Concordancia entre el diagnóstico por imagen y la histología en las malformaciones pulmonares congénitas / Diagnostic accuracy of imaging compared to histology in congenital lung malformations

Introducción: El objetivo fue evaluar la concordancia entre las pruebas de imagen, la ecografía prenatal y la TC posnatal empleadas en el diagnóstico de malformaciones pulmonares congénitas (MPC) y el estudio anatomopatológico (AP).Material y métodos: Estudio retrospectivo de pacientes diagnosticados prenatalmente de MPC en los que se realizó seguimiento posnatal incluyendo una TC y un estudio AP de la lesión. Las variables estudiadas incluyeron: datos demográficos, edad gestacional al diagnóstico, hallazgos ecográficos y existencia de gestación múltiple. Utilizamos el coeficiente estadístico Kappa para establecer la concordancia entre la ecografía y las pruebas postnatales (TC y AP). Se analizaron de forma pareada la presencia de lesiones, la localización, el tipo y el tamaño, y la presencia de vascularización sistémica.Resultados: Se incluyeron 56 pacientes con 57 lesiones. La edad gestacional media al diagnóstico fue 22,42±3,94 semanas y el 57% fueron varones. El pulmón izquierdo y los lóbulos inferiores fueron los más afectados. La concordancia entre TC y AP en la detección de lesiones quísticas fue moderada (Kappa=0,55) pero más relevante que la detectada entre ecografía y AP (Kappa=0,10), siendo discreta entre ambas pruebas de imagen. La concordancia TC/AP fue sustancial (Kappa=0,66) en la detección de vascularización sistémica de la lesión y superior a la determinada entre ecografía y AP. Ambas pruebas de imagen demostraron una precisión muy buena en la identificación de la localización de las lesiones.Conclusiones: La TC posnatal ofrece una concordancia sustancial con el estudio histológico, especialmente en la detección de vascularización, y nos aporta datos predecibles sobre la anatomía de la lesión.(AU)

Introduction: The aim of this study was to evaluate the accuracy of imaging tests (prenatal ultrasound [US] and postnatal computed tomography [CT]) in comparison to histology for diagnosis of congenital lung malformations (CLMs).Material and methods: Retrospective study of patients with a prenatal diagnosis of CLM whose postnatal followup included thoracic CT scan and histological examination of the lesion. We collected data on demographic variables, gestational age at diagnosis, US findings and the history of multiple gestation. We used the kappa coefficient to determine the level of agreement between the findings of prenatal US and postnatal tests (CT and histology). We analysed paired data on the size of the lesion, its location and the presence or absence of systemic arterial vascularization.Results: The sample included 56 patients with 57 lesions. The mean gestational age at diagnosis was 22.42 weeks (SD, 3.94) and 57% were male. Malformations most frequently involved the left lung and the lower lobes. The agreement between CT and histology in the detection of cystic lesions was moderate (κ=.55) but stronger compared to the agreement between US and histology (κ=.10). The agreement between CT and histology was substantial (κ=.66) in the detection of systemic vascularization of the lesion and stronger compared to the agreement between US and histology. Both imaging methods were highly accurate in the identification of the location of the pulmonary lesions.Conclusions: Postnatal CT offers a substantial concordance with histological findings, especially in the detection of systemic vascularization, and an accurate prediction of the anatomy of the lesion.(AU)

Metagenomic sequencing reveals swine lung microbial communities and metagenome-assembled genomes associated with lung lesions—a pilot study / La secuenciación metagenómica revela comunidades microbianas de pulmón porcino y genomas ensamblados en metagenoma asociados con lesiones pulmonares: un estudio piloto

