Primary Surfactant Deficiency Research Articles

The Common Haplotype GATGACA in Surfactant-Protein B Gene Is Protective for Respiratory Distress Syndrome in Preterm Neonates.

BackgroundRespiratory distress syndrome (RDS), a disorder of primary surfactant deficiency resulting in pulmonary insufficiency, remains a significant problem for preterm neonates. Associations between genetic variants of surfactant proteins and RDS have been reported, but haplotypes of the surfactant protein B gene (SFTPB) have not been studied. The aim of the study was to prove the hypothesis that certain haplotypes of SFTPB may be protective or risk factors for RDS.MethodsThe study was performed with 149 preterm infants, born <34 weeks of gestation, with 86 infants with mild RDS or without RDS (control group) and 63 infants with severe RDS (patient group). RDS was considered severe if multiple doses of exogenous surfactant and/or mechanical ventilation within the first 72 h of life were needed. The venous blood sample was used for the analysis of gene polymorphisms associated with RDS, genotyping, and haplotype estimation. Multivariate logistic regression analysis and the odds ratio were calculated to detect the contribution of the studied variables to the development of RDS.ResultsA new association of the common single nucleotide polymorphism (SNP) rs2304566 with RDS in premature infants was detected. Analysis of rs2304566 polymorphisms using a logistic regression model showed that there are two significant predictors inversely related to the occurrence of RDS (Apgar score of 5 min, CT and TT genotype in rs2304566 polymorphism). Gestational age, birth weight, and sex have border significance. Moreover, in the patient group, the frequency of the GATGACA haplotype in the SFTPB gene was lower (p = 0.037), and the GATGGCA haplotype was higher (p = 0.059) in comparison with the control group.ConclusionThe common haplotype GATGACA of the SFTPB gene can be protective against RDS in preterm infants. The trend of a higher frequency of GATGGCA in the SFTPB gene in infants with severe RDS suggests that this haplotype may be a risk factor for RDS susceptibility.

Can lung ultrasound score accurately predict the need for surfactant replacement in preterm neonates?A systematic review and meta-analysis protocol.

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants due to primary surfactant deficiency. Surfactant replacement has greatly improved the short and long term prognosis of RDS but its administration criteria remain uncertain. Lung ultrasound has been recently shown as a non-invasive, repeatable, bedside tool to estimate parenchymal aeration using a semiquantitative score (LUS). The objective of this systematic review and meta-analysis is to evaluate the accuracy of LUS, assessed on the first day of life, to predict surfactant replacement. Methods will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines and the protocol has been registered in PROSPERO database (registration number: CRD42021247888). Primary outcome: in a population of preterm infants, LUS will be compared in neonates who received surfactant replacement versus those who did not. Secondary outcome will be the accuracy of lung ultrasound score to predict the need for ≥ 2 doses of surfactant.

High-Frequency Ventilation in the Treatment of Acute Respiratory Failure

The need for respiratory therapy can reach 90% depending on the category of the intensive care unit and intensive care unit (ICU). Currently is a wide selection of respiratory therapy methods, including fully controlled mechanical ventilation and assist ventilation. The widespread use of mechanical ventilation and its varieties significantly reduced the mortality of ICU patients. However, the mortality of patients from acute respiratory distress syndrome, nosocomial pneumonia, and newborns with respiratory disorders remains high. High-frequency mechanical ventilation (HFMV) is an alternative treatment for severe respiratory failure, but the frequency of use is not yet sufficient. Three main types of HF ventilation is currently available: high-frequency positive pressure ventilation (HFPPV), high-frequency jet ventilation (HFJV) and high-frequency oscillatory ventilation (HFOV). There is an opportunity to choose a specific mode which will be most applicable for a particular patient. The use of the HFOV method allows the successful treatment of newborns with severe respiratory failure due to primary surfactant deficiency, meconial aspiration or multiple organ failure. Recently high amount of publications appeared on the possibilities of non-invasive HFMV in both adult patients and in pediatrics. This mini-review is devoted to this problem.

