Surfactant Replacement Therapy Research Articles

Surfactant replacement therapy: from biological basis to current clinical practice.

This review summarizes the current knowledge on the physiological action of endogenous and exogenous pulmonary surfactant, the role of different types of animal-derived and synthetic surfactants for RDS therapy, different modes of administration, potential risks and strategies of ventilation, and highlights the most promising aims for future development. Scientists have clarified the physicochemical properties and functions of the different components of surfactant, and part of this successful research is derived from the characterization of genetic diseases affecting surfactant composition or function. Knowledge from functional tests of surfactant action, its immunochemistry, kinetics and homeostasis are important also for improving therapy with animal-derived surfactant preparations and for the development of modified surfactants. In the past decade newly designed artificial surfactants and additives have gained much attention and have proven different advantages, but their particular role still has to be defined. For clinical practice, alternative administration techniques as well as postsurfactant ventilation modes, taking into account alterations in lung mechanics after surfactant placement, may be important in optimizing the potential of this most important drug in neonatology.

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.

The Comparison of LISA and INSURE techniques in term of neonatal morbidities and mortality among premature infants.

Background and aim of the work:Respiratory distress syndrome (RDS) is the most common cause of respiratory failure among premature infants. The most important choice for the treatment of RDS is still exogenous surfactant replacement therapy and respiratory support. Today, there are some different surfactant applying techniques. In this study, we aimed to evaluate the effects of the surfactant administration techniques in premature infants less than 33 weeks of gestational age.Methods:The medical data were collected retrospectively from the medical records of Baskent University, Konya Training and Research Hospital between 2010 and 2016. The patient divided into two subgroups as Less Invasive Surfactant Administration (LISA) group (n: 35) and Intubation- Surfactant administration and rapid Extubation (INSURE) group (n: 30). Two surfactant administration techniques were evaluated on the neonatal morbidities and mortality among premature infants.Results:There were no significant differences in maternal and neonatal characteristics between the two groups. Duration on the nasal continues positive airway pressure (nCPAP) is significantly higher in the LISA group as compared with the INSURE group (p<0.001). And also between two groups, there were no significant differences in term of neonatal mortality and morbidities.Conclusion:The technique of the surfactant administration has no effect on the postnatal morbidities. LISA method is safe and effective as much as INSURE method, which is still a good alternative in centers with lack of experience about LISA. We need to perform studies that have larger sample size and prospective randomized controlled trials. (www.actabiomedica.it)

Safety of Early Rescue Surfactant Replacement Therapy for Preterm Neonates with Respiratory Distress Syndrome at Neonatal Intensive Care Unit of a Tertiary Hospital

Introduction: Respiratory distress syndrome (RDS) is an acute disease of preterm neonates and is caused by the deficiency of pulmonary surfactant. Surfactant deficiency can lead to alveolar collapse, atelectasis, impaired gas exchange, severe hypoxia and acidosis. Surfactant replacement therapy (SRT) is an integral part of management of preterm neonates with respiratory distress syndrome. The objective of the study was to evaluate the safety of early rescue surfactant replacement therapy in RDS.&#x0D; Methods: This was a prospective observational study conducted in a 17 bedded teaching and referral NICU of Eastern Nepal over a period of seven months. All preterm neonates with clinical and radiological features of RDS were enrolled in the study. The safety of early rescue SRT was evaluated by measuring the outcomes: incidence of pulmonary haemorrhage, apnea, hypoxia and cardiac arrest. All data were entered into the worksheet of SPSS software version (19.0) and descriptive statistics including percentages and frequencies was analysed. The level of statistical significance adopted was p-value &lt; 0.05. &#x0D; Results: The survival rate of preterm babies with SRT was 64.7% (22 babies). The incidence / prevalence of pulmonary haemorrhage, apnea, hypoxia, and cardiac arrest during or immediately after SRT was 14.7%, 5.9%, 5.9% and 2.9% respectively. &#x0D; Conclusions: This study suggests that SRT is an effective, safe and feasible intervention in level-3 neonatal units and has the potential to reduce neonatal mortality. The study also emphasises on the fact that SRT should be provided in settings where there is adequate manpower, professional skills and desired infrastructure to administer surfactant.

A new clinical respiratory distress score for surfactant therapy in preterm infants with respiratory distress.

