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1.
Zhonghua Er Ke Za Zhi ; 58(1): 19-24, 2020 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-31905471

RESUMO

Objective: To summarize the diagnosis, clinical manifestations, treatment and prognosis of congenital cystic lung lesions. Methods: A retrospective study described the clinical course of 96 patients (46 female and 50 male) diagnosed with congenital cystic lung lesions treated at the Tianjin Children's Hospital from January 2010 to March 2019. The clinical findings, imaging examinations, pathological findings, treatment and follow-up were analyzed. Results: Totally 96 patients (aged from 4 days to 13 years) with congenital cystic lung lesions were included in this study. Eighty-six patients (90%) were diagnosed when they had cough and fever symptoms. Forty (42%) patients exhibited congenital cystic adenomatoid malformation, 30 underwent surgical excision, two were at emergency operations and one dead. There were 12 (13%) patients with pulmonary sequestration and four were surgical treated. Twelve (13%) patients with bronchogenic cyst were included and 4 were surgically treated. There were 3 (3%) patients with congenital lobar emphysema and one was surgically treated. Another patient with pneumothorax was operated in other hospital 2 months after discharge. Twenty-nine (30%) patients with unclassified congenital cystic lung lesions could not be definitively diagnosed by CT. Some of them were difficult to be distinguished from necrotizing pneumonia. Finally, 2 patients were diagnosed as necrotizing pneumonia after 6, 10 months follow-up. After operation 37 out of 39 patients recovered well. Conclusions: The diagnosis of congenital pulmonary cystic disease depend on imaging and pathological examination. Most patients are diagnosed when they have respiratory tract infection. The main clinical manifestations are cough and fever. The prognosis of operative management is good.


Assuntos
Cisto Broncogênico/diagnóstico , Cisto Broncogênico/cirurgia , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico , Enfisema Pulmonar/patologia , Adolescente , Cisto Broncogênico/congênito , Sequestro Broncopulmonar/diagnóstico , Sequestro Broncopulmonar/cirurgia , Criança , Pré-Escolar , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Feminino , Humanos , Lactente , Masculino , Pneumonectomia , Enfisema Pulmonar/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
Forensic Sci Int ; 305: 110029, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31726327

RESUMO

The question whether an injury was sustained during life or not is one of the most important subjects in forensic medicine. Therefore, vital reactions have been a main research topic in forensic medicine for a long period and many renowned forensic pathologists have devoted important papers to this field. The research area ranges from macroscopically visible organ reactions, over tissue alterations (enzyme histochemistry, later on immunohistochemistry with a wide range of enzymes and other analytes, molecular pathology) to biochemical responses to injury. Especially in the field of immunohistochemistry and molecular pathology much progress has been achieved in the last years (e.g. heat-shock-proteins or positive aquaporine3-staining in mechanical skin trauma). Furthermore, 20 years after its implementation postmortem imaging also contributes to the detection and visualization of vital signs. The aim of the present review is to provide an update on forensically relevant vital signs/vital reactions. Systemic vital reactions especially of the circulatory and respiratory system as well as local vital reactions will be addressed. Vital reactions of different organ systems will be discussed in detail regarding pathogenesis and possible postmortem evolution. Current research on immunohistochemically detectable vital reactions (heat-shock-protein expression, aquaporine3-staining in mechanical trauma of the skin) will be addressed as well as biochemical vital reactions (agonochemical stress reaction, myoglobine in electrocution death, hypoxanthine as marker of hypoxia).


Assuntos
Medicina Legal/métodos , Ferimentos e Lesões/patologia , Catecolaminas/sangue , Tosse , Deglutição , Embolia/patologia , Exsanguinação/patologia , Hemorragia/patologia , Humanos , Imuno-Histoquímica , Insulina/sangue , Absorção Intestinal , Isquemia/patologia , Pneumotórax/patologia , Proteínas/metabolismo , Enfisema Pulmonar/patologia , Ventilação Pulmonar , Púrpura/patologia , Aspiração Respiratória/patologia , Salivação
4.
EBioMedicine ; 46: 305-316, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383554

