RESUMO
Introdução: A esclerose sistêmica (ES) é uma doença autoimune do tecido conjuntivo que cursa com fibrose e disfunção microvascular. O envolvimento dos órgãos viscerais, incluindo os pulmões e o coração, é a principal causa de óbito na ES. Nesse contexto, analisamos a relação entre os parâmetros ventriculares direitos (VD) pela ecocardiografia com Doppler tecidual e o acometimento pulmonar em pacientes com ES. Métodos: Os pacientes que preencheram os Critérios de Classificação da ES de 2013 foram submetidos à ecocardiografia com Doppler tecidual para avaliação da função sistólica (fração de ejeção) ventricular esquerda (VE), enquanto a função sistólica do VD foi avaliada por meio da fração de variação de área do VD (fractional area change FAC), velocidade (sistólica) do Doppler tecidual, índice de desempenho miocárdico (IDM) e excursão sistólica do plano anular tricúspide (TAPSE). A pressão sistólica pulmonar foi estimada por insuficiência tricúspide. A tomografia computadorizada de alta resolução (TCAR) de tórax avaliou a presença de fibrose pulmonar. De acordo com os resultados da TCAR, os pacientes foram divididos em 2 subgrupos: Grupo I, incluindo pacientes com fibrose pulmonar (n=26), e Grupo II sem fibrose (n=17). Resultados: Entre os 43 pacientes com ES, a maioria era do sexo feminino (86%) com idade de 51±12 anos. Todos os pacientes apresentavam função ventricular sistólica normal, avaliada pela FEVE>55% e FAC VD>35%. Não houve diferença significativa em termos de idade ou duração da doença para os grupos. Exceto pela diminuição das velocidades do Doppler tecidual em pacientes com fibrose pulmonar, todos os índices de desempenho do VD foram semelhantes. Conclusão: Em pacientes com ES e fibrose pulmonar, o Doppler tecidual identifica acometimento miocárdico longitudinal precoce do VD, apesar do desempenho sistólico radial preservado do VD.(AU)
Introduction: Systemic sclerosis (SSc) is an autoimmune tissue connective disease that courses with fibrosis and microvascular dysfunction. Involvement of the visceral organs, including the lungs and heart, is the main cause of death among patients with SSc. In this context, here we analyzed the relationship between right ventricle (RV) parameters assessed by tissue Doppler echocardiography and lung involvement in patients with SSc. Methods: Patients fulfilling the 2013 SSc Classification Criteria underwent tissue Doppler echocardiography for the assessment of left ventricular (LV) systolic function (ejection fraction) and RV fractional area change (FAC), tissue Doppler s' (systolic) velocity, myocardial performance index, and tricuspid annular plane systolic excursion for the assessment of RV systolic function. Pulmonary systolic pressure was estimated using tricuspid regurgitation. Chest high-resolution computed tomography was used to evaluate the presence of pulmonary fibrosis. The patients were divided into two subgroups accordingly: Group I, patients with pulmonary fibrosis (n=26); and Group II, those without fibrosis (n=17). Results: Among the 43 patients with SSc, most were female (86%), and the mean age was 51 ± 12 years. All patients had normal systolic ventricular function as evidenced by an LV ejection fraction > 55% and an RV FAC > 35%. No significant intergroup difference was noted in age or disease duration. Except for a decreased tissue Doppler s' velocity in patients with lung fibrosis, all indexes of RV performance were similar. Conclusion: In patients with SSc and pulmonary fibrosis, tissue Doppler identified early RV longitudinal myocardial involvement despite preserved RV radial systolic performance.(AU)
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Fibrose Pulmonar/complicações , Escleroderma Sistêmico/diagnóstico , Função Ventricular Direita , Doenças Pulmonares Intersticiais/diagnóstico , Tórax/diagnóstico por imagem , Insuficiência da Valva Tricúspide/complicações , Ecocardiografia Doppler/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. There is evidence that TGF-ß is intimately involved in the fibrogenic process. When activated, TGF-ß promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-ß1 tissue expression) involved in the TGF-ß1 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-ß1 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-ß pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-ß inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.
