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Disease Models & Mechanisms Jun 2024Growing evidence shows that the lung is an organ prone to injury by diabetes mellitus. However, the molecular mechanisms of these pulmonary complications have not yet...
Growing evidence shows that the lung is an organ prone to injury by diabetes mellitus. However, the molecular mechanisms of these pulmonary complications have not yet been characterized comprehensively. To systematically study the effects of insulin deficiency and hyperglycaemia on the lung, we combined proteomics and lipidomics with quantitative histomorphological analyses to compare lung tissue samples from a clinically relevant pig model for mutant INS gene induced diabetes of youth (MIDY) with samples from wild-type (WT) littermate controls. Among others, the level of pulmonary surfactant-associated protein A (SFTPA1), a biomarker of lung injury, was moderately elevated. Furthermore, key proteins related to humoral immune response and extracellular matrix (ECM) organization were significantly altered in abundance. Importantly, a lipoxygenase pathway was dysregulated as indicated by a 2.5-fold reduction of polyunsaturated fatty acid lipoxygenase ALOX15 levels, associated with corresponding changes in the levels of lipids influenced by this enzyme. Our multi-omics study points to an involvement of reduced ALOX15 levels and an associated lack of eicosanoid switching as mechanisms contributing to a proinflammatory milieu in the lungs of subjects suffering from diabetes mellitus.
PubMed: 38900131
DOI: 10.1242/dmm.050650 -
Current Opinion in Pulmonary Medicine Jun 2024The identification of extra-pulmonary symptoms plays a crucial role in diagnosing interstitial lung disease (ILD). These symptoms not only indicate autoimmune diseases...
PURPOSE OF REVIEW
The identification of extra-pulmonary symptoms plays a crucial role in diagnosing interstitial lung disease (ILD). These symptoms not only indicate autoimmune diseases but also hint at potential genetic disorders, suggesting a potential overlap between genetic and autoimmune origins.
RECENT FINDINGS
Genetic factors contributing to ILD are predominantly associated with telomere (TRG) and surfactant-related genes. While surfactant-related gene mutations typically manifest with pulmonary involvement alone, TRG mutations were initially linked to syndromic forms of pulmonary fibrosis, known as telomeropathies, which may involve hematological and hepatic manifestations with variable penetrance. Recognizing extra-pulmonary signs indicative of telomeropathy should prompt the analysis of TRG mutations, the most common genetic cause of familial pulmonary fibrosis. Additionally, various genetic diseases causing ILD, such as alveolar proteinosis, alveolar hemorrhage, or unclassifiable pulmonary fibrosis, often present as part of syndromes that include hepatic, hematological, or skin disorders.
SUMMARY
This review explores the main genetic conditions identified over the past two decades.
PubMed: 38896087
DOI: 10.1097/MCP.0000000000001088 -
Cancers May 2024This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic...
This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61-0.92) and 0.69 (95% CI: 0.56-0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. When stratifying into ever-smokers and never-smokers, the 4MP had respective AUCs of 0.77 (95% CI: 0.63-0.92) and 0.72 (95% CI: 0.17-1.00) for a 1-year risk of lung cancer. The AUCs of the 4MP for predicting metastatic lung cancer within one year and two years of the blood draw were 0.95 (95% CI: 0.87-1.00) and 0.78 (95% CI: 0.62-0.94), respectively. Our findings indicate that a blood-based biomarker panel may be useful in identifying ever- and never-smokers at high risk of a diagnosis of lung cancer within one-to-two years.
PubMed: 38893188
DOI: 10.3390/cancers16112070 -
International Journal of Molecular... May 2024Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with...
Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management.
Topics: Humans; COVID-19; Male; Female; Pulmonary Surfactant-Associated Protein D; Biomarkers; Middle Aged; Severity of Illness Index; Pulmonary Surfactant-Associated Protein A; SARS-CoV-2; Aged; Adult; Prognosis
PubMed: 38891806
DOI: 10.3390/ijms25115620 -
Cells May 2024Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid... (Review)
Review
Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.
Topics: Humans; Lung Diseases; Lipid Metabolism; Animals; Macrophages; Macrophages, Alveolar; Signal Transduction
PubMed: 38891022
DOI: 10.3390/cells13110889 -
Respiratory Research Jun 2024Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge...
Treating sleep-disordered breathing of idiopathic pulmonary fibrosis patients with CPAP and nocturnal oxygen treatment. A pilot study : Sleep-disordered breathing treatment in IPF.
INTRODUCTION
Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge regarding the impact of SDB treatment on IPF. We assessed at one year: (1) the effect of CPAP and/or nocturnal oxygen therapy on IPF regarding lung function, blood mediators, and quality of life; (2) adherence to SDB treatment and SDB changes.
METHODOLOGY
This is a prospective study of consecutive newly diagnosed IPF patients initiating anti-fibrotic treatment. Lung function, polysomnography, blood tests and quality of life questionnaires were performed at inclusion and after one year. Patients were classified as obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and sleep-sustained hypoxemia (SSH). SDB therapy (CPAP and/or nocturnal oxygen therapy) was initiated if needed.