Respiratory distress syndrome in preterm neonates in the era of precision medicine: A modern critical care-based approach

Respiratory distress syndrome (RDS) was recognized to be caused by primary surfactant deficiency almost 70 years ago and continuous positive airway pressure was introduced approximately 50 years ago. Since then, there have been many developments in neonatology; we know many things but others are still controversial. The more we know, the more questions arise. However, this review aims to indicate what is more needed to understand and how should be the modern approach to RDS in the era of precision medicine. The review is divided between new concepts and new tools. We will explain the interaction between steroids, CPAP and surfactant, as well as the surfactant catabolism and the diagnosis of NARDS; lung ultrasound and new tools to optimize CPAP will also be covered. How these concepts are integrated in the author's personal experience is also illustrated.

The Underlying Causes of Respiratory Distress in Late-Preterm and Full-Term Infants Are Different From Those of Early-Preterm Infants

Background: A diagnosis of neonatal respiratory distress syndrome (RDS) is common among newborns in China. Some late-preterm and full-term (LP/FT) infants with respiratory distress (RD) symptoms but not primary surfactant deficiency are also diagnosed with RDS and given exogenous surfactant replacement therapy (SRT). Objectives: An increasing number of neonatologists have proposed that RD etiologies should be specifically classified to guide clinical treatment. Methods: The therapeutic effects of SRT on infants of different gestational ages (GAs) were compared in a large retrospective multicenter cohort study performed at 26 Neonatal Intensive Care units in China. The cause of RD at different GAs was further analyzed by comparing the different risk factors closely related to RDS severity at different GAs. Results: Analysis of 1240 infants diagnosed with RDS showed that SRT was less effective in LP/FT infants than in early-preterm (EP) infants. GA &lt; 30 weeks and no prenatal corticosteroid use were closely related to RDS severity in EP infants, whereas perinatal infection- and perinatal hypoxia-associated risk factors and a high cesarean rate were closely related to RDS severity in LP/FT infants. Conclusions: The causes of RD might differ between LP/FT and EP infants, and the diagnosis of RDS might be overused in LP/FT infants. RD in LP/FT infants is more likely related to perinatal infection, perinatal hypoxia, elective cesarean and hereditary factors, which are important causes of neonatal pulmonary edema. New strategies for the treatment of refractory RD in LP/FT infants should concentrate more on pulmonary edema and neonatal ARDS.

In COVID 19, Do we need surfactant therapy

In premature neonates with a primary surfactant deficiency , there is ARDS and surfactants is the main line of therapy. Now it is well known that the virus is attached to and is replicated within type 11 pneumocytes, the main function of these cells is production of surfactants which decrease surface tension and keep the alveoli patent without collapse. In this condition there is a secondary surfactant deficiency which may play a role in pathogenesis and deterioration of patient clinical condition.So, I suggest that treatment by surfactant therapy either derived from endogenous or exogenous source in severe cases can improve clinical condition, delay or avoid patient ventilation by refilling debilitated surfactants and lavage of bronchial tree, this directly decrease mortality rate.In premature neonates with a primary surfactant deficiency , there is ARDS and surfactants is the main line of therapy. Now it is well known that the virus is attached to and is replicated within type 11 pneumocytes, the main function of these cells is production of surfactants which decrease surface tension and keep the alveoli patent without collapse. In this condition there is a secondary surfactant deficiency which may play a role in pathogenesis and deterioration of patient clinical condition

In vitro characterization and in vivo comparison of the pulmonary outcomes of Poractant alfa and Calsurf in ventilated preterm rabbits.

