Deficiency Of Pulmonary Surfactant Research Articles

Evaluation of the Copy Number Variants and Single-Nucleotide Polymorphisms of ABCA3 in Newborns with Respiratory Distress Syndrome-A Pilot Study.

Background and Objectives: Respiratory distress syndrome (RDS) in preterm infants commonly occurs due to the immaturity-related deficiency of pulmonary surfactant. Beyond prematurity, various environmental and genetic factors can influence the onset and progression of RDS. This study aimed to analyze three single-nucleotide polymorphisms (SNPs) of the ABCA3 gene to assess the ABCA3 gene as a candidate gene for susceptibility to RDS and overall survival in newborns and to evaluate the utility of MLPA in RDS neonatal patients. Materials and Methods: Three SNPs were chosen and genotyped in a cohort of 304 newborns. Data analysis and statistical tests were employed to examine allele frequencies, haplotypes, and measures of pairwise linkage disequilibrium. Results: There was no observed haplotype association with SNPs rs13332514 (c.1059G>A) and rs170447 (c.1741+33T>C) among newborns, both with and without RDS (p > 0.05). The minor C allele frequency of the ABCA3 rs323043 (c.1755G>C) SNP showed a significant increase in preterm infants with RDS. MLPA results indicated that the predominant findings were normal, revealing no CNVs in the genes ABCA3 and SFTPC that were investigated in our patients. Conclusions: The presence of the variant C allele in the rs323043 (c.1755G>C) SNP may be a risk factor for RDS in premature newborns.

The Effect of the Iranian Surfactant (Beraksurf) in the Treatment of Respiratory Distress Syndrome in Premature Neonates

Background: Respiratory distress syndrome (RDS) is a type of lung development defect that is commonly seen in preterm births. Deficiency of pulmonary surfactant due to immaturity is the principal cause of RDS in premature infants. This study was conducted with the aim of Iranian surfactant (Beraksurf)’s effect in treating RDS in premature neonates.
 Methods: In this study, all infants who were premature and had RDS were included in the study. Also, the infants were examined based on primary and secondary outcomes. Primary outcomes include the duration of need for nasal continuous positive airway pressure (NCPAP), number of surfactant administration, and secondary outcomes including bronchopulmonary dysplasia (BPD), pneumothorax, and pulmonary hemorrhage.
 Results: A total of 162 neonates with a mean gestational age of 31.28 ± 2.58 weeks were evaluated. The 120 people (74.1%) used medicine only on the first day, 19 people on other days, and 23 people on the first and second day. Also, 141 children (87.6%) were discharged from the hospital and unfortunately, 20 children (12.4%) died. The prevalence of pneumothorax, BPD, and pulmonary hemorrhage was 1.8%, 1.2%, and 1.2% respectively. Also, 69.7% needed less than five days of mechanical ventilation and 30.2% needed more than 5 days of mechanical ventilation.
 Conclusion: Considering getting better treatment results from taking Beraksurf, as well as fewer side effects and the fact that this drug is Iranian, and due to its easier access and cheaper price, we can pay more attention to the prescription of this drug.

Clinical auditing for surfactant therapy in preterms with respiratory distress syndrome: a single-center study