RESUMO

BACKGROUND: Cigarette smoke is the main risk factor of pulmonary emphysema development, which is characterized by alveolar wall destruction. Mitochondria are important for alveolar type II (ATII) cell metabolism due to ATP generation. METHODS: We isolated ATII cells from control non-smoker and smoker organ donors, and after lung transplant of patients with emphysema to determine mitochondrial function, dynamics and mitochondrial (mt) DNA damage. FINDINGS: We found high mitochondrial superoxide generation and mtDNA damage in ATII cells in emphysema. This correlated with decreased mtDNA amount. We also detected high TOP1-cc and low TDP1 levels in mitochondria in ATII cells in emphysema. This contributed to the decreased resolution of TOP1-cc leading to accumulation of mtDNA damage and mitochondrial dysfunction. Moreover, we used lung tissue obtained from areas with mild and severe emphysema from the same patients. We found a correlation between the impaired fusion and fission as indicated by low MFN1, OPA1, FIS1, and p-DRP1 levels and this disease severity. We detected lower TDP1 expression in severe compared to mild emphysema. INTERPRETATION: We found high DNA damage and impairment of DNA damage repair in mitochondria in ATII cells isolated from emphysema patients, which contribute to abnormal mitochondrial dynamics. Our findings provide molecular mechanisms of mitochondrial dysfunction in this disease. FUND: This work was supported by National Institutes of Health (NIH) grant R01 HL118171 (B.K.) and the Catalyst Award from the American Lung Association (K.B.).


Assuntos
Células Epiteliais Alveolares/metabolismo , Mitocôndrias/metabolismo , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/metabolismo , Trifosfato de Adenosina/biossíntese , Dano ao DNA , DNA Mitocondrial , Progressão da Doença , Metabolismo Energético , Humanos , Mitocôndrias/genética , Estresse Oxidativo , Diester Fosfórico Hidrolases/metabolismo , Transporte Proteico , Enfisema Pulmonar/patologia , Espécies Reativas de Oxigênio/metabolismo , Fumaça/efeitos adversos , Superóxidos/metabolismo
5.
EBioMedicine ; 45: 563-577, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31278070

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and/or obstructive bronchiolitis. Deficiency in vitamin D3 (VD3), which regulates gene expression through binding to vitamin D receptor (VDR), is associated with high risks of COPD susceptibility. Alveolar macrophages (AM), which are generated during early ontogeny and maintained in alveoli by self-renewal in response to cytokine GM-CSF, are positively correlated with severity of emphysema. However, whether and how VD3, VDR and AM interact to contribute to COPD pathogenesis at the molecular and cellular levels are largely unknown. METHODS: We used systems biology approaches to analyze gene expression in mouse macrophages from different tissues to identify key transcription factors (TF) for AM and infer COPD disease genes. We used RNA-seq and ChIP-seq to identify genes that are regulated by VD3 in AM. We used VDR-deficient (Vdr-/-) mice to investigate the role of VD3-VDR axis in the pathogenesis of COPD and characterized the transcriptional and functional alterations of Vdr-/- AM. FINDINGS: We find that VDR is a key TF for AM and a COPD disease gene. VDR is highly expressed in AM and in response to VD3 inhibits GM-CSF-induced AM proliferation. In Vdr-/- AM, genes involved in proliferation and immune response are upregulated. Consistently, Vdr-/- mice progressively accumulate AM and concomitantly develop emphysema without apparent infiltration of immune cells into the lung tissue. Intratracheal transfer of Vdr-/- AM into wildtype mice readily induces emphysema. The production of reactive oxygen species at basal level and in response to heme or lipopolysaccharide is elevated in Vdr-/- AM and suppressed by VD3 in wildtype AM. INTERPRETATION: These results show that the VD3-VDR axis is critical to counteract GM-CSF-induced AM proliferation and defect in this regulation leads to altered AM homeostasis and function. Our findings identify that VD3 deficiency contributes to emphysema by altering AM function without contributing to bronchiolitis. Our findings also suggest possibilities of modulating the VD3-VDR axis for inhibiting emphysema in COPD patients.


