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1.
Respir Res ; 25(1): 129, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500106

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. METHODS: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. RESULTS: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. CONCLUSIONS: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Sepse , Humanos , Elafina , Proteína D Associada a Surfactante Pulmonar , Pulmão , Síndrome do Desconforto Respiratório/diagnóstico , Sepse/diagnóstico , Sepse/complicações
2.
J Surg Res ; 298: 109-118, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603941

RESUMO

INTRODUCTION: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. METHODS: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. RESULTS: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). CONCLUSIONS: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.


Assuntos
Morte Encefálica , Pulmão , Ratos Wistar , Animais , Morte Encefálica/fisiopatologia , Solução Salina Hipertônica/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Ratos , Mecânica Respiratória/efeitos dos fármacos , Transplante de Pulmão
3.
BMC Pulm Med ; 24(1): 22, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195527

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). METHODS: Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-ß expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. RESULTS: The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. CONCLUSION: LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).


Assuntos
Linfangioleiomiomatose , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Remodelação das Vias Aéreas , Biópsia , Colágeno , Fator de Crescimento Transformador beta
4.
Respir Res ; 24(1): 281, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964271

RESUMO

BACKGROUND: Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS: We have quantified different ECM elements and TGF-ß expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS: We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-ß, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-ß was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS: Fatal COVID-19 is associated with an early TGF-ß expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.


Assuntos
COVID-19 , Fibrose Pulmonar , Síndrome do Desconforto Respiratório , Humanos , Feminino , Fibrose Pulmonar/metabolismo , COVID-19/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Pulmão/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Síndrome do Desconforto Respiratório/metabolismo
5.
Pathologica ; 115(5): 263-274, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38054901

RESUMO

COVID-19 identification is routinely performed on fresh samples, such as nasopharyngeal and oropharyngeal swabs, even if, the detection of the virus in formalin-fixed paraffin-embedded (FFPE) autopsy tissues could help to underlie mechanisms of the pathogenesis that are not well understood.The gold standard for COVID-19 detection in FFPE samples remains the qRT-PCR as in swab samples, contextually other methods have been developed, including immunohistochemistry (IHC), and in situ hybridization (ISH). In this manuscript, we summarize the main data regarding the methods of COVID-19 detection in pulmonary and extra-pulmonary post-mortem samples, and especially the sensitivity and specificity of these assays will be discussed.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Reação em Cadeia da Polimerase
6.
J Pathol ; 254(3): 239-243, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33834497

RESUMO

The ability of the new coronavirus SARS-CoV-2 to spread and contaminate is one of the determinants of the COVID-19 pandemic status. SARS-CoV-2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound-guided postmortem biopsies in COVID-19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT-qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS-CoV-2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12 years (range 8-83 years). RT-qPCR for SARS-CoV-2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70-100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti-SARS-CoV-2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS-CoV-2 by immunohistochemistry. Salivary glands are a reservoir for SARS-CoV-2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID-19 and highlight this biological fluid's role in spreading the disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
COVID-19/virologia , SARS-CoV-2/patogenicidade , Saliva/virologia , Glândulas Salivares/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reino Unido , Adulto Jovem
7.
Int J Mol Sci ; 23(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35409273

RESUMO

Fine particulate matter (PM2.5) is a complex mixture of components with diverse chemical and physical characteristics associated with increased respiratory and cardiovascular diseases mortality. Our study aimed to investigate the effects of exposure to concentrated PM2.5 on LPS-induced lung injury onset. BALB/c male mice were exposed to either filtered air or ambient fine PM2.5 in an ambient particle concentrator for 5 weeks. Then, an acute lung injury was induced with nebulized LPS. The animals were euthanized 24 h after the nebulization to either LPS or saline. Inflammatory cells and cytokines (IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-17, TNF) were assessed in the blood, bronchoalveolar lavage fluid (BALF), and lung tissue. In addition, lung morphology was assessed by stereological methods. Our results showed that the PM+LPS group showed histological evidence of injury, leukocytosis with increased neutrophils and macrophages, and a mixed inflammatory response profile, with increased KC, IL-6, IL-1ß, IL-4, and IL-17. Our analysis shows that there is an interaction between the LPS nebulization and PM2.5 exposure, differently modulating the inflammatory response, with a distinct response pattern as compared to LPS or PM2.5 exposure alone. Further studies are required to explain the mechanism of immune modulation caused by PM2.5 exposure.