The guidelines for surfactant therapy are largely based on studies done in developed coun1tries wherein the facility infrastructure, patient profile, and clinical practices are different from low- and middle-income countries (LMICs). Though SRT is widely practiced in developing countries, there exists variability in clinical practice. Our objective was to identify the factors which would predict the need of surfactant administration and develop a "clinical respiratory distress (RD) score" for surfactant administration in preterm neonates with respiratory distress. A prospective observational study was conducted in 153 preterm infants (260/7 to 346/7 weeks gestation) with respiratory distress who were managed with CPAP and/or surfactant where indicated. Gestation < 32 weeks, no antenatal corticosteroid (ANS), hypothermia at admission, Apgar score < 3 at 1 minute, and Silverman score > 2 at 2 hours were found to be the significant factors in predicting surfactant requirement in multivariate regression analysis. A seven point scale was developed and categorized into two categories as < 4 and ≥ 4. The sensitivity, specificity, PPV, and NPV were 67%, 87%, 86%, and 68%, respectively, with a cutoff score ≥ 4. The positive likelihood ratio was 5.07 (95% CI 2.71-9.48), and negative likelihood ratio was 0.38 (95% CI 0.28-0.52). The observed rate of surfactant administration was found to be around 32% when the composite score was below four, and the rate increased to almost 86% when the composite score was ≥ 4. The predictive accuracy of the model was subsequently evaluated in a cohort of 56 preterm infants with respiratory distress.. Sensitivity, specificity and positive and negative predictive value during the validation phase were 97%, 73%, 85%, and 94%, respectively. With a composite score less than 4, the observed rate of surfactant administration was 6% (95% CI 1%-28%) as against the model predicted rate of 24%, while with composite score ≥ 4, the observed rate was 85% (95% CI 69%-94%) as against the model predicted rate of 90%.Conclusion: "Clinical RD score" is a simple score, which can be utilized for decision-making for early surfactant administration for preterm infants (260/7 to 346/7 weeks gestation) with respiratory distress.Trial Registration: NCT03273764What is Known:• Both CPAP and surfactant therapy are effective in management of preterm infants with RDS.• The efficacy of surfactant replacement therapy is better when it is administered early in the course of disease.What is New:• Many of the known risk factors for RDS do not predict surfactant requirement.• "Composite RD score" comprising of five independent predictors of surfactant requirement with a numeric cutoff may help decide which preterm neonates with respiratory distress need early surfactant administration in low- and middle-income countries.

Bronchopulmonary dysplasia.

To present a wide-ranging review of the literature on broncopulmonary dysplasia, covering new definitions, pathophysiology, prevention, treatment, prognosis and progression.The most relevant articles published on the subject since it was first described in 1967 were selected from MEDLINE search results.Bronchopulmonary dysplasia is considered one of the primary causes of chronic lung disease among infants. It is associated with frequent and prolonged hospital admissions, in particular for pulmonary diseases, with high rates of mortality and alterations to neuropsychomotor development and pondero-statural growth. Pathogenesis is complex, being primarily influenced by prematurity, infection, supplementary oxygen and mechanical ventilation. Prevention involves appropriate prenatal care, the prevention of premature delivery, prenatal corticosteroids, surfactant replacement therapy and "protective" ventilatory strategies. Treatment of bronchopulmonary dysplasia patients demands a multidisciplinary team. When indicated, oxygen supplementation is extremely important. Despite increased risk of morbidity and mortality during the first years of life, long term progress is favorable in the majority of cases.Bronchopulmonary dysplasia has been and continues to be studied in great depth with the objective of identifying its causes and possible prevention and treatment strategies. Controversies remain with respect of these issues and also about the prognosis of these patients, in particular when the subject is long-term progress of "new" bronchopulmonary dysplasia patients.