Assuntos
Colecalciferol/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Receptores de Calcitriol/genética , Animais , Proliferação de Células/genética , Regulação da Expressão Gênica/genética , Homeostase/genética , Humanos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Camundongos , Ligação Proteica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/patologia , Espécies Reativas de Oxigênio/metabolismo , Análise de Sequência de RNA , Transdução de Sinais
6.
J Pharmacol Sci ; 140(2): 113-119, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31248767

RESUMO

Pulmonary emphysema, inflammation and senescence-like phenotype are pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Recently, a murine model of COPD has been established by inducing airway-specific overexpression of epithelial Na+ channel ß subunit (ßENaC-Tg mice). However, little is known about the histological and biochemical differences between ßENaC-Tg mice and an existing acute emphysematous mouse model (elastase-induced model). Here, we first utilized whole lung image-based quantification method for histological analysis to determine auto-measure parameters, including alveolar area, alveolar perimeter, (major axis + minor axis)/2 and Feret diameter. Even though the extent of emphysema was similar in both models, the coefficient of variation (CV) of all histological parameters was smaller in ßENaC-Tg mice, indicating that ßENaC-Tg mice show homogeneous emphysema as compared with elastase-induced acute model. Expression analysis of lung tissue RNAs further revealed that elastase-induced model exhibits transient changes of inflammation markers (Kc, Il-6, Lcn2) and senescence-related markers (Sirt1, p21) at emphysema-initiation stage (1 day), which does not last until emphysema-manifestation stage (3 weeks); while the up-regulation is stable at emphysema-manifestation stage in ßENaC-Tg mice (14-week old). Thus, these studies demonstrate that ßENaC-Tg mice exhibit diffuse-type emphysema with stable expression of inflammatory and senescence-like markers.


Assuntos
Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Transcriptoma/genética , Envelhecimento/genética , Animais , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Modelos Animais de Doenças , Canais Epiteliais de Sódio/genética , Feminino , Mediadores da Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipocalina-2/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/patologia , Sirtuína 1/genética , Sirtuína 1/metabolismo
7.
Rev Mal Respir ; 36(5): 638-642, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-31202604

RESUMO

INTRODUCTION: Lung volume reduction can be effective in appropriately selected patients with severe emphysema and is associated with reduced breathlessness and improved survival. Spontaneous resolution of emphysematous bullae can also sometimes occur. CASE REPORT: We report a case of severe smoking-related emphysema in a 60-year-old patient, who presented in October 2013 with a right upper lobe acute community-acquired pneumonia on the background of previously undocumented emphysema. The patient improved following treatment with co-amoxiclav and serial radiology showed progressive cicatricial retraction. Nine months later there had been a major functional improvement characterized by a complete normalization of the patient's ventilatory parameters, specifically a 45% improvement in FEV1. In the literature, the average FEV1 improvement obtained by surgical or endoscopic lung volume reduction techniques does not exceed 28%. CONCLUSION: Rarely, emphysematous bullae resolve following infections. Further studies of the mechanisms involved in these natural regressions may be of interest in the development of new therapeutics.


Assuntos
Pneumonia Associada a Assistência à Saúde/complicações , Pneumonia Associada a Assistência à Saúde/patologia , Pulmão/patologia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/patologia , Doença Aguda , Broncoscopia/métodos , Volume Expiratório Forçado , Pneumonia Associada a Assistência à Saúde/diagnóstico , Pneumonia Associada a Assistência à Saúde/cirurgia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pneumonectomia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/cirurgia , Testes de Função Respiratória , Fumantes
8.
Dis Model Mech ; 12(5)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31036697

RESUMO

Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that predominantly affects male smokers or ex-smokers and it has a mortality rate of 55% and a median survival of 5 years. Pulmonary hypertension (PH) is a frequently fatal complication of CPFE. Despite this dismal prognosis, no curative therapies exist for patients with CPFE outside of lung transplantation and no therapies are recommended to treat PH. This highlights the need to develop novel treatment approaches for CPFE. Studies from our group have demonstrated that both adenosine and its receptor ADORA2B are elevated in chronic lung diseases. Activation of ADORA2B leads to elevated levels of hyaluronan synthases (HAS) and increased hyaluronan, a glycosaminoglycan that contributes to chronic lung injury. We hypothesize that ADORA2B and hyaluronan contribute to CPFE. Using isolated CPFE lung tissue, we characterized expression levels of ADORA2B and HAS. Next, using a unique mouse model of experimental lung injury that replicates features of CPFE, namely airspace enlargement, PH and fibrotic deposition, we investigated whether 4MU, a HAS inhibitor, was able to inhibit features of CPFE. Increased protein levels of ADORA2B and HAS3 were detected in CPFE and in our experimental model of CPFE. Treatment with 4MU was able to attenuate PH and fibrosis but not airspace enlargement. This was accompanied by a reduction of HAS3-positive macrophages. We have generated pre-clinical data demonstrating the capacity of 4MU, an FDA-approved drug, to attenuate features of CPFE in an experimental model of chronic lung injury.This article has an associated First Person interview with the first author of the paper.