RESULTS
Fifty patients were enrolled (36% had OSA, 22% CSA, and 12% SSH). CPAP was started in 54% of patients and nocturnal oxygen therapy in 16%. At one-year, polysomnography found improved parameters, though 17% of patients had to add nocturnal oxygen therapy or CPAP, while 33% presented SDB onset at this second polysomnography. CPAP compliance at one year was 6.74 h/night (SD 0.74). After one year, matrix metalloproteinase-1 decreased in OSA and CSA (p = 0.029; p = 0.027), C-reactive protein in OSA (p = 0.045), and surfactant protein D in CSA group (p = 0.074). There was no significant change in lung function.
CONCLUSIONS
Treatment of SBD with CPAP and NOT can be well tolerated with a high compliance. IPF patients may exhibit SDB progression and require periodic re-assessment. Further studies to evaluate the impact of SDB treatment on lung function and serological mediators are needed.
Topics: Humans; Continuous Positive Airway Pressure; Female; Male; Idiopathic Pulmonary Fibrosis; Pilot Projects; Aged; Prospective Studies; Sleep Apnea Syndromes; Oxygen Inhalation Therapy; Middle Aged; Treatment Outcome; Polysomnography; Quality of Life
PubMed: 38890648
DOI: 10.1186/s12931-024-02871-6 -
American Journal of Respiratory Cell... Jun 2024
PubMed: 38889348
DOI: 10.1165/rcmb.2024-0237ED -
Pediatrics Jul 2024A multidisciplinary comprehensive protocol to use bubble continuous positive airway pressure (bCPAP) as the primary respiratory support in the delivery room (DR) and the...
BACKGROUND
A multidisciplinary comprehensive protocol to use bubble continuous positive airway pressure (bCPAP) as the primary respiratory support in the delivery room (DR) and the NICU was introduced. With this study, we aimed to assess the association of this change with respiratory outcomes over time.
METHODS
Infants with gestational age <32 weeks and birth weight <1250 g admitted between January 2012 and June 2020 were included and categorized into 4 periods, including pre-implementation (P0: 2012-2014), and post-implementation (P1: 2014-2016, P2: 2016-2018, P3: 2018-2020). The primary outcome was the rates of death and severe bronchopulmonary dysplasia (BPD), and the secondary outcomes included the rates of DR and NICU intubation ≤7 days of age, need of surfactant, and pneumothorax. Multivariate logistic regression models accounting for relevant risk factors were used to calculate adjusted odds ratios (ORs).
RESULTS
The study included 440 infants (P0 = 90, P1 = 91, P2 = 128, P3 = 131). Over time, more infants were free of BPD (P < .001), and the rates of death and severe BPD decreased significantly: P1 = OR 1.21 (95% confidence interval [CI] 0.56-2.67), P2 = OR 0.45 (95% CI 0.20-0.99), and P3 = OR 0.37 (95% CI 0.15-0.84). DR intubation decreased from 66% (P0) to 24% (P3) in the entire cohort (P < .001) and from 96% (P0) to 40% (P3) in infants <26 weeks of age (P < .001). The need for NICU intubation was similar (P = .98), with a decreased need for surfactant (P = .001) occurring at higher FiO2 (P0 = 0.35 vs P3 = 0.55, P < .001). Pneumothorax rates were unchanged.
CONCLUSIONS
In very preterm infants, the implementation of a comprehensive bCPAP protocol led to a significant and consistent improvement in respiratory practices and the rates of death and severe BPD.
Topics: Humans; Infant, Newborn; Continuous Positive Airway Pressure; Bronchopulmonary Dysplasia; Male; Female; Intensive Care Units, Neonatal; Clinical Protocols; Retrospective Studies; Infant, Premature; Pulmonary Surfactants; Delivery Rooms; Gestational Age; Pneumothorax
PubMed: 38887808
DOI: 10.1542/peds.2023-065373 -
Biomedical Chromatography : BMC Jun 2024Pulmonary surfactant replacement therapy is a promising improvement in neonatal care for infants with respiratory distress syndrome. Lysophosphatidylcholine (LPC) is an...
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.
PubMed: 38881378
DOI: 10.1002/bmc.5926 -
Arkhiv Patologii 2024Alveolar proteinosis is a rare lung disease characterized by the accumulation of protein-lipid complexes in the alveoli due to impaired surfactant utilization by...
Alveolar proteinosis is a rare lung disease characterized by the accumulation of protein-lipid complexes in the alveoli due to impaired surfactant utilization by alveolar macrophages. The frequency is from 2 to 4 cases per 1 million adult population. We present an observation of pulmonary alveolar proteinosis in a patient with a history of coronavirus pneumonia.
Topics: Humans; Pulmonary Alveolar Proteinosis; COVID-19; SARS-CoV-2; Male; Middle Aged; Female; Macrophages, Alveolar
PubMed: 38881005
DOI: 10.17116/patol20248603146