The Role of Pulmonary Collectins, Surfactant Protein A (SP-A) and Surfactant Protein D (SP-D) in Cancer.

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRMs), able to recognise pathogen- or danger-associated molecular patterns (PAMPs, DAMPs) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self cells and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at the N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at the C-terminus). Pulmonary surfactant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air-liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeostasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term "cancer" includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumorigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy.

The effect of temperature and breathing pattern on the surface activity of ground squirrel pulmonary surfactant.

This study investigates how hibernation affects the surface activity of pulmonary surfactant with respect to temperature and breathing pattern. Surfactant was isolated from a hibernating species, the 13-lined ground squirrel, and a homeotherm, rabbit, and analyzed for biophysical properties on a constrained sessile drop surfactometer. The results showed that surfactant from ground squirrels reduced surface tension better at low temperatures, including when mimicking episodic breathing, as compared to rabbit surfactant. In addition, low temperature adaptation was also observed using only the hydrophobic components of surfactant from ground squirrels. Overall, the data supports the conclusion that ground squirrel surfactant has adapted to maintain surface activity during low temperature episodic breathing patterns, and that temperature adaptation is maintained with the hydrophobic components of the surfactant.

Pulmonary surfactant and prostaglandin E2 in airway smooth muscle relaxation of human and male guinea pigs.

Pulmonary surfactant serves as a barrier to respiratory epithelium but can also regulate airway smooth muscle (ASM) tone. Surfactant (SF) relaxes contracted ASM, similar to ß2-agonists, anticholinergics, nitric oxide, and prostanoids. The exact mechanism of surfactant relaxation and whether surfactant relaxes hyperresponsive ASM remains unknown. Based on previous research, relaxation requires an intact epithelium and prostanoid synthesis. We sought to examine the mechanisms by which surfactant causes ASM relaxation. Organ bath measurements of isometric tension of ASM of guinea pigs in response to exogenous surfactant revealed that surfactant reduces tension of healthy and hyperresponsive tracheal tissue. The relaxant effect of surfactant was reduced if prostanoid synthesis was inhibited and/or if prostaglandin E2-related EP2 receptors were antagonized. Atomic force microscopy revealed that human ASM cells stiffen during contraction and soften during relaxation. Surfactant softened ASM cells, similarly to the known bronchodilator prostaglandin E2 (PGE2) and the cell softening was abolished when EP4 receptors for PGE2 were antagonized. Elevated levels of PGE2 were found in cultures of normal human bronchial epithelial cells exposed to pulmonary surfactant. We conclude that prostaglandin E2 and its EP2 and EP4 receptors are likely involved in the relaxant effect of pulmonary surfactant in airways.

Integrated untargeted and targeted lipidomics discovers LPE 16:0 as a protector against respiratory syncytial virus infection.

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infections, imposing a substantial burden on healthcare systems globally. While lipid disorders have been observed in the lungs of infants and young children with RSV pneumonia, the specific characterization of these lipids and their roles in the development and progression of RSV pneumonia remain largely unexplored. To address this tissue, we established a non-targeted high-resolution lipidomics platform using UHPLC-Q-Exactive-MS to analyze lipid profiles in bronchoalveolar lavage fluid (BALF) obtained from mice infected with RSV. Through the lipidomics analysis, a total of 72 lipids species were identified, with 40 lipids were significantly changed. Notably, the primary changes were observed in ether phospholipids and lysophospholipids. Furthermore, a targeted lipidomics analysis utilizing UHPLC-QQQ-MS/MS was developed to specifically assess the levels of lysophospholipids, including lysophosphocholine 16:0 (LPC 16:0), lysophosphoethanolamine 16:0 (LPE 16:0) and lysophosphoglycerol 16:0 (LPG 16:0), in RSV-infected mice compared to control mice. Animal experiments revealed that LPE 16:0, rather than LPC 16:0 or LPG 16:0, provided protection against RSV-induced weight loss, reduced lung viral load, regulated immune cells and mitigated lung injury in mice afflicted with RSV pneumonia. In summary, our findings suggested that the host responses to RSV infection pathology are closely with various lipid metabolic. Additionally, our results elucidated novel biological functions of LPE 16:0 and offering new avenues for drug development against RSV pneumonia.