Assuntos
Adenosina/efeitos adversos , Ácido Hialurônico/efeitos adversos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/patologia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/patologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Adenosina Desaminase/metabolismo , Animais , Linhagem Celular , Doença Crônica , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Humanos , Hialuronan Sintases/metabolismo , Lesão Pulmonar/complicações , Lesão Pulmonar/patologia , Macrófagos/metabolismo , Camundongos , Receptor A2B de Adenosina/metabolismo
9.
Mol Cell Biochem ; 457(1-2): 41-49, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30993494

RESUMO

In our previous study, we have shown that PARP-1 inhibition (genetic or pharmacological) ameliorates elastase-induced inflammation and emphysema. Since matrix metalloproteinases (MMPs) particularly MMP-2 and MMP-9 are known to play a critical role in emphysema development, the present work was designed to evaluate the effects of PARP-1 inhibition on their expression utilizing elastase-induced mouse model of emphysema. Our data show that olaparib administration at a dose of 5 mg/kg b.wt. (daily) significantly prevented the elastase-induced inflammation as indicated by decreased inflammatory cells particularly macrophages in BALF at 1 week post-injury. In addition, the drug restored the altered redox balance in the lungs of elastase-treated mice toward normal. Further, PCR data show that olaparib administration ameliorates the elastase-induced expression of MMP-2 and MMP-9 without having much effect on the expressions of their inhibitors TIMP-1 and TIMP-2. Next, our data on immunoblot, gelatin zymography, and immunohistochemical analysis indeed confirm that olaparib reduced the elastase-induced expression of MMP-2 and MMP-9. Reduction in the expression of metalloproteinases correlate well with the PARP activity as olaparib treatment suppressed the elastase-induced expression of PAR modified proteins markedly. Overall, our data strongly suggest that PARP-1 inhibition blunts elastase-induced MMP-2 and MMP-9 expression, which may be partly responsible for prevention of emphysema.


Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Elastase Pancreática/toxicidade , Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Enfisema Pulmonar/prevenção & controle , Animais , Modelos Animais de Doenças , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologia , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Inibidor Tecidual de Metaloproteinase-2/biossíntese
10.
PLoS One ; 14(3): e0213990, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30883575

RESUMO

OBJECTIVES: To evaluate frequency and severity of complications after CT-guided lung biopsy using the Society of Interventional Radiology (SIR) classification, and to assess risk factors for overall and major complications. MATERIALS AND METHODS: 311 consecutive biopsies with a non-coaxial semi-automated 18 gauge biopsy system were retrospectively evaluated. Complications after biopsy were classified into minor SIR1-2 and major SIR3-6. Studied risk factors for complications were patient-related (age, sex and underlying emphysema), lesion-related (size, location, morphologic characteristic, depth from the pleura and histopathology), and technique-related (patient position during procedure, thoracic wall thickness at needle path, procedure time length and number of procedural CT images, number of pleural passes, fissure penetration and needle-to-blood vessel angle). Data were analyzed using logistic and ordinal regression. RESULTS: Complications were pneumothorax and pulmonary hemorrhage. The complications were minor SIR1-2 in 142 patients (45.6%), and major SIR3-4 in 25 patients (8%). SIR5-6 complications were not present. Emphysema, smaller deeply located lesion, increased puncture time length and number of procedural CT images, multiple pleural passes and fissure puncture were significant risk factors for complication severity in univariate analysis. Emphysema (OR = 8.8, p<0.001), lesion depth from the pleura (OR = 1.9 per cm, p<0.001), and fissure puncture (OR = 9.4, p = 0.01) were the independent factors for major complications in a multiple logistic regression model. No statistical difference of complication rates between the radiologists performing biopsies was observed. CONCLUSIONS: Knowledge about risk factors influencing complication severity is important for planning and performing CT-guided lung biopsies.