Assuntos
COVID-19/metabolismo , Fibrose Pulmonar/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Actinas/metabolismo , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/complicações , COVID-19/patologia , Caveolina 1/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/metabolismo , Influenza Humana/patologia , Interleucina-4/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Estudos Retrospectivos , Fator de Crescimento Transformador beta1/metabolismo , Tratamento Farmacológico da COVID-19RESUMO
Although pulmonary fibrosis can occur in the absence of a clear-cut inciting agent, and without a clinically clear initial acute inflammatory phase, it is more commonly associated with severe lung injury. This may be due to respiratory infections, chronic granulomatous diseases, medications, and connective tissue disorders. Pulmonary fibrosis is associated with permanent pulmonary architectural distortion and irreversible lung dysfunction. Available clinical, radiographic, and autopsy data has indicated that pulmonary fibrosis is central to severe acute respiratory distress syndrome (SARS) and MERS pathology, and current evidence suggests that pulmonary fibrosis could also complicate infection by SARS-CoV-2. The aim of this review is to explore the current literature on the pathogenesis of lung injury in COVID-19 infection. We evaluate the evidence in support of the putative risk factors for the development of lung fibrosis in the disease and propose risk mitigation strategies. We conclude that, from the available literature, the predictors of pulmonary fibrosis in COVID-19 infection are advanced age, illness severity, length of ICU stay and mechanical ventilation, smoking and chronic alcoholism. With no proven effective targeted therapy against pulmonary fibrosis, risk reduction measures should be directed at limiting the severity of the disease and protecting the lungs from other incidental injuries.
Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Fibrose Pulmonar/complicações , Comportamento de Redução do Risco , Sobreviventes/estatística & dados numéricos , Fatores Etários , Alcoolismo/complicações , COVID-19 , Humanos , Tempo de Internação/estatística & dados numéricos , Pandemias , Respiração Artificial/efeitos adversos , Respiração Artificial/estatística & dados numéricos , SARS-CoV-2 , Índice de Gravidade de Doença , Tabagismo/complicaçõesRESUMO
Abstract The heart and lung are target organs in systemic sclerosis (SSc) and similar symptoms (dyspnea and cough) may make the differential diagnosis between the two lesions difficult. In addition, complete atrioventricular block (CAVB) is a rare complication of this disease. This case report is about a patient with SSc and pulmonary fibrosis who was admitted to the emergency room with CAVB, heart failure (HF) and progressive worsening of the underlying disease.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/complicações , Esclerodermia Difusa/complicações , Bloqueio Atrioventricular/complicações , Fibrose Pulmonar/diagnóstico , Tosse , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/tratamento farmacológico , Diagnóstico Precoce , Diagnóstico Diferencial , Dispneia , Bloqueio Atrioventricular/diagnóstico , Hipertensão PulmonarRESUMO
Ascariasis is considered the most neglected tropical disease, and is a major problem for the public health system. However, idiopathic pulmonary fibrosis (IPF) is a result of chronic extracellular deposition of matrix in the pulmonary parenchyma, and thickening of the alveolar septa, which reduces alveolar gas exchange. Considering the high rates of ascariasis and pulmonary fibrosis, we believe that these two diseases may co-exist and possibly lead to comorbidities. We therefore investigated the mechanisms involved in comorbidity of Ascaris suum (A. suum) infection, which could interfere with the progression of pulmonary fibrosis. In addition, we evaluated whether a previous lung fibrosis could interfere with the pulmonary cycle of A. suum in mice. The most important findings related to comorbidity in which A. suum infection exacerbated pulmonary and liver injury, inflammation and dysfunction, but did not promote excessive fibrosis in mice during the investigated comorbidity period. Interestingly, we found that pulmonary fibrosis did not alter the parasite cycle that transmigrated preferentially through preserved but not fibrotic areas of the lungs. Collectively, our results demonstrate that A. suum infection leads to comorbidity, and contributes to the aggravation of pulmonary dysfunction during pulmonary fibrosis, which also leads to significant liver injury and inflammation, without changing the A. suum cycle in the lungs.
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Ascaríase/complicações , Ascaríase/patologia , Hepatopatias/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , Animais , Ascaris suum/isolamento & purificação , Modelos Animais de Doenças , Feminino , Inflamação/patologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos Endogâmicos C57BLRESUMO
Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis.
