Edema pulmonar por reexpansión. Reporte de Caso / Pulmonary edema due to re-expansion. Case Report

Introducción. El edema pulmonar por reexpansión es una complicación poco frecuente, secundaria a una rápida reexpansión pulmonar posterior al drenaje por toracentesis o toracostomía cerrada. Al día de hoy, se ha descrito una incidencia menor al 1 % tras toracostomía cerrada, con mayor prevalencia en la segunda y tercera década de la vida. Su mecanismo fisiopatológico exacto es desconocido; se ha planteado un proceso multifactorial de daño intersticial pulmonar asociado con un desequilibrio de las fuerzas hidrostáticas. Caso clínico. Presentamos el caso de un paciente que desarrolló edema pulmonar por reexpansión posterior a toracostomía cerrada. Se hizo una revisión de la literatura sobre esta complicación. Resultados. Aunque la clínica sugiere el diagnóstico, la secuencia de imágenes desempeña un papel fundamental. En la mayoría de los casos suele ser autolimitado, por lo que su manejo es principalmente de soporte; sin embargo, se han reportado tasas de mortalidad que alcanzan hasta el 20 %, por tanto, es importante conocer los factores de riesgo y las medidas preventivas. Conclusión. El edema pulmonar de reexpansión posterior a toracostomía es una complicación rara en los casos con neumotórax, aunque es una complicación que se puede presentar en la práctica diaria, por lo cual debe tenerse en mente para poder hacer el diagnóstico y un manejo adecuado.

Introduction. Re-expansion pulmonary edema is a rare complication secondary to rapid pulmonary re-expansion after drainage by thoracentesis and/or closed thoracostomy. As of today, an incidence of less than 1% has been described after closed thoracostomy, with a higher prevalence in the second and third decades of life. Its exact pathophysiological mechanism is unknown; a multifactorial process of lung interstitial damage associated with an imbalance of hydrostatic forces has been proposed. Clinical case. We present the case of a patient who developed pulmonary edema due to re-expansion after closed thoracostomy, conducting a review of the literature on this complication. Results. Although the clinic suggests the diagnosis, the sequence of images plays a fundamental role. In most cases, it tends to be a self-limited disease, so its management is mainly supportive. However, mortality rates of up to 20% have been recorded. Therefore, it is important to identify patients with major risk factors and initiate preventive measures in these patients. Conclusions. Re-expansion pulmonary edema after thoracostomy is a rare complication in cases with pneumothorax; however, it is a complication that can occur in daily practice. Therefore, it must be kept in mind to be able to make the diagnosis and an adequate management.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation

Abstract Background Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. Methods The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. Results XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. Conclusion XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Respiratory system parameters in children with low severity cystic fibrosis: is there early involvement in relation to healthy peers? / Parâmetros do sistema respiratório em crianças com fibrose cística de baixa gravidade: há acometimento precoce em relação a pares saudáveis?

ABSTRACT Objective: To compare and analyze pulmonary function and respiratory mechanics parameters between healthy children and children with cystic fibrosis. Methods: This cross-sectional analytical study included healthy children (HSG) and children with cystic fibrosis (CFG), aged 6-13 years, from teaching institutions and a reference center for cystic fibrosis in Florianópolis/SC, Brazil. The patients were paired by age and sex. Initially, an anthropometric evaluation was undertaken to pair the sample characteristics in both groups; the medical records of CFG were consulted for bacterial colonization, genotype, and disease severity (Schwachman-Doershuk Score — SDS) data. Spirometry and impulse oscillometry were used to assess pulmonary function. Results: In total, 110 children were included, 55 in each group. In the CFG group, 58.2% were classified as excellent by SDS, 49.1% showed the ΔF508 heterozygotic genotype, and 67.3% were colonized by some pathogens. Statistical analysis revealed significant differences between both groups (p<0.05) in most pulmonary function parameters and respiratory mechanics. Conclusions: Children with cystic fibrosis showed obstructive ventilatory disorders and compromised peripheral airways compared with healthy children. These findings reinforce the early changes in pulmonary function and mechanics associated with this disease.

