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Immunity, Inflammation and Disease Jun 2024Severe 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... (Review)
Review
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.
Topics: COVID-19; Humans; SARS-CoV-2; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Biomarkers; Pulmonary Surfactant-Associated Protein D; Prognosis; Lung
PubMed: 38860749
DOI: 10.1002/iid3.1302 -
PloS One 2024Clear amniotic fluid aspiration syndrome (CAF-AS) is a very rare event occurring in 0.25% of our term clear amniotic fluids deliveries. The study's aims were: 1. to... (Observational Study)
Observational Study
BACKGROUND
Clear amniotic fluid aspiration syndrome (CAF-AS) is a very rare event occurring in 0.25% of our term clear amniotic fluids deliveries. The study's aims were: 1. to characterize the risk factors and outcomes associated with Clear Amniotic Fluid Aspiration Syndrome and 2. to compare the outcomes of Clear Amniotic Fluid Aspiration to Meconium Aspiration.
METHODS
This was an observational study over a 22-year period in a single level-3 medical center. Compared were parturient/labor characteristics and neonatal outcomes in cases with suspected Clear Amniotic Fluid Aspiration to cases suspected for Meconium Aspiration.
RESULTS
Out of 79,620 term deliveries there were 66,705 (83.8%) clear amniotic fluids and 12,915 (16.2%) meconium stained amniotic fluid (MSAF). Of neonates born with clear amniotic fluid, 166 (0.25%) were diagnosed with Clear Amniotic Fluid Aspiration Syndrome (CAF-AS), while 202 (15.7%) of those born with MSAF, were diagnosed with aspiration syndrome (MSAF-AS). Both conditions had comparable rates of mild manifestation (67.5% vs 69.2%, p = 0.63). Persistent pulmonary hypertension (PPH) occurred 5 times less in CAF-AS than MSAF-AS (4% vs 20%, OR 0.17, P< 0.0001) Both conditions presented similar rates of surfactant without PPH (11.1% vs 13.4%, p = 0.87). There was 1 postnatal death in CAF-AS vs 10 in MSAF.
CONCLUSION
CAF-AS were quantitatively quite similar in terms of need of actual active intervention of the neonatologists in the delivery room (166 vs 202, i.e. in terms of numbers of cases and not prevalence) to MSAF-AS.We identified in these cases two major specific causes: hyperkinetic explosive deliveries in multiparas and long-lasting episodes of maternal hypotension due to epidural/spinal anaesthesia during labor. Out of 140 million births per year in the world, it should be of concern that 3 million cases are neglected nowadays. Future studies should evaluate if this CAF-AS should benefit from a more active intervention such as immediate endotracheal suction at birth, this clear fluid being very easy to suction.
Topics: Humans; Female; Amniotic Fluid; Pregnancy; Meconium Aspiration Syndrome; Infant, Newborn; Adult; Risk Factors; Male
PubMed: 38857215
DOI: 10.1371/journal.pone.0301595 -
JCI Insight Jun 2024Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel...
Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.
Topics: Extracellular Vesicles; Humans; Animals; Biomarkers; Mice; Male; Female; Pulmonary Fibrosis; Disease Progression; Pulmonary Surfactant-Associated Protein B; Middle Aged; Aged; Lung Diseases, Interstitial; Lung; Proteomics; Disease Models, Animal; Prognosis; Protein Precursors; Pulmonary Surfactant-Associated Proteins
PubMed: 38855869
DOI: 10.1172/jci.insight.177937 -
Translational Pediatrics May 2024Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and...
BACKGROUND
Bronchopulmonary dysplasia (BPD), characterized by impaired lung development, remains a leading cause of morbidity and mortality in premature infants. The synthesis and metabolism of lipids play a critical role in normal lung development, such as dipalmitoylphosphatidylcholine, a key component of pulmonary surfactant (PS). Therefore, we conducted a lipidomics study of rat lung tissue to explore the changes of pulmonary lipid composition in the progression of BPD disease.
METHODS
In this study, we exposed neonatal Sprague-Dawley (SD) rats to hyperoxia for 14 days. After hyperoxia exposure, the lung tissues of rats were analyzed pathologically, and untargeted lipidomics was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
RESULTS
Hematoxylin-eosin (H&E) staining showed that the alveoli enlarged, the number of alveoli decreased and the pulmonary surfactant-associated protein D (SFTPD) decreased in hyperoxia-exposed rats. A total of 620 pulmonary lipids were detected by LC-MS/MS, covering 27 lipid categories. The most common lipids were triacylglycerol (TAG), followed by phosphatidylcholine (PC) and phosphatidylethanolamine (PE).
CONCLUSIONS
Compared with those rats exposed to normoxic conditions, the lipid levels in the lungs of rats exposed to hyperoxia for 14 days generally decreased, with the levels of TAG and PC decreasing most significantly. In short, our results provide a clue for finding therapeutic targets and biomarkers of a BPD rat model lung liposome.
PubMed: 38840687
DOI: 10.21037/tp-23-546 -
Thoracic Cancer Jun 2024The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is...
BACKGROUND
The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population.
METHODS
We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results.
RESULTS
Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm).
CONCLUSION
Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.
PubMed: 38828610
DOI: 10.1111/1759-7714.15385 -
Acta Veterinaria Scandinavica May 2024A syndrome of acute non-cardiogenic pulmonary edema associated with hunting is prevalent in the drever breed, but etiology of this syndrome is currently unknown....
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.
