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1.
J Med Microbiol ; 70(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33830909

RESUMO

Introduction. In recent years, the Herbaspirillum genus has emerged as a pathogen in healthcare-related infections and has became stablished as an opportunistic pathogen.Hypothesis/Gap Statement. Little is known about the pathogenesis induced by Herbaspirillum genus.Aim. To evaluate the cytotoxic effects of genus Herbaspirillum, its ability to adhere to lung human cells and the ability of environmental and clinical strains of Herbaspirillum to induce pneumonia in mice.Methodology. Environmental and clinical isolates of Herbaspirillum were examined for their cytotoxic effects on the Calu-3 cell lineage. Cytotoxic activity of secretome was tested using MTT/neutral red assays and cell morphology analysis. Herbaspirillum adhesion on Calu-3 cells was assessed using bright-field microscopy and cell-associated bacteria were counted. A mouse model of acute lung infection was done using a clinical and an environmental strain. Adult male mice were used, and the pneumonia was inducted by intra-tracheal inoculation of 108 or 109 bacteria. Mice weight variations were evaluated at the end of the experiment. Bronchoalveolar lavage was collected and evaluated for total and differential cytology. A histological examination of lungs was performed giving a histological score.Results. The secretomes of all the strains induced morphological alterations in cells, but only H. seropedicae SmR1 were cytotoxic in MTT and neutral red assays. Clinical strains of H. frisingense AU14459 and H. hutttiense subsp. huttiense AU11883 exhibited low adherence to lung cells, while SmR1 was non-adhesive. Following intratracheal inoculation, mice treated with 109 c.f.u. of the SmR1 and AU11883 strains lost 18 and 6% of their weight over 7 days, respectively, and presented moderate clinical signs. Infected mice showed inflammatory cell infiltration in the perivascular and peribroncheal/peribronchiolar spaces. Bronchoalveolar fluid of mice inoculated with SmR1 109 c.f.u. presented an increase in total leucocyte cells and in neutrophils population.Conclusion. These in vivo and in vitro results provide insights into how some Herbaspirillum strains cause infection in humans, providing a basis for the characterization of pathogenesis studies on this emerging infectious agent.


Assuntos
Exossomos/metabolismo , Infecções por Bactérias Gram-Negativas/microbiologia , Herbaspirillum/patogenicidade , Pneumonia/microbiologia , Animais , Aderência Bacteriana , Líquido da Lavagem Broncoalveolar/citologia , Linhagem Celular , Sobrevivência Celular , Infecções por Bactérias Gram-Negativas/patologia , Herbaspirillum/isolamento & purificação , Herbaspirillum/metabolismo , Humanos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos , Pneumonia/patologia , Virulência
2.
Front Immunol ; 12: 618807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679760

RESUMO

Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that intranasal CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed CD127+ST2+ ILC2s and type 2 lung inflammation during Alternaria and IL-33 exposure. Further, CD127-ST2-Thy1.2+ lung ILCs, which showed a transcriptomic signature consistent with ILC1s, were expanded and activated by CDG combined with either Alternaria or IL-33. CDG-mediated suppression of type 2 inflammation occurred independent of IL-18R, IL-12, and STAT6 but required the stimulator of interferon genes (STING) and type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.


Assuntos
Alternaria/imunologia , Alternariose/imunologia , GMP Cíclico/análogos & derivados , Imunidade Inata , Pulmão/imunologia , Proteínas de Membrana/imunologia , Pneumonia/imunologia , Alternariose/genética , Alternariose/patologia , Animais , GMP Cíclico/genética , GMP Cíclico/imunologia , Citocinas/genética , Citocinas/imunologia , Inflamação/genética , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Pulmão/microbiologia , Pulmão/patologia , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Pneumonia/genética , Pneumonia/microbiologia , Pneumonia/patologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia
3.
Can J Physiol Pharmacol ; 99(3): 328-331, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33657328