RESUMO Objetivo: Comparar e analisar parâmetros de função pulmonar e de mecânica respiratória entre escolares saudáveis e com fibrose cística (FC). Métodos: Estudo transversal que incluiu escolares saudáveis (GES) e com FC (GFC), com idades entre seis e 13 anos, provenientes de instituições de ensino e de um centro de referência da FC em Florianópolis/SC, Brasil, pareados por idade e sexo, respectivamente. Inicialmente, conduziu-se avaliação antropométrica para pareamento e caracterização de ambos os grupos e, no GFC, consultou-se prontuário médico para registro dos dados de colonização bacteriana, genótipo e gravidade da doença (Escore de Schwachman-Doershuk — ESD). Para a avaliação da função pulmonar, realizou-se espirometria e a avaliação da mecânica respiratória foi conduzida por meio do sistema de oscilometria de impulso. Resultados: Participaram 110 escolares, 55 em cada grupo. No GFC, 58,2% foram classificados pelo ESD como excelentes, 49,1% apresentaram genótipo ∆F508 heterozigoto e 67,3% eram colonizados por alguma patógeno. Houve diferença significativa (p<0,05) na maioria dos parâmetros de função pulmonar e de mecânica respiratória entre os grupos. Conclusões: Escolares com FC apresentaram distúrbio ventilatório obstrutivo e com comprometimento de vias aéreas periféricas, em comparação aos escolares hígidos. Esse evento reforça o início precoce da alteração de função pulmonar e de mecânica respiratória nessa enfermidade, evidenciados pelos achados desta investigação.

Protective Effect of Zingiberis Rhizoma Recens on LPS-induced Acute Lung Injury in Mice Through TLR4/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

Lesión pulmonar aguda producida por transfusión (TRALI): Reporte de caso

Introducción: La lesión pulmonar aguda (TRALI) y la sobrecarga circulatoria (TACO) son las principales causas de morbilidad y mortalidad relacionadas con la transfusión. La TRALI se presenta durante o después de las transfusiones de plasma y sus derivados, o por inmunoglobulinas en alta concentración intravenosa; se asocia a procesos sépticos, cirugías y transfusiones masivas. La TACO es la exacerbación de manifestaciones respiratorias en las primeras 6 horas postransfusión. Reporte caso: Paciente de sexo masculino de 38 días de vida, ingresó al servicio de urgencias con un cuadro clínico de 8 días de evolución, caracterizado por dificultad respiratoria dado por retracciones subcostales y aleteo nasal sin otro síntoma asociado, con antecedentes de importancia de prematuridad y bajo peso al nacer. El reporte de hemograma arrojó cifras compatibles con anemia severa, por lo que requirió transfusión de glóbulos rojos empaquetados desleucocitados. El paciente presentó un cuadro respiratorio alterado en un periodo menor a 6 horas, por lo que se descartaron causas infecciosas y finalmente se consideró cuadro compatible con TRALI. Conclusiones: Se debe considerar una lesión pulmonar aguda relacionada con una transfusión de sangre si se produce una insuficiencia respiratoria aguda durante o inmediatamente después de la infusión de hemoderivados que contienen plasma.

Introduction: Acute lung injury (TRALI) and circulatory overload (TACO) are the main causes of transfusion-related morbidity and mortality. TRALI occurs during or after transfusions of plasma or its derivatives, or by immunoglobulins in high intravenous concentration; it is associated with septic processes, surgeries, and massive transfusions. TACO is the exacerbation of respiratory manifestations in the first 6 hours post transfusion. Case report: A 38-day-old male was admitted to the emergency department with clinical symptoms experienced over the course of 8 days and characterized by respiratory distress due to subcostal retractions and nasal flaring with no other associated symptoms. Important antecedents included prematurity and low birth weight. The hemogram report showed figures compatible with anemia, which benefited from transfusion of packed red blood cells without leukocytes. In a period of less than 6 hours, the patient presented altered respiratory symptoms, practitioners ruled out infectious causes and finally considered clinical signs compatible with TRALI. Conclusion: Acute lung injury related to blood transfusion should be considered if acute respiratory failure occurs during or immediately after infusion of plasma-containing blood products.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide / Efeitos das áreas atelectásicas no tecido pulmonar circundante durante a ventilação mecânica em um modelo experimental de lesão pulmonar aguda induzida por lipopolissacarídeo