Assuntos
Lesão Pulmonar Aguda , Material Particulado , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/farmacologia , Interleucina-17/farmacologia , Interleucina-4/farmacologia , Interleucina-6/farmacologia , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Material Particulado/toxicidade
8.
Clin Infect Dis ; 73(Suppl_5): S442-S453, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910174

RESUMO

BACKGROUND: Minimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)-guided MITS as a strategy. METHODS: This case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases. RESULTS: US-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction. CONCLUSIONS: Our data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.


Assuntos
COVID-19 , Autopsia , Brasil/epidemiologia , Teste para COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Ultrassonografia de Intervenção
9.
Respir Res ; 22(1): 32, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514373

RESUMO

BACKGROUND: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. METHODS: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. RESULTS: Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. CONCLUSION: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.


Assuntos
COVID-19/patologia , Lesão Pulmonar/patologia , Pulmão/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Autopsia , COVID-19/complicações , Demografia , Progressão da Doença , Feminino , Humanos , Infarto/epidemiologia , Infarto/patologia , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Trombose/etiologia , Trombose/patologia , Adulto Jovem
10.
BMC Infect Dis ; 21(1): 311, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794785

RESUMO

BACKGROUND: Dengue infection is caused by an arbovirus with a wide range of presentations, varying from asymptomatic disease to unspecific febrile illness and haemorrhagic syndrome with shock, which can evolve to death. In Brazil, the virus circulates since the 1980s with many introductions of new serotypes, genotypes, and lineages since then. Here we report a fatal case of dengue associated with a Dengue virus (DENV) lineage not detected in the country until now. CASE PRESENTATION: The patient, a 58-year-old man arrived at the hospital complaining of fever and severe abdominal pain due to intense gallbladder edema, mimicking acute abdomen. After 48 h of hospital admission, he evolved to refractory shock and death. DENV RNA was detected in all tissues collected (heart, lung, brain, kidney, spleen, pancreas, liver, and testis). Viral sequencing has shown that the virus belongs to serotype 2, American/Asian genotype, in a new clade, which has never been identified in Brazil before. The virus was phylogenetically related to isolates from central America [Puerto Rico (2005-2007), Martinique (2005), and Guadeloupe (2006)], most likely arriving in Brazil from Puerto Rico. CONCLUSION: In summary, this was the first fatal documented case with systemic dengue infection associated with the new introduction of Dengue type 2 virus in Brazil during the 2019 outbreak.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Encéfalo/virologia , Brasil , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vesícula Biliar/patologia , Genótipo , Coração/virologia , Humanos , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Viral/metabolismo
11.
Genet Mol Biol ; 44(1 Suppl 1): e20200302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651876

RESUMO

COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. Here we present a brief review on the known order of events from infection to severe system-wide disturbance due to COVID-19 and summarize potential candidate genes and pathways. Finally, we propose a strategy of subject's ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes.

12.
Histopathology ; 77(2): 186-197, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32443177

RESUMO

AIMS: Brazil ranks high in the number of coronavirus disease 19 (COVID-19) cases and the COVID-19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID-19. In order to follow biosafety recommendations, we used ultrasound-guided minimally invasive autopsy (MIA-US), and we present the results of 10 initial autopsies. METHODS AND RESULTS: We used MIA-US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis. CONCLUSIONS: MIA-US is safe and effective for the study of severe COVID-19. Our findings show that COVID-19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.


Assuntos
Autopsia/métodos , COVID-19/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Ultrassonografia
13.
Histopathology ; 75(5): 638-648, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31087672

RESUMO

AIMS: The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of São Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. METHODS AND RESULTS: All patients were men, aged 16-40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti-YFV antibody directed to wild strain and a goat anti-YF virus antibody), and RT-PCR assays were utilised to detect YFV-RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT-PCR in the liver and in other organs. CONCLUSIONS: Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.


Assuntos
Transplante de Fígado , Necrose Hepática Massiva/virologia , Transplantes/virologia , Febre Amarela , Vírus da Febre Amarela , Adolescente , Adulto , Autopsia , Brasil , Humanos , Transplante de Fígado/mortalidade , Masculino , Febre Amarela/patologia , Febre Amarela/cirurgia , Febre Amarela/virologia , Adulto Jovem
14.
Lasers Med Sci ; 34(7): 1441-1448, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30762192

