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European Respiratory Review : An... Dec 2021Pulmonary surfactant is a crucial and dynamic lung structure whose primary functions are to reduce alveolar surface tension and facilitate breathing. Though disruptions... (Review)
Review
Pulmonary surfactant is a crucial and dynamic lung structure whose primary functions are to reduce alveolar surface tension and facilitate breathing. Though disruptions in surfactant homeostasis are typically thought of in the context of respiratory distress and premature infants, many lung diseases have been noted to have significant surfactant abnormalities. Nevertheless, preclinical and clinical studies of pulmonary disease too often overlook the potential contribution of surfactant alterations - whether in quantity, quality or composition - to disease pathogenesis and symptoms. In inflammatory lung diseases, whether these changes are cause or consequence remains a subject of debate. This review will outline 1) the importance of pulmonary surfactant in the maintenance of respiratory health, 2) the diseases associated with primary surfactant dysregulation, 3) the surfactant abnormalities observed in inflammatory pulmonary diseases and, finally, 4) the available research on the interplay between surfactant homeostasis and smoking-associated lung disease. From these published studies, we posit that changes in surfactant integrity and composition contribute more considerably to chronic inflammatory pulmonary diseases and that more work is required to determine the mechanisms underlying these alterations and their potential treatability.
Topics: Environmental Exposure; Humans; Infant, Newborn; Infant, Premature; Lung; Lung Diseases; Pulmonary Surfactants
PubMed: 34911693
DOI: 10.1183/16000617.0077-2021 -
The Cochrane Database of Systematic... Feb 2020In the 1960s and 1970s, pulmonary haemorrhage (PH) occurred mainly in full-term infants with pre-existing illness with an incidence of 1.3 per 1000 live births. Risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the 1960s and 1970s, pulmonary haemorrhage (PH) occurred mainly in full-term infants with pre-existing illness with an incidence of 1.3 per 1000 live births. Risk factors for PH included severity of illness, intrauterine growth restriction, patent ductus arteriosus (PDA), coagulopathy and the need for assisted ventilation. Presently, PH occurs in 3% to 5% of preterm ventilated infants with severe respiratory distress syndrome (RDS) who often have a PDA and have received surfactant. The cause of PH is thought to be due to rapid lowering of intrapulmonary pressure, which facilitates left to right shunting across a PDA and an increase in pulmonary blood flow. Retrospective case reports and one prospective uncontrolled study have shown promising results for surfactant in treating PH.
OBJECTIVES
To evaluate the effect of surfactant treatment compared to placebo or no intervention on mortality and morbidities in neonates with PH.
SEARCH METHODS
For this update The Cochrane Library, Issue 2, 2012; MEDLINE; EMBASE; CINAHL; Clinicaltrials.gov; Controlled-trials.com; proceedings (2000 to 2011) of the Annual Meetings of the Pediatric Academic Societies (Abstracts2View) and Web of Science were searched on 8 February 2012.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials that evaluated the effect of surfactant in the treatment of PH in intubated term or preterm (< 37 weeks) neonates with PH. Infants were included up to 44 weeks' postmenstrual age. The interventions studied were intratracheal instillation of surfactant (natural or synthetic, regardless of dose) versus placebo or no intervention.
DATA COLLECTION AND ANALYSIS
If studies were identified by the literature search, the planned analyses included risk ratio, risk difference, number needed to treat to benefit or to harm for dichotomous outcomes, and mean difference for continuous outcomes, with their 95% confidence intervals. A fixed-effect model would be used for meta-analyses. The risk of bias for included trials would be assessed. Heterogeneity tests, including the I statistic, would be performed to assess the appropriateness of pooling the data and the results would be reported.
MAIN RESULTS
No trials were identified.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised trials that evaluated the effect of surfactant in PH were identified. Therefore, no conclusions from such trials can be drawn. In view of the promising results from studies with less strict study designs than a randomised controlled trial, there is reason to conduct further trials of surfactant for the treatment of PH in neonates.