ABSTRACT Objective: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Methods: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. Results: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Conclusion: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

RESUMO Objetivo: Avaliar o efeito da atelectasia durante a ventilação mecânica nas regiões periatelectáticas e pulmonares normais em um modelo de atelectasia em ratos com lesão pulmonar aguda induzida por lipopolissacarídeo. Métodos: Foram distribuídos aleatoriamente 24 ratos em quatro grupos, cada um com 6 animais: Grupo Salina-Controle, Grupo Lipopolissacarídeo-Controle, Grupo Salina-Atelectasia e Grupo Lipopolissacarídeo-Atelectasia. A lesão pulmonar aguda foi induzida por injeção intraperitoneal de lipopolissacarídeo. Após 24 horas, a atelectasia foi induzida por bloqueio brônquico. Os animais foram submetidos à ventilação mecânica por 2 horas com parâmetros ventilatórios protetores, e a mecânica respiratória foi monitorada durante esse período. Em seguida, foram realizadas análises histológicas de duas regiões de interesse: as áreas periatelectásicas e o pulmão normalmente aerado contralateral às áreas atelectásicas. Resultados: O escore de lesão pulmonar foi significativamente maior no Grupo Controle-Lipopolissacarídeo (0,41 ± 0,13) do que no Grupo Controle-Solução Salina (0,15 ± 0,51), com p < 0,05. As regiões periatelectásicas apresentaram escores maiores de lesão pulmonar do que as regiões normalmente aeradas nos Grupos Atelectasia-Solução Salina (0,44 ± 0,06 versus 0,27 ± 0,74, p < 0,05) e Atelectasia-Lipopolissacarídeo (0,56 ± 0,09 versus 0,35 ± 0,04, p < 0,05). O escore de lesão pulmonar nas regiões periatelectásicas foi maior no Grupo Atelectasia-Lipopolissacarídeo (0,56 ± 0,09) do que na região periatelectásica do Grupo Atelectasia-Solução Salina (0,44 ± 0,06), p < 0,05. Conclusão: A atelectasia pode causar lesão no tecido circundante após um período de ventilação mecânica com parâmetros ventilatórios protetores. Seu efeito foi mais significativo em pulmões previamente lesionados.

Ischemic Postconditioning Attenuates Myocardial Ischemia-Reperfusion-Induced Acute Lung Injury by Regulating Endoplasmic Reticulum Stress-Mediated Apoptosis

ABSTRACT Objective: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). Methods: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. Results: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. Conclusion: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.

Diagnóstico por imagen de abscesos hepáticos y pulmonares por estreptococos del grupo viridans. Presentación de caso / Imaging diagnosis of liver and lung abscesses due to viridans streptococci. Case presentation

Resumen El Streptococcus viridans es conocido más comúnmente como agente infeccioso en las endocarditis, sin embargo, poco se conoce sobre su potencial infeccioso en otros órganos o sistemas, donde ha demostrado una elevada mortalidad. El reconocimiento del Streptococcus viridans como agente productor de abscesos en otras localizaciones como a nivel hepático o pulmonar, permitirá un diagnóstico oportuno mediante los distintos métodos de imagen, reduciendo las graves consecuencias para el paciente y los tiempos de hospitalización. Se presenta el caso de un paciente del sexo masculino de 33 años de edad sin antecedentes crónico degenerativos, que inició con sintomatología 7 meses previos a su ingreso, con fiebre intermitente, fatiga, astenia, anorexia y pérdida de peso. A la exploración física presentó dolor a la palpación media y profunda en hipocondrio derecho, en el panel de laboratorios presentó llamativa neutrofilia, en la tomografía de tórax y abdomen se mostró lesión cavernomatosa en pulmón y quistes complicados hepáticos, a los cuales se les realizó drenaje percutáneo guiado por ultrasonido, con envío de muestras a cultivo con resultado positivo para Streptococcus viridans, lo que permitió brindar el tratamiento dirigido al paciente, y que remitiera la enfermedad.

