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1.
Chemosphere ; 263: 128133, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297121

RESUMO

BACKGROUND: Understanding the roles of long noncoding RNAs (lncRNAs) in EMT would help with establishing novel avenues for further uncovering the mechanisms of lung fibrosis and identifying preventative and therapeutic targets. This study aimed to identify silica-induced specific lncRNAs and investigate the feedback loop regulation among their upstream and downstream genes. METHODS AND MATERIALS: A microarray assay, quantitative real-time polymerase chain reaction and Western blot analysis dual-luciferase reporter gene activity and chromatin immunoprecipitation assays were used. Moreover, a silica-induced lung fibrosis mouse model was used to verify the roles of the lncRNAs. RESULTS: Following silica exposure, both RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and p53 were significantly upregulated during the EMT. The upregulation of p53 upon silica exposure activated RMRP expression, which promoted the EMT. When RMRP is overexpressed, additional RMRP acts as a sponge to bind to miR122, thus decreasing miR122 levels. Using microarrays, miR122 was identified as a potential upstream regulator of p53. This relationship was also verified using the dual-luciferase reporter gene. Hence, decreased miR122 levels result in an increase in p53 activity. More importantly, RMRP promotes the transcription of Notch 1, which, in turn, results in Notch pathway activation. We show that the p53/RMRP/miR122 pathway creates a positive feedback loop that promotes EMT progress by activating the Notch signaling pathway. CONCLUSION: Our data indicated that p53/RMRP/miR122 feedback loop might contribute to the EMT development by activating Notch pathway, which provides new sight into understanding of the complex network regulating silica-induced lung fibrosis.


Assuntos
MicroRNAs , Fibrose Pulmonar , Animais , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Camundongos , MicroRNAs/genética , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Transdução de Sinais , Dióxido de Silício/toxicidade , Proteína Supressora de Tumor p53/genética
2.
4.
N Engl J Med ; 383(25): 2485-2486, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33326734
5.
Vnitr Lek ; 66(6): 365-370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380141

RESUMO

Familial pulmonary fibrosis (FPF) is defined as interstitial lung involvement in at least two members of the same biological family. Pathogenesis of FPF involves background of genetic risk factors further modified by environmental exposures and aging. Manifesta tion of FPF mirrors manifestation of interstitial lung diseases generally. Patients may present also with involvement of other organs, as seen usually in those affected by complex syndromes or telomeropaties. Described mutations concern telomeres homeostasis genes (TERT, TERC, RTEL1, PARN, DKC1, TINF, NAF1), surfactant genes (SFTPC, ABCA3, NFKX21) or genes associated with complex syndromes (COPA, TMEM173, HPS18, NF1, FAM111B, NDUFAF6, GATA 2). Genetic tests are indicated by specialist in clinical genetics, optimaly after consultation with respiratory specialist involved in interstitial lung diseases. Treatment of FPF is currently unknown. In patients with multiorgan involvement growing number of organs may be affected in time and sometimes dysfunction of mostly severe affected organ may manifest before interstitial lung involvement.


Assuntos
Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/terapia , Mutação
6.
Front Immunol ; 11: 556335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343561

RESUMO

Introduction: Right now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared. We need an urgent solution for the prevention, treatment, and recovery of the involved patients. Methods: Modulated electro-hyperthermia (mEHT) is known as an immuno-supportive therapy in oncology. Our proposal is to apply this method to prevent the progression of the disease after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic-often fatal-consequences of the infection. Hypothesis: The effects of mEHT, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences. The hypothesized mEHT effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.


Assuntos
/reabilitação , Terapia por Estimulação Elétrica , Hipertermia Induzida , Imunoterapia , Fibrose Pulmonar/reabilitação , /complicações , Humanos , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/etiologia
7.
Front Immunol ; 11: 590459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362771

RESUMO

Background: SARS-CoV-2 causes ongoing pandemic coronavirus disease of 2019 (COVID-19), infects the cells of the lower respiratory tract that leads to a cytokine storm in a significant number of patients resulting in severe pneumonia, shortness of breathing, respiratory and organ failure. Extensive studies suggested the role of Vitamin D in suppressing cytokine storm in COVID-19 and reducing viral infection; however, the precise molecular mechanism is not clearly known. In this work, bioinformatics and systems biology approaches were used to understand SARS-CoV-2 induced cytokine pathways and the potential mechanism of Vitamin D in suppressing cytokine storm and enhancing antiviral response. Results: This study used transcriptome data and identified 108 differentially expressed host genes (DEHGs) in SARS-CoV-2 infected normal human bronchial epithelial (NHBE) cells compared to control. Then, the DEHGs was integrated with the human protein-protein interaction data to generate a SARS-CoV-2 induced host gene regulatory network (SiHgrn). Analysis of SiHgrn identified a sub-network "Cluster 1" with the highest MCODE score, 31 up-regulated genes, and predominantly associated immune and inflammatory response. Interestingly, the iRegulone tool identified that "Cluster 1" is under the regulation of transcription factors STAT1, STAT2, STAT3, POU2F2, and NFkB1, collectively referred to as "host response signature network". Functional enrichment analysis with NDEx revealed that the "host response signature network" is predominantly associated with critical pathways, including "cytokines and inflammatory response", "non-genomic action of Vitamin D", "the human immune response to tuberculosis", and "lung fibrosis". Finally, in-depth analysis and literature mining revealed that Vitamin D binds with its receptor and could work through two different pathways: (i) it inhibits the expression of pro-inflammatory cytokines through blocking the TNF induced NFkB1 signaling pathway; and (ii) it initiates the expression of interferon-stimulating genes (ISGs) for antiviral defense program through activating the IFN-α induced Jak-STAT signaling pathway. Conclusion: This comprehensive study identified the pathways associated with cytokine storm in SARS-CoV-2 infection. The proposed underlying mechanism of Vitamin D could be promising in suppressing the cytokine storm and inducing a robust antiviral response in severe COVID-19 patients. The finding in this study urgently needs further experimental validations for the suitability of Vitamin D in combination with IFN-α to control severe COVID-19.


