Surfactant Replacement Therapy Research Articles

Surfactant Therapy in Respiratory Distress Syndrome

Respiratory distress syndrome (RDS) is the leading cause of neonatal respiratory morbidity and mortality. Advancements in neonatal care, along with extended insurance coverage, have resulted in increased utilization of surfactant replacement therapy (SRT) for RDS. This has contributed to a decrease in neonatal mortality. The primary mode of respiratory support in infants with RDS has dramatically changed over the last decades, transitioning from invasive to noninvasive support. Therefore, less invasive surfactant therapy has emerged as a widely adopted approach for SRT, establishing itself as a standard method in preterm infants’ care. This review addresses pulmonary surfactant, from its discovery to application in newborns with RDS. It also reviews the history of guidelines of SRT and health insurance issues. Future studies should evaluate various emerging noninvasive respiratory support modalities along with SRT for the respiratory management of neonates, given the lack of sufficient evidence regarding these approaches.

The Synthetic Surfactant CHF5633 Restores Lung Function and Lung Architecture in Severe Acute Respiratory Distress SyndromeinAdult Rabbits.

Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decreased lung compliance and alveolar collapse. Lung function in ARDS could potentially be restored with surfactant replacement therapy, and synthetic surfactants with modified peptide analogues may better withstand inactivation in ARDS alveoli than natural surfactants. This study aimed to investigate the activity in vitro and the bolus effect (200mg phospholipids/kg) of synthetic surfactant CHF5633 with analogues of SP-B and SP-C, or natural surfactant Poractant alfa (Curosurf®, both preparations Chiesi Farmaceutici S.p.A.) in a severe ARDS model (the ratio of partial pressurearterial oxygen and fractionof inspired oxygen, P/F ratio ≤ 13.3kPa) induced by hydrochloric acid instillation followed by injurious ventilation in adult New Zealand rabbits. The animals were ventilated for 4h after surfactant treatment and the respiratory parameters, histological appearance of lung parenchyma and levels of inflammation, oxidative stress, surfactant dysfunction, and endothelial damage were evaluated. Both surfactant preparationsyielded comparable improvements in lung function parameters,reductions inlung injuryscore, pro-inflammatory cytokines levels, and lung edema formation compared to untreated controls. This study indicates that surfactant replacement therapy with CHF5633 improves lung function andlung architecture, and attenuates inflammation in severe ARDS in adult rabbits similarly to Poractant alfa. Clinical trials have so far not yielded conclusive results, but exogenous surfactant may be a valid supportive treatment for patients with ARDS given its anti-inflammatory and lung-protective effects.

Gastric Fluid Metabolomics Predicting the Need for Surfactant Replacement Therapy in Very Preterm Infants Results of a Case-Control Study.

Respiratory distress syndrome (RDS) is a major morbidity of prematurity. In this case-control study, we prospectively evaluated whether untargeted metabolomic analysis (gas chromatography-mass spectrometry) of the gastric fluid could predict the need for surfactant in very preterm neonates. 43 infants with RDS necessitating surfactant (cases) were compared with 30 infants who were not treated with surfactant (controls). Perinatal-neonatal characteristics were recorded. Significant differences in gastric fluid metabolites (L-proline, L-glycine, L-threonine, acetyl-L-serine) were observed between groups, but none could solely predict surfactant administration with high accuracy. Univariate analysis revealed significant predictors of surfactant administration involving gastric fluid metabolites (L-glycine, acetyl-L-serine) and clinical parameters (gestational age, Apgar scores, intubation in the delivery room). Multivariable models were constructed for significant clinical variables as well as for the combination of clinical variables and gastric fluid metabolites. The AUC value of the first model was 0.69 (95% CI 0.57-0.81) and of the second, 0.76 (95% CI 0.64-0.86), in which acetyl-L-serine and intubation in the delivery room were found to be significant predictors of surfactant therapy. This investigation adds to the current knowledge of biomarkers in preterm neonates with RDS, but further research is required to assess the predictive value of gastric fluid metabolomics in this field.

Use of surfactant beyond respiratory distress syndrome, what is the evidence?

