Respiratory Distress Syndrome Treatment

The study was aimed at exploring the clinical value of a 14-zone lung ultrasound scoring (LUS) method in treating neonatal respiratory distress syndrome (NRDS) with pulmonary surfactant (PS) and determining the timing of mechanical ventilation (MV). In this study, 88 neonates with NRDS who received PS replacement therapy were selected. We applied a new 14-zone LUS method before and 12, 24, 48 and 72 h after PS treatment to explore the clinical value of assessing PS replacement therapy efficacy in NRDS. Additionally, 67 patients with NRDS under MV received LUS during extubation. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of LUS in the timing of extubation. LUS score was inversely associated with PS treatment. At 12 h after PS, only the 14-zone LUS method was significantly different (t=4.08, p < 0.05) as compared with before PS, which was consistent with the change on chest x-ray (CXR); the other LUS methods did not differ (p > 0.05). The 14-zone LUS method exhibited better diagnostic performance for withdrawal time. A score of 41.0 points was used as the diagnostic threshold to predict the risk of withdrawal failure, with an area under the curve of 0.955, sensitivity of 92.4% and specificity of 93.8%. The new 14-zone LUS method improved scoring in the early efficacy of PS and had good diagnostic efficiency for timing the removal of MV in NRDS.

Pulmonary Surfactant Replacement Therapy for Respiratory Distress Syndrome in Neonates: a Nationwide Epidemiological Study in Korea.

BackgroundPulmonary surfactant (PS) replacement therapy, as a safe and effective treatment for respiratory distress syndrome (RDS) may have further increased with the extended insurance coverage since 2011 in Korea. Thus, this study aimed to investigate the epidemiologic data of PS replacement therapy for RDS in Korea and to analyze the complications associated with RDS.MethodsWe included 19,442 infants who were treated with PS and diagnosed with RDS (International Classification of Diseases-10 codes: P22.0) between 2014 and 2018 from the Health Insurance Review and Assessment database. Birth certificate data from Statistics Korea were used to estimate the incidence of RDS.ResultsThe average incidence of RDS within the study period was 0.99% among live births. Repeated doses of PS were administered to 1,688 infants (8.7%), ranging from 2 doses in 929 infants (4.8%) to 9 doses in 1 infant (0.01%). The incidence of RDS in term infants markedly increased over 5 years from 0.2% to 0.34%. The incidence was similarly increased among the preterm infants. The RDS mortality rate was 6.3% and showed a decreasing trend according to year. The mortality rate was significantly higher in the lower gestational age group. A decreasing trend was observed in the incidence of the complications, such as patent ductus arteriosus, intraventricular hemorrhage, and bronchopulmonary dysplasia, except for pneumothorax in term infants. The complications were also higher in the lower gestational age group and the lower birth weight group. However, pneumothorax was the most frequent complication in the term infant group and in infants with birth weight ≥ 2,500 g.ConclusionAdvancements in neonatal care and extended insurance coverage have increased the use of PS replacement therapy for RDS. This, in turn, decreased neonatal mortality and the incidence of the associated complications. The appropriate therapeutic strategy for RDS should be decided according to the gestational age and lung pathology.

Different Causes of Respiratory Distress in Neonates at Different Gestational Ages in China: A Retrospective Multi-Center Cohort Study

Background: Pulmonary surfactant replacement therapy (SRT) is currently the main treatment for neonatal respiratory distress syndrome (NRDS), but not all infants, particularly late-preterm and full-term (LP/FT) infants, with NRDS can achieve a satisfactory outcome despite intensive care and SRT in China. Few studies have been done to investigate the risk factors associated with respiratory distress at different gestational ages to guide clinical treatment. Methods: Therapeutic effects of SRT(conventional dose) in infants at different gestational ages (GAs) were compared in a large retrospective multicenter cohort study performed in 26 neonatal intensive care units in China. The cause of respiratory distress was further analyzed by comparing the different risk factors closely related to NRDS severity at different GAs. Results: The study of 1240 infants with NRDS showed that SRT in a conventional dose was less effective in LP/FT infants than in early-preterm infants. Further analysis of the risk factors of respiratory distress revealed that a GA less than 30 weeks and a lack of prenatal corticosteroid use were closely related to NRDS severity in early-preterm infants, whereas perinatal infection- and perinatal hypoxia-associated risk factors were closely related to NRDS severity in LP/FT infants. Conclusion: The cause of respiratory distress in LP/FT infants might differ from that in early-preterm infants in China. Respiratory distress in early-preterm infants is mostly due to primary surfactant deficiency. However, respiratory distress in LP/FT infants is more likely related to perinatal infection and perinatal hypoxia. Funding: This trial was designed, organized, and implemented by the first author and the corresponding author’s research center. Public funding was obtained from the Emergency Project of the National Science Foundation of China (No. 81741065) and Scientific Research Projects Unit of Chongqing (Project-cstc2016shms-ztzx13001) (Project-cstc2015shmszx1201114). Declaration of Interest: None of the authors have conflicts of interest to disclose. Ethical Approval: The ethics committee of Daping Hospital approved the study protocols, according to the Chinese regulations for clinical investigation.