RESUMO

A total of 115 convalescent inpatients with COVID-19 were enrolled. According to the results of scans of lung lesions via computed tomography (CT), the patients were divided into mild, moderate, and severe groups. The clinical data of the patients were collected, including age, gender, finger pulse oxygen pressure, ventricular rate, body temperature, etc. The correlation between the clinical indicators and the lesions of high-resolution CT (HRCT) and bronchiectasis was analyzed. Among the 115 patients, 82 had no bronchiectasis and 33 had bronchiectasis. The bronchodilation-prone layers mainly included the left and right lower lobe of the lung. The probability of branching in the inflamed area was greater than that in the noninflamed area in patients with COVID-19. There were significant differences in gender, CT lesion range, and number of incidents of bronchiectasis between noninflamed and inflamed areas (P < 0.05). Moreover, there were significant differences in age, total proportion of CT lesions, volume of CT lesions, and total number of patients with bronchiectasis among the three groups (P < 0.05). CT lesion range was positively correlated with the total number of patients with bronchiectasis and patient age (respectively, r = 0.186, P < 0.05; r = 0.029, P < 0.05). The lesion range in HRCT images of lungs in patients with COVID-19 is correlated with bronchodilation. The larger the lesion, the higher the probability of bronchiectasis and the more incidents of bronchiectasis.


Assuntos
Bronquiectasia/patologia , Bronquiectasia/virologia , /virologia , Pulmão/patologia , Pulmão/virologia , Pneumonia/patologia , Pneumonia/virologia , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos
4.
Med Sci Monit ; 27: e928837, 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33580949

RESUMO

BACKGROUND Coronavirus 2 (SARS-CoV-2) was declared a pandemic by the World Health Organization (WHO) in March 2020. To further reveal the pathologic associations between coronavirus and hypoxemia, we report the findings of 4 complete systematic autopsies of severe acute respiratory syndrome coronavirus 2-positive individuals who died of multiple organ failure caused by severe hypoxemia. MATERIAL AND METHODS We examined the donated corpses of 4 deceased patients who had been diagnosed with severe acute respiratory syndrome coronavirus 2. A complete post-mortem examination was carried out on each corpse, and multiple organs were macroscopically examined. RESULTS The 4 corpses were 2 males and 2 females, with an average age of 69 years. Bilateral lungs showed various degrees of atrophy and consolidation, with diffusely tough and solid texture in the sections. A thromboembolism was found in the main pulmonary artery extending into the atrium in 1 corpse, and significant atherosclerotic plaques tagged in the inner wall of the aortic arch were found in 2 corpses. Two corpses were found to have slightly atrophied bilateral renal parenchyma. Atrophic changes in the spleen were found in 2 corpses. Notably, there were significantly expanded alveolar septa and prominent fibroblastic proliferation. CONCLUSIONS The laboratory data of these corpses showed a progressive decrease in blood oxygen saturation, followed by refractory and irreversible hypoxemia. Clinical and laboratory information and autopsy and histologic presentations of multiple organs showed insufficient air exchange due to abnormalities in the respiratory system, and reduced erythropoiesis in bone marrow may play a role.


Assuntos
Autopsia , /virologia , Hipóxia/complicações , Hipóxia/patologia , Pneumonia/patologia , Pneumonia/virologia , /fisiologia , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Agregação Celular , Feminino , Humanos , Pulmão/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Muco/metabolismo , Miocárdio/patologia , Necrose , Pneumonia/complicações , Cavidade Torácica/patologia
5.
JAMA Netw Open ; 4(2): e2037053, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566109