Poractant alfa and Calsurf are two natural surfactants widely used in China for the treatment of neonatal respiratory distress syndrome, which are extracted from porcine and calf lungs, respectively. The purpose of this experimental study was to compare their in vitro characteristics and in vivo effects in the improvement of pulmonary function and protection of lung injury. The biophysical properties, ultrastructure, and lipid composition of both surfactant preparations were respectively analysed in vitro by means of Langmuir-Blodgett trough (LBT), atomic force microscopy (AFM), and liquid-chromatography mass-spectrometry (LC-MS). Then, as core pharmacological activity, both head-to-head (100 and 200 mg/kg for both surfactants) and licensed dose comparisons (70 mg/kg Calsurf vs. 200 mg/kg Poractant alfa) between the two surfactants were conducted as prophylaxis in preterm rabbits with primary surfactant deficiency, assessing survival time and rate and dynamic compliance of the respiratory system (Cdyn). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (Vv), and lung injury scores were determined post mortem. AFM and LC-MS analysis revealed qualitative differences in the ultrastructure as well as in the lipid composition of both preparations. Calsurf showed a longer plateau region of the LBT isotherm and lower film compressibility. In vivo, both surfactant preparations improved Cdyn at any dose, although maximum benefits in terms of Vv and intrapulmonary surfactant pools were seen with the 200 mg/kg dose in both surfactants. The group of animals treated with 200 mg/kg of Poractant alfa showed a prolonged survival time and rate compared to untreated but ventilated controls, and significantly ameliorated lung injury compared to Calsurf at any dose, including 200 mg/kg. The overall outcomes suggest the pulmonary effects to be dose dependent for both preparations. The group of animals treated with 200 mg/kg of Poractant alfa showed a significant reduction of mortality. Compared to Calsurf, Poractant alfa exerted better effects if licensed doses were compared, which requires further investigation.

Acute Respiratory Distress Syndrome in Preterm Newborns (Morphological Study)

The aim of the study is to provide a rationale for the morphological diagnostic criteria of respiratory distress syndrome (RDS) and acute respiratory distress syndrome of the newborn (ARDSN) in extremely preterm newborn infants.Materials and methods. Autopsy protocols of 31 newborns were studied. The average gestational age of children was 28.9±5.3 weeks, body weight at birth was 1404±945 grams. Fifty eight percent of newborns in the sample had extremely low body weight (ELBW). At birth, all newborns were found to have severe asphyxia, and the median score on the Apgar scale at the 1st minute of life was 3 [2; 5] points. In all cases there was an unfavorable course of the disease. The median life span was 72 [22; 181] hours.The results of the study. The study revealed two variants of hyaline membrane formation in preterm newborns with acute respiratory failure. Hyaline membranes in the lungs were found in 93.5% of newborns, in 51.6% of cases there was ARDSN due to the primary surfactant deficiency, in 41.9% of children ARDS was due to immature lung being exposed to various direct and indirect damaging factors. In all cases a distinct morphological pattern in newborns with the hyaline membranes was identified: immaturity and antenatal damage to air-blood barrier, pneumonia, microaspiration, ischemia of the lungs.Conclusion. Acute respiratory distress syndrome is typical for 41.9% of extremely preterm infants, its development is favored by exposure of immature lungs to direct (congenital pneumonia, amniotic fluid aspiration) and indirect (severe perinatal hypoxia with ischemia, shock, hemorrhagic syndrome) damaging factors. Morphological signs of ARDS were most often found in newborns with congenital pneumonia, asphyxia, neonatal aspiration of amniotic fluid.

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.

Personalising care of acute respiratory distress syndrome according to patients' age

