Escaping from Flatland: the role of proteins SP-B and SP-C in the formation of 3D structures in interfacial pulmonary surfactant films.

Pulmonary surfactant is a vital component of respiratory physiology. Surfactant homeostasis is disrupted in various pulmonary disease states, and exogenous surfactant therapy has been proposed as a treatment to improve lung function and recovery. Although this therapy has demonstrated clinically significant benefit in neonatal respiratory distress syndrome, for adult patients with acute respiratory distress syndrome (ARDS), the evidence is inconclusive. To understand the potential shortcomings of past trials and potential opportunities for more effective exogenous surfactant use in ARDS, we review in detail past trials and literature involving exogenous surfactant therapy in adult patients with ARDS. We assess various factors that may have impacted trial results and propose potential solutions and areas for future research. Advances in surfactant research suggest a potential role for exogenous surfactant therapy for adult patients with ARDS.

The correlation between lung surfactant function inhibition in vitro and the effect on breathing of mice during inhalation exposure - A study of spray-formulated engine/brake cleaners and lubricating products.

Molecular dynamics insights of organic and inorganic aerosol interactions with a DPPC-based lung surfactant membrane model

Using diffusion-induced growth instabilities to measure line tension at liquid condensed-liquid expanded domain boundaries.

Microplastics bound to fine particulate matter in subway air: A pathway for toxic metal transport to enhanced carcinogenicity in human lungs.

Hyaline Membrane Disease (HMD) in newborns, also known as neonatal respiratory distress syndrome, is a common critical illness in premature infants, with an incidence inversely correlated with gestational age, posing a serious threat to the life and health of newborns. This paper systematically reviews the core pathogenesis of HMD, focusing on the abnormal metabolism of pulmonary surfactant (PS), genetic factors, immature lung development, and the synergistic effects of inflammatory oxidative stress. It highlights the advances in non-invasive ventilation (NIV) therapy for HMD, including the mechanisms of action, clinical application effects, and optimization strategies of mainstream modalities such as nasal continuous positive airway pressure ventilation (NCPAP), nasal intermittent positive pressure ventilation (NIPPV), and heated humidified high-flow nasal cannula ventilation (HHHFNC). The aim is to provide references for standardized clinical treatment.

Pulmonary surfactant (PS) is the standard treatment for respiratory distress syndrome in preterm infants. Budesonide, a corticosteroid with anti-inflammatory properties, has been studied for use with PS to potentially improve respiratory outcomes and reduce bronchopulmonary dysplasia (BPD) risk while minimizing systemic steroid exposure. This study aimed to compare the efficacy of PS with budesonide versus PS alone in infants born ≤ 28 weeks' gestational age (GA). A systematic review and meta-analysis was conducted by searching PubMed, Scopus, Embase, and the Cochrane Library databases from inception to October 21, 2025. Inclusion was restricted to randomized controlled trials (RCTs) examining PS with budesonide efficacy in extremely preterm populations. Risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was assessed with GRADE methodology. The primary outcomes were the incidence and severity of BPD; secondary outcomes included other respiratory measures, pre-discharge mortality, hospital stay duration, and complications related to prematurity. Compared to PS alone, PS with budesonide did not significantly reduce BPD incidence (RR, 0.96; 95% CI, 0.86 to 1.08; p = 0.51; I2 = 40%; low-certainty evidence), duration of mechanical ventilation (MD, - 0.45 days; 95% CI, - 2.26 to 1.36; p = 0.62; I2 = 0%; moderate-certainty evidence), pre-discharge mortality (RR, 0.92; 95% CI, 0.76 to 1.13; p = 0.44; I2 = 0%; low-certainty evidence), or duration of of hospitalization (MD, 0.27 days; 95% CI, - 3.29 to 3.84; p = 0.88; I2 = 0%; moderate-certainty evidence). PS with budesonide probably has little or no effect on BPD, respiratory outcomes, other prematurity-related outcomes, or pre-discharge mortality compared to surfactant alone. Most outcomes are based on low- to moderate-certainty evidence. Therefore, current evidence is insufficient to support the superior efficacy of pulmonary surfactant with budesonide over surfactant alone in extremely preterm infants.