Assuntos
Bleomicina , Modelos Animais de Doenças , Hepatopatias/etiologia , Fibrose Pulmonar/complicações , Actinas/metabolismo , Animais , Antígenos CD1/metabolismo , Colágeno/metabolismo , Antígeno Ki-67/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Escleroderma Sistêmico , Pele/efeitos dos fármacos , Pele/patologiaRESUMO
Ultrasound (US) is increasing its potential in the assessment of several rheumatic disorders. Recently, different applications of this imaging technique have emerged. Interesting data supporting its utility and validity in the assessment of the lung to detect and quantify interstitial pulmonary fibrosis in rheumatic diseases, even in subclinical phases, have been reported. The main purpose of this review is to provide an overview of the role of US in the assessment of interstitial pulmonary fibrosis in rheumatic disorders and to discuss the current evidence supporting its clinical relevance in daily clinical practice.
Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Doenças Reumáticas/diagnóstico por imagem , Humanos , Doenças Pulmonares Intersticiais/complicações , Fibrose Pulmonar/complicações , Doenças Reumáticas/complicações , Avaliação de Sintomas , UltrassonografiaRESUMO
The aim of this work was to develop an innovative tool for the treatment of pulmonary fibrosis based on our previous findings, which demonstrated that intranasally administered soluble bovine hyaluronidase (HYAL) increases the numbers of mesenchymal (MSC)-like cells in the bronchoalveolar fluid (BALF) and thus reduces the bleomycin-induced fibrosis. To this end, we developed poly(D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) loaded with HYAL (HYAL-MP) to preserve the enzyme's biological activity and to facilitate its delivery to the lung. Nonloaded MPs (Control-MPs) and HYAL-MPs were prepared using the emulsion and solvent evaporation methods and thoroughly characterized. The HYAL-MPs and Control-MPs exhibited an average diameter of 4.3±2.1 and 4.4±1.5 µm, respectively. The encapsulation efficiency of the HYAL-MPs was 68%, and encapsulation led to a reduced release rate. Additionally, the HYAL-MPs were efficiently phagocytosed by J-774.1 cells. Compared with the soluble HYAL, the HYAL-MPs increased the proportion of MSC-like cells in the BALF of C57BL6 mice 96 h after treatment. The efficacy of the HYAL-MPs was also tested in C57BL6 mice that were previously exposed to 4 U/kg of bleomycin to induce lung fibrosis. The results demonstrated that the HYAL-MPs reduced neutrophil recruitment after bleomycin treatment more effectively than did the soluble HYAL, whereas the Control-MPs did not exhibit any effect. The HYAL-MPs also reduced the bleomycin-induced fibrosis more efficiently, and 134% of the collagen deposition in the lung compared with the soluble HYAL and the Control-MPs. In summary, our data indicate that HYAL-MPs are an effective delivery system that could feasibly be used in the treatment of pulmonary fibrosis.
Assuntos
Hialuronoglucosaminidase/uso terapêutico , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Fibrose Pulmonar/tratamento farmacológico , Animais , Bovinos , Contagem de Células , Linhagem Celular , Colágeno/metabolismo , Citoesqueleto/metabolismo , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Fagócitos/citologia , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Solubilidade , Eletricidade Estática , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis.
Assuntos
Enfisema Pulmonar/complicações , Fibrose Pulmonar/complicações , Progressão da Doença , Humanos , Hipertensão Pulmonar/complicações , Prognóstico , EspirometriaRESUMO
Aspiration is a common but underrecognized clinicopathologic entity, with varied radiographic manifestations. Aspiration represents a spectrum of diseases, including diffuse aspiration bronchiolitis, aspiration pneumonitis, airway obstruction by foreign body, exogenous lipoid pneumonia, interstitial fibrosis, and aspiration pneumonia with or without lung abscess formation. Many patients who aspirate do not present with disease, suggesting that pathophysiology is related to a variety of factors, including decreased levels of consciousness, dysphagia, impaired mucociliary clearance, composition of aspirate, and impaired host defenses. In this pictorial essay, we will review the different types of aspiration lung diseases, focusing on their imaging features and differential diagnosis.