RESUMO

To evaluate the feasibility of a 980-nm contact diode laser (CDL) as a method for creating a posterior laryngofissure in live pigs. Twenty-eight Landrace pigs (15-20 kg) were anesthetized, intubated, ventilated, and submitted to a cervical tracheostomy. An anterior and posterior midline longitudinal laryngofissure incision was created according to randomization-control (n = 4), posterior laryngofissure with a scalpel blade; electrocautery (n = 12), posterior laryngofissure by electrocautery (10, 15, 20, 25 W powers); CDL (n = 12), posterior laryngofissure by the CDL (10, 15, 20, 25 W peak powers in pulsed mode). Larynx and proximal trachea were excised, prepared for histopathology, and digital morphometric analysis. Measurements in and within each group were analyzed (Kruskal-Wallis and Dunn test) with a level of significance of p < 0.05. Incision width was not different between the groups, as well as in the powers used in CDL (p = 0.161) and electrocautery group (p = 0.319). The depth of the incisions was smaller in the Laser group compared to control (p = 0.007), and in the electrocautery compared to control (p = 0.026). Incision area was smaller in CDL compared with the control (p = 0.027), and not different between laser and electrocautery groups (p = 0.199). The lateral thermal damage produced by electrocautery was the largest, with a significant difference between laser and electrocautery (p = 0.018), and between electrocautery and control (p = 0.004), whereas the comparison between laser and control showed no significant differences (p = 0.588). The posterior laryngofissure incision using a 980-nm CDL is feasible resulting in smaller incisional area and less lateral thermal damage.


Assuntos
Laringe/cirurgia , Lasers Semicondutores , Animais , Eletrocoagulação , Estudos de Viabilidade , Terapia a Laser/métodos , Suínos
15.
Respir Res ; 19(1): 83, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29739412

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a low-grade neoplasm characterized by the pulmonary infiltration of smooth muscle-like cells (LAM cells) and cystic destruction. Patients usually present with airway obstruction in pulmonary function tests (PFTs). Previous studies have shown correlations among histological parameters, lung function abnormalities and prognosis in LAM. We investigated the lung tissue expression of proteins related to the mTOR pathway, angiogenesis and enzymatic activity and its correlation with functional parameters in LAM patients. METHODS: We analyzed morphological and functional parameters of thirty-three patients. Two groups of disease severity were identified according to FEV1 values. Lung tissue from open biopsies or lung transplants was immunostained for SMA, HMB-45, mTOR, VEGF-D, MMP-9 and D2-40. Density of cysts, density of nodules and protein expression were measured by image analysis and correlated with PFT parameters. RESULTS: There was no difference in the expression of D2-40 between the more severe and the less severe groups. All other immunohistological parameters showed significantly higher values in the more severe group (p ≤ 0.002). The expression of VEGF-D, MMP-9 and mTOR in LAM cells was associated with the density of both cysts and nodules. The density of cysts and nodules as well as the expression of MMP-9 and VEGF-D were associated with the impairment of PFT parameters. CONCLUSIONS: Severe LAM represents an active phase of the disease with high expression of VEGF-D, mTOR, and MMP-9, as well as LAM cell infiltration. Our findings suggest that the tissue expression levels of VEGF-D and MMP-9 are important parameters associated with the loss of pulmonary function and could be considered as potential severity markers in open lung biopsies of LAM patients.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Pulmonares/metabolismo , Linfangioleiomiomatose/metabolismo , Metaloproteinase 9 da Matriz/biossíntese , Serina-Treonina Quinases TOR/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Linfangioleiomiomatose/patologia , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Estudos Retrospectivos , Serina-Treonina Quinases TOR/análise , Fator A de Crescimento do Endotélio Vascular/análise
16.
BMC Pulm Med ; 18(1): 50, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29554886

RESUMO

BACKGROUND: Mortality related to asthma has decreased worldwide since the introduction of inhaled corticosteroid therapy in the past decades. However, there are still some asthma fatalities identified mainly in populations with less access to regular treatment. Pulmonary interstitial emphysema due to alveolar rupture has been rarely described as a complication of an acute severe asthma attack, and its identification in pathological analysis can be difficult. Previous studies reported the association of pulmonary interstitial emphysema and bronchial ductal gland ectasia in asthma. CASE PRESENTATION: We present the case of a 42-year- old man that died due to a fatal asthma attack. Postmortem computed tomography revealed the unusual finding of acute Pulmonary Interstitial Emphysema, confirmed by pathological analysis. We reviewed 28 cases of fatal asthma tissue and identified the presence of pulmonary interstitial emphysema in 10% of the cases. CONCLUSIONS: Postmortem computed tomography is a useful complimentary diagnostic tool for autopsies. Pulmonary Interstitial Emphysema in acute exacerbations of asthma seems to be more frequent than reported. Alveolar hyperdistension and bronchial duct gland ectasia causing tissue rupture are possible mechanisms involved in the formation of Pulmonary Interstitial Emphysema. The clinical impact of Pulmonary Interstitial Emphysema in asthma is unknown.