Liraglutide alleviates sepsis-induced acute lung injury by regulating pulmonary surfactant through inhibiting autophagy.

BACKGROUND: Pulmonary surfactant (PS) plays an important role in the treatment of sepsis-induced acute lung injury (ALI). Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, improves the secretion and function of PS in ALI, but the underlying mechanism remains unknown. This study aimed to investigate how liraglutide regulates PS secretion in ALI. METHODS: C57BL/6 mice were injected subcutaneously with normal saline containing different concentrations of liraglutide after the establishment of the ALI model. MLE-12 cells were treated with liraglutide after LPS stimulation. The survival rate of mice, wet/dry weight ratio, inflammatory factors in bronchoalveolar lavage fluid (BALF), pulmonary injury, and apoptosis were analyzed. Cell viability, proliferation, apoptosis, the expression of SP-A, SP-B, and expression of autophagy-related proteins in cells were measured. RESULTS: ALI mice showed reduced pulmonary injury, less apoptosis, and less inflammation compared to the controls. Liraglutide prolonged survival, decreased the wet/dry weight ratio, reduced inflammatory responses, and attenuated pulmonary edema compared with the ALI group. Moreover, LPS-induced cell damage and reduction of SP-A and SP-B expression were markedly reversed by liraglutide in MLE-12 cells. Furthermore, the protective effects of liraglutide were reversed by rapamycin. CONCLUSION: Liraglutide alleviate sepsis-induced ALI by inhibiting autophagy and regulating PS.

Effects of pulmonary surfactant combined with noninvasive positive pressure ventilation in neonates with respiratory distress syndrome.

BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is one of the most common diseases in neonatal intensive care units, with an incidence rate of about 7% among infants. Additionally, it is a leading cause of neonatal death in hospitals in China. The main mechanism of the disease is hypoxemia and hypercapnia caused by lack of surfactant. AIM: To explore the effect of pulmonary surfactant (PS) combined with noninvasive positive pressure ventilation on keratin-14 (KRT-14) and endothelin-1 (ET-1) levels in peripheral blood and the effectiveness in treating NRDS. METHODS: Altogether 137 neonates with respiratory distress syndrome treated in our hospital from April 2019 to July 2021 were included. Of these, 64 control cases were treated with noninvasive positive pressure ventilation and 73 observation cases were treated with PS combined with noninvasive positive pressure ventilation. The expression of KRT-14 and ET-1 in the two groups was compared. The deaths, complications, and PaO2, PaCO2, and PaO2/FiO2 blood gas indexes in the two groups were compared. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic value of KRT-14 and ET-1 in the treatment of NRDS. RESULTS: The observation group had a significantly higher effectiveness rate than the control group. There was no significant difference between the two groups in terms of neonatal mortality and adverse reactions, such as bronchial dysplasia, cyanosis, and shortness of breath. After treatment, the levels of PaO2 and PaO2/FiO2 in both groups were significantly higher than before treatment, while the level of PaCO2 was significantly lower. After treatment, the observation group had significantly higher levels of PaO2 and PaO2/FiO2 than the control group, while PaCO2 was notably lower in the observation group. After treatment, the KRT-14 and ET-1 levels in both groups were significantly decreased compared with the pre-treatment levels. The observation group had a reduction of KRT-14 and ET-1 levels than the control group. ROC curve analysis showed that the area under the curve (AUC) of KRT-14 was 0.791, and the AUC of ET-1 was 0.816. CONCLUSION: Combining PS with noninvasive positive pressure ventilation significantly improved the effectiveness of NRDS therapy. KRT-14 and ET-1 levels may have potential as therapeutic and diagnostic indicators.

Comparative Biophysical Study of Clinical Surfactants using Constrained Drop Surfactometry.