History of Pulmonary Surfactant Replacement Therapy for Neonatal Respiratory Distress Syndrome in Korea.

Neonatal respiratory distress syndrome (RDS) is a disease that is unique to newborn infants. It is caused by a deficiency of pulmonary surfactant (PS), which is usually ready to be activated around the perinatal period. Until RDS was more clearly understood, it was not known why premature infants died from respiratory failure, although pathology revealed hyaline membranes in the alveoli. Surprisingly, the era of PS replacement therapy began only relatively recently. The first clinical trial investigating neonatal RDS was conducted in 1980. Since then, newborn survival has improved dramatically, which has led to significant advances in the field of neonatology. The present comprehensive review addresses PS, from its discovery to the application of artificial PS in newborns with RDS. It also reviews the history of PS in Korea, including its introduction, various commercial products, present and past research, newborn registries, and health insurance issues. Finally, it describes the inception of the Korean Society of Neonatology and future directions of research and treatment.

Progress of non-invasive ventilation in the treatment of neonatal respiratory distress syndrome

Neonatal respiratory distress syndrome(NRDS) is an important cause of neonatal death.The major clinical treatments are pulmonary surfactant replacement therapy and mechanical ventilation.In order to reduce the serious complications associated with invasive mechanical ventilation, non-invasive ventilation has increasingly been chosen by clinicians.There are many new types of non-invasive ventilation, such as nasal ventilation intermittent positive pressure, nasal continuous positive airway pressure, heated, humidified high-flow nasal cannula.We review literatures to further understand the application of non-invasive ventilation. Key words: Non-invasive ventilation; Respiratory distress syndrome; Nasal intermittent positive pressure ventilation; Nasal continuous positive airway pressure; Neonate

The effect of perfluorooctadecanoic acid on a model phosphatidylcholine–peptide pulmonary lung surfactant mixture

Fluorinated surface active molecules have demonstrated potential for applications in pulmonary surfactant replacement therapy. To characterize molecular-level interactions between constituents in model replacement formulations, the mixing thermodynamics, surfactant recovery and morphology of a mixed surfactant monolayer containing a phospholipid, a perfluorinated fatty acid and a peptide-based mimetic of a pulmonary surfactant protein has been investigated at the air–water interface. The synthetic peptide (amino acid sequence KLLKLLLKLCLKLLKLLL; KLL) was added to mixed films of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and perfluorooctadecanoic acid (C18F) on a simplified lung fluid mimic subphase (pH 7.4, 150 mM NaCl), and compression isotherms of the films were used to extract excess Gibbs free energies of mixing, along with hysteresis (surfactant recovery) response data. It was observed that, at low peptide content, KLL mixed non-ideally with the other film components, exhibiting negative deviations from ideality. Surfactant recovery upon repeated compression-expansion cycles for ternary films that contained DPPC, C18F and KLL were comparable with mixed DPPC–C18F films, indicating that this performance parameter is only minimally improved by the addition of the peptide. Film morphologies were significantly different for the peptide-containing mixed monolayers in comparison with control samples containing DPPC alone or DPPC–C18F, with films consisting of discrete DPPC-rich domains that tended to fuse as a function of increased film compression. Mixing thermodynamics, film structures and behavior upon compression are discussed in the context of affiliated systems described previously in the literature.

