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The European Respiratory Journal May 2024Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We...
BACKGROUND
Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers.
METHODS
We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers.
RESULTS
We identified 99 SRG adult variant carriers ( (n=18), (n=31), (n=24), (n=14) and (n=12)), including 20 (20.2%) with lung cancer ( (n=7), (n=8), (n=3), (n=2) and (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and / variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients TRG patients was 18.1 (95% CI 7.1-44.7).
CONCLUSIONS
The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.
Topics: Humans; Lung Neoplasms; Male; Female; Middle Aged; Aged; Cross-Sectional Studies; Pulmonary Surfactant-Associated Protein C; Pulmonary Surfactant-Associated Protein A; Adult; Thyroid Nuclear Factor 1; ATP-Binding Cassette Transporters; Risk Factors; Genetic Predisposition to Disease; Lung Diseases, Interstitial; Heterozygote; Pulmonary Surfactant-Associated Proteins
PubMed: 38575158
DOI: 10.1183/13993003.01809-2023 -
The Journal of Clinical Investigation Apr 2024BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific... (Clinical Trial)
Clinical Trial
BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).
Topics: Humans; Biomarkers; Male; Female; Child; Child, Preschool; Respiratory Distress Syndrome; Infant; Inflammation; Prospective Studies; Adolescent; Multiple Organ Failure; Cytokines
PubMed: 38573766
DOI: 10.1172/JCI177896 -
Seminars in Perinatology Mar 2024Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support... (Review)
Review
Respiratory insufficiency is almost ubiquitous in infants born preterm, with its incidence increasing with lower gestational age. A wide range of respiratory support management strategies are available for these infants, separable into non-invasive and invasive forms of respiratory support. Here we review the history and evolution of respiratory care for the preterm infant and then examine evidence that has emerged to support a non-invasive approach to respiratory management where able. Continuous positive airway pressure (CPAP) is the non-invasive respiratory support mode currently with the most evidence for benefit. CPAP can be delivered safely and effectively and can commence in the delivery room. Particularly in early life, time spent on non-invasive respiratory support, avoiding intubation and mechanical ventilation, affords benefit for the preterm infant by virtue of a lessening of lung injury and hence a reduction in incidence of bronchopulmonary dysplasia. In recent years, enthusiasm for application of non-invasive support has been further bolstered by new techniques for administration of exogenous surfactant. Methods of less invasive surfactant delivery, in particular with a thin catheter, have allowed neonatologists to administer surfactant without resort to endotracheal intubation. The benefits of this approach appear to be sustained, even in those infants subsequently requiring mechanical ventilation. This cements the notion that any reduction in exposure to mechanical ventilation leads to alleviation of injury to the vulnerable preterm lung, with a long-lasting effect. Despite the clear advantages of non-invasive respiratory support, there will continue to be a role for intubation and mechanical ventilation in some preterm infants, particularly for those born <25 weeks' gestation. It is currently unclear what role early non-invasive support has in this special population, with more studies required.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Respiration, Artificial; Continuous Positive Airway Pressure; Gestational Age; Pulmonary Surfactants; Surface-Active Agents; Respiratory Distress Syndrome, Newborn
PubMed: 38570268
DOI: 10.1016/j.semperi.2024.151885 -
Medical Archives (Sarajevo, Bosnia and... 2024Respiratory distress syndrome (RDS) is a major cause of morbidity and mortality in preterm infants. Early nasal CPAP and selective administration of surfactant via the...
BACKGROUND
Respiratory distress syndrome (RDS) is a major cause of morbidity and mortality in preterm infants. Early nasal CPAP and selective administration of surfactant via the endotracheal tube are widely used in the treatment of RDS in preterm infants.
OBJECTIVE
The aim of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery between LISA-treated and INSURE-treated premature infants with respiratory distress syndrome (RDS).
METHODS
Retrospective registry-based cohort study enrolled 36 newborns admitted to the neonatal intensive care unit of the "Santa Maria" Hospital of Terni between 2016 and 2023. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 hours of life, while the secondary outcomes were major neonatal morbidities and death before discharge.
RESULTS
The LISA group and the INSURE group included 13 and 23 newborns respectively. Demographic features showed no significant differences between the two groups. The need for mechanical ventilation in the first 72 hours of life was similar in both groups (p >0.99). There were no significant differences in morbidities.
CONCLUSION
LISA and INSURE are equally effective modalities for surfactant administration for the treatment of RDS in preterm infants.