Introduction. Severe pneumonia complicated by acute respiratory distress syndrome (ARDS) is associated with high mortality, necessitating the search for additional pathogenetic treatment methods. One of the key pathogenesis factors is secondary pulmonary surfactant deficiency. Despite compelling theoretical support, the clinical efficacy of inhaled exogenous surfactants in adult patients remains controversial. Aim. To retrospectively analyze the efficacy and safety of inhaled surfactant in combination therapy for patients with severe pneumonia complicated by ARDS. Mat erials and methods. This retrospective cohort study included 48 patients with severe pneumonia (community-acquired – 56.3%, influenza-associated – 27.1%, COVID-19 – 16.6%) who received inhaled surfactant-BL at a dose of 75 mg twice daily for 7 [5; 9] days in addition to standard therapy, including respiratory support and antimicrobial therapy. Efficacy was assessed based on changes in oxygen saturation (SpO 2 ). R e s u l t s . All patients initially experienced severe hypoxemia (median SpO 2 before therapy 86 [80; 92] %). Positive changes were observed during therapy: after 72 hours, the median SpO 2 increased to 92 [89; 96] %, and by the time of discharge, it reached 96 [89; 99] %. Overall survival in the cohort was 66.7% (32 patients). Mortality (33.3%, 16 patients) was recorded in the most severe subgroup with a fulminant course and severe comorbidity. Conclusion. The addition of inhaled surfactant-BL to combination therapy for severe pneumonia with ARDS is associated with a significant improvement in oxygenation and acceptable survival rates in critically ill patients.

Pulmonary surfactant is a lipoproteinaceous material secreted exclusively by alveolar type 2 cells into the alveolar space. It is primarily responsible for reducing the work of breathing by reducing surface tension at the air-liquid interface, though has important additional roles in the innate immune response. Packaging of pulmonary surfactant is complex, involving specialised trafficking and post translational modification of both lipid and protein components to facilitate the formation of lamellar bodies in which surfactant is packaged before exocytosis. Aberrancies of pulmonary surfactant maturation, secretion, function and recycling can have profound impacts on alveolar epithelial dysfunction and respiratory function. Manifestations are diverse, ranging from fatal neonatal respiratory failure to adult-onset interstitial lung disease. Here, we consider aspects of pulmonary surfactant genesis, function and clearance in health and disease, also highlighting current and future therapies for surfactant-associated disease and the challenges of progressing research in the field.

ContextSurfactant protein B (SP-B) is a critically important component of pulmonary surfactant (PS), responsible for much of the lipid restructuring activity necessary to maintain proper respiratory function. Despite its functional and biological importance, there is a significant lack of knowledge regarding the structural characteristics of SP-B, exacerbated by a lack of a complete, experimentally determined structure. Comparative modeling with homologous saposin-family proteins was used to generate predicted structures for SP-B in both an open (hydrophobic residues exposed) and closed (hydrophobic residues buried) conformation. These structures were then used for further study with molecular dynamics. Five replicate simulation systems were prepared for both conformations in different solvent conditions, including water and chloroform, a hydrophobic solvent. These simulations indicate the relative stability of the closed conformation protein in water, with the open conformation structure undergoing a large conformational change due to hydrophobic forces in water quantified by relevant intramolecular distances. Solvent distribution analysis elucidated the varying affinity of different regions of the protein to hydrophobic and hydrophilic environments, providing insight into the structural–functional characteristics of SP-B in the varied PS environment.MethodsFor each system, a minimum of 900 ns production time per simulation was collected in 5 replicate simulations. Production time was measured after the system RMSD reached a steady state. All simulations used the FF19SB force field and OPC water model when applicable. Overall RMSD, per-residue RMSF, specific geometric parameters, and solvent distribution information were collected over the course of the simulations and analyzed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00894-025-06585-4.