Surfactant replacement therapy is currently approved by the United States Food and Drug Administration (FDA) for premature infants with respiratory distress syndrome (RDS) caused by surfactant deficiency due to immaturity. There is strong evidence that surfactant decreases mortality and air leak syndromes in premature infants with RDS. However, surfactant is also used "off-label" for respiratory failure beyond classic RDS. This review discusses current evidence for the use of off-label surfactant therapy for (1) term infants with lung disease such as meconium aspiration syndrome (MAS), pneumonia/sepsis, and congenital diaphragmatic hernia (2) premature infants after 72 h for acute respiratory failure, and (3) the use of surfactant lavage. At last, we briefly describe the use of surfactants for drug delivery and the current evidence on evaluating infants for surfactant deficiency.

Outcome of Surfactant Replacement Therapy in Premature Neonates in ICU of Ibn Sina Teaching Hospital of Sirte, Libya in Period Between May – 2019 to May – 2022

Introduction :Respiratory distress syndrome (RDS) is an acute lung disease of preterm babies caused by surfactant insufficiency . Decreased surfactant results in insufficient surface tension in the alveolus during expiration leading to alveolar collapse , atelectasis , impaired gas exchange , severe hypoxia and acidosis , leading to respiratory failure . Surfactant replacement therapy (SRT) is now accepted as the standard treatment of preterm babies with RDS . Objective : The objective of this study was to analyze the incidence and outcome of surfactant replacement therapy in preterm babies with RDS . Methodology : This is Quantitative retrospective study , conducted in Neonatal Intensive Care Units (NICU) of Ibn Sina Teaching Hospital , Sirte , Libya . Study duration was of three years period ( May – 2019 to May – 2022 ) . Preterm babies from 24 wks to 36 wks of gestation with RDS received SRT were included in this study . The surfactant was administrated intra- tracheally according to standard procedures . Results :In this study of 41 preterm babies with RDS received SRT , 30 ( 73.2% ) were male and 11 ( 26.8% ) were female . The mean gestational age was 33.12 weeks . Among 41 preterm babies with RDS receiving SRT , 21 ( 51.2% ) discharged from the hospital and 20 ( 48.8% ) expired . Maximum survival was seen in the gestational age of ≥32 wks and birth weight ≥ 1500 gms . Conclusion : The use of SRT has improved the survival outcome and decreased the associated morbidities in babies with RDS . The maximum impact of survival was seen in the oreterm babies of ≥ 32 weeks with birth weight of ≥ 1500 grams .

Diagnostic utility of lung ultrasound in predicting the need for surfactant therapy in preterm neonates with respiratory distress.

Lung ultrasound is an accurate and early predictor for surfactant replacement therapy in respiratory distress syndrome (RDS) as compared to clinical parameters and chest x-ray. However, lung pathologies for respiratory distress at birth have overlapping symptomatology and low middle-income countries have a higher incidence of congenital pneumonia, in addition to RDS, making the immediate diagnosis difficult. Thus, there is a need for assessing a cutoff for lung ultrasound scores in the given setting. The primary objective was to determine the diagnostic accuracy of the lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to the fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A), and chest x-ray (CXR) findings. A prospective observational study was carried out at a tertiary-level neonatal intensive care unit in India in 2022 enrolling 100 neonates <34 weeks gestational age with respiratory distress at birth. After initial stabilization of the neonate, LUS was performed and baseline parameters were noted. Surfactant was administered as per the 2019 European Consensus guidelines and LUS was repeated after 6 h of therapy. The mean gestation of enrolled neonates was 31.06 ± 2.12 weeks and the mean birthweight was 1,412 ± 391 g. Approximately 58% were diagnosed with RDS and 30% had congenital pneumonia. Surfactant was administered to 40% of neonates. The cutoff LUS for surfactant therapy was 7 [area under the curve (AUC) 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 92.5%, specificity 96.67%, PPV 94.87%, and NPV 95.08%] and the cutoff LUS for the second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001). The score decreased by 3.24 (2.44-4.05) after 6 h of the first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650), and CXR findings (0.801). The study predicted an optimal LUS cutoff of 7 and 10 for the need for the first dose of surfactant and re-treatment, respectively, in neonates <34 weeks gestational age with respiratory distress.

