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NEJM Evidence Dec 2023In August of 1963, Patrick Bouvier Kennedy, the fourth child of Jackie Onassis Kennedy and John F. Kennedy, died less than 48 hours after his birth from respiratory...
In August of 1963, Patrick Bouvier Kennedy, the fourth child of Jackie Onassis Kennedy and John F. Kennedy, died less than 48 hours after his birth from respiratory distress syndrome (RDS) of the newborn. His tragic death inspired research into the physiology of RDS, one product of which was the development of surfactant replacement therapies which have saved millions of neonates from a similar fate. Shortly after the demonstration of its efficacy in 1980, exogenous surfactant replacement therapy became the mainstay intervention for RDS. Exogenous surfactant was originally administered via an endotracheal tube in mechanically ventilated neonates, a practice which may lead to ventilator-induced injury to the immature lung.
Topics: Humans; Infant, Newborn; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 38320509
DOI: 10.1056/EVIDe2300297 -
Seminars in Fetal & Neonatal Medicine Dec 2023Whilst exogenous surfactant therapy is central to the management of newborn infants with respiratory distress syndrome, its use in other neonatal lung diseases remains... (Review)
Review
Whilst exogenous surfactant therapy is central to the management of newborn infants with respiratory distress syndrome, its use in other neonatal lung diseases remains inconsistent and controversial. Here we discuss the evidence and experience in relation to surfactant therapy in newborns with other lung conditions in which surfactant may be deficient or dysfunctional, including meconium aspiration syndrome, pneumonia, congenital diaphragmatic hernia and pulmonary haemorrhage. We find that, for all of these diseases, administration of exogenous surfactant as bolus therapy is frequently associated with transient improvement in oxygenation, likely related to temporary mitigation of surfactant inhibition in the airspaces. However, for none of them is there a lasting clinical benefit of surfactant therapy. By virtue of interrupting disease pathogenesis, lavage therapy with dilute surfactant in MAS offers the greatest possibility of a more pronounced therapeutic effect, but this has yet to be definitively proven. Lavage therapy also involves a greater degree of procedural risk.
Topics: Female; Humans; Infant, Newborn; Surface-Active Agents; Meconium Aspiration Syndrome; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Lung Diseases; Lipoproteins
PubMed: 38040584
DOI: 10.1016/j.siny.2023.101501 -
Chemical Reviews Dec 2023Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing... (Review)
Review
Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides.
Topics: Infant, Newborn; Humans; Pulmonary Surfactants; Phospholipids; Surface-Active Agents; Surface Tension; Chemical Phenomena
PubMed: 37862151
DOI: 10.1021/acs.chemrev.3c00146 -
Seminars in Fetal & Neonatal Medicine Dec 2023Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The... (Review)
Review
Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The inherent chemical properties of surfactant allows it to readily distribute throughout the respiratory system. Therapeutic agents delivered by surfactant can primarily confer additional benefits but have potential to improve surfactant function. It is critically important that additional agents do not interefere with the innate surface tension lowering function of surfactant. Systemic evaluation through benchtop, translational and human trials are required to translate this potential technique into clinical practice.
Topics: Humans; Infant, Newborn; Surface-Active Agents; Drug Carriers; Pulmonary Surfactants; Drug Delivery Systems; Lipoproteins; Respiratory Distress Syndrome, Newborn
PubMed: 38040583
DOI: 10.1016/j.siny.2023.101499 -
Seminars in Fetal & Neonatal Medicine Dec 2023The introduction of exogenous surfactant in the 1980s has resulted in an improved survival of very preterm infants with respiratory distress syndrome (RDS). Randomized... (Review)
Review
The introduction of exogenous surfactant in the 1980s has resulted in an improved survival of very preterm infants with respiratory distress syndrome (RDS). Randomized controlled trials conducted before 2000 have shown that the magnitude of this beneficial effect strongly depends on the timing of surfactant treatment, i.e. the earlier surfactant is administered after birth the better. However, the initial mode of respiratory support in infants with RDS has changed dramatically over the last decades, moving from invasive to non-invasive support. Furthermore, new, less invasive techniques to administer surfactant have been introduced to match this non-invasive approach. This review summarizes the evidence on how these practice changes impacted the effect of surfactant timing on mortality and morbidity in preterm infants with RDS.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Surface-Active Agents; Respiratory Distress Syndrome, Newborn; Pulmonary Surfactants; Respiration, Artificial; Continuous Positive Airway Pressure; Lipoproteins
PubMed: 38012889
DOI: 10.1016/j.siny.2023.101495 -
European Journal of Pediatrics Aug 2020Preterm neonates with respiratory distress syndrome (RDS) are commonly treated with surfactant by intubate surfactant extubate (InSurE) technique. Mode of surfactant... (Comparative Study)
Comparative Study Randomized Controlled Trial
Minimally invasive surfactant therapy versus InSurE in preterm neonates of 28 to 34 weeks with respiratory distress syndrome on non-invasive positive pressure ventilation-a randomized controlled trial.