Acute respiratory distress was described by Ashbaugh and colleagues 1 Ashbaugh DG Bigelow DB Petty TL Levine BE Acute respiratory distress in adults. Lancet. 1967; 2: 319-323 Summary PubMed Google Scholar in a pivotal paper in The Lancet in 1967. Soon after publication, it became clear that this acute, severe, and hypoxaemic respiratory failure was a syndrome and not a disease, with many possible triggers, epidemiological causes, and clinical courses. Modern definitions of acute respiratory distress syndrome (ARDS) have recognised the peculiarities of the syndrome, taking into account patients' age and the latest innovations in critical care (table). 2 The ARDS Definition Task ForceAcute respiratory distress syndrome: The Berlin Definition. JAMA. 2012; 307: 2526-2533 Crossref PubMed Scopus (6505) Google Scholar , 3 Khemani RG Smith LS Zimmerman JJ Erickson S Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Concensus Conference. Pediatr Crit Care Med. 2015; 16: S23-S40 Crossref PubMed Scopus (251) Google Scholar , 4 De Luca D van Kaam AH Tingay DG et al. The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity. Lancet Respir Med. 2017; 5: 657-666 Summary Full Text Full Text PDF PubMed Scopus (149) Google Scholar In paediatrics, the few children affected by paediatric ARDS (PARDS) and the lack of networks for clinical research have been the main barriers to the advancement of knowledge. In The Lancet Respiratory Medicine, Robinder G Khemani and colleagues 5 Khemani RG Smith L Lopez-Fernandez YM et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med. 2018; (published online Oct 22.)http://dx.doi.org/10.1016/S2213-2600(18)30344-8 Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar report an international, multicentre, cross-sectional study that describes PARDS epidemiology according to the new Pediatric Acute Lung Injury Consensus Conference (PALICC) definition. 5 Khemani RG Smith L Lopez-Fernandez YM et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med. 2018; (published online Oct 22.)http://dx.doi.org/10.1016/S2213-2600(18)30344-8 Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar TableThe three definitions of ARDS by age group Neonatal definition: Montreux Paediatric definition: PALICC Adult definition: Berlin Age From birth until 44 weeks, or until 4 weeks, postnatal age (for neonates born after 40 weeks, postmenstrual age) Beyond the period covered by Montreux definition and until adolescence * Both the PALICC and Berlin definitions can be used for adolescents or young adults, according to clinicians' experience. Adults Timing Acute onset (ie, within 1 week) from a known or suspected clinical insult Acute onset (ie, within 1 week) from a known or suspected clinical insult Acute onset (ie, within 1 week) from a known or suspected clinical insult Imaging Diffuse, bilateral, and irregular opacities or infiltrates, or complete opacification of the lungs, which are not fully explained by local effusions, atelectasis, infant respiratory disease, † Hyaline membrane disease or primary surfactant deficiency. transient tachypnoea of the neonate, or congenital lung anomalies New infiltrates consistent with acute parenchymal process; No need for bilaterality Bilateral opacities not fully explained by effusions, lobar or lung collapse, or nodules Origin of oedema Not fully explained by congenital heart disease (this includes ductus arteriosus with pulmonary overflow if no acute pulmonary haemorrhage exists) Not fully explained by cardiac failure or fluid overload Not fully explained by cardiac failure or fluid overload Severity classes According to oxygenation index classes (same classes as the PALICC definition) According to PaO2:FIO2 ratio or oxygenation or oxygen saturation index classes (depending on ventilation strategy, with preference for PaO2) According to PaO2:FIO2 ratio classes Similarities and differences are evident and based on the best knowledge of ARDS biology and physiopathology across patients' age. ARDS=acute respiratory distress syndrome. PALICC=Pediatric Acute Lung Injury Consensus Conference. PaO2:FIO2=partial pressure of oxygen to fractional concentration of oxygen inspired air. * Both the PALICC and Berlin definitions can be used for adolescents or young adults, according to clinicians' experience. † Hyaline membrane disease or primary surfactant deficiency. Open table in a new tab Similarities and differences are evident and based on the best knowledge of ARDS biology and physiopathology across patients' age. ARDS=acute respiratory distress syndrome. PALICC=Pediatric Acute Lung Injury Consensus Conference. PaO2:FIO2=partial pressure of oxygen to fractional concentration of oxygen inspired air. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational studyThe PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS. Full-Text PDF

Different Causes of Respiratory Distress in Neonates at Different Gestational Ages