Comparison of the efficacy of two natural surfactants (BERAKSURF and BLES) in the treatment of respiratory distress syndrome among preterm neonates

BackgroundThe benefit of surfactant replacement therapy for respiratory distress syndrome (RDS) has been demonstrated. However, some surfactants are expensive and usually inaccessible. Consequently, the Iranian Survanta was produced, but its effect on complications and mortality of RDS is unknown. This study aimed to compare the therapeutic outcomes of Iranian surfactant (beraksurf) and BLES (bovine lipid extract surfactant) on RDS treatment among preterm neonates.MethodsThis triple blinded randomized controlled trial study was performed on 128 eligible neonates diagnosed with RDS in Afzalipour hospital in Kerman, Iran. Diagnosis of RDS, gestational age of 28–34 weeks and weight ≥ 1 kg were considered as inclusion criteria. Congenital anomalies such as congenital cyanotic heart diseases, digestive system anomalies and chromosome abnormalities were the exclusion criteria Neonates were randomly assigned into two equal groups: (1) those treated with BLES (n = 64) and (2) those treated with beraksurf (n = 64). Complications including patent ductus arteriosus (PDA), sepsis, intraventricular hemorrhage (IVH), pneumothorax, pulmonary hemorrhage, mortality, and also, the number of days required for invasive mechanical ventilation (using ventilator) and non-invasive continuous positive airway pressure (CPAP) were evaluated for all neonates. The risk ratio (RR) was calculated at 95% of confidence intervals (CI).ResultsCompared with BLES group, the RR estimate among neonates in beraksurf group was 0.89 (0.66–1.20) for PDA, 0.71 (0.23–2.13) for IVH, 0.44 (0.14–1.36) for sepsis, 0.35 (0.13–0.93) for pneumothorax, 0.33 (0.12–0.86) for pulmonary hemorrhage, and 0.55 (0.28–1.05) for mortality.ConclusionsDespite advances in the use of exogenous surfactants for the treatment of neonatal respiratory distress syndrome; There are still some controversial topics in this field. The results obtained in the present study showed that the two types of surfactant (BERAKSURF and BLES) have similar efficacy for the treatment and short-term outcomes in preterm infants with respiratory distress syndrome. Therefore, due to the cost-effectiveness of BRAKSURF compared to BLES, We recommend choosing BERAKSURF in terms of treatment.

Inhaled pulmonary surfactant biomimetic liposomes for reversing idiopathic pulmonary fibrosis through synergistic therapeutic strategy

Idiopathic pulmonary fibrosis (IPF) stands as a highly heterogeneous and deadly lung disease, yet the available treatment options remain limited. Combining myofibroblast inhibition with ROS modulation in damaged AECs offers a comprehensive strategy to halt IPF progression, but delivering drugs separately to these cell types is challenging. Inspired by the successful application of pulmonary surfactant (PS) replacement therapy in lung disease treatment, we have developed PS nano-biomimetic liposomes (PSBs) to utilize its natural transport pathway for targeting AECs while reducing lung tissue clearance. In this collaborative pulmonary drug delivery system, PSBs composed of DPPC/POPG/DPPG/CHO (20:9:5:4) were formulated for inhalation. These PSBs loaded with ROS-scavenger astaxanthin (AST) and anti-fibrosis drug pirfenidone (PFD) were aerosolized for precise quantification and mimicking patient inhalation. Through aerosol inhalation, the lipid membrane of PSBs gradually fused with natural PS, enabling AST delivery to AECs by hitchhiking with PS circulation. Simultaneously, PFD was released within the PS barrier, effectively penetrating lung tissue to exert therapeutic effects. In vivo results have shown that PSBs offer numerous therapeutic advantages in mice with IPF, particularly in terms of lung function recovery. This approach addresses the challenges of drug delivery to specific lung cells and offers potential benefits for IPF patients.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study)

BackgroundThe management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT.Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group.Methods/designIn this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks’ gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group.DiscussionBased on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores.Trial registrationClinicalTrials.gov identifier NCT05198375. Registered on 20 January 2022.