Low microbial biomass in the lungs, high host-DNA contamination and sampling difficulty limit the study on lung microbiome. Therefore, little is still known about lung microbial communities and their functions. Here, we perform a preliminary exploratory study to investigate the composition of swine lung microbial community using shotgun metagenomic sequencing and compare the microbial communities between healthy and severe-lesion lungs. We collected ten lavage-fluid samples from swine lungs (five from healthy lungs and five from severe-lesion lungs), and obtained their metagenomes by shotgun metagenomic sequencing. After filtering host genomic DNA contamination (93.5% ± 1.2%) in the lung metagenomic data, we annotated swine lung microbial communities ranging from four domains to 645 species. Compared with previous taxonomic annotation of the same samples by the 16S rRNA gene amplicon sequencing, it annotated the same number of family taxa but more genera and species. We next performed an association analysis between lung microbiome and host lung-lesion phenotype. We found three species (Mycoplasma hyopneumoniae, Ureaplasma diversum, and Mycoplasma hyorhinis) were associated with lung lesions, suggesting they might be the key species causing swine lung lesions. Furthermore, we successfully reconstructed the metagenome-assembled genomes (MAGs) of these three species using metagenomic binning. This pilot study showed us the feasibility and relevant limitations of shotgun metagenomic sequencing for the characterization of swine lung microbiome using lung lavage-fluid samples. The findings provided an enhanced understanding of the swine lung microbiome and its role in maintaining lung health and/or causing lung lesions.(AU)

Glutamine inhibits inflammation, oxidative stress, and apoptosis and ameliorates hyperoxic lung injury

Glutamine (Gln) is the most widely acting and abundant amino acid in the body and has anti-inflammatory properties, regulates body metabolism, and improves immune function. However, the mechanism of Gln’s effect on hyperoxic lung injury in neonatal rats is unclear. Therefore, this work focused on examining Gln’s function in lung injury of newborn rats mediated by hyperoxia and the underlying mechanism. We examined body mass and ratio of wet-to-dry lung tissue weights of neonatal rats. Hematoxylin and eosin (HE) staining was performed to examine histopathological alterations of lung tissues. In addition, enzyme-linked immunoassay (ELISA) was conducted to measure pro-inflammatory cytokine levels within bronchoalveolar lavage fluid (BALF). Apoptosis of lung tissues was observed using TUNEL assay. Western blotting was performed for detecting endoplasmic reticulum stress (ERS)-associated protein levels. The results showed that Gln promoted body weight gain, significantly reduced pathological damage and oxidative stress in lung tissue, and improved lung function in neonatal rats. Gln reduced pro-inflammatory cytokine release as well as inflammatory cell production in BALF and inhibited apoptosis in lung tissue cells. Furthermore, we found that Gln could downregulate ERS-associated protein levels (GRP78, Caspase-12, CHOP) and inhibit c-Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) phosphorylation. These results in an animal model of bronchopulmonary dysplasia (BPD) suggest that Gln may have a therapeutic effect on BPD by reducing lung inflammation, oxidative stress, and apoptosis and improving lung function; its mechanism of action may be related to the inhibition of the IRE1α/JNK pathway. (AU)

Rosavin inhibits neutrophil extracellular traps formation to ameliorate sepsis-induced lung injury by regulating the MAPK pathway

Background: Sepsis is a systemic organ dysfunction caused by infection, and the most affected organ is the lungs. Rosavin, a traditional Tibetan medicine, exerts an impressive anti--inflammatory effect. However, its effects on sepsis-related lung damage have not been investigated. Purpose: This study aimed to investigate the effects of Rosavin on cecal ligation and puncture (CLP)-induced lung injury. Methods: The sepsis mouse model was established by CLP, and the mice were pretreated with Rosavin to explore whether it contributed to the alleviation of lung injury. Hematoxylin-eosin (H&E) stain and lung injury score were used to assess the severity of lung injury. The bronchoalveolar lavage fluid (BALF) inflammatory mediators (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], IL-1β, and IL-17A) were detected by ELISA. The number of neutrophils in BALF was detected using flow cytometry. The immunofluorescence assay was used to detect histone and myeloperoxidase (MPO) in lung tissues. Then, the western blot was performed to detect the expression of mitogen-activated protein kinase (MAPK) pathways (extracellular regulated kinase [ERK], p-ERK, p38, p-p38, Jun N-terminal kinase 1/2 [JNK1/2], and p-JNK1/2) in lung tissues. Results: We found that Rosavin significantly attenuated sepsis-induced lung injury. Specifically, Rosavin significantly inhibited inflammation response by decreasing the secretion of inflammatory mediators. The level of neutrophil extracellular traps (NETs) and MPO activity in CLP were decreased after administration with Rosavin. Moreover, the western blot showed that Rosavin could suppress NETs formation by inhibiting the MAPK/ERK/p38/JNK signaling pathway. Conclusion: These findings demonstrated that Rosavin inhibited NETs formation to attenuate sepsis-induced lung injury, and the inhibitory effect may be exerted via deregulation of the MAPK pathways (AU)