Topics: Animals; Dogs; Pulmonary Edema; Dog Diseases; Pulmonary Surfactants; Male; Female; Bronchoalveolar Lavage Fluid; Case-Control Studies
PubMed: 38822358
DOI: 10.1186/s13028-024-00745-x -
Asian Pacific Journal of Cancer... May 2024Radiation-induced lung disease is a potentially fatal, dose-limiting toxicity commonly seen after radiotherapy of thoracic malignancies, including breast cancer. (Comparative Study)
Comparative Study
Dosimetry and Biochemical Comparison of Early Radiation-Induced Lung Toxicity in Breast Cancer Patients Treated with 3D-CRT and IMRT: the Role of Serum Interleukin-6 and Pulmonary Surfactant Protein-D.
BACKGROUND
Radiation-induced lung disease is a potentially fatal, dose-limiting toxicity commonly seen after radiotherapy of thoracic malignancies, including breast cancer.
AIM
To evaluate and compare the early lung toxicity induced by 3D-CRT and IMRT radiotherapy treatment modalities in breast cancer female patients using biochemical, dosimetry and clinical data.
SUBJECTS AND METHODS
this study included 15 normal healthy controls, 15 breast cancer patients treated with IMRT, and 15 breast cancer patients treated with 3D-CRT. One blood sample was obtained from the control group and 3 blood samples were withdrawn from cases before RT, after RT and after 3 months of RT.
RESULT
IMRT delivered higher radiation dose to the breast tumor and lower doses to the lung as an organ at risk. There was a non-significant increase in the serum levels of IL-6 before IMRT and 3D-CRT compared with its levels in the control group. There were significant increases in serum levels of IL-6 after RT (IMRT and 3DCRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of IL-6 after 3 months of RT (IMRT and 3D-CRT) compared with its serum levels immediately after RT. There was a non-significant increase in the serum levels of SP-D before RT (IMRT and 3D-CRT) compared with its levels in the control group. There were significant-increases in serum levels of SP-D after RT (IMRT and 3D-CRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of SP-D after 3 months of radiotherapy (IMRT and 3D-CRT) compared with its serum levels immediately after RT.
CONCLUSION
serum of levels IL-6 and SP-D can be used to diagnose the occurrence of early lung toxicity due to radiotherapy and the rate of recovery from radiation pneumonitis is apparent in case of IMRT than 3D-CRT.
Topics: Humans; Female; Interleukin-6; Radiotherapy, Intensity-Modulated; Breast Neoplasms; Middle Aged; Pulmonary Surfactant-Associated Protein D; Case-Control Studies; Radiotherapy Dosage; Radiotherapy, Conformal; Follow-Up Studies; Adult; Radiation Injuries; Prognosis; Radiation Pneumonitis; Radiotherapy Planning, Computer-Assisted; Lung; Aged; Radiometry
PubMed: 38809643
DOI: 10.31557/APJCP.2024.25.5.1707 -
JAMA Network Open May 2024Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of...
IMPORTANCE
Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population.
OBJECTIVE
To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled.
EXPOSURE
Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making.
MAIN OUTCOMES AND MEASURES
The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed.
RESULTS
A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted β, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted β, 0.2; 95% CI, 0.1-0.3; P < .001).
CONCLUSIONS AND RELEVANCE
In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.
Topics: Humans; Infant, Newborn; Pulmonary Surfactants; Prospective Studies; Infant, Premature; Female; Ultrasonography; Male; Lung; Respiratory Distress Syndrome, Newborn; Gestational Age
PubMed: 38805223
DOI: 10.1001/jamanetworkopen.2024.13446 -
F1000Research 2022Pulmonary alveolar proteinosis is a very rare diffuse lung disease characterized by the accumulation of amorphous and periodic acid Schiff-positive lipoproteinaceous...
Pulmonary alveolar proteinosis is a very rare diffuse lung disease characterized by the accumulation of amorphous and periodic acid Schiff-positive lipoproteinaceous material in the alveolar spaces due to impaired surfactant clearance by alveolar macrophages. Three main types were identified: Autoimmune, secondary and congenital. Pulmonary alveolar proteinosis has been previously reported to be associated with several systemic auto-immune diseases. Accordingly, we present the first case report of pulmonary alveolar proteinosis associated with myasthenia gravis. A 27-year-old female patient, ex-smoker, developed a dyspnea on exertion in 2020. The chest X-ray detected diffuse symmetric alveolar opacities. Pulmonary infection was ruled out, particularly COVID-19 infection. The chest scan revealed the "crazy paving" pattern. The bronchoalveolar lavage showed a rosy liquid with granular acellular eosinophilic material Periodic acid-Schiff positive. According to the lung biopsy results, she was diagnosed with pulmonary alveolar proteinosis. The granulocyte macrophage colony-stimulating factor autoantibodies were negative. Nine months later, she was diagnosed with bulbar seronegative myasthenia gravis, confirmed with the electroneuromyography with repetitive nerve stimulation showing significant amplitude decrement of the trapezius and spinal muscles. She was treated with pyridostigmine, oral corticosteroids and azathioprine. Given the worsening respiratory condition of the patient, a bilateral whole lung lavage was performed with a partial resolution of symptoms. Thus, this previously unreported association was treated successfully with rituximab, including improvement of dyspnea, diplopia and muscle fatigability at six months of follow-up. This case emphasizes on the possible association of auto-immune disease to PAP, which could worsen the disease course, as the specific treatment does not exist yet. Hence, further studies are needed to establish clear-cut guidelines for PAP management, particularly when associated to auto-immune diseases.
Topics: Humans; Pulmonary Alveolar Proteinosis; Female; Adult; Myasthenia Gravis
PubMed: 38779463
DOI: 10.12688/f1000research.127299.2 -
The Clinical Respiratory Journal May 2024This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment... (Review)
Review
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.
Topics: Humans; Pulmonary Surfactants; Contusions; Lung Injury; Respiratory Distress Syndrome; Animals; Respiration, Artificial; Treatment Outcome; Bronchoscopy
PubMed: 38778673
DOI: 10.1111/crj.13776