RESUMO

Importance: Alpha 1-adrenergic receptor blocking agents (α1-blockers) have been reported to have protective benefits against hyperinflammation and cytokine storm syndrome, conditions that are associated with mortality in patients with coronavirus disease 2019 and other severe respiratory tract infections. However, studies of the association of α1-blockers with outcomes among human participants with respiratory tract infections are scarce. Objective: To examine the association between the receipt of α1-blockers and outcomes among adult patients hospitalized with influenza or pneumonia. Design, Setting, and Participants: This population-based cohort study used data from Danish national registries to identify individuals 40 years and older who were hospitalized with influenza or pneumonia between January 1, 2005, and November 30, 2018, with follow-up through December 31, 2018. In the main analyses, patients currently receiving α1-blockers were compared with those not receiving α1-blockers (defined as patients with no prescription for an α1-blocker filled within 365 days before the index date) and those currently receiving 5α-reductase inhibitors. Propensity scores were used to address confounding factors and to compute weighted risks, absolute risk differences, and risk ratios. Data were analyzed from April 21 to December 21, 2020. Exposures: Current receipt of α1-blockers compared with nonreceipt of α1-blockers and with current receipt of 5α-reductase inhibitors. Main Outcomes and Measures: Death within 30 days of hospital admission and risk of intensive care unit (ICU) admission. Results: A total of 528 467 adult patients (median age, 75.0 years; interquartile range, 64.4-83.6 years; 273 005 men [51.7%]) were hospitalized with influenza or pneumonia in Denmark between 2005 and 2018. Of those, 21 772 patients (4.1%) were currently receiving α1-blockers compared with a population of 22 117 patients not receiving α1-blockers who were weighted to the propensity score distribution of those receiving α1-blockers. In the propensity score-weighted analyses, patients receiving α1-blockers had lower 30-day mortality (15.9%) compared with patients not receiving α1-blockers (18.5%), with a corresponding risk difference of -2.7% (95% CI, -3.2% to -2.2%) and a risk ratio (RR) of 0.85 (95% CI, 0.83-0.88). The risk of ICU admission was 7.3% among patients receiving α1-blockers and 7.7% among those not receiving α1-blockers (risk difference, -0.4% [95% CI, -0.8% to 0%]; RR, 0.95 [95% CI, 0.90-1.00]). A comparison between 18 280 male patients currently receiving α1-blockers and 18 228 propensity score-weighted male patients currently receiving 5α-reductase inhibitors indicated that those receiving α1-blockers had lower 30-day mortality (risk difference, -2.0% [95% CI, -3.4% to -0.6%]; RR, 0.89 [95% CI, 0.82-0.96]) and a similar risk of ICU admission (risk difference, -0.3% [95% CI, -1.4% to 0.7%]; RR, 0.96 [95% CI, 0.83-1.10]). Conclusions and Relevance: This cohort study's findings suggest that the receipt of α1-blockers is associated with protective benefits among adult patients hospitalized with influenza or pneumonia.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Mortalidade Hospitalar , Hospitalização , Inflamação/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Unidades de Terapia Intensiva , Pneumonia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , /patologia , Estudos de Coortes , Dinamarca , Feminino , Humanos , Inflamação/etiologia , Influenza Humana/mortalidade , Influenza Humana/patologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia/mortalidade , Pneumonia/patologia , Pontuação de Propensão , Índice de Gravidade de Doença
6.
Curr Opin Infect Dis ; 34(2): 169-174, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394726

RESUMO

PURPOSE OF REVIEW: This review aims to evaluate the evidence and recommendations for the prescription of corticosteroids as adjunctive therapy in patients with severe community-acquired pneumonia. RECENT FINDINGS: Corticosteroids have been prescribed with the objective to attenuate the marked and persistent activation of the immune system. However, some causes of community-acquired pneumonia, namely viral, are associated with unexpected low levels of cytokines and depressed cellular immunity. As a result, several recent randomized controlled trials and large prospective observational studies repeatedly showed that corticosteroids had no impact on survival, and in some types of pneumonia like influenza, its use was associated with potential harmful effects like invasive aspergillosis. Apart from this, adverse effects, namely hyperglycemia, superinfections and increased length-of-stay, were frequent findings in the corticosteroid-treated patients. SUMMARY: According to the current evidence, corticosteroids are recommended in Pneumocystis jiroveci pneumonia in HIV-infected patients and recommendations are against its use in influenza. In all other forms of severe community-acquired pneumonia, with the exclusion of SARS-CoV-2 pneumonia, the strength of the evidence does not support the safe and widespread use of corticosteroids as adjunctive therapy. Further studies are needed to identify subgroups of severe community-acquired pneumonia that can benefit or not from corticosteroids.