Abstract Streptococcus viridans is more commonly known as an infectious agent in endocarditis, however, little is known about its infectious potential in other organs or systems, where it has shown high mortality. The recognition of Streptococcus viridans as an abscess-producing agent in other locations, such as the liver or lungs, will allow timely diagnosis using different imaging methods, reducing serious consequences for the patient and hospitalization times. We present the case of a 33-year-old male patient with no chronic degenerative history, who started symptoms 7 months prior to admission, with intermittent fever, fatigue, asthenia, anorexia and weight loss, on physical examination he presented pain at the medium and deep palpation in the right hypochondrium, in the laboratory panel I present striking neutrophilia, in the tomography of the thorax and abdomen a cavernous lesion in the lung and complicated hepatic cysts are shown, to which percutaneous drainage guided by ultrasound is performed, with sending of cultured samples with a positive result for Streptococcus viridans. Thus, allowing treatment to be provided to the patient, thereby achieving remission of the disease.

Rinitis alérgica asociada al grado de compromiso pulmonar por COVID-19 en pacientes de un hospital general peruano / Allergic rhinitis associated with the degree of pulmonary involvement due to COVID-19 in patients from a peruvian general hospital

Objetivos. Evaluar la asociación entre rinitis alérgica y el grado de compromiso pulmonar en pacientes con COVID-19 y evaluar las frecuencias de las variables principales. Materiales y métodos. Se realizó un estudio de tipo observacional, transversal y analítico mediante la revisión de historias clínicas de pacientes atendidos en el Hospital Nacional Cayetano Heredia entre el año 2020 y 2021 con diagnóstico de COVID-19. Se determinó el antecedente de rinitis alérgica, y el compromiso pulmonar se evaluó mediante una tomografía sin contraste usando el puntaje tomográfico (PT), además de, variables sociodemográficas y clínicas. Se estimaron razones de prevalencias tanto crudas (RP) como ajustadas (RPa) con sus respectivos intervalos de confianza (IC) al 95% y se empleó un modelo lineal generalizado de la familia Poisson con función de enlace logarítmica y varianzas robustas. Resultados. Se evaluaron 434 pacientes predominantemente varones, mayores de 60 años y sin antecedentes médicos relevantes. El 56,2% tenía el antecedente de rinitis alérgica y el 43,1% tuvo un compromiso pulmonar moderado a severo. En el modelo de regresión ajustado, se encontró que el antecedente de rinitis alérgica disminuyó la gravedad de COVID-19 evaluada a través del compromiso pulmonar según el PT (RPa: 0,70; IC 95%: 0,56-0,88; p=0,002). Conclusiones. El antecedente de rinitis alérgica representó una disminución en la gravedad de COVID-19 según el PT score del 30,0% en pacientes hospitalizados.

Objectives. To evaluate the association between allergic rhinitis and the degree of pulmonary involvement in patients with COVID-19 and to determine the frequencies of the main variables. Materials and methods. An observational, cross-sectional and analytical study was carried out by reviewing the medical records of patients diagnosed with COVID-19 from the Cayetano Heredia National Hospital between 2020 and 2021. We obtained information regarding the history of allergic rhinitis; pulmonary involvement was assessed by non-contrast tomography results using the chest computed tomography (CT) score. Data regarding sociodemographic and clinical variables was also obtained. Both crude (PR) and adjusted (aPR) prevalence ratios with their respective 95% confidence intervals (CI) were estimated. We also used a generalized linear Poisson family model with log link function and robust variances. Results. We evaluated 434 patients, who were mostly male, older than 60 years and had no relevant medical history. Of these, 56.2% had a history of allergic rhinitis and 43.1% had moderate to severe pulmonary involvement. The adjusted regression model showed that the history of allergic rhinitis reduced the severity of COVID-19 according to the pulmonary involvement assessed by the CT score (aPR: 0.70; 95%CI: 0.56-0.88; p=0.002). Conclusions. The history of allergic rhinitis resulted in a 30.0% decrease in COVID-19 severity according to the CT score in hospitalized patients.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