Background Respiratory distress syndrome (RDS) of prematurity is a major cause of morbidity and mortality in preterm infants, caused by deficiency of pulmonary surfactant and structural immaturity of the lungs. Preterms with RDS should be given a natural surfactant as early as possible. Early surfactant therapy (within 2 h of birth) should be considered for preterms with gestation periods less than or equal to 31 weeks if the need for intubation in the delivery room arises. Lack and unavailability of surfactant in middle-income and low-income countries can occur, and preterms with RDS are treated with ventilation only.Aim The aim of this study was to study the effectiveness of surfactant application in preterms less than 36 weeks with RDS. Short-term effectiveness was monitored by improvement of chest radiograph, oxygen saturation (SpO2), and blood gases with decreasing ventilatory settings after 6 h. Long-term effectiveness was monitored by fate, duration of oxygen therapy, and duration of hospital stay. Moreover, the adverse effects of surfactant were detected.Patients and methods This cross-sectional study was carried out over a period of 18 months in the neonatal ICUs of the Department of Pediatrics, Cairo University hospitals, and included 180 preterms less than 36 weeks of gestational age. We compared 90 preterms less than 36 weeks with RDS who received more than or equal to one dose of surfactant therapy, with 90 controls who had RDS and were eligible for the criteria of administration of surfactant but could not receive surfactant because of its unavailability in the unit at their time of admission. The two groups were compared regarding the period of ventilation, the improvement in ventilator settings and the capillary blood gases after surfactant application, hospital stay, and complications of prematurity.Results Surfactant application significantly improved the preterms, as seen in improvement of radiograph, capillary blood gases, and SpO2. Six hours after administration of surfactant in the case group, 59 (65.6%) cases showed an improvement in capillary blood gases, and after 6 h of ventilation in the control group, only 21 (23.3%) showed improvement in capillary blood gases, with a P value of 0.001. A total of 60 (66.7%) cases had an improved SpO2 after 4 h, but this was seen in only 17 (18.9%) controls, with a P value less than 0.001. Findings of RDS in chest radiograph showed improvement in 60 (66.7%) preterms in the cases group, whereas in the control group, 37 (41.1%) preterms were only improved. However, the mortality rates and the incidence of bronchopulmonary dysplasia were slightly higher in the group that received surfactant, with P values of 0.488 and 0.530, respectively.Conclusion Surfactant application showed significant improvement in preterms with RDS, as seen in improvement of radiograph, capillary blood gases, and SpO2. The mortality rate and the incidence of bronchopulmonary dysplasia were significantly higher in the surfactant group. Risk factors that significantly increased the mortality rates and the hospital stay in cases that received surfactant were very low body weight, gestational age less than 32 weeks, Downe’s score more than 7, severe pulmonary hypertension, and late-onset sepsis. Sustainable efforts to provide all preterms with RDS in low-middle income countries with surfactant therapy should be encouraged.

A novel synonymous ABCA3 variant identified in a Chinese family with lethal neonatal respiratory failure

BackgroundLethal respiratory failure is primarily caused by a deficiency of pulmonary surfactant, and is the main cause of neonatal death among preterm infants. Pulmonary surfactant metabolism dysfunction caused by variants in the ABCA3 gene is a rare disease with very poor prognosis. Currently, the mechanisms associated with some ABCA3 variants have been determined, including protein mistrafficking and impaired phospholipid transport. However, some novel variants and their underlying pathogenesis has not been fully elucidated yet. In this study we aimed to identify the genetic features in a family with lethal respiratory failure.MethodsWe studied members of two generations of a Chinese family, including a female proband, her parents, her monozygotic twin sister, and her older sister. Trio whole exome sequencing (WES) were used on the proband and her parents to identify the ABCA3 variants. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) were used on the monozygotic twin sister of proband to validate the ABCA3 synonymous variant and exon deletion, respectively. The potential pathogenicity of the identified synonymous variant was predicted using the splice site algorithms dbscSNV11_AdaBoost, dbscSNV11_RandomForest, and Human Splicing Finder (HSF).ResultsAll patients showed severe respiratory distress, which could not be relieved by mechanical ventilation, supplementation of surfactant, or steroid therapy, and died at an early age. WES analysis revealed that the proband had compound heterozygous ABCA3 variants, including a novel synonymous variant c.G873A (p.Lys291Lys) in exon 8 inherited from the mother, and a heterozygous deletion of exons 4–7 inherited from the father. The synonymous variant was consistently predicted to be a cryptic splice donor site that may lead to aberrant splicing of the pre-mRNA by three different splice site algorithms. The deletion of exons 4–7 of the ABCA3 gene was determined to be a likely pathogenic variant. The variants were confirmed in the monozygotic twin sister of proband by Sanger sequencing and qPCR respectively. The older sister of proband was not available to determine if she also carried both ABCA3 variants, but it is highly likely based on her clinical course.ConclusionsWe identified a novel synonymous variant and a deletion in the ABCA3 gene that may be responsible for the pathogenesis in patients in this family. These results add to the known mutational spectrum of the ABCA3 gene. The study of ABCA3 variants may be helpful for the implementation of patient-specific therapies.