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.

Comparison of mortality and short-term outcomes between classic, intubation-surfactant-extubation, and less invasive surfactant administration methods of surfactant replacement therapy.

Intubation-Surfactant-Extubation (InSurE) and less invasive surfactant administration (LISA) are alternative surfactant replacement therapy methods for reducing the complications associated with invasive mechanical ventilation. This study aimed to compare the Classic, InSurE, and LISA methods in Very-Low-Birth-Weight infants (VLBWIs) in South Korea. The Korean Neonatal Network (KNN) enrolled VLBWIs born between January 1, 2019 and December 31, 2020. They were analyzed retrospectively to compare the duration of respiratory support, length of hospitalization, mortality, and short-term outcomes of the three groups. The duration of invasive ventilator support was shorter in the following order: InSurE (3.99 ± 11.93 days), LISA (8.78 ± 29.32 days), and the Classic group (22.36 ± 29.94 days) (p = 0.014, p < 0.01) and InSurE had the shortest hospitalization (64.91 ± 24.07 days, p < 0.05) although the results couldn't adjust for confounding factor because of irregular distribution. InSurE had the lower risk of intraventricular hemorrhage (IVH) grade II-IV [odds ratio (OR) 0.524 [95% confidence interval (CI): 0.287-0.956], p = 0.035] than in the Classic group. Mortality was lower in the InSurE [OR 0.377 (95% CI: 0.146-0.978), p = 0.045] and LISA [OR 0.296 (95% CI: 0.102-0.862), p = 0.026] groups than in the Classic group. There was a reduced risk of moderate to severe bronchopulmonary dysplasia (BPD) [OR 0.691 (95% CI: 0.479-0.998, p = 0.049), OR 0.544 (95% CI: 0.355-0.831, p = 0.005), respectively], pulmonary hypertension [OR 0.350 (95% CI: 0.150-0.817, p = 0.015), OR 0.276 (95% CI: 0.107-0.713, p = 0.008), respectively], periventricular leukomalacia (PVL) [OR 0.382 (95% CI: 0.187-0.780, p = 0.008), OR 0.246 (95% CI: 0.096-0.627, p = 0.003), respectively], and patent ductus arteriosus (PDA) with treatment [OR 0.628 (95% CI: 0.454-0.868, p = 0.005), OR 0.467 (95% CI: 0.313-0.696, p < 0.001) respectively] in the InSurE and LISA groups compared to the Classic group. InSurE showed the lowest duration of invasive ventilator support, length of hospitalization. InSurE and LISA exhibited reduced mortality and decreased risks of moderate to severe BPD, pulmonary hypertension, PVL, and PDA with treatment compared to the Classic group.

Surface Pressure-Area Mechanics of Water-Spread Poly(ethylene glycol)-Based Block Copolymer Micelle Monolayers at the Air-Water Interface: Effect of Hydrophobic Block Chemistry.

Amphiphilic block copolymer micelles can mimic the ability of natural lung surfactant to reduce the air-water interfacial tension close to zero and prevent the Laplace pressure-induced alveolar collapse. In this work, we investigated the air-water interfacial behaviors of polymer micelles derived from eight different poly(ethylene glycol) (PEG)-based block copolymers having different hydrophobic block chemistries to elucidate the effect of the core block chemistry on the surface mechanics of the block copolymer micelles. Aqueous micelles of about 30 nm in hydrodynamic diameter were prepared from the PEG-based block copolymers via equilibration-nanoprecipitation (ENP) and spread on the water surface using water as the spreading medium. Surface pressure-area isotherm and quantitative Brewster angle microscopy (QBAM) measurements were performed to investigate how the micelle/monolayer structures change during lateral compression of the monolayer; widely varying structural behaviors were observed, including the wrinkling/collapse of micelle monolayers and deformation and/or the desorption of individual micelles. By bivariate correlation regression analysis of surface pressure-area isotherm data, it was found that the rigidity and hydrophobicity of the hydrophobic core domain, which are quantified by glass-transition temperature (Tg) and water contact angle (θ) measurements, respectively, are coupled factors that need to be taken into account concurrently in order to control the surface mechanical properties of polymer micelle monolayers; micelles having rigid and strongly hydrophobic cores exhibited high surface pressure and a high compressibility modulus under high compression. High surface pressure and a high compressibility modulus were also found to be correlated with the formation of wrinkles in the micelle monolayer (visualized by Brewster angle microscopy (BAM)). From this study, we conclude that polymer micelles based on hydrophobic block materials having higher Tg and θ are more suitable for surfactant replacement therapy applications that require the therapeutic surfactant to produce a high surface pressure and modulus at the alveolar air-water interface.