Minimally invasive surfactant therapy versus intubation for surfactant administration in very low birth weight infants with respiratory distress syndrome

Minimally invasive surfactant therapy (MIST) is a new mode of surfactant administration without intubation to spontaneously breathing preterm infants with respiratory distress syndrome (RDS). The aims of this study were to assess the feasibility, efficacy and safety of using MIST to give surfactant for very low birth weight (VLBW) infants with RDS. In total, 53 VLBW infants who were born before 32 gestational weeks with spontaneous breathing, respiratory distress, and requiring surfactant therapy were divided into two groups. The infants in group A (n=29) were intubated and received surfactant replacement therapy via endotracheal tube, followed by mechanical ventilation (MV). The infants in group B (n=24) received tracheal instillation of surfactant via a semirigid vascular catheter during spontaneous breathing under nasal continuous positive airway pressure (nCPAP). After surfactant instillation, the infants in group B were still placed on nCPAP. Our data showed that infants in group B (MIST group) had significantly lower rate (P<0.05) of composite outcome of death or bronchopulmonary dysplasia (BPD), duration of intermittent positive airway pressure ventilation (IPPV) or MV, drug treatment of patent ductus arteriosus (PDA), and surgical ligation of PDA than group A. MIST is feasible, safe and it may reduce the composite outcome of death or BPD for VLBW infants with RDS requiring surfactant replacement therapy.

SP-B and SP-C analogues within CHF5633 synthetic surfactant probed by fluorescence labeling

Surfactant replacement therapy, commonly consisting of bovine or porcine lung surfactant extracts, is a life-saving treatment for preterm newborns that suffer for respiratory distress syndrome (RDS). Recently, a synthetic surfactant, CHF5633, has been developed by Chiesi Farmaceutici (Italy) for the treatment of neonatal RDS. CHF5633 contains two phospholipids forming multilamellar vesicles and two peptides which are analogues of surfactant protein B and surfactant protein C. By conjugating the solvatochromic fluorophore dansyl to the peptides we aimed at characterizing their environment and distribution within the formulation. The fluorescence properties of dansyl-conjugated SP-B Analogue and SP-C Analogue were characterized in different solvents and compared with their emission properties when individually formulated in CHF5633. Both peptides exhibited a close interaction with the phospholipid matrix, as observed for the natural counterparts. In particular, SP-C Analogue is more deeply inserted in the phospholipid bilayer compared to SP-B Analogue. The localization of the fluorescent peptides within CHF5633 did not experience significant changes over a storage period of nine months.

Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures. Our recently developed numerical model has demonstrated that transition from success to failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. Here, we present the first numerical simulations of surfactant delivery into a realistic asymmetric conducting airway tree of the rat lung and compare them with experimental results. The roles of dose volume (VD), flow rate, and multiple aliquot delivery are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with our experimental data. In particular, we show that the monopodial architecture of the rat airway tree plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. In addition, we observe that increasing VD increases the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume, VCC. Finally, we quantitatively assess the improvement resulting from a multiple aliquot delivery, a method sometimes employed clinically, and find that a much larger fraction of surfactant reaches the alveolar regions in this case. This is the first direct qualitative and quantitative comparison of our numerical model with experimental studies, which enhances our previous predictions in adults and neonates while providing a tool for predicting, engineering, and optimizing patient-specific surfactant delivery in complex situations.

Cardiorespiratory Physiology following Minimally Invasive Surfactant Therapy in Preterm Infants

Introduction: Surfactant replacement therapy through the endotracheal tube has been shown to improve lung compliance and reduce pulmonary pressures. Minimally invasive surfactant therapy (MIST) combines the benefits of continuous positive airway pressure (CPAP) and surfactant for spontaneously breathing preterm infants. We aimed to characterize the haemodynamic changes accompanying the first dose of MIST in preterm infants. Methods: Poractant alfa (200 mg/kg) was administered as MIST while on CPAP support. Echocardiograms were performed before (T1) and 30 (T2) and 60 min (T3) after MIST to assess serial change. Results: Twenty infants (mean gestational age 29.5 ± 2.8 weeks, median birth weight 1,102 g, IQR 840–1,940) received MIST at a median age of 16 h (IQR 3–24). FiO₂ decreased significantly at 30 min (0.41 ± 0.08 to 0.27 ± 0.03, p < 0.001). Significant changes were noted at T2 for ductal parameters (decreased % time right to left shunt: 25% [15–33] to 14.5% [6–22], p = 0.013). Reduced pulmonary vascular resistance (PVR; increased pulmonary artery time velocity ratio 0.23 ± 0.05 to 0.28 ± 0.04 ms, p = 0.004) and improved longitudinal (tricuspid annular plane systolic excursion 4.5 ± 0.8 to 5.3 ± 0.9 mm, p = 0.004) and global (fractional area change 25 ± 2.3 vs. 27 ± 2%, p = 0.002) ventricular function were noted. Conclusions: This is the first study assessing cardiovascular adaptation to MIST, a procedure fast gaining acceptance in the neonatal community. Increased pulmonary blood flow is likely due to a combined effect of increased ductal flow, reduced PVR, and increased ventricular function.