Assuntos
Biópsia Guiada por Imagem/efeitos adversos , Pulmão/patologia , Feminino , Hemorragia/etiologia , Humanos , Biópsia Guiada por Imagem/instrumentação , Pulmão/diagnóstico por imagem , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/patologia , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
11.
Int J Mol Sci ; 20(5)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836679

RESUMO

In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD). The pathological mechanisms linking MS and COPD are largely unknown. It remains unclear whether the effect of MS (possible obesity) has a major impact on the progression of COPD. This complicates the development of effective approaches for the treatment of patients with a diagnosis of MS and COPD. Experiments were performed on female C57BL/6 mice. Introduction of monosodium glutamate and extract of cigarette smoke was modeled to simulate the combined pathology of lipid disorders and emphysema. Biological effects of glucagon-like peptide 1 (GLP-1) and GLP-1 on endothelial progenitor cells (EPC) in vitro and in vivo were evaluated. Histological, immunohistochemical methods, biochemical methods, cytometric analysis of markers identifying EPC were used in the study. The CD31⁺ endothelial cells in vitro evaluation was produced by Flow Cytometry and Image Processing of each well with a Cytation™ 3. GLP-1 reduces the area of emphysema and increases the number of CD31⁺ endothelial cells in the lungs of mice in conditions of dyslipidemia and damage to alveolar tissue of cigarette smoke extract. The regenerative effects of GLP-1 are caused by a decrease in inflammation, a positive effect on lipid metabolism and glucose metabolism. EPC are proposed as pathogenetic and diagnostic markers of endothelial disorders in combination of MS with COPD. Based on GLP-1, it is proposed to create a drug to stimulate the regeneration of endothelium damaged in MS and COPD.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/genética , Síndrome Metabólica/genética , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Animais , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Células Progenitoras Endoteliais/metabolismo , Citometria de Fluxo , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos/genética , Pulmão/efeitos dos fármacos , Pulmão/patologia , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/tratamento farmacológico , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/patologia , Glutamato de Sódio/toxicidade
12.
Respir Res ; 20(1): 49, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832670

RESUMO

Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathological changes are not complete. In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation. We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations. We discuss the need to specifically target SAD to attenuate the progression of COPD.


Assuntos
Remodelação das Vias Aéreas/fisiologia , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/patologia , Animais , Previsões , Humanos , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/patologia , Pulmão/imunologia , Pulmão/patologia , Muco/efeitos dos fármacos , Muco/imunologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/imunologia , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/imunologia , Fumar/efeitos adversos
13.
Medicine (Baltimore) ; 98(7): e14438, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762753

RESUMO

A new method of quantitative computed tomography (CT) measurements of pulmonary vessels are applicable to morphological studies and may be helpful in defining the progression of emphysema in smokers. However, limited data are available on the relationship between the smoking status and pulmonary vessels alteration established in longitudinal observations. Therefore, we investigated the change of pulmonary vessels on CTs in a longitudinal cohort of smokers.Chest CTs were available for 287 current smokers, 439 non-smokers, and 80 former smokers who quit smoking at least 2 years after the baseline CT. CT images obtained at the baseline and 1 year later were assessed by a new quantitative CT measurement method, computing the total number of pulmonary vessels (TNV), mean lung density (MLD), and the percentage of low-attenuation areas at a threshold of -950 (density attenuation area [LAA]%950). Analysis of variance (ANOVA) and the independent sample t test were used to estimate the influence of the baseline parameters. The t paired test was employed to evaluate the change between the baseline and follow-up results.The current smokers related to have higher whole-lung MLD, as well as less and lower TNV values than the non-smokers (P <.05). But no significant differences in LAA%950 were found between smokers and non-smokers. After one year, the increase in LAA%950 was more rapid in the current (additional 0.3% per year, P <. 05-.01) than in the former smokers (additional 0.2% per year, P = .3). Additionally, the decline in TNV was faster in the current (additional -1.3 per year, P <.05-.01) than that in the former smokers (additional -0.2 per year, P = .6). Current smoke, pack-years, weight, and lung volume independently predicted TNV at baseline (P <.001) in multivariate analysis.The findings of this study reveal that the decline in the pulmonary vessels in smokers can be measured and related to their smoking status.