The Experience of Surfactant Therapy in Severe COVID-19 Pneumonia: A Case Report

The COVID-19 pandemic has presented challenges to finding effective treatment for lung damage. Medical researchers from different countries recognize the deficiency of pulmonary surfactant (PS) as a significant cause of the alveolar collapse, followed by microatelectasis and severe disturbances in the ventilation-perfusion relationship. Due to the pathophysiological rationale, experimental confirmations, and accumulated clinical experience, the PS preparations can be used to treat patients with severe COVID-19. The article provides a description of a case when ST was successfully used in a patient with severe COVID-19 pneumonia.

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.
 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 < 0.05. 
 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. 
 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.

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.

The role of miR-431-5p in regulating pulmonary surfactant expression in vitro

BackgroundPulmonary surfactant is the complex mixture of lipid and protein that covers the alveolar surface. Pulmonary surfactant deficiency is one of the main causes of neonatal respiratory distress. Recent studies showed that miRNA plays an important role in lung development, but research into miR-431 regulation of pulmonary surfactant are sparse. In this study, we explored the regulatory role of miR-431-5p in the expression of pulmonary surfactant and identified its potential target gene, Smad4.MethodsThe bioinformatics tool TargetScan was used to predict the targets of miR-431. The expression of miR-431-5p was achieved via transfection of miR-431-5p mimics, an miR-431-5p inhibitor and corresponding negative control. The level of miR-431-5p was determined using quantitative real-time PCR. The CCK8 assay was conducted to confirm cell growth 12 h after transfection with miR-431-5p mimics, inhibitor or NC. Smad4 and surfactant-associated proteins in A549 were analyzed using western blot and quantitative real-time PCR.ResultsSmad4 was validated as a target of miR-431 in A549 cells. Overexpression of miR-431 accelerated A549 proliferation and inhibited A549 apoptosis. The mRNA and protein levels for the surfactant proteins (SP-A, SP-B, SP-C and SP-D) were found to be differentially expressed in A549 cells over- or under-expressing miR-431-5p.ConclusionOur results show that miR-431-5p is critical for pulmonary surfactant expression and that its regulation is closely related to the TGF-β/Smad4 pathway. These results will help us to study the pathophysiological mechanism of lung developmental diseases.

TREATMENT OF RESPIRATORY DISTRESS-SYNDROME IN PRETERM NEWBORNS WITH THE USE OF EXOGENOUS SURFACTANT (PORACTANT ALFA): CLINLCAL GUIDLINES

Respiratory distress-syndrome (RDS) is an acute lung disease that occurs mainly in pretermnewborns due to deficiency of pulmonary surfactant and immaturity of the respiratory system. Its symptoms appear shortly after birth, and the clinical course in the absence of treatment is characterized by a worsening condition during the first 2 days of life.Despite the improvement and effectiveness of the prevention and treatment of RDS, this disease remains an important cause of death in newborns. According to European data, mortality associated with RDS can reach 10%, and according to the latest official statistical data from the United States, this disease ranks 8thamong the most important causes of death in infants.According to official statistical data from obstetrical hospitals, the incidence of RDS in Ukraine in 2016 was 194 cases per 1000 premature babies. The majority of patients in modern Ukrainianneonatal intensive care units die from the complications associated with this disease, especially intraventricular hemorrhages.The clinical recommendations contain sections on the etiology, pathogenesis, clinical presentation, antenatal prevention of RDS with recommendations for stabilizationafter birth and further,at the neonatal intensive care unit. Separately, the metabolism of surfactant, the importance of drug selection and the correct dose of surfactant use, practical recommendations on its use, indications, preparation for use and administration techniques are presented taking into account the international evidence-based data.Clinical guideline was elaborated for neonatologists, pediatric anesthesiologists and residents to improve the quality of medical care for preterm newborns at risk for developing or having RDS; the optimization of methods of medical care for preterm newborns to decrease the incidence of the disease, development of complications and mortality of premature babies at risk for or developing RDS.

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.