Background: Surfactant replacement therapy has been widely used for the treatment of neonatal respiratory distress syndrome (NRDS). However, not all infants, especially near-term and term infants, with respiratory distress can achieve a satisfactory outcome despite intensive care and surfactant replacement therapy. Few studies have attempted to distinguish and analyze the causes of respiratory distress according to gestational age. Methods: A retrospective multicenter study was performed in 26 neonatal intensive care units (NICU) in China from 2011 to 2016. The therapeutic effect of surfactant therapy in infants at different gestational ages was compared. By comparing the differences in risk factors that are closely related to the severity of NRDS at different gestational ages, the cause of respiratory distress at different gestational ages was further analyzed. Results: In total, 1240 infants with NRDS were included in this study. Surfactant therapy was less effective in the near-term and term infants than that in the early preterm infants. Further analysis of the causes of respiratory distress at different gestational ages revealed that a gestational age of less than 30 weeks and a lack of prenatal corticosteroid use were closely related to the severity of NRDS in the early preterm infants. However, perinatal infection- and perinatal hypoxia-associated risk factors were closely related to the severity of NRDS in the near-term and term infants. Conclusion: The cause of respiratory distress in near-term and term infants differs from that in early preterm infants. Some newborn infants with respiratory distress may not have NRDS. Respiratory distress in early preterm infants is mostly due to primary surfactant deficiency, which belongs in the category of NRDS. However, respiratory distress in near-term and term infants is more likely related to perinatal infection and perinatal hypoxia and may belong to the category of NARDS. Trial Registration Number: NCT03385863 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) Conflict of Interest: None of the authors have conflicts of interest to disclose. Ethical Approval Statement: See link in PDF.

Neonatal acute respiratory distress syndrome—is the Montreux definition useful?

A recent publication has attempted to define neonatal acute respiratory distress syndrome (ARDS), using a consensus conference of the opinion of 13 experts from Europe, USA and Australia (1). RDS is a well-defined entity in neonates characterized by the presence of clinical features (evidence of respiratory distress as manifested by tachypnea, sub-costal and inter-costal retractions, use of accessory muscles of respiration, and grunting) at birth or within the first 6 hours of life, in a preterm neonate, along with a characteristic radiograph (diffuse reticulo-granular opacification with air bronchograms and decreased lung volumes) suggesting a primary surfactant deficiency. The terminology of “adult” RDS was subsequently used to designate the presence of symptomatology of surfactant deficiency in adult patients and referred to as ARDS. However, since secondary surfactant deficiency can occur in children, too, the “A” in ARDS was changed to “acute” to be inclusive.

Regulation of PACAP receptors in respiratory distress syndrome (RDS) of preterms and newborns

s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Gottingen, Germany 16-17 April 2015 This supplement has not been sponsored. Meeting abstracts Background Prevalence of respiratory distress syndrome (RDS) caused by primary surfactant deficiency reaches 50% in infants below 32 weeks of gestational age. Increased alveolar surface tension leads to atelectatic and/or dystelectatic lung areas followed by inflammation resulting in development of a bronchopulmonary dysplasia (BPD) in 8% of these children. Standard RDS treatment consists of administration of exogenous surfactant. With the introduction of less invasive application (LISA) of exogenous surfactant, the use of Surfactant has significantly increased. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (VPAC1, VPAC2, PAC1) trigger inflammatory reactions as well as anti-inflammatory processes. Materials and methods Using cell cultures, FACS and ELISA methods we analyzed surfactant effects on inflammation and PACAP-regulation and of its receptors in vivo and ex vivo. Results We were able to show that lipopolysaccharide (LPS) in prestimulated cells (PBMC) after surfactant treatment resulted in a significant up-regulation of pro-inflammatory interleukin (IL)-8. In tracheal secretory cells of surfactant-treated neonates we found an up-regulation of pro-inflammatory receptor VPAC1. Furthermore, in cell cultures we identified changes in the proliferation rates. Amniotic infection syndrome (AIS) is one of the major causes for premature birth resulting in RDS requiring exogenous surfactant. After pre-stimulation of PBMCs and subsequent addition of surfactant, pro-inflammatory signals were fortified. These results were confirmed by analysis of tracheal secretions of preterms and newborns. Conclusions Current findings may imply that safety and efficacy of routine surfactant administration should be reassessed as surfactant potentially triggers pulmonary inflammation and thus may contribute to BPD development.