Optimal timing and cutoff range of lung ultrasound in predicting surfactant administration in neonates: A meta-analysis and systematic review.

Timely application of surfactant replacement therapy is critical for neonates with respiratory distress syndrome (RDS). Presently, early clinical decision on surfactant use relies solely on ventilator parameters. However, ventilator parameters are unable to truly recapitulate the extent of surfactant deficiency. Lung ultrasound has been increasingly used in the early prediction of surfactant use in recent years, but its predictive value remains unclear. Therefore, we conducted this study to examine its predictive value in surfactant use and determine the optimal timing and cutoff value. Studies on neonates with respiratory distress or diagnosed with RDS were collected from PubMed, Embase, Cochrane Library, and Web of Science. Primary outcomes included sensitivity, specificity, and positive and negative predictive values of lung ultrasound. Ten eligible studies with 1162 participants were included. The sensitivity and specificity of lung ultrasound in predicting surfactant use were 0.86 (95% CI: 0.81-0.90) and 0.82 (95% CI: 0.71-0.90), respectively. Lung ultrasound performed within 1-3 h after birth had a sensitivity of 0.89 (95% CI: 0.79-0.95) and a Youden's index of 0.67. Compared with a lung ultrasound score (LUS) cutoff of ≤6/7, ≤8, >5, >6/7, and >8, a LUS cutoff of ≤5 had higher Youden's index (0.73) and sensitivity (0.94, 95% CI: 0.85-0.97) in predicting surfactant use. Lung ultrasound is effective for predicting surfactant use in neonates. Lung ultrasound within 1-3 h after birth and a LUS cutoff of 5 are recommended. However, the symptoms and oxygenation of the neonatal patients must also be considered.

Outcomes Comparison of Early versus Late Surfactant Replacement Therapy in Neonates with Respiratory Distress Syndrome

Objective: To compare durations of invasive mechanical ventilator (IMV), other types of ventilator support and neonatal outcomes between neonates who received early versus late surfactant replacement therapy (E-SRT vs. L-SRT). Materials and Methods: This retrospective study included neonates with gestational age (GA) less than 35 weeks or birth weight (BW) less than 2,000 grams, born between January 1, 2017 to December 31, 2021. Neonates who received SRT before 2 hours of life were defined as E-SRT and neonates who received SRT later were defined as L-SRT. Durations of IMV, other types of ventilator support, neonatal outcomes and length of stays were documented. Results: Eighty-three neonates had received SRT with 52 (62.7%) had E-SRT and 31 (37.3%) had L-SRT. Neonates in E-SRT group had significantly lower GA and BW than neonates in L-SRT group (median GA 27 vs. 30 weeks; p = 0.002 and median BW 885 vs. 1330 grams; p = 0.003) and had longer duration of IMV but not significant (median 19.0 vs. 10.5 days; p = 0.219). There were no significant differences in durations of other types of ventilator support. After adjusted for sex, GA and BW, there were no significant differences in neonatal outcomes between neonates in each group. Ventilator-associated pneumonia (VAP) and septicemia were independent factors associated with prolonged IMV, ventilator supports and length of stays. Conclusion: Timing of SRT was not associated with duration of IMV. VAP and septicemia were important factors prolonging ventilator durations and length of stays and should be prevented.Keywords: surfactant replacement therapy, respiratory distress syndrome, timing of surfactant, neonatal outcomes

Polymer Lung Surfactants Attenuate Direct Lung Injury in Mice.