Factores de riesgo asociados a la falla en el procedimiento INSURE (Intubación - Surfactante - Extubación) para la administración de surfactante en recién nacidos prematuros < 1,500 g

Neonatal Respiratory Distress Syndrome (RDS) is caused by pulmonary surfactant deficiency. The initial respiratory support is currently nasal continuous positive airway pressure (Nasal CPAP), and is associated with the decreased need of intubation and mechanical ventilation. The INSURE procedure (Intubation-Surfactant-Extubation) for surfactant administration, is associated with a lower need of supplementary oxygen at 28 days of life. The aim of this study is to identify the frequency of failure of the INSURE procedure, defined as the need for re-intubation in the following 72hours, the risk factors and neonatal outcomes associated with the failure of this procedure. Material and methodsAn observational, retrospective, analytical study was conducted that included all newborns with birth weight <1500g, and in whom surfactant was administered using the INSURE procedure, between 1 March 2011 and 31 March 2014. ResultsA total of 183 cases were managed using the INSURE procedure, finding that 38.8% of the failures were due to the technique, with the main cause being apnoea. Risk factors found were, a lower gestational age, lower birth weight, and a higher grade of respiratory distress prior to using INSURE. Within the neonatal outcomes, a significant association was found with the increased use of mechanical ventilation, days of supplemental oxygen, and bronchopulmonary disease, and mortality in the failure group. ConclusionAn increased risk of failure in the INSURE procedure was associated with lower gestational age and lower birth weight.

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call ‘endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named ‘exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

Use of Ambroxol and Treatment of Klebsiella Ozaenae in Extremely Low Birth Weight Preterm: Case Report and Literature Review

Introduction: Respiratory distress syndrome (RDS) is the most common respiratory complication occurring in preterm newborns due to deficiency of endogenous pulmonary surfactant. Ambroxol, is a promoter of fetal lung maturity and indicated as secretolytic therapy in bronchopulmonary diseases. Klebsiella ozaenae, whose antibiotic susceptibility data is limited, is associated with ozena; a primary atrophic rhinitis (AR), RTIs, cerebral abscess, meningitis, UTIs, and is one of the leading cause of (ICU) acquired pneumonia. This case study reports the use of post-natal intravenous amroxol to treat RDS, and use of cefoperazone sulbactam to treat Klebsiella ozaenae and Pseudomonas aeruginosa. Case Presentation: A Chinese preterm, extremely low birth weight female (birth weight was 750 grams) was delivered by emergency caesarian section to a pregnancy-induced hypertensive G2P2 mother at 27 weeks’ gestational age and was admitted in the pediatric ward because of severe dyspnoea with grunting respiration, tachypnoea, cyanosis and crackles in the lung fields. A working diagnosis of RDS was made and she was placed in incubator and neonatal continuous positive airway pressure (NCPAP) was applied immediately. She was managed with ambroxol for RDS and cefoperazone sulbactam for Klebsiella ozaenae and Pseudomonas aeruginosa bacteria and was successfully treated by 3 days’ intravenous gamma globulin therapy and 10 days’ antibiotics administration. On 67th day of hospitalization, baby was discharged with a body weight of more than 2100 grams. Conclusions: The early application of NCPAP and ambroxol reduced the severity of this disease in preterm neonate and improved the clinical course of RDS. The combination of cefoperazone and sulbactam is effective against both of K. ozaenae and Pseudomonas aeruginosa bacteria.

Ambroxol for women at risk of preterm birth for preventing neonatal respiratory distress syndrome.

Respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant (an active agent that keeps pulmonary alveoli open and facilitates the entry of air to the lungs, thus improving the oxygenation of the newborn).A number of interventions such as pulmonary surfactant and prenatal corticosteroids are used to prevent RDS. Ambroxol has been studied as a potential agent to prevent RDS, but effectiveness and safety has yet to be evaluated. To evaluate the efficacy and safety of giving ambroxol to pregnant women who are at risk of preterm birth, for preventing neonatal RDS. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 November 2013), CENTRAL (The Cochrane Library 2013, Issue 11),Embase (1988 to November 2013), MEDLINE (PubMed 1970 to November 2013), LILACS (1982 to November 2013), the WHO International Clinical Trials Registry Platform (ICTRP) (November 2013) and reference lists of retrieved studies. Randomised controlled trials (RCTs) comparing the administration of ambroxol given to pregnant women at risk of preterm birth versus placebo, antenatal corticosteroids (betamethasone or dexamethasone), or no treatment.We did not identify any trials comparing ambroxol with dexamethasone (corticosteroid) in this review. Nor did we identify any trials comparing ambroxol combined with corticosteroid versus corticosteroid alone, or placebo/no treatment. Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data. Data were checked for accuracy. We included 14 studies (in 18 trial reports), involving 1047 pregnant women at risk of preterm birth with 1077 newborns. However, three of the included studies did not report on this review's outcomes of interest. We carried out two main comparisons: ambroxol versus antenatal corticosteroids (betamethasone); and ambroxol versus placebo or no treatment. Seven RCTs provided data for our comparison of ambroxol versus corticosteroid (betamethasone) and two trials contributed data to our comparison of ambroxol compared to placebo or no treatment.The included studies were generally judged as having either 'low' risk of bias or 'unclear' risk of bias (because the trial reports provided insufficient details about methods of sequence generation, allocation concealment and blinding). Primary outcomesThere was no clear evidence of a difference in the incidence of RDS among newborns born to women who received ambroxol when compared to newborns of women who were given the corticosteroid, betamethasone (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.59 to 1.07, seven RCTs, 728 women/758 newborns, moderate quality evidence) or placebo/no treatment (average RR 0.74; 95% CI 0.46 to 1.20, two studies, 204 women/204 newborns,T2= 0.07; I(2)= 53%, low-quality evidence). Results were imprecise and consistent with appreciable benefit as well as negligible effect.Similarly, there was no clear evidence of a difference in the rates of perinatal mortality between the group of women who received ambroxol and women in the corticosteroid (betamethasone) group (RR 0.51, 95% CI 0.23 to 1.12, six studies, 648 women/657 newborns, moderate quality evidence) or the placebo/no treatment group (RR 0.61; 95% CI 0.19 to 1.98, one study, 116 women/116 newborns, low-quality evidence).In terms of maternal adverse effects, there was no clear differences (in nausea or vomiting) between those women who received ambroxol compared to either those women who received corticosteroids (betamethasone) (average RR 3.45; 95% CI 0.34 to 35.51, three studies, 305 women, T(2)= 2.82; I(2)= 67%, very low-quality evidence), or women who received placebo or no treatment (RR 1.79; 95% CI 0.45 to 7.13, one study, 116 women, low-quality evidence). No other adverse effects (e.g. diarrhoea, gastric irritation and headache) were reported in the included studies. Secondary outcomesFor the review's secondary outcomes, none of the included studies reported on the incidence of bronchopulmonary dysplasia, periventricular haemorrhage, necrotising enterocolitis or rate of maternal mortality.One small trial (involving 88 women) comparing ambroxol with placebo or no treatment, reported no difference between groups in terms of the need for mechanical ventilation in the neonate (RR 0.94; 95% CI 0.73 to 1.21, 88 women/88 babies, low-quality evidence) or the administration of pulmonary surfactant (RR 1.19; 95% CI 0.61 to 2.30, one RCT, 88 women/88 babies, low-quality evidence). This review is based on very low to moderate quality evidence from 14 small trials (many are published in the form of conference abstracts with minimal methodological details provided). There is insufficient evidence to support or refute the practice of giving ambroxol to women at risk of preterm birth for preventing neonatal RDS, perinatal mortality and adverse effects. More research is needed in order to fully evaluate the benefits and risks of this intervention.

Interaction of Particles with the Pulmonary Interface: Effects on Surface Elasticity

We present an experimental study of the interactions of negative and positive model particles and their influence on the surface elasticity of biomimetic pulmonary surfactant. In this purpose we have measured the adhesion force between negative (G) and positive (GS) particles and supported lipid bilayer by Atomic Force Spectroscopy. In addition, the modification in surface elasticity of lipid monolayer under quasistatic compression when interacting with negative and positive particles was investigated on a Langmuir trough. We found that, positive particles interact poorly with biomimetic pulmonary surfactant, therefore no modifications in surface elasticity were observed. Conversely, negative charged particles interact strongly with the biomimetic pulmonary surfactant, decreasing the surface elasticity. The results are directly relevant for understanding the interactions and the effects of particulate matter on pulmonary structures which could lead to pulmonary surfactant inhibition or deficiency causing severe respiratory distress or pathologies.

Charged particles interacting with a mixed supported lipid bilayer as a biomimetic pulmonary surfactant.