Surfactant replacement therapy is crucial in managing neonatal respiratory distress syndrome (RDS). Currently licensed clinical surfactants in the United States and Europe, including Survanta, Infasurf, Curosurf, and Alveofact, are all derived from bovine or porcine sources. We conducted a comprehensive examination of the biophysical properties of these four clinical surfactant preparations under physiologically relevant conditions, utilizing constrained drop surfactometry (CDS). The assessed biophysical properties included the adsorption rate, quasi-static and dynamic surface activity, resistance to surfactant inhibition by meconium, and the morphology of the adsorbed surfactant films. This comparative study unveiled distinct in vitro biophysical properties of these clinical surfactants and revealed correlations between their chemical composition, lateral film structure, and biophysical functionality. Notably, at 1 mg/mL, Survanta exhibited a significantly lower adsorption rate compared to the other preparations at the same surfactant concentration. At 10 mg/mL, Infasurf, Curosurf, and Survanta all demonstrated excellent dynamic surface activity, while Alveofact exhibited the poorest quasi-static and dynamic surface activity. The suboptimal surface activity of Alveofact is found to be correlated with its unique monolayer-predominant morphology, in contrast to other surfactants forming multilayers. Curosurf, in particular, showcased superior resistance to biophysical inhibition by meconium compared to other preparations. Understanding the diverse biophysical behaviors of clinical surfactants provides crucial insights for precision and personalized design in treating RDS and other respiratory conditions. The findings from this study contribute valuable perspectives for development of more efficacious and fully synthetic surfactant preparations.

Inhalable mRNA Nanoparticle with Enhanced Nebulization Stability and Pulmonary Microenvironment Infiltration.

The delivery of mRNA into the lungs is the key to solving infectious and intractable diseases that frequently occur in the lungs. Since inhalation using a nebulizer is the most promising method for mRNA delivery into the lungs, there have been many attempts toward adapting lipid nanoparticles for mRNA inhalation. However, conventional lipid nanoparticles, which have shown great effectiveness for systemic delivery of mRNA and intramuscular vaccination, are not effective for pulmonary delivery due to their structural instability during nebulization and their inability to adapt to the pulmonary microenvironment. To address these issues, we developed an ionizable liposome-mRNA lipocomplex (iLPX). iLPX has a highly ordered lipid bilayer structure, which increases stability during nebulization, and its poly(ethylene glycol)-free composition allows it to infiltrate the low serum environment and the pulmonary surfactant layer in the lungs. We selected an inhalation-optimized iLPX (IH-iLPX) using a multistep screening procedure that mimics the pulmonary delivery process of inhaled nanoparticles. The IH-iLPX showed a higher transfection efficiency in the lungs compared to conventional lipid nanoparticles after inhalation with no observed toxicity in vivo. Furthermore, analysis of lung distribution revealed even protein expression in the deep lungs, with effective delivery to epithelial cells. This study provides insights into the challenges and solutions related to the development of inhaled mRNA pulmonary therapeutics.

Factors influencing airway smooth muscle tone: a comprehensive review with a special emphasis on pulmonary surfactant.

A thin film of pulmonary surfactant lines the surface of the airways and alveoli, where it lowers the surface tension in the peripheral lungs, preventing collapse of the bronchioles and alveoli and reducing the work of breathing. It also possesses a barrier function for maintaining the blood-gas interface of the lungs and plays an important role in innate immunity. The surfactant film covers the epithelium lining both large and small airways, forming the first line of defense between toxic airborne particles/pathogens and the lungs. Furthermore, surfactant has been shown to relax airway smooth muscle (ASM) after exposure to ASM agonists, suggesting a more subtle function. Whether surfactant masks irritant sensory receptors or interacts with one of them is not known. The relaxant effect of surfactant on ASM is absent in bronchial tissues denuded of an epithelial layer. Blocking of prostanoid synthesis inhibits the relaxant function of surfactant, indicating that prostanoids might be involved. Another possibility for surfactant to be active, namely through ATP-dependent potassium channels and the cAMP-regulated epithelial chloride channels [cystic fibrosis transmembrane conductance regulators (CFTRs)], was tested but could not be confirmed. Hence, this review discusses the mechanisms of known and potential relaxant effects of pulmonary surfactant on ASM. This review summarizes what is known about the role of surfactant in smooth muscle physiology and explores the scientific questions and studies needed to fully understand how surfactant helps maintain the delicate balance between relaxant and constrictor needs.