Anti-inflammatory and antioxidant properties of betaine protect against sepsis-induced acute lung injury: CT and histological evidence

The aim of this research was to determine the anti-inflammatory effect of betaine on sepsis-induced acute respiratory distress syndrome (ARDS) in rats through histopathological examination, radiologic imaging, and biochemical analysis. Eight rats were included in the control group, and no procedure was performed. Feces intraperitoneal procedure (FIP) was performed on 24 rats to create a sepsis-induced ARDS model. These rats were separated into three groups as follows: FIP alone (sepsis group, n=8), FIP + saline (1 mL/kg, placebo group, n=8), and FIP + betaine (500 mg/kg, n=8). Computed tomography (CT) was performed after FIP, and the Hounsfield units (HU) value of the lungs was measured. The plasma levels of tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), IL-6, C-reactive protein, malondialdehyde (MDA), and lactic acid (LA) were determined, and arterial oxygen pressure (PaO2) and arterial CO2 pressure (PaCO2) were measured from an arterial blood sample. Histopathology was used to evaluate lung damage. This study completed all histopathological and biochemical evaluations in 3 months. All evaluated biomarkers were decreased in the FIP + betaine group compared to FIP + saline and FIP alone (all P<0.05). Also, the parenchymal density of the rat lung on CT and histopathological scores were increased in FIP + saline and FIP alone compared to control and these findings were reversed by betaine treatment (all P<0.05). Our study demonstrated that betaine suppressed the inflammation and ameliorated acute lung injury in a rat model of sepsis.

Lesión pulmonar autoinfligida por el paciente / Patient self inflicted lung injury / Lesão pulmonar autoinfligida pelo paciente

Resumen: La optimización del esfuerzo espontáneo en la ventilación mecánica tiene un lugar central en la Unidad de Cuidados Intensivos; aporta beneficios a los pacientes como la mejoría en el intercambio de gases, ayuda a recuperar la función del diafragma y el mantenimiento de los músculos periféricos. Por otro lado, también puede estar asociado al deterioro de la oxigenación y la lesión pulmonar. El incremento del impulso respiratorio neural aumenta el esfuerzo muscular inspiratorio, lo que condiciona presiones de distensión pulmonar lesivas, que en el contexto del síndrome de insuficiencia respiratoria aguda es de vital relevancia, ya que puede provocar el colapso y la sobredistensión regional alveolar de forma cíclica, con distribución heterogénea del estrés y tensión pulmonar. Existen tres mecanismos de lesión pulmonar por esfuerzo espontáneo: sobredistensión, aumento de la perfusión pulmonar y asincronía paciente-ventilador. La lesión pulmonar causa fuga capilar, edema pulmonar y alteración del intercambio de gases. Esto conduce a un aumento del impulso respiratorio y mayores volúmenes corrientes de las propias respiraciones espontáneas del paciente, que provocan fuga capilar y mayor daño pulmonar de forma similar a la lesión pulmonar inducida por ventilador.