The present investigation was carried out in P.V.Narasimha raoTelangana Veterinary University, Veterinary Clinical complex, C.V.Sc, Rajendranagar. A total of 12 dogs belonging to five different breeds were selected for the study and was divided into two groups (Group I and II) of six each. The first samples of amniotic fluid from 6 pregnant dogs were collected through amniocentesis on day 63 or the last day of pregnancy. Amniotic fluid samples were analysed for the presence of lung surfactant, using bubble test. Bubble test prognostic indicator in newborns diagnosing death due to Respiratory Disstress Syndrome.

Lung surfactant (LS) plays an essential role in preventing lung collapse due to physical forces by forming surface-active lipid-protein membranous films at the respiratory air-liquid interface. Throughout its biological cycle, LS exists in a variety of metabolically related, conspicuous morphological forms. Epithelial alveolar type II cells store LS as intracellular, tightly packed, multilayered organelles known as lamellar bodies. These are secreted as still-condensed material in the form of lamellar body-like particles, which, upon adsorption, give rise to the interfacial film and surface-associated structures. Surfactant material purified from bronchoalveolar lavage fluids has been extensively examined by conventional transmission electron microscopy (TEM), providing important information about LS ultrastructure. However, potential artifacts associated with classical TEM preparation methods-such as staining, dehydration, resin embedding, and sectioning-hinder the observation of surfactant biological samples in their truly native state. In this work, we have taken advantage of cutting-edge cryo-microscopy techniques to visualize the structural complexity present in LS preparations without fixation, in a frozen-hydrated state, and thus closer to physiological conditions. The implementation of cryopreservation approaches has allowed us to unveil unprecedented ultrastructural details of the diverse morphological states in which LS is present in the alveolar spaces, such as the presence of a protein-based pore connecting the lumen of the lamellar body-like particles (LBPs) with the external milieu, and an onion-like structure that suggests a mechanism that uses the energy accumulated upon LB assembly in the pneumocytes for a rapid release of the membranous complexes to the exterior. These morphological features shed light on the dynamic processes by which LS is unpacked from secreted condensed states to the more disorganized, interconnected membranous networks that sustain breathing mechanics.NEW & NOTEWORTHY We have applied some of the most advanced methodologies in cryo-electron microscopy and X-ray tomography to the characterization of native pulmonary surfactant. We still do not understand the way lung surfactant membranes unravel, once secreted, at the respiratory air-liquid interface, and current models are still based on structural observations made when the methodologies available 30 years ago required extensive manipulation/perturbation of membrane materials. Our study reveals new features on the architecture of this system.

Interaction of isoniazid derivatives active against drug-resistant tuberculosis with models of the lung surfactant and of the Mycobacterium tuberculosis cell wall.

Pulmonary surfactant protein SP-C regulates lipid vesicle uptake by alveolar type II cells and macrophages: Role of lipids, palmitoylation, and environment.