Biophysical impact of lubricating base oil aerosols on natural pulmonary surfactant film.

Lubricating base oils have been extensively employed for producing various industrial and consumer products. Therefore, their environmental and health impacts should be carefully evaluated. Although there have been many reports on pulmonary cytotoxicity and inflammatory responses of inhaled lubricating base oils, their potential influences on pulmonary surfactant (PS) films that play an essential role in maintaining respiratory mechanics and pulmonary immunity remains largely unknown. Here a systematic study on the interactions between an animal-derived natural PS and aerosols of water and representative mineral and vegetable base oils is performed using a novel biophysical assessing technique called constrained drop surfactometry capable of providing in vitro simulations of normal tidal breathing and physiologically relevant temperature and humidity in the lung. It was found that the mineral oil aerosols can impose strong inhibitions to the biophysical property of PS film, while the airborne vegetable oils and water show negligible adverse effects within the studied concentration range. The inhibitory effect is originated from the strong hydrophobicity of mineral oil, which makes it able to disrupt the interfacial molecular ordering of both phospholipid and protein compositions and consequently suppress the formation of condensed phase and multilayer scaffolds in a PS film. ENVIRONMENTAL IMPLICATION: Understanding the biophysical influence of airborne lubricating base oils on pulmonary surfactant (PS) films can provide new insights into the environmental impacts and health concerns of various industrial lubricant products. Here a comparative study on interactions between an animal-derived natural PS film and the aerosols of water and representative mineral and vegetable base oils under the true physiological conditions was conducted in situ using constrained drop surfactometry. We show that the most frequently used mineral base oil can cause strong inhibitions to the PS film by disrupting the molecular ordering of saturated phospholipids and surfactant-associated proteins at the interface.

Prospective, non-blinded, randomized controlled trial on early administration of pulmonary surfactant guided by lung ultrasound scores in very preterm infants: study protocol.

Background: Bedside lung ultrasonography has been widely used in neonatal intensive care units (NICUs). Lung ultrasound scores (LUS) may predict the need for pulmonary surfactant (PS) application. PS replacement therapy is the key intervention for managing moderate to severe neonatal respiratory distress syndrome (NRDS), with early PS administration playing a positive role in improving patient outcomes. Lung ultrasonography aids in the prompt diagnosis of NRDS, while LUS offers a semi-quantitative assessment of lung health. However, the specific methodologies for utilizing LUS in clinical practice remain controversial. This study hypothesizes that, in very preterm infants [<32 weeks gestational age (GA)] exhibiting respiratory distress symptoms, determining PS application through early postnatal LUS combined with clinical indicators, as opposed to relying solely on clinical signs and chest x-rays, can lead to more timely PS administration, reduce mechanical ventilation duration, improve patient outcomes, and lower the occurrence of bronchopulmonary dysplasia (BPD). Methods and design: This is a protocol for a prospective, non-blinded, randomized controlled trial that will be conducted in the NICU of a hospital in China. Eligible participants will include very preterm infants (< 32 weeks GA) exhibiting signs of respiratory distress. Infants will be randomly assigned in a 1:1 ratio to either the ultrasound or control group. In the ultrasonography group, the decision regarding PS administration will be based on a combination of lung ultrasonography and clinical manifestations, whereas in the control group, it will be determined solely by clinical signs and chest x-rays. The primary outcome measure will be the mechanical ventilation duration. Statistical analysis will employ independent sample t-tests with a significance level set at α = 0.05 and a power of 80%. The study requires 30 infants per group (in total 60 infants). Results: This study aims to demonstrate that determining PS application based on a combination of LUS and clinical indicators is superior to traditional approaches. Conclusions: This approach may enhance the accuracy of NRDS diagnosis and facilitate early prediction of PS requirements, thereby reducing the duration of mechanical ventilation. The findings of this research may contribute valuable insights into the use of LUS to guide PS administration.