Abstract: The optimization of spontaneous effort in mechanical ventilation has a central place in the intensive care unit; provides benefits to patients such as improved gas exchange, helps to regain function of the diaphragm and maintenance of peripheral muscles. On the other hand, it can also be associated with impaired oxygenation and lung injury. The increase in the neural respiratory drive increases the inspiratory muscular effort, conditioning damaging pulmonary distension pressures, which in the context of acute respiratory distress syndrome is of vital importance, since it can cause collapse and regional alveolar overdistention in a cyclical way. with heterogeneous distribution of pulmonary stress and strain. There are three mechanisms of lung injury due to spontaneous effort: overdistention, increased pulmonary perfusion, and patient-ventilator asynchrony. Lung injury causes capillary leakage, pulmonary edema, and impaired gas exchange. This leads to increased respiratory drive and higher tidal volumes of the patient's own spontaneous breaths, causing capillary leakage and increased lung damage like ventilator-induced lung injury.

Resumo: A otimização do esforço espontâneo na ventilação mecânica tem lugar central na unidade de terapia intensiva; Proporciona benefícios aos pacientes como melhora nas trocas gasosas, auxilia na recuperação da função do diafragma e na manutenção da musculatura periférica. Por outro lado, também pode estar associada ao deterioro da oxigenação e lesão pulmonar. O incremento do impulso respiratório neural aumenta o esforço muscular inspiratório, condicionando pressões de distensão pulmonar prejudiciais, o que no contexto da síndrome de insuficiência respiratória aguda é de vital relevância, pois pode causar colapso e hiperdistensão alveolar regional de forma cíclica, com distribuição heterogênea do estresse e tensão pulmonar. Existem três mecanismos de lesão pulmonar espontânea por esforço: hiperdistensão, aumento da perfusão pulmonar e assincronia paciente-ventilador. A lesão pulmonar causa vazamento capilar, edema pulmonar e troca gasosa prejudicada. Isso leva ao aumento do impulso respiratório e aos volumes correntes mais altos das próprias respirações espontâneas do paciente, causando vazamento capilar e danos pulmonares adicionais semelhantes aos danos pulmonares induzidos pelo ventilador.

Clinical-epidemiological evaluation of victims of thoracic trauma in a reference hospital in Aracaju-SE / Avaliação clínico-epidemiológica dos pacientes vítimas de trauma torácico em um hospital de referência de Aracaju-SE

ABSTRACT Introduction: thoracic trauma is defined as anything that involves the rib cage, the musculoskeletal framework that houses the heart, lungs, pleurae and mediastinal structures. It can be superficial or immediately lifethreatening for victims. In Brazil, most assistance is due to urban violence. Objective: evaluate the clinical and epidemiological aspect of patients who are victims of thoracic trauma treated at Hospital de Urgência de Sergipe, Aracaju/SE, Brazil. Method: cross-sectional, observational and prospective study, carried out for eleven months, with 100 polytraumatized patients. A semi-structured form was applied, and the data were systematized, analyzed and statistically tested considering a 5% margin of error. Results: 85% of the patients were male, with a mean age of 39.3 and an age range of 30 to 49 years; 57% of them had incomplete primary education, 70% had a family income of up to 2 minimum wages and 41% were from Greater Aracaju. As for the mechanism of trauma, 33% were car-related, with blunt trauma as the main mechanism, and rib fractures as the main consequence. Among penetrating injuries, CWI (26%) and GSW (21%) were the most prevalent, with hemothorax being the main consequence. Most patients underwent thoracostomy (59%). Conclusion: the profile found was of young men, victims of urban violence. The thoracostomy was resolving in most cases and should be instituted promptly when necessary. A smaller number of patients may require thoracotomy, especially in the presence of hemodynamic instability.