Assuntos
Asma/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Enfisema Pulmonar/diagnóstico , Adulto , Autopsia , Evolução Fatal , Humanos , Masculino , Tomografia Computadorizada por Raios X
17.
Int J Sports Med ; 39(2): 133-140, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29161746

RESUMO

Air pollution is a growing problem worldwide, inducing and exacerbating several diseases. Among the several components of air pollutants, particulate matter (PM), especially thick (10-2.5 µm; PM 10) and thin (≤2.5 µm; PM 2.5), are breathable particles that easily can be deposited within the lungs, resulting in pulmonary and systemic inflammation. Although physical activity is strongly recommended, its effects when practiced in polluted environments are questionable. Therefore, the present study evaluated the pulmonary and systemic response of concomitant treadmill training with PM 2.5 and PM 10 exposure. Treadmill training inhibited PM 2.5- and PM 10-induced accumulation of total leukocytes (p<0.001), neutrophils (p<0.001), macrophages (p<0.001) and lymphocytes (p<0.001) in bronchoalveolar lavage (BAL), as well as the BAL levels of IL-1beta (p<0.001), CXCL1/KC (p<0.001) and TNF-alpha (p<0.001), whereas it increased IL-10 levels (p<0.05). Similar effects were observed on accumulation of polymorphonuclear (p<0.01) and mononuclear (p<0.01) cells in the lung parenchyma and in the peribronchial space. Treadmill training also inhibited PM 2.5- and PM 10-induced systemic inflammation, as observed in the number of total leukocytes (p<0.001) and in the plasma levels of IL-1beta (p<0.001), CXCL1/KC (p<0.001) and TNF-alpha (p<0.001), whereas it increased IL-10 levels (p<0.001). Treadmill training inhibits lung and systemic inflammation induced by particulate matter.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Pulmão/imunologia , Material Particulado/efeitos adversos , Condicionamento Físico Animal , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/prevenção & controle , Pulmão/citologia , Linfócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais , Neutrófilos/metabolismo
19.
Respir Res ; 18(1): 147, 2017 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-28774302

RESUMO

BACKGROUND: Diffuse alveolar damage (DAD), which is the histological surrogate for acute respiratory distress syndrome (ARDS), has a multifactorial aetiology. Therefore it is possible that the immunopathology differs among the various presentations of DAD. The aim of this study is to compare lung immunopathology of viral (influenza A(H1N1)pdm09) to non-viral, extrapulmonary aetiologies in autopsy cases with DAD. METHODS: The lung tissue of 44 patients, was divided in the H1N1 group (n = 15) characterized by severe pulmonary injury due to influenza A(H1N1)pdm09 infection; the ARDS group (n = 13), characterized by patients with DAD due to non-pulmonary causes; and the Control group (n = 16), consisting of patients with non-pulmonary causes of death. Immunohistochemistry and image analysis were used to quantify, in the parenchyma and small airways, several immune cell markers. RESULTS: Both DAD groups had higher expression of neutrophils and macrophages in parenchyma and small airways. However, there was a higher expression of CD4+ and CD8+ T lymphocytes, CD83+ dendritic cells, granzyme A+ and natural killer + cell density in the lung parenchyma of the H1N1 group (p < 0.05). In the small airways, there was a lower cell density of tryptase + mast cells and dendritic + cells and an increase of IL-17 in both DAD groups (p < 0.05). CONCLUSION: DAD due to viral A(H1N1)pdm09 is associated with a cytotoxic inflammatory phenotype, with partially divergent responses in the parenchyma relative to the small airways. In non-viral DAD, main immune cell alterations were found at the small airway level, reinforcing the role of the small airways in the pathogenesis of the exudative phase of DAD.


Assuntos
Células Dendríticas/patologia , Imunidade Celular/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Alvéolos Pulmonares/patologia , Síndrome do Desconforto Respiratório/patologia , Linfócitos T/patologia , Adulto , Idoso , Células Dendríticas/imunologia , Feminino , Humanos , Influenza Humana/imunologia , Influenza Humana/patologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/imunologia , Síndrome do Desconforto Respiratório/imunologia , Estudos Retrospectivos , Linfócitos T/imunologia
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