A Review on Hydrodynamical Stability of Thin Film Flowing Along an Inclined Plane

The dynamics and stability of thin liquid films have fascinated scientists over many decades. Thin film flows occur over a wide range of length scales and are central to numerous areas of engineering, geophysics and biophysics. These include nanofluidics and microfluidics, lava flows, coating flows, tear-film rupture, dynamics of continental ice sheets and surfactant replacement therapy. Study of falling film instability has its wide applications in the practical field of industry and engineering. Practical applications in industrial processing motivate the recent research to investigate the factors which may affect the formation of waves on the surface of the coating layers and/or to determine the ways to overcome or to minimize the unwanted factors within the desired limit of tolerance. The dynamics of a liquid film flowing down a plane under the action of gravity is a problem which appears in many technological and natural systems, namely large scale geophysical environments such as lava flows or spillways, daily life scenarios such as water flowing down a window pane or a slippery road on a rainy day, chemical engineering processes such as evaporators, heat exchanges and falling film reactors or surface coating. The aim of this paper is to throw light on the studies conducted on hydrodynamical stability.

Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs

BackgroundThe amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb.MethodsTwelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200 mg/kg) and 5 lambs were managed with mechanical ventilation for 120 min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH2O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant.ResultsSurfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance (p < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs.ConclusionsApplying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.

Tracing exogenous surfactant in vivo in rabbits by the natural variation of 13C

BackgroundRespiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug.MethodsForty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn’s multiple comparison were used to assess differences among experimental groups.ResultsBased on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24–40] of dose.ConclusionsWe reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques.

Surfactant dysfunction and alveolar collapse are linked with fibrotic septal wall remodeling in the TGF-β1-induced mouse model of pulmonary fibrosis

In human idiopathic pulmonary fibrosis (IPF), collapse of distal airspaces occurs in areas of the lung not (yet) remodeled. Mice lungs overexpressing transforming growth factor-β1 (TGF-β1) recapitulate this abnormality: surfactant dysfunction results in alveolar collapse preceding fibrosis and loss of alveolar epithelial type II (AE2) cells' apical membrane surface area. Here we examined whether surfactant dysfunction-related alveolar collapse due to TGF-β1 overexpression is linked to septal wall remodeling and AE2 cell abnormalities. Three and 6 days after gene transfer of TGF-β1, mice received either intratracheal surfactant (Surf-groups: Curosurf®, 100 mg/kg bodyweight) or 0.9% NaCl (Saline-groups). On days 7 (D7) and 14 (D14), lung mechanics were assessed followed by design-based stereology at light and electron microscopic level to quantify structures. Compared with Saline, Surf showed significantly improved tissue elastance, increased numbers of open alveoli, as well as reduced alveolar size heterogeneity on D7. Deterioration in lung mechanics was highly correlated to the loss of open alveoli. On D14, lung mechanics, number of open alveoli, and alveolar size heterogeneity remained significantly improved in the Surf-group. Volumes of extracellular matrix and collagen fibrils in septal walls were significantly reduced, whereas the apical membrane surface area of AE2 cells was increased in Surf compared with Saline. In remodeled tissue with collapsed alveoli, three-dimensional reconstruction of AE2 cells based on scanning electron microscopy array tomography revealed that AE2 cells were trapped without contact to airspaces in the TGF-β1 mouse model. Similar observations were made in human IPF. Based on correlation analyses, the number of open alveoli and of alveolar size heterogeneity were highly linked with the loss of apical membrane surface area of AE2 cells and deposition of collagen fibrils in septal walls on D14. In conclusion, surfactant replacement therapy stabilizes alveoli and prevents extracellular matrix deposition in septal walls in the TGF-β1 model.

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.

Helical side chain chemistry of a peptoid-based SP-C analogue: Balancing structural rigidity and biomimicry.