RESUMO Introdução: o trauma torácico é definido como toda aquele que envolve a caixa torácica, arcabouço osteomuscular que aloja o coração, os pulmões, as pleuras e as estruturas do mediastino. Pode ser superficial ou causar risco de vida imediato às vítimas. No Brasil, a maioria dos atendimentos é decorrente da violência urbana. Objetivo: avaliar o aspecto clínico-epidemiológico dos pacientes vítimas de trauma torácico atendidos no Hospital de Urgência de Sergipe, Aracaju/SE, Brasil. Métodos: estudo transversal, observacional e prospectivo, realizado durante onze meses, com 100 pacientes politraumatizados. Formulário semiestruturado foi aplicado, e os dados sistematizados, analisados e testados estatisticamente considerando-se a margem de erro de 5%. Resultados: 85% dos pacientes eram do gênero masculino, com idade média de 39,3 e faixa etária de 30 a 49 anos; 57% deles possuíam ensino fundamental incompleto, 70% tinham renda familiar de até 2 salários mínimos e 41% eram provenientes da Grande Aracaju. Quanto ao mecanismo de trauma, 33% foi automobilístico, tendo como principal mecanismo o trauma contuso, e a principal consequência a fratura de arcos costais. Dentre os ferimentos penetrantes, os FAB (26%) e FAF (21%) foram os mais prevalentes, sendo o hemotórax sua principal consequência, sendo maioria dos pacientes submetida a toracostomia (59%). Conclusão: o perfil encontrado foi de homens, jovens, vítimas da violência urbana. A toracostomia foi resolutiva na maioria dos casos e deve ser instituída prontamente quando necessário. Uma menor parte dos pacientes necessitou de toracotomia, principalmente na presença de instabilidade hemodinâmica.

Cellular and molecular mechanisms of Notch signal in pulmonary microvascular endothelial cells after acute lung injury

Abstract This study focused on the effect and mechanism of Notch signal on pulmonary microvascular endothelial cells (PMVECs) following acute lung injury. PMVECs were cultured in vitro and randomly divided into eight groups. Grouping was based on whether cells were co-cultured with T cells (splenic CD4+T cells were isolated using MACS microbeads) and the level of Notch expression: Normal group and Normal+T cells group, Model group and Model+T cells group, Notch low-expression group and Notch low-expression+T cells group, and Notch overexpression group and Notch overexpression+T cells group. Except for the Normal group and Normal+T cells group, all other groups were treated with 500 μL lipopolysaccharide (1 μg/mL). The expression of VE-cadherin and Zo-1 protein in the Model group (with or without T cells) was lower than that in the normal group (with or without T cells), their expression in the Notch low-expression group (with or without T cells) was significantly increased, and their expression in the Notch overexpression group (with or without T cells) was significantly decreased. Compared with the normal+T cells group, the number of Treg cells in the Notch low-expression+T cells group decreased significantly (P<0.01). The number of Th17 cells in the Notch overexpression+T cells group was higher than that in the Model+T cells group (P<0.01), while the number of Treg cells decreased (P<0.01). Our results demonstrated that activated Notch signal can down-regulate the expression of the tight junction proteins VE-Cadherin and Zo-1 in PMVECs and affect Th17/Treg immune imbalance. Autophagy was discovered to be involved in this process.

Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study

Abstract Background Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 µg.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response. Results Significant hemodynamic alterations were observed after 30 minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19 ± 2 mmHg to LPS30 52 ± 4 mmHg, p< 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 ± 29 to LPS180 334 ± 49, p< 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 ± 4 mmHg at LPS30, p< 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Pulmonary involvement from animal toxins: the cellular mechanisms

Abstract Venomous animals and their venom have always been of human interest because, despite species differences, coevolution has made them capable of targeting key physiological components of our bodies. Respiratory failure from lung injury is one of the serious consequences of envenomation, and the underlying mechanisms are rarely discussed. This review aims to demonstrate how toxins affect the pulmonary system through various biological pathways. Herein, we propose the common underlying cellular mechanisms of toxin-induced lung injury: interference with normal cell function and integrity, disruption of normal vascular function, and provocation of excessive inflammation. Viperid snakebites are the leading cause of envenomation-induced lung injury, followed by other terrestrial venomous animals such as scorpions, spiders, and centipedes. Marine species, particularly jellyfish, can also inflict such injury. Common pulmonary manifestations include pulmonary edema, pulmonary hemorrhage, and exudative infiltration. Severe envenomation can result in acute respiratory distress syndrome. Pulmonary involvement suggests severe envenomation, thus recognizing these mechanisms and manifestations can aid physicians in providing appropriate treatment.