Preterm neonates with respiratory distress syndrome (RDS) are commonly treated with surfactant by intubate surfactant extubate (InSurE) technique. Mode of surfactant administration has evolved towards less invasive technique in the last few years. We randomised 58 preterm infants of 28-34 weeks of gestation with RDS within 6 h of birth to receive surfactant by InSurE or minimally invasive surfactant therapy (MIST). Non-invasive positive pressure ventilation (NIPPV) was used as primary respiratory support. The main objective was to compare the need of invasive mechanical ventilation (IMV) in first 72 h of life and secondarily hemodynamically significant patent ductus arteriosus (hsPDA), intraventricular haemorrhage (IVH) (> grade 2), bronchopulmonary dysplasia (BPD) and composite outcome of BPD/mortality. We did not find any difference in need of IMV in first 72 h between MIST and InSurE (relative risk with MIST, 0.62; 95% confidence interval, 0.22 to 1.32). No difference was observed in terms of hs PDA, IVH (> grade 2), BPD and composite outcome of BPD/mortality.Conclusion: There is no difference between MIST and InSurE in preterm neonates with RDS with NIPPV as a primary mode of respiratory support. Larger multicentre studies are needed to further explore differences in treatment failure and other secondary outcomes.Trial registration: www.ctri.nic.in id CTRI/2019/03/017992, registration date March 8, 2019. What is Known • InSurE is commonly used for many years for treatment of RDS in preterm neonates. • MIST has been introduced as a newer tool. What is New • MIST with feeding tube is comparable with InSurE in preterm infants with RDS in developing countries. •NIPPV can be used as primary respiratory support for MIST.
Topics: Combined Modality Therapy; Female; Humans; Infant, Newborn; Infant, Premature; Intubation, Intratracheal; Male; Noninvasive Ventilation; Positive-Pressure Respiration; Prospective Studies; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 32462483
DOI: 10.1007/s00431-020-03682-9 -
Frontiers in Immunology 2022Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism the respiratory surface. The presence of... (Review)
Review
Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.
Topics: Humans; Lung; Pulmonary Surfactants; Respiration, Artificial; Surface-Active Agents; COVID-19 Drug Treatment
PubMed: 35592339
DOI: 10.3389/fimmu.2022.842453 -
Frontiers in Immunology 2023Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder that is characterized by the abnormal accumulation of surfactant within the alveoli. Alveolar... (Review)
Review
Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder that is characterized by the abnormal accumulation of surfactant within the alveoli. Alveolar macrophages (AMs) have been identified as playing a pivotal role in the pathogenesis of PAP. In most of PAP cases, the disease is triggered by impaired cholesterol clearance in AMs that depend on granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in defective alveolar surfactant clearance and disruption of pulmonary homeostasis. Currently, novel pathogenesis-based therapies are being developed that target the GM-CSF signaling, cholesterol homeostasis, and immune modulation of AMs. In this review, we summarize the origin and functional role of AMs in PAP, as well as the latest therapeutic strategies aimed at addressing this disease. Our goal is to provide new perspectives and insights into the pathogenesis of PAP, and thereby identify promising new treatments for this disease.
Topics: Humans; Pulmonary Alveolar Proteinosis; Macrophages, Alveolar; Granulocyte-Macrophage Colony-Stimulating Factor; Pulmonary Alveoli; Pulmonary Surfactants; Rare Diseases; Surface-Active Agents
PubMed: 37388737
DOI: 10.3389/fimmu.2023.1195988 -
Archives of Disease in Childhood. Fetal... Jul 2023
Topics: Humans; Infant, Newborn; Surface-Active Agents; Pulmonary Surfactants; Infant, Premature; Neonatology; Respiratory Distress Syndrome, Newborn
PubMed: 37185271
DOI: 10.1136/archdischild-2022-325061 -
Biochimica Et Biophysica Acta.... Jun 2022Pulmonary surfactant is a mixture of lipids and proteins, consisting of 90% phospholipid, and 10% protein by weight, found predominantly in pulmonary alveoli of... (Review)
Review
Pulmonary surfactant is a mixture of lipids and proteins, consisting of 90% phospholipid, and 10% protein by weight, found predominantly in pulmonary alveoli of vertebrate lungs. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), are present within the alveoli at very high concentrations, and exert anti-inflammatory effects by regulating multiple Toll like receptors (TLR2/1, TLR4, and TLR2/6) by antagonizing cognate ligand-dependent activation. POPG also attenuates LPS-induced lung injury in vivo. In addition, these lipids bind directly to RSV and influenza A viruses (IAVs) and block interaction between host cells and virions, and thereby prevent viral replication in vitro. POPG and PI also inhibit RSV and IAV infection in vivo, in mice and ferrets. The lipids markedly inhibit SARS-CoV-2 infection in vitro. These findings suggest that both POPG and PI have strong potential to be applied as both prophylaxis and post-infection treatments for problematic respiratory viral infections.
Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Ferrets; Lung; Mice; Phospholipids; Pulmonary Surfactants; SARS-CoV-2; Toll-Like Receptor 2; COVID-19 Drug Treatment
PubMed: 35240310
DOI: 10.1016/j.bbalip.2022.159139