Surfactant protein C (SP-C) is an important constituent of lung surfactant (LS) and, along with SP-B, is included in exogenous surfactant replacement therapies for treating respiratory distress syndrome (RDS). SP-C's biophysical activity depends upon the presence of a rigid C-terminal helix, of which the secondary structure is more crucial to functionality than precise side-chain chemistry. SP-C is highly sequence-conserved, suggesting that the β-branched, aliphatic side chains of the helix are also important. Nonnatural mimics of SP-C were created using a poly-N-substituted glycine, or "peptoid," backbone. The mimics included varying amounts of α-chiral, aliphatic side chains and α-chiral, aromatic side chains in the helical region, imparting either biomimicry or structural rigidity. Biophysical studies confirmed that the peptoids mimicked SP-C's secondary structure and replicated many of its surface-active characteristics. Surface activity was optimized by incorporating both structurally rigid and biomimetic side chain chemistries in the helical region indicating that both characteristics are important for activity. By balancing these features in one mimic, a novel analogue was created that emulates SP-C's in vitro surface activity while overcoming many of the challenges related to natural SP-C. Peptoid-based analogues hold great potential for use in a synthetic, biomimetic LS formulation for treating RDS.

Comparing the Efficacy of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Positive Pressure Ventilation in Early Management of Respiratory Distress Syndrome in Preterm Infants.

ObjectivesThere is a tendency to use noninvasive ventilation (NIV) as a substitute for mechanical ventilation in preterm infants who need respiratory support. Two important modes of NIV include nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV). We sought to compare the efficacy of NCPAP and NIPPV as early respiratory support in preterm infants with respiratory distress syndrome in reducing the need for intubation, surfactant administration, and mechanical ventilation.MethodsWe conducted a randomized clinical trial. Sixty-one preterm infants with a gestational age of 28–32 weeks and a birth weight < 1500 g were randomly allocated to early NCPAP (n = 31) or NIPPV (n = 30) groups. The primary outcome was the need for intubation and mechanical ventilation in first 72 hours of life and the secondary outcome was oxygen dependency beyond day 28 post-birth.ResultsSurfactant replacement therapy was done in 15 neonates (50.0%) in the NIPPV group and 19 neonates (61.3%) in the NCPAP group, odds ratio (OR) = 1.58 (95% confidence interval (CI): 0.57–4.37; p = 0.370). Intubation and mechanical ventilation in the first 72 hours of life were needed in five cases (16.7%) in the NIPPV group and two cases (6.5%) in the NCPAP group, OR = 2.90 (95% CI: 0.51–16.27; p = 0.250). The mean duration of hospitalization was 26.2±17.4 days in the NIPPV group and 38.4±19.2 days in the NCPAP group, p = 0.009. Bronchopulmonary dysplasia (BPD) occurred in two (6.7%) neonates in the NIPPV group and eight (25.8%) neonates in the NCPAP group, p = 0.080.ConclusionsNIPPV and NCPAP are similarly effective as initial respiratory support in preterm infants in reducing the need for mechanical ventilation and occurrence of BPD. The duration of hospitalization was significantly reduced using NIPPV in our study.KeywordsNasal Continuous Positive Airway Pressure; Preterm Infants; Mechanical Ventilation; Bronchopulmonary Dysplasia; Respiratory Distress Syndrome, Newborn.

On the rheology of pulmonary surfactant: Effects of concentration and consequences for the surfactant replacement therapy.

The role of pulmonary surfactant is to reduce the surface tension in the lungs and to facilitate breathing. Surfactant replacement therapy (SRT) aims at bringing a substitute by instillation into the airways, a technique that has proven to be efficient and lifesaving for preterm infants. Adapting this therapy to adults requires to scale the administered dose to the patient body weight and to increase the lipid concentration, whilst maintaining its surface and flow properties similar. Here, we exploit a magnetic wire-based microrheology technique to measure the viscosity of the exogenous pulmonary surfactant Curosurf® in various experimental conditions. The Curosurf® viscosity is found to increase exponentially with lipid concentration following the Krieger-Dougherty law of colloids. The Krieger-Dougherty behavior also predicts a divergence of the viscosity at the liquid-to-gel transition. For Curosurf® the transition concentration is found close to the concentration at which it is formulated (117 g L-1versus 80 g L-1). This outcome suggests that for SRT the surfactant rheological properties need to be monitored and kept within a certain range. The results found here could help in producing suspensions for respiratory distress syndrome adapted to adults. The present work also demonstrates the potential of the magnetic wire microrheology technique as an accurate tool to explore biological soft matter dynamics.