If not properly managed, acute lung injuries, either through direct or indirect causes, have the potential to present serious risk for many patients worldwide. One of the mechanisms for the transition from acute lung injury (ALI) to the more serious acute respiratory distress syndrome (ARDS) is the deactivation of the native lung surfactant by injury-induced infiltrates to the alveolar space. Currently, there are no surfactant replacement therapies that are used to treat ALI and subsequent ARDS. In this paper, we present an indepth efficacy study of using a novel polymer lung surfactant (PLS, composed of poly(styrene-block-ethylene glycol) (PS-PEG) block copolymer micelles), which has unique properties compared to other tested surfactant replacements, in two different mouse models of lung injury. The results demonstrate that pharyngeal administration of PLS after the instillation of either acid (HCl) or lipopolysaccharide (LPS) can decrease the severity of lung injury as measured by multiple injury markers.

Surfactant Proteins SP-B and SP-C in Pulmonary Surfactant Monolayers: Physical Properties Controlled by Specific Protein-Lipid Interactions.

The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled air and the circulation. Despite decades of advancements in the study of the pulmonary surfactant, the molecular scale behavior of the surfactant and the inherent role of the number of different lipids and proteins in surfactant behavior are not fully understood. The most important proteins in this complex system are the surfactant proteins SP-B and SP-C. Given this, in this work we performed nonequilibrium all-atom molecular dynamics simulations to study the interplay of SP-B and SP-C with multicomponent lipid monolayers mimicking the pulmonary surfactant in composition. The simulations were complemented by z-scan fluorescence correlation spectroscopy and atomic force microscopy measurements. Our state-of-the-art simulation model reproduces experimental pressure-area isotherms and lateral diffusion coefficients. In agreement with previous research, the inclusion of either SP-B and SP-C increases surface pressure, and our simulations provide a molecular scale explanation for this effect: The proteins display preferential lipid interactions with phosphatidylglycerol, they reside predominantly in the lipid acyl chain region, and they partition into the liquid expanded phase or even induce it in an otherwise packed monolayer. The latter effect is also visible in our atomic force microscopy images. The research done contributes to a better understanding of the roles of specific lipids and proteins in surfactant function, thus helping to develop better synthetic products for surfactant replacement therapy used in the treatment of many fatal lung-related injuries and diseases.

Effect of Evidence-Based Guideline on Nurses' Performance Regarding Care of High-Risk Neonates Undergoing Surfactant Replacement Therapy

Background: The main course of treatment for respiratory distress syndrome includes surfactant replacement therapy (SRT), which prevents alveolar collapse, boosts survival, and lowers respiratory morbidities. Evidence-based nursing guidelines improve neonatal care and bridge the gap between research findings and clinical practice. Aim of the study was to assess the effect of evidence-based guidelines on nurses' performance regarding care of high-risk neonates undergoing SRT. Design: a quasi–experimental research design was utilized to conduct this study. Setting: This study was conducted in Neonatal Intensive Care Unit (NICU) at Benha University Hospital. Sample: A convenient sample of all available nurses (64 nurses) who were responsible for providing care to high-risk neonates and purposive sample of high-risk neonates (30 neonates) who receive SRT and admitted to NICUs. Tools of data collection: Two tools were used: Tool (I): A structured interviewing questionnaire sheet to assess characteristics of the studied subjects and nurses' knowledge regarding care of high-risk neonates undergoing SRT. Tool (II): Observational checklists to assess nurses’ practices regarding care of high-risk neonates undergoing SRT. Results: The majority of the studied nurses had satisfactory total level of knowledge in post-implementation of guideline, there was an improvement in total nurses practices post-implementation of guideline compared to pre-implementation. Conclusion: The evidence-based guideline was effective in improving nurses’ knowledge and practices regarding care of high-risk neonates undergoing SRT post- implementation of guideline. Recommendation: Enhancing nurses’ knowledge and practices regarding care of high-risk neonates undergoing surfactant replacement therapy by encouraging them to attend periodical training courses.