Surfactant protein B (SP-B) is essential for surface tension reducing function of pulmonary surfactant and alveolar unfolding processes during inspiration. SP-B is reduced early in acute lung injury. Hence, we hypothesize that 1) reduced SP-B expression increases susceptibility to ventilation-induced lung injury (VILI), and 2) deep inflations (DI) are protective against VILI. Conditional SP-B knockout mice were randomized into OFF (reduced SP-B) and ON groups (normal SP-B) and subjected to mechanical ventilation at zero end-expiratory pressure. Over 4 h of ventilation, either 4 or 16 DI were administered. Lung mechanics were recorded, and pulmonary structure was quantified by design-based stereology. Inflammatory cells and bulk RNA sequencing were measured in bronchoalveolar lavage (BAL) and tissue, respectively. No differences in inflammatory cells in BAL were detected between ON and OFF groups. During ventilation, alveolar derecruitment-related increase in elastance was most pronounced in OFF-4DI but reversible by DI so that lung mechanics did not worsen. Finally, volumes of the alveolar liquid lining layer and the intracellular surfactant were largest, whereas the surface area of the apical plasma membrane of type II pneumocytes was smallest in OFF-4DI, suggesting impaired surfactant secretion. A higher frequency of DI prevented these abnormalities. Electron microscopy revealed disorganized tight junctions between alveolar epithelial cells in OFF-4DI, which was linked with decreased expression of genes relevant to the apical junctional complex. Reduced SP-B resulted in a progressive increase in surface tension and a disturbed fluid balance without triggering definite VILI. Maintenance of residual surfactant function is highly dependent on DI in conditions of reduced SP-B levels.NEW & NOTEWORTHY Surfactant protein B (SP-B) is critical for efficient surfactant function in the lung. Reduced SP-B levels occur at an early stage of acute lung injury and impair alveolar unfolding. In this study, we demonstrate that mechanical ventilation of lungs with reduced SP-B levels does not trigger ventilation-induced lung injury but results in disbalance of alveolar fluid volume and increase in surface tension due to failure of surfactant maintenance. Deep inflations prevent these ventilation-induced effects.

This study aimed to evaluate the effects of infrared photobiomodulation (PBM) on alveolar surfactant cells and explore cellular-level biological responses in preterm rat lungs. The development of supportive treatments for lung diseases could be advanced by understanding PBM's influence on alveolar type II cell function, surfactant production, and inflammatory responses. Sixty-eight preterm Sprague-Dawley rats were divided into three groups: a control group and two experimental groups receiving either 660nm and 830nm photobiomodulation therapy (PBMT) at 30 mW and 3J/cm², administered three times daily for three days. Key physiological parameters were monitored, and surfactant proteins were quantified using ELISA. Additionally, cytotoxicity and genotoxicity were evaluated in H-6053 cells, and histological assessments were performed to identify structural changes. The results demonstrated that 660nm PBMT significantly increased Surfactant B, C, and D levels. Crucially, this intervention showed no evidence of cytotoxic or phototoxic damage. In contrast, the 830nm PBMT yielded more variable increases in surfactant proteins and was associated with minimal cytotoxic effects. These findings suggest that 660nm PBMT is a promising, noninvasive modality for augmenting surfactant production. This approach holds potential as a supportive therapy for neonates with respiratory distress syndrome. Further clinical investigations are warranted to validate these findings in human preterm infants and to fully elucidate the underlying cellular mechanisms.

HighlightsWhat are the main findings?Lung ultrasound-guided surfactant administration reduced invasive ventilation and radiation exposure in preterm infants.It enabled earlier and more precise PS use than FiO2-based methods.What are the implications of the main findings?Lung ultrasound improves NRDS management and supports safer, evidence-based neonatal care.Incorporating lung ultrasound into clinical protocols may optimize resource use and guide updates to neonatal respiratory guidelines.Objectives: Current guidelines for pulmonary surfactant (PS) administration in preterm infants with respiratory distress rely on clinical signs and FiO2 thresholds. Lung ultrasound offers a promising alternative for accurately diagnosing neonatal respiratory distress syndrome (NRDS) and assessing its severity. This randomized controlled trial aimed to evaluate whether a lung ultrasound-guided strategy for NRDS diagnosis and lung ultrasound scores (LUS)-guided PS administration could improve respiratory outcomes in preterm infants (<32 weeks’ gestation), compared to conventional methods. Methods: In this non-blinded randomized controlled trial, 89 preterm infants (≤32 weeks’ gestation) with respiratory distress after birth were enrolled. Participants were randomly assigned to either the ultrasound group (PS administration based on ultrasound-confirmed NRDS and LUS criteria) or the control group (PS administration according to standard clinical signs and FiO2 requirements). Results: The ultrasound group demonstrated a significantly lower rate of invasive mechanical ventilation (p = 0.007) and a shorter duration of ventilation (p = 0.005) compared to the control group. Furthermore, the ultrasound group required less PS (p = 0.03), received their first dose at an earlier time (p = 0.017), and experienced fewer radiation exposures both before surfactant treatment and within the first week after birth (p = 0.023 and p = 0.019, respectively). Conclusions: The integration of lung ultrasound for NRDS diagnosis and LUS-guided surfactant therapy facilitates more precise and timely PS use. This strategy reduces the need for and duration of invasive mechanical ventilation and limits early radiation exposure in very preterm infants.