Assuntos
Pulmão/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Fumar/patologia , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adulto , Idoso , Progressão da Doença , Seguimentos , Humanos , Estudos Longitudinais , Pulmão/irrigação sanguínea , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/patologia , Veias Pulmonares/patologia , Fumar/efeitos adversos , Abandono do Hábito de Fumar , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos
14.
Histopathology ; 74(7): 1103-1108, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30715748

RESUMO

AIMS: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that results from tobacco smoking. Emphysema and fibrosis in CPFE patients have been considered to exist separately, with emphysema in the upper lobes and interstitial pneumonia in the lower lobes. The aim of this study was to examine the intrapulmonary distribution of fibrosis and emphysema in clinically diagnosed patients with idiopathic pulmonary fibrosis (IPF) and coexisting emphysema. METHODS AND RESULTS: Among IPF patients (n = 40) who had been autopsied or pneumonectomised for lung transplantation from 1993 to 2018, we retrospectively selected patients with IPF and coexisting emphysema (n = 19) on the basis of the appearance on chest computed tomography (IPF patients with emphysema). We then histologically determined the intrapulmonary distribution of emphysema and fibrosis in the upper lobes and the lower lobes separately. In 15 of the 19 IPF patients with emphysema (79%), fibrosis and emphysema coexisted in the upper lobes and the lower lobes. No patients showed emphysema exclusively in the upper lobes and fibrosis exclusively in the lower lobes. CONCLUSIONS: In the autopsied and pneumonectomised specimens of IPF patients with emphysema, craniocaudal separation of emphysema and fibrosis (emphysema in the upper lobes and interstitial pneumonia in the lower lobes) was histologically rare; coexistence or collision of fibrosis and emphysema in each lobe was common.


Assuntos
Fibrose Pulmonar Idiopática/patologia , Enfisema Pulmonar/patologia , Fumar Tabaco/patologia , Autopsia , Humanos , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/patologia , Transplante de Pulmão , Registros Médicos , Pneumonectomia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Fumar Tabaco/efeitos adversos , Tomografia Computadorizada por Raios X
15.
Ann Diagn Pathol ; 39: 78-85, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30798075

RESUMO

Pulmonary malformations are rare disorders, with cystic and pseudocystic pulmonary malformations (CPPM) the most frequent, and constitute the first cause of lobectomy in children <1 year of age. Morphological overlap of congenital cystic pulmonary lesions might correspond to a spectrum of lesions in which bronchial atresia is a common etiopathogenetic mechanism. We aimed to report the frequency of CPPM resected in a tertiary-level hospital and to evaluate the degree of agreement between presurgical and anatomopathological diagnoses. We studied 44 surgical pieces with a diagnosis of CPPM received at the Pathology Service from 2009 to 2014, resected from 39 patients, 51.3 % males, with a median age of 16.8 months. Up to 69.2% of the patients had adenomatoid malformation of pulmonary airway (AMPA), with type 2 the most frequent (55.5%). Pulmonary sequestration was present in 15.4% of patients; in two cases the diagnosis was an incidental finding during surgery for the repair of a diaphragmatic hernia. Congenital lobar hyperinflation (CLH) occurred in 7.6% cases. Bronchogenic cyst (BC) was present in 7.6% cases. Presurgical and anatomopathological diagnoses in all patients coincided in 71.8% of cases. Kappa coefficient was 0.56 for global concordance in patients with AMPA, and 0.72, 0.64, 0.37 and 0.33 for CLH, BC, and types 1 and 2 AMPA, respectively. This relatively low interobserver agreement could reflect the low reproducibility of diagnoses used in the current nomenclature. Thus, the new nomenclature must be promoted in order to allow for better reproducibility and greater clinico-pathological concordance. The anatomopathological analysis must include the intentional search for bronchial atresia.