Topics: Infant, Newborn; Humans; Infant, Premature; Surface-Active Agents; Retrospective Studies; Cohort Studies; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Lipoproteins
PubMed: 38566872
DOI: 10.5455/medarh.2024.78.112-116 -
Heliyon Apr 2024This study aimed to assess the diagnostic value of Krebs von den Lungen-6 (KL-6), Surfactant protein-A (SP-A), SP-D and molecular matrixmetalloproteinase-7 (MMP-7) in...
BACKGROUND
This study aimed to assess the diagnostic value of Krebs von den Lungen-6 (KL-6), Surfactant protein-A (SP-A), SP-D and molecular matrixmetalloproteinase-7 (MMP-7) in discriminating patients with interstitial lung diseases (ILDs) from disease control subjects.
METHODS
Serum levels of KL-6, SP-A, SP-D and MMP-7 were measured in both the ILD and non-ILD (NILD) groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these markers and laboratory indices. High-resolution computed tomography (HRCT) fibrosis scores were determined, and their correlation with the serum markers was analyzed.
RESULTS
Serum levels of KL-6 and MMP-7 were significantly elevated in the ILD group compared to the control group, while no significant differences were observed for SP-A and SP-D. ROC analysis of KL-6 demonstrated superior diagnostic accuracy, with a sensitivity of 76.36%, specificity of 91.07%, and an area under curve (AUC) of 0.902 (95%CI 0.866-0.945). These findings were consistent across an additional cohort. Correlation analysis revealed a link between KL-6 levels at initial diagnosis and HRCT fibrosis scores, indicating disease severity. Moreover, a negative correlation was found between KL-6 and pulmonary function indices, reflecting disease progression. Patients with increased 12-month HRCT fibrosis score showed higher lactate dehydrogenase (LDH) levels, with LDH exhibiting an AUC of 0.767 (95% CI: 0.520-0.927) as a predictor of progression.
CONCLUSIONS
Serum KL-6 detection proves to be a valuable tool for accurately distinguishing ILDs from control subjects. While KL-6 shows a correlation with HRCT fibrosis scores and a negative association with pulmonary function indices, its predictive value for ILDs prognosis is limited.
TRIAL REGISTRATION
This study received retrospective approval from the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (institutional review board ID: TJ-IRB20210331, date: 2021.03.30).
PubMed: 38560233
DOI: 10.1016/j.heliyon.2024.e27561 -
Journal of Oleo Science 2024Polyhexamethylene guanidine (PHMG) is a guanidine-based chemical that has long been used as an antimicrobial agent. However, recently raised concerns regarding the...
Polyhexamethylene guanidine (PHMG) is a guanidine-based chemical that has long been used as an antimicrobial agent. However, recently raised concerns regarding the pulmonary toxicity of PHMG in humans and aquatic organisms have led to research in this area. Along with PHMG, there are concerns about the safety of non-guanidine 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT) in human lungs; however, the safety of such chemicals can be affected by many factors, and it is difficult to rationalize their toxicity. In this study, we investigated the adsorption characteristics of CMIT/ MIT on a model pulmonary surfactant (lung surfactant, LS) using a Langmuir trough attached to a fluorescence microscope. Analysis of the π-A isotherms and lipid raft morphology revealed that CMIT/MIT exhibited minimal adsorption onto the LS monolayer deposited at the air/water interface. Meanwhile, PHMG showed clear signs of adsorption to LS, as manifested by the acceleration of the L phase growth with increasing surface pressure. Consequently, in the presence of CMIT/MIT, the interfacial properties of the model LS monolayer exhibited significantly fewer changes than PHMG.
Topics: Humans; Pulmonary Surfactants; Adsorption; Lung; Anti-Infective Agents; Guanidines; Guanidine; Disinfectants
PubMed: 38556278
DOI: 10.5650/jos.ess23165 -
Journal of Oleo Science 2024Phospholipids and surfactants form membranes and other self-assembled structures in water. However, it is not fully understood how the surrounding water (hydration... (Review)
Review
Phospholipids and surfactants form membranes and other self-assembled structures in water. However, it is not fully understood how the surrounding water (hydration water) is involved in their structure formation. In this paper, I summarize the results of our investigation of the long-range hydration state of phospholipids and surfactants at their surfaces by means of terahertz spectroscopy. By observing the collective rotational dynamics of water in the picosecond time scale, this technique allows us to observe not only the water directly bound to the solute, but also the weakly affected water outside of it. For example, PC phospholipids inhibit water dynamics over long distances, whereas PE phospholipids make water more mobile than bulk water. The causes of this difference in hydration and how it is involved in the structural formation of the membrane are reviewed.