Assuntos
Corticosteroides/uso terapêutico , Pneumonia/tratamento farmacológico , Corticosteroides/efeitos adversos , Tomada de Decisão Clínica , Terapia Combinada , Infecções Comunitárias Adquiridas , Humanos , Pneumonia/etiologia , Pneumonia/imunologia , Pneumonia/patologia , Guias de Prática Clínica como Assunto , Segurança
7.
Am J Emerg Med ; 42: 49-54, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33450707

RESUMO

INTRODUCTION: Low muscle mass is associated with an increased mortality risk due to medical comorbidities such as chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease. Computed tomography (CT) has been identified as the gold standard for measuring body composition. We evaluated the relationship between the L1 SMI measured from CT and in-hospital mortality in patients with community-acquired pneumonia (CAP). METHODS: From January 2015 to June 2015, 311 patients who were diagnosed with CAP and underwent CT in the ED were retrospectively analyzed. Multivariate binary logistic regression analysis was used to assess independent predictors of in-hospital mortality. All variables with a significance level < 0.1 by univariate analysis were included in a multivariate logistic regression model. The primary outcome was all-cause in-hospital mortality. RESULTS: Among the 311 patients, 33 (10.6%) died. We divided the patients into two groups based on the optimal sex-specific cut-off value of the L1 SMI (45 cm2/m2 in males and 40 cm2/m2 in females). A low L1 SMI was present in 90 (28.9%) of the 311 patients. In multivariate analysis, low L1 SMI, diabetes mellitus, albumin and APACHE II score were significantly associated with in-hospital mortality (aOR 3.39, 3.73, 0.09 and 1.10, respectively). CONCLUSION: SMI assessment at L1 is achievable in patients with CAP receiving routine chest CT, and the L1 SMI is associated with high in-hospital mortality, more hospitalizations and ventilator application in patients with CAP in the ED. This could help establish an early strategy for critical care of patients with L1 SMI obtained by chest CT for diagnosis in CAP patients in the ED.


Assuntos
Infecções Comunitárias Adquiridas/mortalidade , Mortalidade Hospitalar , Músculo Esquelético/patologia , Pneumonia/mortalidade , Sarcopenia/complicações , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/patologia , Infecções Comunitárias Adquiridas/terapia , Cuidados Críticos , Feminino , Hospitalização , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Pneumonia/complicações , Pneumonia/patologia , Pneumonia/terapia , Respiração Artificial , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Tomografia Computadorizada por Raios X
8.
Cell Death Dis ; 12(1): 53, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414457

RESUMO

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.


Assuntos
/metabolismo , Imunidade Inata/efeitos dos fármacos , Influenza Humana/metabolismo , Interleucinas/farmacologia , Pneumonia/prevenção & controle , Poli I-C/toxicidade , Sistema Respiratório/imunologia , Animais , /virologia , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/imunologia , Influenza Humana/virologia , Interleucina-1/sangue , Interleucinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/patologia , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , /isolamento & purificação
9.
Int J Mol Sci ; 22(1)2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401552

RESUMO

Gender differences in pulmonary inflammation have been well documented. Although low molecular mass hyaluronan (LMMHA) is known to trigger pulmonary lung inflammation, sex differences in susceptibility to LMMHA are still unknown. In this study, we test the hypothesis that mice may display sex-specific differences after LMMHA administration. After LMMHA administration, male mice have higher neutrophil, cytokine, and chemokine counts compared to that of their female counterparts. Additionally, Ovariectomized (OVX) mice show greater LMMHA-induced inflammation compared to that of mice with intact ovaries. Injections of OVX mice with 17ß-estradiol can decrease inflammatory responses in the OVX mice. These results show that ovarian hormones regulate LMMHA induced lung inflammation.


Assuntos
Ácido Hialurônico/toxicidade , Pneumonia/patologia , Viscossuplementos/toxicidade , Doença Aguda , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Pneumonia/induzido quimicamente , Fatores Sexuais
10.
PLoS One ; 16(1): e0245924, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481950

RESUMO

SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. Here we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1ß, IL-6, IL-12p70, IL-23, and IL-27 in serum. SAP also reduced D-dimer levels in the lung fluid. In human peripheral blood mononuclear cells, SAP attenuated ORN06-induced extracellular accumulation of IL-6. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms and/or a cytokine storm.