Assuntos
Procedimentos Cirúrgicos Pulmonares/métodos , Anormalidades do Sistema Respiratório/diagnóstico , Anormalidades do Sistema Respiratório/cirurgia , Adolescente , Cisto Broncogênico/diagnóstico , Cisto Broncogênico/patologia , Cisto Broncogênico/cirurgia , Sequestro Broncopulmonar/diagnóstico , Sequestro Broncopulmonar/patologia , Sequestro Broncopulmonar/cirurgia , Criança , Pré-Escolar , Estudos Transversais , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico , Malformação Adenomatoide Cística Congênita do Pulmão/patologia , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Variações Dependentes do Observador , Enfisema Pulmonar/congênito , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/patologia , Enfisema Pulmonar/cirurgia , Anormalidades do Sistema Respiratório/patologia , Estudos Retrospectivos , Centros de Atenção Terciária
16.
Am J Physiol Lung Cell Mol Physiol ; 316(4): L608-L620, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30675803

RESUMO

Deterioration of lung functions and degradation of elastin fibers with age are accelerated during chronic obstructive pulmonary disease (COPD). Excessive genesis of soluble elastin peptides (EP) is a key factor in the pathophysiology of COPD. We have previously demonstrated that 6-wk-old mice exhibited emphysematous structural changes associated with proinflammatory immune response after EP instillation. In this study, we investigated the consequences of aging on inflammatory, immune, and histological criteria associated with murine emphysema progression after EP exposure. Young (6 wk old) and elderly (15 mo old) C57BL/6J mice were endotracheally instilled with EP, and, at various time points after treatment, the inflammatory cell profiles from bronchoalveolar lavage fluids (BALF) and the T-lymphocyte phenotypes, at local and systemic levels, were analyzed by flow cytometry. Lungs were also prepared to allow morphological and histological analysis by confocal microscopy. Elderly mice exhibited an earlier development of pulmonary emphysema, characterized by an increase of the inflammatory and lymphocytic infiltrates, extracellular matrix breakdown, and airspace enlargement compared with young mice. This age-dependent parenchymal tissue remodeling was associated with an increase of the matrix metalloproteinase expressions and desmosine levels in BALF and/or sera of EP-treated mice. In addition, both the proportion of CD4+CD28- and CD8+CD28- T cells in the tissues of EP-treated mice and the interferon-γ levels in the EP-specific memory T-cell clones were significantly higher in elderly versus younger mice. This study demonstrates that aging accelerates emphysema development and that this effect is linked to increased EP production and their effects on inflammatory and immune response.


Assuntos
Envelhecimento/imunologia , Envelhecimento/patologia , Enfisema Pulmonar/imunologia , Enfisema Pulmonar/patologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Desmosina/metabolismo , Modelos Animais de Doenças , Elastina/administração & dosagem , Elastina/metabolismo , Feminino , Inflamação/imunologia , Inflamação/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/patologia , Proteólise , Enfisema Pulmonar/etiologia
17.
Biomarkers ; 24(3): 232-239, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30411980

RESUMO

Background: The aetiology and inflammatory profile of combined pulmonary fibrosis and emphysema (CPFE) remain uncertain currently. Objective: We aimed to examine the levels of inflammatory proteins in lung tissue in a cohort of patients with emphysema, interstitial pulmonary fibrosis (IPF), and CPFE. Materials and methods: Explanted lungs were obtained from subjects with emphysema, IPF, CPFE, (or normal subjects), and tissue extracts were prepared. Thirty-four inflammatory proteins were measured in each tissue section. Results: The levels of all 34 proteins were virtually indistinguishable in IPF compared with CPFE tissues, and collectively, the inflammatory profile in the emphysematous tissues were distinct from IPF and CPFE. Moreover, inflammatory protein levels were independent of the severity of the level of diseased tissue. Conclusions: We find that emphysematous lung tissues have a distinct inflammatory profile compared with either IPF or CPFE. However, the inflammatory profile in CPFE lungs is essentially identical to lungs from patients with IPF. These data suggest that distinct inflammatory processes collectively contribute to the disease processes in patients with emphysema, when compared to IPF and CPFE.