Topics: Lipoproteins; Phospholipids; Pulmonary Surfactants; Surface-Active Agents; Terahertz Spectroscopy; Water
PubMed: 38556277
DOI: 10.5650/jos.ess23188 -
Scientific Reports Mar 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common cause of liver disease in the United States due to the increased incidence of...
Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common cause of liver disease in the United States due to the increased incidence of metabolic dysfunction and obesity. Surfactant protein A (SPA) regulates macrophage function, strongly binds to lipids, and is implicated in renal and idiopathic pulmonary fibrosis (IPF). However, the role of SPA in lipid accumulation, inflammation, and hepatic fibrosis that characterize MASLD remains unknown. SPA deficient (SPA) and age-matched wild-type (WT) control mice were fed a Western diet for 8 weeks to induce MASLD. Blood and liver samples were collected and used to analyze pathological features associated with MASLD. SPA expression was significantly upregulated in livers of mice with MASLD. SPA deficiency attenuated lipid accumulation along with downregulation of genes involved in fatty acid uptake and reduction of hepatic inflammation as evidenced by the diminished macrophage activation, decreased monocyte infiltration, and reduced production of inflammatory cytokines. Moreover, SPA inhibited stellate cell activation, collagen deposit, and liver fibrosis. These results highlight the novel role of SPA in promoting fatty acid uptake into hepatocytes, causing excessive lipid accumulation, inflammation, and fibrosis implicated in the pathogenesis of MASLD.
Topics: Mice; Animals; Pulmonary Surfactant-Associated Protein A; Diet, Western; Fatty Liver; Liver Cirrhosis; Fibrosis; Inflammation; Lipids; Fatty Acids
PubMed: 38553537
DOI: 10.1038/s41598-024-58291-5 -
Medicine Mar 2024Congenital surfactant deficiency, often caused by mutations in genes involved in surfactant biosynthesis such as ABCA3, presents a significant challenge in neonatal care...
INTRODUCTION
Congenital surfactant deficiency, often caused by mutations in genes involved in surfactant biosynthesis such as ABCA3, presents a significant challenge in neonatal care due to its severe respiratory manifestations. This study aims to analyze the clinical data of a newborn male diagnosed with pulmonary surfactant metabolism dysfunction type 3 resulting from ABCA3 gene mutations to provide insights into the management of this condition.
PATIENT CONCERNS
A newly born male child aged 1 day and 3 hours was referred to our department due to poor crying and shortness of breath.
DIAGNOSIS
Primary diagnoses by the duty physicians were: neonatal pneumonia, neonatal respiratory failure, persistent neonatal pulmonary hypertension, birth asphyxia, myocardial damage, and arteriovenous catheterization. Genetic test revealed a compound heterozygous variant in the ABCA3 gene. One allele may be exon variant c.4561C>T, the second allele may be intron variant c.1896 + 2_1896 + 17del. The associated disease included pulmonary surfactant metabolism dysfunction type 3.
INTERVENTIONS
He was initially treated with an antiinfective therapeutic regimen.
OUTCOMES
The family was informed of this condition and signed off, and the child died.
CONCLUSION
Hereditary pulmonary surfactant deficiency is a rare and untreatable disease. The case highlights the challenges in managing congenital surfactant deficiencies and emphasizes the need for heightened awareness of this rare cause of infant respiratory failure.
Topics: Humans; Infant, Newborn; Male; ATP-Binding Cassette Transporters; Lung Diseases, Interstitial; Mutation; Pulmonary Alveolar Proteinosis; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Surface-Active Agents
PubMed: 38552044
DOI: 10.1097/MD.0000000000037622 -
BioMed Research International 2024[This retracts the article DOI: 10.1155/2021/4117800.].
Retracted: Effects of Pulmonary Surfactant Combined with Noninvasive Positive Pressure Ventilation on KRT-14 and ET-1 Levels in Peripheral Blood and Therapeutic Effects in Neonates with Respiratory Distress Syndrome.
[This retracts the article DOI: 10.1155/2021/4117800.].
PubMed: 38550110
DOI: 10.1155/2024/9897420