This study shows the interactions of charged particles with mixed supported lipid bilayers (SLB) as biomimetic pulmonary surfactants. We tested two types of charged particles: positively charged and negatively charged particles. Two parameters were measured: adsorption density of particles on the SLB and the diffusion coefficient of lipids by FRAPP techniques as a measure of interaction strength between particles and lipids. We found that positively charged particles do not adsorb on the bilayer, probably due to the electrostatic repulsion between positively charged parts of the lipid head and the positive groups on the particle surface, therefore no variation in diffusion coefficient of lipid molecules was observed. On the contrary, the negatively charged particles, driven by electrostatic interactions are adsorbed onto the supported bilayer. The adsorption of negatively charged particles increases with the zeta-potential of the particle. Consecutively, the diffusion coefficient of lipids is reduced probably due to binding onto the lipid heads which slows down their Brownian motion. The results are directly relevant for understanding the interactions of particulate matter with pulmonary structures which could lead to pulmonary surfactant inhibition or deficiency causing severe respiratory distress or pathologies.

Optical versus impedance lamellar body counts on the Sysmex XT‐2000 automated hematology analyzer (834.13)

Introduction: Respiratory distress syndrome, the ninth leading cause of newborn mortality in the US, is caused by fetal lung immaturity due to pulmonary surfactant deficiency. Lamellar body counts (LBC) are often employed for fetal lung maturity assessment. The Sysmex XT‐2000 hematology analyzer measures LBC in amniotic fluid using either impedance or optical platelet counts. The objective of this study was to compare impedance versus optical LBCs.Methods: LBC tests were performed on 18 residual frozen amniotic fluid specimens on a Sysmex XT‐2000 analyzer in an Intermountain Healthcare laboratory, following manufacturer’s instructions for impedance and optical platelet counts.Results: Results were highly correlated (r2=0.99). Mean impedance and optical LBC values were 60.6 and 62.1 x103/uL, respectively (p=0.0079). The mean difference between paired values was ‐2.7% (range ‐7.8% to +3.1%).Conclusions: Impedance and optical LBCs are highly comparable using the Sysmex XT‐2000 analyzer.

Genetic risk factors associated with respiratory distress syndrome.

Respiratory distress syndrome (RDS) among preterm infants is typically due to a quantitative deficiency of pulmonary surfactant. Aside from the degree of prematurity, diverse environmental and genetic factors can affect the development of RDS. The variance of the risk of RDS in various races/ethnicities or monozygotic/dizygotic twins has suggested genetic influences on this disorder. So far, several specific mutations in genes encoding surfactant-associated molecules have confirmed this. Specific genetic variants contributing to the regulation of pulmonary development, its structure and function, or the inflammatory response could be candidate risk factors for the development of RDS. This review summarizes the background that suggests the genetic predisposition of RDS, the identified mutations, and candidate genetic polymorphisms of pulmonary surfactant proteins associated with RDS.

Discordance in Lamellar Body Counts Between Sysmex XS-1000 and Sysmex XE-5000 Analyzers

Respiratory distress syndrome, the ninth leading cause of newborn mortality in the US, is caused by fetal lung immaturity due to pulmonary surfactant deficiency. Accordingly, the American College of Obstetrics and Gynecology recommends fetal lung maturity (FLM) testing at <39 weeks gestation. Lamellar body counts (LBC) are often employed for FLM assessment. Most studies established …

An Update of Surfactant

In preterm infants, RDS is primarily caused by deficiency of pulmonary surfactant in an immature lung. For the past 50 years, related research and experiments with regards to surfactant replacement therapy have been encouraging and inspiring.Numerous trials have been conducted to demonstrate that surfactant plays an important role in the management of respiratory distress syndrome in preterm babies, whether it is synthetic, natural or recombinant. The use of surfactant regarding aspects of other disease has been explored as well, including meconium aspiration syndrome, congenital pneumonia and acute respiratory distress syndrome.With the advance of science, the molecular structure and function of most surfactant components has been well understood and well established. Pulmonary surfactant associated proteins (SPs) consist of a heterogeneous composition of lipids and proteins and it has been identified as SP-A, SP-B, SP-C, and SP-D.Recently, US FDA approved the first synthetic peptide-containing surfactant (Lucinactant) to treat RDS in preterm newborns. Surfactant replacement therapy has been one of the greatest achievements in the management of preterm newborns in the past few decades.