BackgroundThere is few treatments for bronchopulmonary dysplasia (BPD), and systemic glucocorticoid therapy has serious side effects.MethodsLow birth weight infants were classified randomly into control group administered with pulmonary surfactant (200 mg/kg) and intervention group administered with pulmonary surfactant (200 mg/kg) and budesonide suspension (0.25 mg/kg) to explore the efficacy of combination of pulmonary surfactant and budesonide suspension is better than that of pulmonary surfactant alone.ResultsThe incidence of bronchopulmonary dysplasia was significantly lower in the intervention group (45%) compared to the control group (64%). Additionally, the duration of invasive ventilator use was significantly shorter in the intervention group (66.39 ± 37.09 h) than in the control group (82.05 ± 54.55 h); and the infants from the intervention group had a significantly shorter supplemental oxygen time, with the intervention group at 775.32 ± 396.06 h and the control group at 844.01 ± 414.18 h. Comparison of the basic conditions of the two groups of children showed no statistically significant differences in maternal medical history, gestational age, birth weight, sex, whether hormones were used prenatally, and delivery method (P > 0.05). There was no difference in the incidence of complications, such as neonatal infection, intracranial hemorrhage, necrotizing enterocolitis, and retinopathy between the two groups.ConclusionCombination of pulmonary surfactant with budesonide suspension can significantly decrease the incidence of bronchopulmonary dysplasia in very low birth weight infants, reduce the duration of invasive mechanical ventilation, and promote earlier weaning from oxygen supplement.Clinical Trial RegistrationEffect of budesonide combined with pulmonary surfactant on lung development in very low birth weight infants, ChiCTR2400086677, https://www.chictr.org.cn/showproj.html?proj=233373.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in both indoor and outdoor air, and there is increasing need to effectively screen this diverse class of chemicals for inhalation toxicity potential. Since PFAS have strong surface-active properties, we hypothesized they may interfere with lung surfactant (LS) activity. We investigated the ability of 17 PFAS delivered as liquid aerosols to inhibit LS function in a newly developed constrained drop surfactometer (CDS). Using both fluorescent tracers and mass spectrometry techniques, deposition of PFAS aerosols onto exposed LS was determined. Nine of the 17 PFAS increased surface tension (ST) above the inhibition threshold, defined as mean minimum post-exposure ST above 10 mN/m. Inhibitory compounds included legacy PFAS (perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)), emerging compounds (hexafluoropropylene oxide dimer acid, perfluoro-2-methoxyacetic acid), perfluorooctyltriethoxysilane, and perfluorooctane-sulfonamides and -sulfonamidoethanols. These compounds represent a wide range of molecular weights and functional head groups (carboxylic and sulfonic acids, sulfonamides, and siloxane). Among these compounds, the lowest modeled inhibitory doses were for N-methyl-perfluorooctane-sulfonamidoethanol (0.34 ppm) and N-ethyl-perfluorooctane-sulfonamidoethanol (0.14 ppm). Concentrations of PFOA and PFOS required to inhibit LS were significantly lower when aerosolized than when directly mixed with LS, demonstrating the importance of interactions with surfactant at the air-liquid interface. Our results show that a combination of size, functional groups, and hydrophobicity influence the ability of PFAS to inhibit LS function. Under high exposure conditions, inhaled PFAS may initiate an adverse outcome pathway through surfactant inhibition, which may ultimately produce a reduction of lung function.