Assuntos
/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Pneumonia/tratamento farmacológico , Componente Amiloide P Sérico/uso terapêutico , Animais , /patologia , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/patologia , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/complicações , Pneumonia/patologia , Componente Amiloide P Sérico/administração & dosagem
11.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33300070

RESUMO

Pneumonia accounts for ~1.3 million mortalities in children per year worldwide. MicroRNAs are implicated in several diseases, including cancer and pneumonia; however, the role of let7f­5p in pneumonia is not completely understood. In the present study, lipopolysaccharide (LPS) was used to establish an in vitro pneumonia model in A549 and WI­38 cells. The reverse transcription­quantitative PCR (RT­qPCR) and western blotting results demonstrated that let7f­5p expression levels were significantly decreased, whereas MAPK6 expression levels were significantly increased in the peripheral venous blood of patients with pneumonia and in LPS­induced A549 and WI­38 cells compared with healthy volunteers and control cells, respectively. Furthermore, the dual­luciferase reporter assay demonstrated that let7f­5p targeted the 3'­untranslated region of MAPK6. The ELISA and RT­qPCR results demonstrated that let7f­5p mimic ameliorated LPS­induced inflammatory injury in A549 and WI­38 cells, as demonstrated by decreased expression levels of proinflammatory cytokines, including TNF­α and IL­6. In addition, the Cell Counting Kit­8 assay results indicated that let7f­5p mimic ameliorated LPS­induced reductions in cell viability, and the western blotting results demonstrated that let7f­5p mimic reversed LPS­induced activation of the STAT3 signaling pathway. Notably, the aforementioned let7f­5p­mediated effects were reversed by MAPK6 overexpression. Collectively, the results of the present study suggested that let7f­5p inhibited inflammation by targeting MAPK6 in the in vitro pneumonia model, thus let7f­5p may serve as a potential novel therapeutic target for pneumonia.


Assuntos
Lesão Pulmonar/metabolismo , MicroRNAs/metabolismo , Proteína Quinase 6 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Pneumonia/metabolismo , Células A549 , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Inflamação , Lesão Pulmonar/genética , Lesão Pulmonar/patologia , Masculino , MicroRNAs/genética , Proteína Quinase 6 Ativada por Mitógeno/genética , Pneumonia/genética , Pneumonia/patologia
12.
Eur J Radiol ; 134: 109442, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33321459

RESUMO

PURPOSE: The vascular enlargement (VE) pattern differs from previously described imaging patterns for pneumonia. This study aimed to investigate the incidence, computed tomography (CT) characteristics, and diagnostic value of the VE pattern in coronavirus disease 2019 (COVID-19). METHOD: The CT data of 106 patients with COVID-19 from January 19 to February 29, 2020, and 52 patients with influenza virus pneumonia (IVP) from January 2018 to February 2020 were retrospectively collected. The incidences of the VE pattern between the two groups were compared. The CT manifestations of COVID-19 were analyzed with a particular focus on the VE pattern's specific CT signs, dynamic changes, and relationships with lesion size and disease severity. RESULTS: Peripheral and multilobar ground-glass opacities (GGOs) or mixed GGOs with various sizes and morphologies were typical features of COVID-19 on initial CT. The VE pattern was more common in COVID-19 (88/106, 83.02 %) than in IVP (10/52, 19.23 %) on initial CT (P < 0.001). Three special VE-pattern-specific CT signs, including central vascular sign, ginkgo leaf sign, and comb sign, were identified. Four types of dynamic changes in the VE pattern were observed on initial and follow-up CT, which were closely associated with the evolution of lesions and the time interval from the onset of symptoms to initial CT scan. The VE pattern in COVID-19 was more commonly seen in larger lesions and patients with severe-critical type (all P < 0.001). CONCLUSIONS: The VE pattern is a valuable CT sign for differentiating COVID-19 from IVP, which correlates with more extensive or serious disease. A good understanding of the CT characteristics of the VE pattern may contribute to the early and accurate diagnosis of COVID-19 and prediction of the evolution of lesions.