Tamibarotene targets heparin-binding protein for attenuating lung injury in sepsis

Background: Excessively active pulmonary inflammation is a hallmark of sepsis-induced lung damage. A synthetic retinoid drug called tamibarotene reduces inflammation in a variety of conditions, including acute promyelocytic leukemia (APL), renal fibrosis, and neuroinflammation. Its effect on sepsis-related lung injury, however, has not been explained. Purpose: The purpose of the study was to investigate how tamibarotene affected lung damage induced by cecal ligation and puncture (CLP) procedure. Methods: A CLP sepsis mouse model was developed, and tamibarotene was pretreated to determine whether it improved lung injury and survival. The degree of lung injury was evaluated using the Hematoxylin and eosin staining and lung injury score. In order to determine pulmonary vascular permeability, measurements were taken for total protein and cell content of bronchoalveolar lavage fluid (BALF), wet/dry ratio of the lung, and Evans blue stain. The BALF inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-17A were discovered by enzyme-linked immunosorbent serologic assay (ELISA). Then, the levels of heparin-binding protein (HBP), and phospho-nuclear factor kappa-B (p-NF-κB) P65, and NF-κB P65 were determined using ELISA and Western blot analysis, respectively. Results: Tamibarotene considerably increases survival and lessens lung damage stimulated by sepsis. Specifically, tamibarotene significantly relieves pulmonary vascular permeability and inhibits inflammation response in sepsis. Moreover, we further confirmed that these ameliorating effects of tamibarotene on sepsis may be exerted by targeting HBP and regulating the activation of NF-κB signaling pathway. Conclusion: These findings demonstrated that tamibarotene lessens sepsis-induced lung injury, and the effect could be exerted by targeting HBP and thereby deregulating the NF-κB signaling pathway (AU)

Dimethyl itaconate inhibits LPS-induced inflammatory release and apoptosis in alveolar type II epithelial and bronchial epithelial cells by activating pulmonary surfactant proteins A and D

Background Injury to the lung is a common, clinically serious inflammatory disease. However, its pathogenesis remains unclear, and the existing treatments, including cytokine therapy, stem cell therapy, and hormone therapy, are not completely effective in treating this disease. Dimethyl itaconate (DMI) is a surfactant with important anti-inflammatory effects. Objective The present study used alveolar type II (AT II) and bronchial epithelial cells as models to determine the role of DMI in lung injury. Material and Methods First, the effects of DMI were established on the survival, inflammatory release, and apoptosis in lipopolysaccharide (LPS)-induced AT II and bronchial epithelial cells. The association between DMI and Sirtuin1 (SIRT1) was assessed using molecular docking. Next, by constructing interference plasmids to inhibit surfactant protein (SP)-A and SP-D expressions, the effect of DMI was observed on inflammatory release and apoptosis. Results The results revealed that DMI increased the survival rate and expression levels of SP-A, SP-D, and SIRT1, and inhibited inflammatory factors as well as apoptosis in LPS-induced cells. Furthermore, DMI could bind to SIRT1 to regulate SP-A and SP-D expressions. After SP-A and SP-D expressions were inhibited, the inhibitory effect of DMI was reversed on inflammatory release and apoptosis. Conclusion The findings of the present study revealed that DMI inhibited LPS-induced inflammatory release and apoptosis in cells by targeting SIRT1 and then activating SP-A and SP-D. This novel insight into the pharmacological mechanism of DMI lays the foundation for its later use for alleviating lung injury (AU)

Deoxyelephantopin alleviates lipopolysaccharide-induced septic lung injury through inhibiting NF-kB/STAT3 axis