Surfactant Therapy of Pulmonary Conditions Excluding those with Primary Surfactant Deficiency and Bronchoscopy as Delivery Method: An Overview of Russian Patents and Publications

Preparations of pulmonary surfactant are used for the treatment of respiratory distress syndrome in a newborn. Their applicability as a method of routine for lung diseases beyond the neonatal period is questionable. Some publications from the former Soviet Union (SU) have reported on successful surfactant therapy of ARDS in children and adults as well as for inhalation injuries, pneumonia, and tuberculosis. Bronchoscopy was used and recommended as a method of surfactant delivery for ARDS, some types of pneumonia and tuberculosis. Manufacturing processes of surfactant preparations from bovine lung and amniotic fluid, described by Russian patents, and bronchoscopy as a delivery mode are discussed here. A concluding point is that some reports from the former SU about administration of exogenous surfactant in pulmonary conditions, excluding those with primary surfactant deficiency, are only partly confirmed by the international literature.

The role of surfactant treatment in preterm infants and term newborns with acute respiratory distress syndrome

Surfactant treatment in preterm infants and term newborns with (acute respiratory distress syndrome) ARDS-like severe respiratory failure has become part of an individualized treatment strategy in many intensive care units around the world. These babies constitute heterogeneous groups of gestational ages, lung maturity, as well as of the underlying disease processes and postnatal interventions. The pathophysiology of respiratory failure in preterm infants is characterized by a combination of primary surfactant deficiency and surfactant inactivation as a result of plasma proteins leaking into the airways from areas of epithelial disruption and injury. Various pre- and postnatal factors, such as exposure to chorioamnionitis, pneumonia, sepsis and asphyxia, induce an injurious inflammatory response in the lungs of preterm infants, which may subsequently affect surfactant function, synthesis and alveolar stability. Surfactant inactivation--and dysfunction--is also a hallmark in newborns with meconium aspiration syndrome (MAS), pneumonia and other disorders affecting the pulmonary function. Although for the majority of suggested indications no data from randomized controlled trials exist, a surfactant replacement that counterbalances surfactant inactivation seems to improve oxygenation and lung function in many babies with ARDS without any apparent negative side effects. Newborns with MAS will definitely benefit from a reduced need for extracorporeal membrane oxygenation (ECMO). Clinical experience seems to justify surfactant treatment in neonates with ARDS.

Früh- und Neugeborene mit einemAcute Respiratory Distress Syndrome (ARDS): welche Rolle spielt die Surfactantsubstitution?

Surfactant treatment in preterm infants and term newborns with ARDS-like severe respiratory failure has become part of an individualised treatment strategy in many intensive care units around the world. These babies constitute heterogeneous groups with regards to gestational age, lung maturity, underlying disease processes and postnatal interventions. The pathophysiology of respiratory failure in preterm infants is characterised by a combination of primary surfactant deficiency and surfactant inactivation as a result of plasma proteins leaking into the airways from areas of epithelial disruption and injury. Various pre- and postnatal factors, - such as exposure to chorioamnionitis, pneumonia, fluid lung, sepsis and asphyxia - can induce an injurious inflammatory response in the lung which may subsequently affect surfactant function, synthesis and alveolar stability. Surfactant inactivation and dysfunction is also a hallmark in newborns with meconium aspiration syndrome (MAS), for which a beneficial effect of exogenous surfactant replacement. i.e., reduction of need for ECMO, could be shown. Although for the majority of the above-mentioned diseases process data from randomised, controlled trials are lacking, it is evident from clinical experience that surfactant replacement which counterbalances surfactant inactivation seems to improve oxygenation and lung function in many babies with ARDS without apparent negative side effects. Thus surfactant treatment seems to be justified in many neonates with ARDS.

Depressed exocytosis and endocytosis of type II alveolar epithelial cells are responsible for the surfactant deficiency in the lung of newborn with congenital diaphragmatic hernia

Exocytosis and endocytosis are the way of macromolecules transmembrane transport. Pulmonary surfactant (PS), one of such macromolecules, is secreted via exocytosis of lamellar bodies and recycled via endocytosis by type II alveolar epithelial cells (AEC II). It maintains low alveolar surface tension and is therefore essential to normal lung function. PS deficiency causes respiratory distress syndrome in infants. Congenital diaphragmatic hernia is an abnormal condition in which low lung compliance is involved. This condition is multifactorial and a primary surfactant deficiency may be responsible for it. We hypothesize that surfactant deficiency is involved in CDH and depressed activity of exocytosis and endocytosis in AEC II is responsible for the surfactant deficiency in the lung of newborn with congenital diaphragmatic hernia.