To investigate the prevention and treatment of common complications of replacement therapy with pulmonary surfactant in neonates

Objective To investigate the clinical characteristic and prophylactic -therapeutic measures of common complications of pulmonary surfactant(PS) replacement therapy in neonates. Methods We analyzed the clinical data of 65 cases preterm neonates treated with PS replacement therapy in neonatal intensive care unit(NICU) of our hospital. Results In 65 cases,32 cases had one to five complications,totally 60 times. Those included 14 times pneumonia (21.5%), 10 times (15.4%)pneumorrhagia, 8times(12.3%) apnoea, intraventricular hemorrhage and bronchopulmonary dysplasia respectively 6 times(9.2%), patent ductus arteriosus, 3 times(4.6%), atelectasis and retinopathy of prematurity respectively 11 times(16.9%). 18 cases Of 32 xtremely low birth weight infants (56.3%) had different degree complications, and as that of 6 cases of 8 very low birth weight infants.54 cases after complex treatment were survival (survival rate 83.1%) and 11 cases died (mortality 16.9%). Conclusion Active precaution and early discovery and treatment all kinds of complications immediately could improve the effect of PS replacement therapy and reduce the mortality of the preterms. Key words: Pulmonary surfactant; Respiratory distress syndrome; Complication; Newborn Infant

Clinical findings of severe amniotic fluid aspiration pneumonia and effects of surfactant replacement therapy

Purpose: Severe aspiration of the amniotic fluid is known to cause fatal respiratory distress in neonates. We conducted this study to investigate the clinical findings of severe amniotic fluid aspiration pneumonia (AFAP) in neonates and the effect of pulmonary surfactant replacement therapy (SRT). Methods: Retrospective analysis of medical records was conducted on 28 patients who received ventilator care due to severe AFAP in a neonatal intensive care unit over a 7-year period (2000-2006). Patients whose amniotic fluid was contaminated with meconium were excluded. Results: A large number of cases were term infants (82.1%) and infants born by caesarean section (85.7%), and the 1and 5-min Apgar scores of these patients were 6.5±1.2 and 7.5±1.3, respectively. Soon after birth, the amount of amniotic fluid sucked out from airway below the vocal cord was 16.0±10.1 mL. All patients received SRT with a modified bovine-derived surfactant (120 mg/kg/dose), and one dose was administered in most cases (75%). Compared with pre-SRT, the oxygenation index (8.0±9.6 vs. 18.9±7.3) according to ventilator care was a significant improvement at 12 h after SRT (P<0.001). Furthermore, most cases showed radiological improvement for aeration at 12 h post-treatment. Many cases (46.4%) had cardiorespiratory complications, but their final outcomes were excellent (survival rate, 96.4%). Conclusion: AFAP may be an important cause of serious respiratory distress in near-term and term infants, and SRT seems to be an effective adjuvant therapy in mechanically ventilated neonates with severe AFAP. (Korean J Pediatr 2009;52: 429-434)

Findings on chest radiographs after prophylactic pulmonary surfactant treatment of premature infants.

Clinical trials are underway that use pulmonary surfactant replacement therapy in an attempt to prevent respiratory distress syndrome (RDS) in premature infants. This study was undertaken to determine the relationship between the clinical course of infants receiving prophylactic "first-breath" endotracheal surfactant and their initial posttreatment radiographs. The study population consisted of 80 premature infants of 24-32 weeks gestational age. All received 3 ml of calf-lung surfactant extract via endotracheal tube at birth. Anteroposterior chest radiographs taken within 1 hr of treatment were reviewed and correlated with gestational age, birth weight, days of endotracheal intubation, mean airway pressure, and days of oxygen requirement greater than 30%. Three distinct patterns of radiographic abnormality were encountered: typical RDS with hypoinflation, diffuse granularity, and air bronchograms (30%); central clearing of RDS (14%); and disproportionate clearing of RDS in the right lung (8%). No significant differences in ventilator requirements or clinical course were seen among these three groups. A fourth group (49%), whose posttreatment radiographs showed no evidence of RDS, required significantly less ventilatory support. Prophylactic first-breath surfactant treatment of premature infants occasionally results in radiographic patterns that are atypical for RDS. Familiarity with these patterns and their clinical significance will be important if surfactant augmentation becomes prevalent.