Activation of alveolar epithelial ER stress by ß-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.

COVID-19 syndrome is characterized by acute lung injury, hypoxemic respiratory failure, and high mortality. Alveolar type 2 (AT2) cells are essential for gas exchange, repair, and regeneration of distal lung epithelium. We have shown that the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other members of the ß-coronavirus genus induce an endoplasmic reticulum (ER) stress response in vitro; however, the consequences for host AT2 cell function in vivo are less understood. To study this, two murine models of coronavirus infection were used-mouse hepatitis virus-1 (MHV-1) in A/J mice and a mouse-adapted SARS-CoV-2 strain. MHV-1-infected mice exhibited dose-dependent weight loss with histological evidence of distal lung injury accompanied by elevated bronchoalveolar lavage fluid (BALF) cell counts and total protein. AT2 cells showed evidence of both viral infection and increased BIP/GRP78 expression, consistent with activation of the unfolded protein response (UPR). The AT2 UPR included increased inositol-requiring enzyme 1α (IRE1α) signaling and a biphasic response in PKR-like ER kinase (PERK) signaling accompanied by marked reductions in AT2 and BALF surfactant protein (SP-B and SP-C) content, increases in surfactant surface tension, and emergence of a reprogrammed epithelial cell population (Krt8+ and Cldn4+). The loss of a homeostatic AT2 cell state was attenuated by treatment with the IRE1α inhibitor OPK-711. As a proof-of-concept, C57BL6 mice infected with mouse-adapted SARS-CoV-2 demonstrated similar lung injury and evidence of disrupted surfactant homeostasis. We conclude that lung injury from ß-coronavirus infection results from an aberrant host response, activating multiple AT2 UPR stress pathways, altering surfactant metabolism/function, and changing AT2 cell state, offering a mechanistic link between SARS-CoV-2 infection, AT2 cell biology, and acute respiratory failure.NEW & NOTEWORTHY COVID-19 syndrome is characterized by hypoxemic respiratory failure and high mortality. In this report, we use two murine models to show that ß-coronavirus infection produces acute lung injury, which results from an aberrant host response, activating multiple epithelial endoplasmic reticular stress pathways, disrupting pulmonary surfactant metabolism and function, and forcing emergence of an aberrant epithelial transition state. Our results offer a mechanistic link between SARS-CoV-2 infection, AT2 cell biology, and respiratory failure.

Investigating the effects of dexamethasone on pulmonary surfactant lipids based on lipidomics studies.

Dexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side effects such as reduced lung function and decreased immunity. Pulmonary surfactant lipids are closely linked to lung disease and play a role in reducing surface tension, immune response and antiviral activity. The dysregulation of lipid metabolism is closely associated with lung disease. Hence, untargeted lipidomics may be instrumental in elucidating the effects of dexamethasone on pulmonary surfactant lipids. We obtained surfactant lipid samples from the bronchoalveolar lavage fluid of young mice injected subcutaneously with dexamethasone and conducted a comprehensive lipidomic analysis, comparing them with a control group. We observed a decrease in lipids, such as phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine, and an increase in ceramide, fatty acid, diacylglycerol and monoglyceride, which may impact lung health. This study revealed the influence of dexamethasone on pulmonary surfactant lipids, offering new insights into adverse reactions in clinical settings.

Biophysical properties of alveolar surfactant in drever dogs with hunting associated pulmonary edema.