Assuntos
/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/diagnóstico por imagem , Influenza Humana/patologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia/patologia , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Adulto Jovem
13.
Life Sci ; 267: 118912, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33338503

RESUMO

AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1ß, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1ß and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1ß, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1ß and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.


Assuntos
Cloro/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/patologia , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Cloro/metabolismo , Inflamação/patologia , Exposição por Inalação , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
PLoS One ; 15(12): e0244627, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370397

RESUMO

BACKGROUND AND AIMS: Identification of SARS-CoV-2-infected patients at high-risk of poor prognosis is crucial. We aimed to establish predictive models for COVID-19 pneumonia severity in hospitalized patients. METHODS: Retrospective study of 430 patients admitted in Vall d'Hebron Hospital (Barcelona) between 03-12-2020 and 04-28-2020 due to COVID-19 pneumonia. Two models to identify the patients who required high-flow-oxygen-support were generated, one using baseline data and another with also follow-up analytical results. Calibration was performed by a 1000-bootstrap replication model. RESULTS: 249 were male, mean age 57.9 years. Overall, 135 (31.4%) required high-flow-oxygen-support. The baseline predictive model showed a ROC of 0.800 based on: SpO2/FiO2 (adjusted Hazard Ratio-aHR = 8), chest x-ray (aHR = 4), prior immunosuppressive therapy (aHR = 4), obesity (aHR = 2), IL-6 (aHR = 2), platelets (aHR = 0.5). The cut-off of 11 presented a specificity of 94.8%. The second model included changes on the analytical parameters: ferritin (aHR = 7.5 if ≥200ng/mL) and IL-6 (aHR = 18 if ≥64pg/mL) plus chest x-ray (aHR = 2) showing a ROC of 0.877. The cut-off of 12 exhibited a negative predictive value of 92%. CONCLUSIONS: SpO2/FiO2 and chest x-ray on admission or changes on inflammatory parameters as IL-6 and ferritin allow us early identification of COVID-19 patients at risk of high-flow-oxygen-support that may benefit from a more intensive disease management.


Assuntos
/diagnóstico , Pneumonia/diagnóstico , Pneumonia/patologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
Int J Mol Sci ; 21(24)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352854

RESUMO

Air pollution is mainly caused by burning of fossil fuels, such as diesel, and is associated with increased morbidity and mortality due to adverse health effects induced by inflammation and oxidative stress. Dimethyl fumarate (DMF) is a fumaric acid ester and acts as an antioxidant and anti-inflammatory agent. We investigated the potential therapeutic effects of DMF on pulmonary damage caused by chronic exposure to diesel exhaust particles (DEPs). Mice were challenged with DEPs (30 µg per mice) by intranasal instillation for 60 consecutive days. After the first 30 days, the animals were treated daily with 30 mg/kg of DMF by gavage for the remainder of the experimental period. We demonstrated a reduction in total inflammatory cell number in the bronchoalveolar lavage (BAL) of mice subjected to DEP + DMF as compared to those exposed to DEPs alone. Importantly, DMF treatment was able to reduce lung injury caused by DEP exposure. Intracellular total reactive oxygen species (ROS), peroxynitrite (OONO), and nitric oxide (NO) levels were significantly lower in the DEP + DMF than in the DEP group. In addition, DMF treatment reduced the protein expression of kelch-like ECH-associated protein 1 (Keap-1) in lung lysates from DEP-exposed mice, whereas total nuclear factor κB (NF-κB) p65 expression was decreased below baseline in the DEP + DMF group compared to both the control and DEP groups. Lastly, DMF markedly reduced DEP-induced expression of nitrotyrosine, glutathione peroxidase-1/2 (Gpx-1/2), and catalase in mouse lungs. In summary, DMF treatment effectively reduced lung injury, inflammation, and oxidative and nitrosative stress induced by chronic DEP exposure. Consequently, it may lead to new therapies to diminish lung injury caused by air pollutants.