Sepsis induces multiple organ dysfunction syndromes, such as acute kidney, liver, or lung injury. Septic lung injury is associated with excessive apoptosis and inflammatory responses in hepatocytes. Deoxyelephantopin is a sesquiterpene lactone found in Elephantopus scaberL, and has immunomodulatory, antibacterial, anti-inflammatory, and antifungal properties. The role of deoxyelephantopin in sepsis-associated lung injury was investigated. First, human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) were treated with lipopolysaccharide to induce cytotoxicity. Treatment with lipopolysac-charide reduced cell viability of BEAS-2B and HPAEC, and promoted cell apoptosis through down-regulation of poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma 2 (Bcl-2), and up-regulation of cleaved PARP and B-cell lymphoma-associated X protein (Bax). Second, lipo-polysaccharide-treated BEAS-2B and HPAEC were incubated with increasing concentrations of deoxyelephantopin, that is, 1, 5, or 10 μM. Deoxyelephantopin enhanced cell viability and reduced cell apoptosis of lipopolysaccharide-treated BEAS-2B and HPAEC. Third, deoxyele-phantopin attenuated lipopolysaccharide-induced decrease of superoxide dismutase and glutathione, and increase of malondialdehyde and myeloperoxidase in BEAS-2B and HPAEC. Moreover, deoxyelephantopin also weakened lipopolysaccharide-induced increase of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, deoxyelephantopin decreased pro-tein expression of p-p65 and p-signal transducer and activator of transcription 3 (STAT3) in lipopolysaccharide-treated BEAS-2B and HPAEC. In conclusion, deoxyelephantopin exhibited anti-oxidative and anti-inflammatory effects against lipopolysaccharide-treated BEAS-2B and HPAEC through inactivation of nuclear factor kappa B/STAT3 signaling (AU)

Broncoscopia guiada por navegación electromagnética / Electromagnetic navigation bronchoscopy

La broncoscopia guiada por navegación electromagnética es una técnica que posibilita el diagnóstico de lesiones pulmonares periféricas de pequeño tamaño con una gran precisión y seguridad, permitiendo en muchos casos la detección precoz de cáncer de pulmón. Facilita la realización tanto de biopsias transbronquiales como de punciones y cepillados. Este procedimiento ofrece la posibilidad de evitar métodos diagnósticos invasivos como la cirugía, con el consiguiente ahorro económico, de tiempo y de complicaciones. Asimismo, es útil para la colocación de marcadores fiduciales para la radioterapia estereotáxica en pacientes con cáncer de pulmón que no son candidatos a la resección pulmonar.(AU)

Electromagnetic navigation-guided bronchoscopy is a technique that enables the diagnosis of small peripheral lung lesions with great precision and safety, allowing early detection of lung cancer. It facilitates the performance of both transbronchial biopsies, punctures and brushings. This procedure offers the possibility of avoiding invasive diagnostic methods such as surgery, with the consequent economic, time and complication savings. It is also useful for placement of fiducial markers for stereotactic radiation therapy in lung cancer patients who are not candidates for lung resection.(AU)

Transmogrificación placentaria del pulmón / Placental Transmogrification of the Lung

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[Translated article] Placental Transmogrification of the Lung / Transmogrificación placentaria del pulmón

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SARS-CoV-2 en Pediatría: abordaje de la transmisión, fisiopatología ehipótesis de presentación clínica / Sars-cov-2 in pediatrics: transmission approach, pathophysiology and clinical presentation hypothesis

La pandemia de COVID-19 causada por el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) es una infección producida por inhalación de gotas o contacto directo con superficies infectadas. Los síntomas clínicos son similares a cualquier infección viral respiratoria aguda; la enfermedad suele ser más leve en los niños. El objetivo fue describir el abordaje de la transmisión, la fisiopatología y las manifestaciones clínicas del SARS-CoV-2 en población pediátrica. Se realizó una revisión bibliográfica en bases de datos académicas PubMed, LILACS, OVID-MEDLINE usando términos DECS-LILACS, aplicando filtros de búsqueda y se seleccionaron textos científicos e información relevante para la investigación. Los resultados evidencian una menor incidencia, prevalencia, hospitalizaciones e ingreso a unidades de cuidados intensivos. Es necesario corroborar las hipótesis planteadas para fortalecer estos conocimientos y determinar las características que predominan en la lesión pulmonar por infección de SARS-CoV-2 en Pediatría.(UA)

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infection caused by inhalation of droplets or direct contact with infected surfaces. The clinical symptoms are similar to any acute respiratory viral infection; the disease is usually milder in children. The objective was to describe the transmission approach, pathophysiology and clinical manifestations of SARS-CoV-2 in the pediatric population. A bibliographic review was carried out in PubMed, LILACS, OVID-MEDLINE academic databases using DECS-LILACS terms, applying search filters and scientific texts and relevant information for the research were selected. The results show a lower incidence, prevalence, hospitalizations and admission to intensive care units. It is necessary to corroborate the hypotheses proposed to strengthen this knowledge and determine the characteristics that predominate in pulmonary injury due to SARS-CoV-2 infection in pediatrics.(AU)

Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock / La resucitación hemodinámica con bolos de fluidos y noradrenalina incrementa la severidad del daño pulmonar en un modelo experimental de shock séptico

Objective Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. Design Randomized in vivo study in rabbits. Setting University animal research laboratory. Patients Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). Interventions Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg−1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. Main variables of interestAn indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. Results The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. Conclusions In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury. (AU)

Objetivo La resucitación hemodinámica es considerada piedra angular en el tratamiento inicial del shock séptico. Sin embargo, existe creciente preocupación sobre sus efectos indeseables. Nuestro objetivo fue evaluar la relación entre la administración de fluidos e infusión de noradrenalina y el desarrollo de lesión pulmonar. Diseño Estudio aleatorizado en animales vivos. Ámbito Laboratorio universitario de investigación. Participantes Dieciocho conejos de raza New Zealand White. Grupo control (SHAM, n=6), grupo séptico con o sin resucitación hemodinámica (ETX-R, n=6; ETX-NR, n=6). Intervención La sepsis fue inducida tras administración intravenosa de lipopolisacárido, y los animales fueron seguidos durante 4h. La resucitación hemodinámica mediante suero Ringer lactato (20ml·kg-1) y posterior noradrenalina fue iniciada a las 3h de ser inducida la sepsis. Al final del estudio, el pulmón izquierdo fue extraído. Principales variables de interés Fueron empleados catéter arterial y doppler esofágico. La mecánica pulmonar fue monitorizada con sensor de flujo. El daño pulmonar fue analizado mediante examen histopatológico. Resultados El grupo control no mostró cambios hemodinámicos ni respiratorios. La administración del lipopolisacárido produjo un incremento del gasto cardíaco e hipotensión arterial. En el grupo ETX-NR, los animales permanecieron hipotensos hasta el final del estudio. La resucitación con fluidos y noradrenalina revirtió la hipotensión arterial. Comparados con el grupo ETX-NR, en el grupo ETX-R el estudio histopatológico mostró mayor acumulación de neutrófilos, así como mayor presencia de neumocitos activados tipo II, engrosamiento de la pared alveolar, hemorragia alveolar y zonas pulmonares no aireadas. La escala final de daño pulmonar fue mayor en el grupo ETX-R. Conclusiones En nuestro estudio experimental ... (AU)

SEMA3A protects against hyperoxia-induced lung injury in a bronchopulmonary dysplasia model of newborn rat by inhibiting ERK pathway

Background Hyperoxia induces lung injury through lung inflammation in premature infants, leading to bronchopulmonary dysplasia (BPD). Semaphorin 3A (SEMA3A) participates in diverse biological processes, including cell migration, angiogenesis, and inflammation. The effect of SEMA3A on hyperoxic lung injury of neonatal rats with BPD was investigated in this study. Methods Neonatal rats with BPD were established through hyperoxia treatment. Hematoxylin-eosin staining was used to evaluate histopathological analysis in lung tissues. SEMA3A expression was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Adeno-associated virus (AAV)-mediated over-expression of SEMA3A (AAV-SEMA3A) was administrated into hyperoxia-induced rats, and apoptosis was evaluated by TUNEL staining. Levels of inflammatory cytokines were investigated by enzyme-linked-immunosorbent serologic assay (ELISA). Results Hyperoxia-induced histopathological changes in lung tissue reduced alveolar number and enhanced alveolar interval and alveolar volume. SEMA3A was downregulated in lung tissue of hyperoxia-induced rats. AAV-SEMA3A injection attenuated hyperoxia-induced cell apoptosis in lung tissues by increasing Bcl-2 and decreasing Bax and cleaved caspase-3. Moreover, the enhanced levels of Interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor-α (TNF-α) in hyperoxia-induced rats were restored by AAV-SEMA3A injection by the downregulation of nuclear factor kappa B (NF-κB) phosphorylation. AAV-SEMA3A injection also ameliorated histopathological changes in lung tissues of hyperoxia-induced rats by increasing the number of radial alveolar count and decreasing the volume of mean linear intercept. Besides, the protein expression levels of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation were reduced in hyperoxia-induced rats post-AAV-SEMA3A injection (AU)