BACKGROUND: A syndrome of acute non-cardiogenic pulmonary edema associated with hunting is prevalent in the drever breed, but etiology of this syndrome is currently unknown. Alveolar surfactant has a critical role in preventing alveolar collapse and edema formation. The aim of this study was to investigate, whether the predisposition to hunting associated pulmonary edema in drever dogs is associated with impaired biophysical properties of alveolar surfactant. Seven privately owned drever dogs with recurrent hunting associated pulmonary edema and seven healthy control dogs of other breeds were included in the study. All affected dogs underwent thorough clinical examinations including echocardiography, laryngeal evaluation, bronchoscopy, and bronchoalveolar lavage (BAL) as well as head, neck and thoracic computed tomography imaging to rule out other cardiorespiratory diseases potentially causing the clinical signs. Alveolar surfactant was isolated from frozen, cell-free supernatants of BAL fluid and biophysical analysis of the samples was completed using a constrained sessile drop surfactometer. Statistical comparisons over consecutive compression expansion cycles were performed using repeated measures ANOVA and comparisons of single values between groups were analyzed using T-test. RESULTS: There were no significant differences between groups in any of the biophysical outcomes of surfactant analysis. The critical function of surfactant, reducing the surface tension to low values upon compression, was similar between healthy dogs and affected drevers. CONCLUSIONS: The etiology of hunting associated pulmonary edema in drever dogs is not due to an underlying surfactant dysfunction.

The Underlying Mechanism of Poisoning after the Accidental Inhalation of Aerosolised Waterproofing Spray.

Waterproofing sprays can cause acute respiratory symptoms after inhalation, including coughing and dyspnoea shortly after use. Here, we describe two cases where persons used the same brand of waterproofing spray product. In both cases the persons followed the instructions on the product and maximized the ventilation by opening windows and doors; however, they still became affected during the application of the product. Products with the same batch number as that used in one case were tested for their effect on respiration patterns of mice in whole-body plethysmographs and lung surfactant function inhibition in vitro. The product was used in spraying experiments to determine the particle size distribution of the aerosol, both using a can from one case and a can with an identical batch number. In addition, the aerosols in the mouse exposure chamber were measured. Aerosol data from a small-scale exposure chamber and data on the physical and temporal dimensions of the spraying during one case were used to estimate the deposited dose during the spraying events. All collected data point to the spraying of the waterproofing product being the reason that two people became ill, and that the inhibition of lung surfactant function was a key component of this illness.

Validation of a high-performance liquid chromatography method for determining lysophosphatidylcholine content in bovine pulmonary surfactant medication.

Pulmonary surfactant replacement therapy is a promising improvement in neonatal care for infants with respiratory distress syndrome. Lysophosphatidylcholine (LPC) is an undesirable component that can hinder surfactant proteins from enhancing the adsorption of surfactant lipids to balance surface tensions by creating a saturated coating on the interior of the lungs. A novel normal-phase liquid chromatography method utilizing UV detection and non-toxic solvents was developed and validated for the first time to analyze LPC in the complex matrix of pulmonary surfactant medication. The analytical method validation included evaluation of system suitability, repeatability, intermediate precision, linearity, accuracy, limit of detection (LOD), limit of quantification (LOQ), stability and robustness. The method yielded detection and quantification limits of 4.4 and 14.5 µg/ml, respectively. The calibration curve was modified linearly within the LOQ to 1.44 mg/ml range, with a determination coefficient of 0.9999 for standards and 0.9997 for sample solutions. Given the lack of reliable published data on LPC analysis in pulmonary surfactant medications, this newly developed method demonstrates promising results and offers advantages of HPLC methodology, including simplicity, accuracy, specificity, sensitivity and an exceptionally low LOD and LOQ. These attributes contribute to considering this achievement as an innovative method.

Unraveling the enigma: The emerging significance of pulmonary surfactant proteins in predicting, diagnosing, and managing COVID-19.