Assuntos
Fumarato de Dimetilo/farmacologia , Estresse Oxidativo , Pneumonia/etiologia , Pneumonia/metabolismo , Emissões de Veículos , Poluentes Atmosféricos/efeitos adversos , Animais , Biomarcadores , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , NF-kappa B/metabolismo , Oxirredução , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos/toxicidade
16.
Medicine (Baltimore) ; 99(50): e23671, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327356

RESUMO

BACKGROUND: The aim of this meta-analysis was to evaluate the diagnostic value of lung ultrasound (LUS) in comparison to chest radiography (CXR) in children with pneumonia. METHODS: Computer-based retrieval was performed on PubMed and EMBASE. Quality was evaluated according to the quality assessment of diagnostic accuracy studies-2, and Meta-Disc was adopted to perform meta-analysis. Heterogeneity was assessed using Q and I statistics. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CIs) as the primary outcomes were calculated for each index test. RESULTS: Twenty two studies with a total of 2470 patients met the inclusion criteria. Our results showed that the pooled sensitivity, specificity, and DOR for children with pneumonia diagnosed by LUS were 0.95 (95% CI: 0.94 to 0.96), 0.90 (95% CI: 0.87 to 0.92), and 137.49 (95% CI: 60.21 to 313.98), respectively. The pooled sensitivity, specificity, and DOR for pediatric pneumonia diagnosed by CXR was 0.91 (95% CI: 0.90 to 0.93), 1.00 (95% CI: 0.99 to 1.00), and 369.66 (95% CI: 137.14 to 996.47), respectively. Four clinical signs, including pulmonary consolidation, positive air bronchogram, abnormal pleural line, and pleural effusion were most frequently observed using LUS in the screening of children with pneumonia. CONCLUSIONS: The available evidence suggests that LUS is a reliable, valuable, and alternative method to CXR for the diagnosis of pediatric pneumonia.


Assuntos
Pneumonia/diagnóstico , Radiografia Torácica/métodos , Ultrassonografia/métodos , Adolescente , Fatores Etários , Broncografia/métodos , Broncografia/normas , Criança , Pré-Escolar , Humanos , Lactente , Pulmão/diagnóstico por imagem , Derrame Pleural/patologia , Pneumonia/diagnóstico por imagem , Pneumonia/patologia , Radiografia Torácica/normas , Sensibilidade e Especificidade , Fatores Sexuais , Ultrassonografia/normas
17.
Nat Commun ; 11(1): 5859, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203833

RESUMO

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Betacoronavirus/patogenicidade , Biomarcadores/urina , Infecções por Coronavirus/urina , Progressão da Doença , Humanos , Tolerância Imunológica , Pandemias , Pneumonia/imunologia , Pneumonia/patologia , Pneumonia/urina , Pneumonia Viral/urina , Proteoma/análise , Junções Íntimas/patologia
18.
PLoS One ; 15(11): e0241663, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33147270

RESUMO

BACKGROUND/AIM: The coronavirus disease 2019 (COVID-19) had become a big threat worldwide. Liver injury is not uncommon in patients with COVID-19, and clarifying its characteristics is needed. This study aimed to identify factors associated with liver injury and to develop a new classification of predictive severity in patients with COVID-19. METHODS: Confirmed patients with COVID-19 (n = 60) were recruited retrospectively from Musashino Red Cross Hospital. The factors of liver injury especially on the elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were analyzed. Grading was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: During a median hospitalization follow-up of 15 (4-41) days, 51 (85.0%) patients had COVID-19 pneumonia. In clinical courses, oxygenation was needed for 25 (41.6%) patients and intubation was needed for 9 (15.0%) patients. A total of 27 (45.0%) patients had gastrointestinal symptoms (GS), such as appetite loss, diarrhea, and nausea. A logistic regression analysis revealed that C-reactive protein (CRP) at baseline, oxygenation, intubation, and GS were significant factors of liver injury. Based on these results, patients were classified into three groups: group 1, no oxygenation pneumonia; group 2, pneumonia with oxygenation or GS; and group 3, intubation. We classified 25 (41.7%), 26 (43.3%), and 9 (15.0%) patients into mild, moderate, and severe groups, respectively. The peak of AST and ALT levels was significantly stratified with this criteria (mild [median AST, 28 IU/L; median ALT, 33 IU/L], moderate [median AST, 48 IU/L; median ALT, 47.5 IU/L], and severe [median AST, 109 IU/L; median ALT, 106 IU/L]; P<0.001 and P = 0.0114, respectively). CONCLUSION: COVID-19-related liver injury was significantly stratified based on GS and severity of pneumonia.