Unilateral Atelectasis during Total Hip Replacement Surgery under Regional Anesthesia: A case report

Even though atelectasis develops rare during anesthesia and/or surgical operation, it may be very important complication because it can be fatal. Atelectasis may be due to airway or bronchus obstruction, compression of the lung by position, primary surfactant deficiency, increased pleural pressure due to fluid or air in the pleural space, chest wall restriction due to skeletal deformity and/or muscular weakness. We report a case of acute intraoperative unilateral lobar atelectasis in 87-years-old woman patient undergoing regional anesthetic for total hip replacement surgery.

Surfactant replacement therapy on ECMO does not improve outcome in neonates with congenital diaphragmatic hernia

Background purpose Respiratory failure in neonates with congenital diaphragmatic hernia (CDH) may in part be caused by a primary or secondary surfactant deficiency. Knowledge of the optimal approach to surfactant replacement in neonates with CDH and respiratory failure is limited. The aim of this study was to determine if surfactant replacement on extracorporeal membrane oxygenation (ECMO) results in improved outcomes in neonates ≥35 weeks’ gestation with unrepaired CDH. Methods Using the CDH Study Group Registry, the authors identified 448 neonates with CDH who were ≥35 weeks’ gestation, had no major anomalies, were treated with ECMO within the first 7 days of life, and underwent repair on or after ECMO therapy. Patients in 2 groups were compared: group 1 (− Surf, n = 334) consisted of patients who received no surfactant and group 2 (+ Surf, n = 114) consisted of patients who received at least 1 dose of surfactant while on ECMO. An analysis of all patients in both groups was performed. Additionally, subgroup analyses stratified by gestational age were performed for patients 351/7 to 366/7 weeks’ gestation and for patients ≥37 weeks’ gestation. Primary end-points for the study were survival and length of ECMO run. Secondary end-points were length of intubation, need for supplemental oxygen at 30 days of life, and at discharge to home. Demographic, clinical, and outcome variables were examined using Fisher’s Exact tests for categorical variables and using unpaired t tests for continuous variables. Odds ratios were calculated for categorical end-point variables. Results Demographic and clinical variables were similar between groups. Analyses of aggregate data showed no significant differences between groups in length of ECMO run, survival, number of days intubated, and percent of patients requiring supplemental oxygen at 30 days or discharge. Subgroup stratification by gestational age did not show significant differences between groups in any of the outcome variables. Conclusions The data from this study suggest that surfactant replacement on ECMO for neonates with congenital diaphragmatic hernia does not provide significant benefit in the infant’s clinical course with respect to survival, length of ECMO course, length of intubation, or subsequent need for supplemental oxygen.

Les déficits secondaires en surfactant

Preterm babies born before the 33rd week of gestation often exhibit primary surfactant deficiency responsible for the respiratory distress syndrome or hyaline membrane disease. In that situation, there is a limited and insufficient production of surfactant by type II alveolar cells of the lung due to immaturity. Secondary surfactant deficiencies occur in patients with prior normal surfactant synthesis and can be related to sepsis, hypoxia, ventilator induced lung injury or surfactant inhibition by a variety of substances reaching the alveolar spaces. They occur in full-term newborns with meconium aspiration syndrome, acute respiratory distress syndrome and congenital diaphragmatic hernia. In children and adults, acute respiratory distress syndrome and respiratory syncytial virus bronchiolitis can be responsible. In prematures they occur after the initial primary deficiency during pulmonary hemorrhage, pneumonia and bronchopulmonary dysplasia. Treatment with exogenous surfactant may be beneficial. There is a need for randomized controlled studies for evaluation of this treatment. Next generation of surfactants containing recombinant surfactant protein or synthetic peptides appear as promising agents in these situations of secondary surfactant deficiencies.