BACKGROUND: Severe cases of COVID-19 often lead to the development of acute respiratory syndrome, a critical condition believed to be caused by the harmful effects of SARS-CoV-2 on type II alveolar cells. These cells play a crucial role in producing pulmonary surfactants, which are essential for proper lung function. Specifically focusing on surfactant proteins, including Surfactant protein A (SP-A), Surfactant protein B, Surfactant protein C, and Surfactant protein D (SP-D), changes in the levels of pulmonary surfactants may be a significant factor in the pathological changes seen in COVID-19 infection. OBJECTIVE: This study aims to gain insights into surfactants, particularly their impacts and changes during COVID-19 infection, through a comprehensive review of current literature. The study focuses on the function of surfactants as prognostic markers, diagnostic factors, and essential components in the management and treatment of COVID-19. FINDING: In general, pulmonary surfactants serve to reduce the surface tension at the gas-liquid interface, thereby significantly contributing to the regulation of respiratory mechanics. Additionally, these surfactants play a crucial role in the innate immune system within the pulmonary microenvironment. Within the spectrum of COVID-19 infections, a compelling association is observed, characterized by elevated levels of SP-D and SP-A across a range of manifestations from mild to severe pneumonia. The sudden decline in respiratory function observed in COVID-19 patients may be attributed to the decreased synthesis of surfactants by type II alveolar cells. CONCLUSION: Collectin proteins such as SP-A and SP-D show promise as biomarkers, offering potential avenues for predicting and monitoring pulmonary alveolar injury in the context of COVID-19. This clarification enhances our understanding of the molecular complexities contributing to respiratory complications in severe COVID-19 cases, providing a foundation for targeted therapeutic approaches using surfactants and refined clinical management strategies.

Exposure to O3 and NO2 on the interfacial chemistry of the pulmonary surfactant and the mechanism of lung oxidative damage.

Exposure to ozone (O3) and nitrogen dioxide (NO2) are related to pulmonary dysfunctions and various lung diseases, but the underlying biochemical mechanisms remain uncertain. Herein, the effect of inhalable oxidizing gas pollutants on the pulmonary surfactant (PS, extracted from porcine lungs), a mixture of active lipids and proteins that plays an important role in maintaining normal respiratory mechanics, is investigated in terms of the interfacial chemistry using in-vitro experiments; and the oxidative stress induced by oxidizing gases in the simulated lung fluid (SLF) supplemented with the PS is explored. The results showed that O3 and NO2 individually increased the surface tension of the PS and reduced its foaming ability; this was accompanied by the surface pressure-area isotherms of the PS monolayers shifting toward lower molecular areas, with O3 exhibiting more severe effects than NO2. Moreover, both O3 and NO2 produced reactive oxygen species (ROS) resulting in lipid peroxidation and protein damage to the PS. The formation of superoxide radicals (O2•-) was correlated with the decomposition of O3 and the reactions of O3 and NO2 with antioxidants in the SLF. These radicals, in the presence of antioxidants, led to the formation of hydrogen peroxide and hydroxyl radicals (•OH). Additionally, the direct oxidation of unsaturated lipids by O3 and NO2 further caused an increase in the ROS content. This change in the ROS chemistry and increased •OH production tentatively explain how inhalable oxidizing gases lead to oxidative stress and adverse health effects. In summary, our results indicated that inhaled O3 and NO2 exposure can significantly alter the interfacial properties of the PS, oxidize its active ingredients, and induce ROS formation in the SLF. The results of this study provide a basis for the elucidation of the potential hazards of inhaled oxidizing gas pollutants in the human respiratory system.

Exogenous surfactant for lung contusion causing ARDS: A systematic review of clinical and experimental reports.

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.

[Impact of different angles of pulmonary surfactant administration on bronchopulmonaryplasia and intracranial hemorrhage in preterm infants: a prospective randomized controlled study]. / ä¸åŒè§’åº¦æ³¨å ¥è‚ºè¡¨é¢æ´»æ€§ç‰©è´¨å¯¹æ—©äº§å„¿æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯å’Œé¢ å† å‡ºè¡€çš„å½±å“ï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants. METHODS: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups. RESULTS: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups (P<0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group (P<0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group (P<0.05). CONCLUSIONS: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.