Topics: Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Lung Diseases; Pulmonary Surfactants; Randomized Controlled Trials as Topic
PubMed: 32012227
DOI: 10.1002/14651858.CD005254.pub4 -
Expert Review of Respiratory Medicine Feb 2019In physiological conditions, neonatal airways are well-protected against aspiration of fluid or particulate material into the lungs, with laryngeal chemoreflex (LCR)... (Review)
Review
In physiological conditions, neonatal airways are well-protected against aspiration of fluid or particulate material into the lungs, with laryngeal chemoreflex (LCR) being the most powerful mechanism. Failure of this protection allows substances to enter the lower airways, which starts a series of pathophysiological events initiated by inflammation and surfactant inactivation. The condition is defined as neonatal acute respiratory distress syndrome (ARDS), and its symptoms can range from mild respiratory distress to respiratory failure, often accompanied by persistent pulmonary hypertension (PPHN), in turn even leading to death. The management, therefore, may be very challenging. Areas covered: This review covers protection mechanisms of the neonatal lower airways, the etiology, and pathophysiology of neonatal aspiration syndrome (NAS), its definition in view of current literature, possible treatment options, and future trends. Expert commentary: Inflammation and secondary surfactant deficiency stand in the foreground of neonatal aspiration. Management focuses mainly on appropriate oxygenation, ventilation, improvement in PPHN, and maintenance of systemic circulation, which is largely symptomatic and supportive. Future research is required to evaluate the justification of using exogenous surfactants, antibiotics, anti-inflammatory and antioxidative drugs, or their combinations.
Topics: High-Frequency Ventilation; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Oxygen; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency
PubMed: 30571925
DOI: 10.1080/17476348.2019.1562340 -
Journal of Controlled Release :... Jan 2021This work explores the potential for strategizing pulmonary surfactant (PS) for drug delivery over the respiratory air-liquid interface: the interfacial delivery. The...
This work explores the potential for strategizing pulmonary surfactant (PS) for drug delivery over the respiratory air-liquid interface: the interfacial delivery. The efficacy of PS- and interface-assisted drug vehiculization was determined both in vitro and in vivo using a native purified porcine PS combined with the hydrophobic anti-inflammatory drug Tacrolimus (TAC), a calcineurin inhibitor. In vitro assays were conducted in a novel double surface balance setup designed to emulate compression-expansion dynamics applied to interfacially connected drug donor and recipient compartments. In this setup, PS transported TAC efficiently over air-liquid interfaces, with compression/expansion breathing-like dynamics enhancing rapid interface-assisted diffusion and drug release. The efficacy of PS-assisted TAC vehiculization was also evaluated in vivo in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). In anesthetized mice, TAC combined with PS was intra-nasally (i.n) instilled prior administering i.n. LPS. PS/TAC pre-treatment caused greater TAC internalization into a higher number of lung cells obtained from bronchoalveolar lavages (BAL) than TAC pre-treatment alone. Additionally, the PS/TAC combination but not TAC or PS alone attenuated the LPS-induced pro-inflammatory effects reducing cells and proteins in BAL fluid. These findings indicated that PS-mediated increase in TAC uptake blunted the pro-injurious effects of LPS, suggesting a synergistic anti-inflammatory effect of PS/drug formulations. These in vitro and in vivo results establish the potential utility of PS to open novel effective delivery strategies for inhaled drugs.
Topics: Animals; Drug Delivery Systems; Mice; Pharmaceutical Preparations; Pulmonary Surfactants; Surface-Active Agents; Swine; Tacrolimus
PubMed: 33245954
DOI: 10.1016/j.jconrel.2020.11.042 -
Annals of the American Thoracic Society May 2015Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with... (Review)
Review
Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.
Topics: Humans; Lung Diseases; Pulmonary Surfactants; Respiratory Tract Infections
PubMed: 25742123
DOI: 10.1513/AnnalsATS.201411-507FR -
Langmuir : the ACS Journal of Surfaces... Mar 2023The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled...
The lining of the alveoli is covered by pulmonary surfactant, a complex mixture of surface-active lipids and proteins that enables efficient gas exchange between inhaled air and the circulation. Despite decades of advancements in the study of the pulmonary surfactant, the molecular scale behavior of the surfactant and the inherent role of the number of different lipids and proteins in surfactant behavior are not fully understood. The most important proteins in this complex system are the surfactant proteins SP-B and SP-C. Given this, in this work we performed nonequilibrium all-atom molecular dynamics simulations to study the interplay of SP-B and SP-C with multicomponent lipid monolayers mimicking the pulmonary surfactant in composition. The simulations were complemented by -scan fluorescence correlation spectroscopy and atomic force microscopy measurements. Our state-of-the-art simulation model reproduces experimental pressure-area isotherms and lateral diffusion coefficients. In agreement with previous research, the inclusion of either SP-B and SP-C increases surface pressure, and our simulations provide a molecular scale explanation for this effect: The proteins display preferential lipid interactions with phosphatidylglycerol, they reside predominantly in the lipid acyl chain region, and they partition into the liquid expanded phase or even induce it in an otherwise packed monolayer. The latter effect is also visible in our atomic force microscopy images. The research done contributes to a better understanding of the roles of specific lipids and proteins in surfactant function, thus helping to develop better synthetic products for surfactant replacement therapy used in the treatment of many fatal lung-related injuries and diseases.