Assuntos
Inflamação/genética , Proteínas/genética , Enfisema Pulmonar/genética , Fibrose Pulmonar/genética , Idoso , Humanos , Inflamação/complicações , Inflamação/diagnóstico por imagem , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Mucina-5B/genética , Polimorfismo de Nucleotídeo Único , Enfisema Pulmonar/complicações , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Tomografia Computadorizada por Raios X
18.
Clin Imaging ; 53: 115-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30340073

RESUMO

OBJECTIVES: The aim of this study was to investigate the extent of dose reduction and comparability of standard dose CT vs Ultra low dose CT in evaluating pulmonary emphysema. METHODS: Forty-nine patients with emphysema were recruited from a tertiary referral respiratory clinic. Each patient had a non-contrast Standard Dose (SD) and Ultra Low Dose (ULD) thoracic CT. The images were reconstructed using contemporary iterative reconstruction with a standard lung kernel. Lung volumes and emphysema severity was calculated using a commercially available automated densitometry segmentation package. The effective dose was calculated for both CT protocols. RESULTS: Automated densitometry calculated the total lung volume and percentage lung area of emphysema. The findings were highly comparable between ULD and SD protocols. A strong correlation was seen between ULD and SD images in measurement of total lung volume (R = 0.925, p < 0.001) and percentage lung involvement by densitometry (R = 0.940, p < 0.001). There is a 95% dose reduction with the ULD protocol, the mean effective dose is 0.12 ±â€¯0.09 mSv versus 2.33 ±â€¯1.54 mSv for the SD protocol. CONCLUSIONS: ULD thoracic CT is a comparable protocol for the assessment of emphysema severity relative to standard dose CT. ULD CT is performed at a 95% dose reduction compared to SD CT.


Assuntos
Pulmão/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Doses de Radiação , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/patologia , Tórax/diagnóstico por imagem , Tórax/patologia
19.
Chest ; 155(2): 266-271, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30080996

RESUMO

Developing an effective treatment for COPD, and especially pulmonary emphysema, will require an understanding of how fundamental changes at the molecular level affect the macroscopic structure of the lung. Currently, there is no accepted model that encompasses the biochemical and mechanical processes responsible for pulmonary airspace enlargement. We propose that pulmonary emphysematous changes may be more accurately described as an emergent phenomenon, involving alterations at the molecular level that eventually reach a critical structural threshold where uneven mechanical forces produce alveolar wall rupture, accompanied by advanced clinical signs of COPD. The coupling of emergent morphologic changes with biomarkers to detect the process, and counteract it therapeutically, represents a practical approach to the disease.


Assuntos
Broncodilatadores/uso terapêutico , Alvéolos Pulmonares/parasitologia , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Alvéolos Pulmonares/ultraestrutura , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Enfisema Pulmonar/patologia , Enfisema Pulmonar/fisiopatologia , Medição de Risco , Resultado do Tratamento
20.
Early Hum Dev ; 128: 77-80, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30583279

RESUMO

INTRODUCTION: Congenital cystic adenomatoid malformation (CCAM), especially type-III, shares similar sonographic features with congenital lobar emphysema (CLE) in routine ultrasound scan. Thus, prenatal differentiation of CLE from a microcystic CCAM is challenging and difficult in practice. Discovery of molecular biomarkers has important clinical significance. METHODS: We profiled gene expression in lung tissue from four CCAM type-III and five CLE subjects by microarray. A bioinformatic tool was used for signal pathways enrichment analysis. Further, quantitative reverse transcriptase PCR (qRT-PCR) was used to verify the results. RESULTS: A total of 426 genes were identified to be significantly differentially expressed (fold-change >2.0, q value <0.05) between microcystic CCAM and CLE. Of these differentially expressed genes (DEGs), 392 were upregulated and 34 were downregulated in microcystic CCAM compared with CLE. Unsupervised clustering of the "expressed" genes could clearly delineate the CCAM and CLE samples. We also confirmed that eight randomly chose genes were differentially expressed at the mRNA level between CCAM and CLE. CONCLUSIONS: CCAM type-III and CLE have differential gene expression patterns. Our pilot study may gain a deeper understanding of the organogenetic origins and pathogenesis of these conditions. The suggestive candidates may serve as potential biomarkers for definitive diagnosis of congenital cystic lung lesions and eventually to treat them appropriately.


Assuntos
Malformação Adenomatoide Cística Congênita do Pulmão/genética , Enfisema Pulmonar/congênito , Transcriptoma , Biomarcadores/metabolismo , Malformação Adenomatoide Cística Congênita do Pulmão/metabolismo , Malformação Adenomatoide Cística Congênita do Pulmão/patologia , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Masculino , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologia
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