Outcome of Surfactant Replacement Therapy in Preterm Babies with Hyaline Membrane Disease at Neonatal Intensive Care Unit of a Tertiary Hospital

Introduction: Hyaline membrane disease (HMD) 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 HMD.&#x0D; Objective: The objective of this study was to analyze the outcome of surfactant replacement therapy in preterm babies with hyaline membrane disease.&#x0D; Methodology: This is a prospective observational study conducted at 10 bedded neonatal unit of Pediatrics Department, Kathmandu Medical College Teaching Hospital, Sinamangal. Study duration was of one year period (15 May 2017 – 14 May 2018). Preterm babies from 26 wks–35 wks of gestation with Hyaline Membrane Disease were included in this study whereas babies with lethal congenital malformations eg: Meningomyelocele, Anencephaly, Gastrochisis, Diaphragmatic Hernia were excluded. All preterm babies who had clinical and radiological features of HMD were considered for Surfactant Replacement Therapy (SRT). The surfactant (Survanta; Abboti Laboratories, USA; Dose: 4 ml/kg) was administered intra-tracheally according to standard procedures in four divided aliquot applying INSURE (intubation, surfactant administration and extubation to Bubble CPAP) Technique. Ethical clearance was received from Institutional Review Committee (IRC) of Kathmandu Medical College and Statistical analysis was done with SPSS 19 version with frequency and cross tabulation.&#x0D; Results: In this study of 30 preterm babies with HMD received SRT, 47% (14) were male and 53% (16) were female. The mean birth weight of preterm babies with HMD was 1372.17 ± 395 gms and mean gestational age was 30.1±2.6 weeks. Among 30 preterm babies with HMD receiving SRT, 73.3% (22 babies) discharged from the hospital and 6.3% (8 babies) expired. Among eight expired babies, five died due to pulmonary hemorrhage and three died due to septicemia with DIC. Maximum survival was seen in the gestational age of 30-35 wks and birth weight 1200-2100gms.&#x0D; Conclusion: The use of SRT has improved the survival outcome and decreased the associated morbidities in babies with HMD. The maximum impact of survival was seen among the preterm babies of 30- 35 weeks with birth weight of 1200 -2100 grams.

Risk Factors and Outcome of Neonatal Pneumothorax in Tuzla Canton.

Aim:The aim of this study was to analyze risk factors and outcome of neonatal pneumothorax in Tuzla Canton.Methods:Neonates with chest X-ray confirmed pneumothorax in University Clinical Center of Tuzla, within a three-year period, from January 2015 to December 2017, were retrospectively studied. Participants were evaluated for baseline characteristics, predisposing factors of neonatal pneumothorax, accompanying disorders and mortality.Results:During the observed three-year period 11425 neonates were born in Tuzla Canton, with 7.33 % of preterm births, and 604 neonates were treated in NICU, with 265 neonates who required mechanical ventilation. Neonatal pneumothorax (NP) was diagnosed in 22 patients (9 term, 13 preterm), 12 (54.5%) were male. The incidence was 0.20% of total births, respectively 3.64% of those treated in NICU. The mean gestational age were 35.1 ± 3.0 weeks and birth weight 2 506.8 ± 727.7 grams. NP was mostly unilateral (72.7%) and right-sided. The most commonly associated diseases were: respiratory distress syndrome, intracranial haemorrhage, pneumonia, transient tachypnea and sepsis. In 8 (36.4%) neonates, the underlying cause of NP could be mechanical ventilation (secondary), whereas in 14 (63.6%) NP was spontaneous, without previous mechanical ventilation, although 11 of them required mechanical ventilation after pneumothorax.Conclusion:All perinatal risk factors were investigate, and significant differences in two observed groups related to mechanical ventilation were found for birth weight, gestational age, Caesarean section, length of mechanical ventilation, surfactant replacement therapy and outcome. Three (13.64%) neonates with NP died, and among risk factors with poor outcome, significant was only Apgar score in the first minute ≤ 5.