Topics: Biophysical Phenomena; Phospholipids; Proteins; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Surface Properties; Surface-Active Agents; Pulmonary Surfactant-Associated Protein C
PubMed: 36917773
DOI: 10.1021/acs.langmuir.2c03349 -
Seminars in Fetal & Neonatal Medicine Dec 2023Surfactant replacement therapy (SRT) has revolutionized the management of respiratory distress syndrome (RDS) in premature infants, leading to improved survival rates... (Review)
Review
Surfactant replacement therapy (SRT) has revolutionized the management of respiratory distress syndrome (RDS) in premature infants, leading to improved survival rates and decreased morbidity. SRT may, however, be associated with hemodynamic changes, which can have both positive and negative effects on the immature cardiovascular system, during the transitional adaptation from fetal to extrauterine environment. However, there is a relative paucity of evidence in this domain, with most of them derived from small heterogeneous observational studies providing conflicting results. In this review, we will discuss the hemodynamic changes that occur with surfactant administration during this vulnerable period, focusing on available evidence regarding changes in pulmonary and systemic blood flow, cerebral circulation and their clinical implications.
Topics: Humans; Infant, Newborn; Hemodynamics; Infant, Premature; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface-Active Agents; Observational Studies as Topic
PubMed: 38040585
DOI: 10.1016/j.siny.2023.101498 -
Chemistry and Physics of Lipids Jan 2015The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the... (Review)
Review
The respiratory surface in the mammalian lung is stabilized by pulmonary surfactant, a membrane-based system composed of multiple lipids and specific proteins, the primary function of which is to minimize the surface tension at the alveolar air-liquid interface, optimizing the mechanics of breathing and avoiding alveolar collapse, especially at the end of expiration. The goal of the present review is to summarize current knowledge regarding the structure, lipid-protein interactions and mechanical features of surfactant membranes and films and how these properties correlate with surfactant biological function inside the lungs. Surfactant mechanical properties can be severely compromised by different agents, which lead to surfactant inhibition and ultimately contributes to the development of pulmonary disorders and pathologies in newborns, children and adults. A detailed comprehension of the unique mechanical and rheological properties of surfactant layers is crucial for the diagnostics and treatment of lung diseases, either by analyzing the contribution of surfactant impairment to the pathophysiology or by improving the formulations in surfactant replacement therapies. Finally, a short review is also included on the most relevant experimental techniques currently employed to evaluate lung surfactant mechanics, rheology, and inhibition and reactivation processes.
Topics: Animals; Biomechanical Phenomena; Cell Membrane; Extracellular Space; Humans; Mechanical Phenomena; Pulmonary Surfactants
PubMed: 25260665
DOI: 10.1016/j.chemphyslip.2014.09.002 -
Biomedical Journal Dec 2021This issue of the Biomedical Journal provides a comprehensive insight into the role of pulmonary surfactant and influencing its components as well as involved molecules...
This issue of the Biomedical Journal provides a comprehensive insight into the role of pulmonary surfactant and influencing its components as well as involved molecules to treat a variety of respiratory distress disorders. We also discover how epithelial mesenchymal transition (EMT) could be targeted as part of a therapeutic strategy against lung cancer. Furthermore, a method is described to eliminate chemoresistance against gemcitabine, a drug administered to treat pancreatic cancer. We gain an insight into the composition of salivary calcium particles in periodontitis, a technique to circumvent complications in hip surgery, and a potential treatment to accelerate diabetic wound healing. Moreover, we get to know an essential oil that exerts a similar effect as diazepam on the central nervous system. A trial in patients with myofascial pain syndrome demonstrates how laser assisted trigger point therapy leads to immediate relief. Finally, a case study outlines the discovery of a genetic mutation that plays a role in intellectual disability.
Topics: Epithelial-Mesenchymal Transition; Humans; Pancreatic Neoplasms; Pulmonary Surfactants; Wound Healing
PubMed: 34942391
DOI: 10.1016/j.bj.2021.12.003 -
Biomedical Journal Aug 2022The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement... (Review)
Review
The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.
Topics: Animals; Humans; Infant, Newborn; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 35272060
DOI: 10.1016/j.bj.2022.03.001