Prevalence and Missed Cases of Respiratory Distress Syndrome Disease Amongst Neonatal Deaths Enrolled in the Kenya Child Health and Mortality Prevention Surveillance Network (CHAMPS) Program Between 2017 and 2021

Objectives. To describe RDS in neonatal deaths at the CHAMPS-Kenya site between 2017 and 2021. Methods. We included 165 neonatal deaths whose their Causes of death (COD) were determined by a panel of experts using data from post-mortem conducted through minimally invasive tissue specimen testing, clinical records, and verbal autopsy. Results. Twenty-six percent (43/165) of neonatal deaths were attributable to RDS. Most cases occurred in low birthweight and preterm neonates. From these cases, less than half of the hospitalizations were diagnosed with RDS before death, and essential diagnostic tests were not performed in most cases. Most cases received suboptimal levels of supplemental oxygen, and critical interventions like surfactant replacement therapy and mechanical ventilation were not adequately utilized when available. Conclusion. The study highlights the urgent need for improved diagnosis and management of RDS, emphasizing the importance of increasing clinical suspicion and enhancing training in its clinical management to reduce mortality rates.

Thermophoretic particle deposition in Carreau-Yasuda fluid over chemical reactive Riga plate

Marangoni convection is very useful in coating flow technology, surfactant replacement therapy for neonatal children, microfluidics, drying of semi-conductor vapors in microelectronics, foams, and film drainage in emulsions. The behavior of gyrotactic microorganisms and chemical reaction on the Marangoni convected Carreau-Yasuda liquid flowing over Riga plate with thermophoretic particle deposition is reported in this research. The Riga plate is self-possessed of magnets and electrodes. The fluid conducted electricity and the vertical Lorentz force has been exponentially increased. Thermal and mass species phenomena are investigated within the context of Dufour and Soret impacts. The PDEs are transformed into ODEs by the implication of suitable transformations. The resulting system of equations is solved by using homotopy analysis method (HAM). Using tables and graphs, the effects of dimensionless parameters on flow fields are described. The wall drag coefficient and pertinent flow rates are organized and stated. The results revealed that the temperature, concentration, and microorganisms profiles decay but the velocity profile augmented as the Marangoni ratio parameter increases.

THE OUTLOOKS FOR THE SURFACTANT REPLACEMENT THERAPY OF COVID-19 INDUCED RESPIRATORY DISTRESS SYNDROME IN CHILDREN

Nearly 6.5 million people have died worldwide from the COVID-19 pandemic. Improvement of pediatric patients survival depends on the continued provision of basic health services to women and children all over the world. The world scientific community must start more scientific clinical investigations and receive more data in order to know the impact of COVID-19 on children`s health andmortality, and to ensure that children and adolescents do not die from preventable events. Such trends in the spread of morbidity and mortality from COVID-19 require an interdisciplinary approach as soon as possible tofurther contain the spread of the disease and prevent complications in order to improve the quality of life. Insufficiently studied molecular changes in lung morpho-biology due to the action of COVID-19 complicate its clinical treatment. An in-depth genetic mechanisms investigation during pathogenetic disorders caused by virus can help in the development of new treatment methods, in articular, the use of surfactant drugs as a component of basic therapy. Recently, it became known that COVID-19-associated lung damage is characterized by typical pathophysiological changes for RDS. Diffuse alveolar damage occurs due to edema of the interstitium, the formation of hyaline membranes, as well as the proliferation of fibroblasts at the stage of recovery. When COVID-19 affects the lungs, surfactantsynthesis is dysregulated, as viral proteins suppress the expression of regulatory genes. Changes during the reparation process also lead to loss of surfactant function. Surfactant replacement therapy can be an alternative in the treatment of patients with COVID-19-associated lung damage, there are a number of studies that prove the effectiveness of such therapy in other infections. COVID-19 can be especially dangerous for children with chronic lung disease, congenital malformations, previously undiagnosed genetic defects in thesurfactant production system. However, timely use of surfactant replacement therapy can prevent one of the worst complications duringmechanical ventilation - air leakage syndrome.