Changes of complement fragment C3a and its receptor in lung injury induced by silica nanoparticles / 环境与职业医学

Background Silica nanoparticles (SiNPs) enter the human body through respiratory tract, digestive tract, and skin, causing body damage. Lung is one of the main damaged organs. Objective To observe the expressions of complement activated fragment C3a and its receptor C3aR in the lungs of mice exposed to SiNPs through respiratory tract, and to explore the involvement of C3a/C3aR in lung injury induced by SiNPs exposure. Methods The ultrastructure of SiNPs (particle size 5-20 nm) was determined under a transmission electron microscope, and the hydrodynamic diameter and surface Zeta potential of SiNPs were determined using a nanoparticle size analyzer. A total of 88 SPF C57BL/6J mice were randomly divided into five groups: a blank control group without any treatment (14 mice), a vehicle control group treated with 50 μL stroke-physiological saline solution by intratracheal instillation (14 mice), and three SiNPs exposure groups (low-dose group, medium-dose group, and high-dose group with 20 mice in each group, who were given 50 μL SiNPs suspension of 7, 21, and 35 mg·kg−1 respectively and exposed once every 3 days for 5 times). The mice were anesthetized on day 1 (1-day model group) and day 15 (15-day model group) after exposure, then sacrificed after extraction of bronchoalveolar lavage fluid (BALF), and lung tissues were retained. The morphological changes of lung tissues were observed by HE staining, the expression level of C3a in BALF was detected by enzyme-linked immunosorbent assay, the deposition of C3a and C3aR in lung tissues were observed by immunohistochemistry, the protein expression level of C3aR was determined by Western blotting, and the localization and semi-quantitative detection of C3a and C3aR in lung tissues was observed by immunofluorescence. Results SiNPs agglomerated in stroke-physiological saline solution. The average hydrodynamic diameter was (185.60±7.39) nm and the absolute value of Zeta potential was (43.33±0.76) mV. The condition of mice in the 1-day model group and the 15-day model group was good, while 2 mice died in the medium-dose group of the 1-day model group due to misoperation. The autopsy results of the two mice showed congestion of the lung tissue, emphysema, and no imperfection of trachea integrity. No death was observed in other dose groups. The HE staining results showed pathological damage to the mouse lung, including alveolar wall thickening and inflammatory cell infiltration after SiNPs exposure. The pathological damage became more serious with the increase of dose. Regarding pathological changes, the 15-day model group was slightly relieved compared with the 1-day model group, but there were still pathological changes. The enzyme-linked immunosorbent assay results showed that there was no difference in the expression level of C3a between the blank control group and the vehicle control group (P＞0.05), the expression levels of C3a in the medium-dose group and the high-dose group were significantly higher than that in the vehicle control group (P<0.05). The immunohistochemistry results showed that C3a deposition was consistent with the enzyme-linked immunosorbent assay results. The Western blotting and the immunohistochemistry results showed that C3aR expression was low in the blank control group and the vehicle control group, while the expression in each dose group tended to increase with the increase of dose. The immunofluorescence results showed that the fluorescence signals of C3a and C3aR were weak in the blank control group and the vehicle control group in the 1-day model group and the 15-day model group, while the fluorescence signals in the lung tissues of mice in the SiNPs exposure groups tended to increase with the increase of dose. Conclusion The increased expressions of C3a and C3aR in complement activation may be related to lung injury induced by intratracheal instillation of SiNPs, suggesting that C3a/C3aR may be involved in lung injury induced by SiNPs exposure.

Mechanism of racanisodamine on alleviating radiation-induced lung injury in mice / 中华放射医学与防护杂志

Objective:To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods:C57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.Results:Compared with the model group, the scores of HE staining were decreased ( t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased ( t=10.70, P<0.01), and protein concentration in BALF had lower levels ( t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly ( t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced ( t=6.42, 7.30, P<0.01), while the expression of p62 was reduced ( t=4.62, P<0.01) in the treatment group. Conclusions:Racanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.