Assuntos
Infecções por Coronavirus/patologia , Doenças do Sistema Digestório/patologia , Doenças do Sistema Digestório/virologia , Hepatopatias/patologia , Hepatopatias/virologia , Pneumonia Viral/patologia , Pneumonia/patologia , Pneumonia/virologia , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Proteína C-Reativa/metabolismo , Doenças do Sistema Digestório/metabolismo , Feminino , Seguimentos , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Hepatopatias/metabolismo , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia/metabolismo , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
J Pharmacol Sci ; 144(4): 189-196, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070837

RESUMO

Pneumonia is a common illness that continues to be the major killer of remaining to be a significant source of morbidity and mortality in the patient population. Many microorganisms cause pneumonia, and now concern is turning to the importance of the cause the new therapies for viral pneumonia. In the current study, we report the effect of andrographolide sulfonate, a water-soluble form of andrographolide (trade name: Xi-Yan-Ping Injection), on poly I: C-induced pneumonia. Andrographolide sulfonate was administrated through intraperitoneal injection to mice with poly I: C-induced pneumonia. Recruitment of airway inflammatory cells, alteration of lung histological induced by Poly I: C were significantly ameliorated by andrographolide sulfonate. The protein levels of pro-inflammatory cytokines in bronchoalveolar fluid (BALF) and serum were reduced by andrographolide sulfonate treatment. The levels of MUC5AC and MUC5B in lung tissue were also suppressed. These results reveal that andrographolide sulfate remarkably alleviated pneumonia induced by poly I:C in mice. Moreover, andrographolide sulfonate markedly inhibited the activation of nuclear factor-κB (NF-κB). Taken together, we demonstrated that andrographolide sulfonate ameliorated poly I: C-induced pneumonia in mice, suggesting the possible use of andrographolide sulfonate for virus-induced pneumonia in clinical.


Assuntos
Diterpenos/administração & dosagem , Diterpenos/farmacologia , NF-kappa B/metabolismo , Fitoterapia , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Poli I-C/efeitos adversos , Animais , Citocinas/sangue , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos Endogâmicos C57BL , Mucina-5AC/metabolismo , Mucina-5B/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/patologia , Pneumonia Viral/tratamento farmacológico
20.
J Am Heart Assoc ; 9(18): e017368, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896206

RESUMO

E-cigarette or vaping product use-associated lung injury was recognized in the United States in the summer of 2019 and is typified by acute respiratory distress, shortness of breath, chest pain, cough, and fever, associated with vaping. It can mimic many of the manifestations of coronavirus disease 2019 (COVID-19). Some investigators have suggested that E-cigarette or vaping product use-associated lung injury was due to tetrahydrocannabinol or vitamin E acetate oil mixed with the electronic cigarette liquid. In experimental rodent studies initially designed to study the effect of electronic cigarette use on the cardiovascular system, we observed an E-cigarette or vaping product use-associated lung injury-like condition that occurred acutely after use of a nichrome heating element at high power, without the use of tetrahydrocannabinol, vitamin E, or nicotine. Lung lesions included thickening of the alveolar wall with foci of inflammation, red blood cell congestion, obliteration of alveolar spaces, and pneumonitis in some cases; bronchi showed accumulation of fibrin, inflammatory cells, and mucus plugs. Electronic cigarette users should be cautioned about the potential danger of operating electronic cigarette units at high settings; the possibility that certain heating elements may be deleterious; and that E-cigarette or vaping product use-associated lung injury may not be dependent upon tetrahydrocannabinol, vitamin E, or nicotine.


Assuntos
Dronabinol/toxicidade , Vapor do Cigarro Eletrônico/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Pneumonia/induzido quimicamente , Vaping/efeitos adversos , Vitamina E/toxicidade , Animais , Exposição por Inalação , Pulmão/patologia , Lesão Pulmonar/patologia , Modelos Animais , Óleos , Pneumonia/patologia , Ratos , Medição de Risco
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