Assuntos
/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Biologia de Sistemas/métodos , Vitamina D/uso terapêutico , Antivirais/uso terapêutico , Citocinas/sangue , Perfilação da Expressão Gênica , Humanos , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Transcriptoma/genética
8.
Front Immunol ; 11: 585647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133104

RESUMO

Cytokine storm resulting from SARS-CoV-2 infection is one of the leading causes of acute respiratory distress syndrome (ARDS) and lung fibrosis. We investigated the effect of inflammatory molecules to identify any marker that is related to lung fibrosis in coronavirus disease 2019 (COVID-19). Seventy-six COVID-19 patients who were admitted to Youan Hospital between January 21 and March 20, 2020 and recovered were recruited for this study. Pulmonary fibrosis, represented as fibrotic volume on chest CT images, was computed by an artificial intelligence (AI)-assisted program. Plasma samples were collected from the participants shortly after admission, to measure the basal inflammatory molecules levels. At discharge, fibrosis was present in 46 (60.5%) patients whose plasma interferon-γ (IFN-γ) levels were twofold lower than those without fibrosis (p > 0.05). The multivariate-adjusted logistic regression analysis demonstrated the inverse association risk of having lung fibrosis and basal circulating IFN-γ levels with an estimate of 0.43 (p = 0.02). Per the 1-SD increase of basal IFN-γ level in circulation, the fibrosis volume decreased by 0.070% (p = 0.04) at the discharge of participants. The basal circulating IFN-γ levels were comparable with c-reactive protein in the discrimination of the occurrence of lung fibrosis among COVID-19 patients at discharge, unlike circulating IL-6 levels. In conclusion, these data indicate that decreased circulating IFN-γ is a risk factor of lung fibrosis in COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Interferon gama/sangue , Pneumonia Viral/complicações , Fibrose Pulmonar/etiologia , Idoso , Inteligência Artificial , Biomarcadores/sangue , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/imunologia , Estudos Transversais , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/imunologia , Fibrose Pulmonar/sangue , Fibrose Pulmonar/diagnóstico por imagem , Fatores de Risco , Tomografia Computadorizada por Raios X
9.
Drug Discov Ther ; 14(5): 259-261, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33116043

RESUMO

Regardless of the severity of coronavirus disease 2019 (COVID-19), a high proportion of patients struggle with persistent respiratory or systemic symptoms after recovery. This is called "postCOVID syndrome", for which pulmonary fibrosis is one of the pathogenesis. Besides T-lymphocytes and macrophages, mast cells also contribute to the development of cytokine storm and thus stimulate the activity of fibroblasts. Additionally, by the exocytotic release of fibroblast-activating factors, mast cells directly facilitate the progression of pulmonary fibrosis. In our previous basic studies, anti-allergic drugs (olopatadine, ketotifen), antibiotics (clarithromycin) and corticosteroids (hydrocortisone, dexamethasone) inhibited the process of exocytosis and showed their potency as highly effective mast cell stabilizers. Given such pharmacological properties of these commonly used drugs, they may be useful in the treatment of post-COVID-19 pulmonary fibrosis and in relieving the symptoms of post-COVID syndrome.


Assuntos
Corticosteroides/uso terapêutico , Antialérgicos/uso terapêutico , Antibacterianos/uso terapêutico , Betacoronavirus/patogenicidade , Degranulação Celular/efeitos dos fármacos , Infecções por Coronavirus/virologia , Mastócitos/efeitos dos fármacos , Pneumonia Viral/virologia , Fibrose Pulmonar/tratamento farmacológico , Animais , Infecções por Coronavirus/imunologia , Interações Hospedeiro-Patógeno , Humanos , Mastócitos/imunologia , Mastócitos/virologia , Pandemias , Pneumonia Viral/imunologia , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/virologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-33093775

RESUMO

Purpose: To evaluate the Right Upper Lobe Bronchus Angle (RUL-BA) on chest CT in patients with Stage 4 sarcoidosis and compare to others with non-fibrotic sarcoidosis. Methods: IRB approval was obtained for review of all chest CT scans performed from January 2015 through December 2017 that contained the word sarcoidosis using the computer program Montage. The most recent CT scans of 633 people were reviewed. The patients' age and sex at the time of their most recent CT scan were recorded. The radiographic diagnosis and the Right Upper Lobe Bronchus Angle (RUL-BA) were determined by a chest radiologist with 20 years of experience. Results: The RUL-BA increased with Stage 4 sarcoidosis, measuring on average 104 degrees, compared to the average angle of 88 degrees for those without fibrotic sarcoid. More often men's CT scans exhibited the earlier stages of sarcoidosis, and a higher number of women's scans showed fibrotic sarcoidosis. As would be expected, scans with advanced disease were typically from older patients; however, there was no correlation between age and degree of fibrosis as measured by increasing RUL-BA. Conclusion: The RUL-BA assists radiologists in differentiating fibrotic sarcoidosis from non-fibrotic sarcoidosis. Further research will determine if the RUL-BA measurement can help differentiate fibrotic sarcoid from other fibrotic lung diseases and if the angle can be used to follow disease progression. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 99-103).


Assuntos
Brônquios/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Adulto Jovem
11.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 231-233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093788

RESUMO

Background: A subgroup of patients with fibrotic ILD experience progression and several risk factors for ILD progression have been reported, such as male sex, older age, lower baseline pulmonary function, and a radiological or pathological pattern of usual interstitial pneumonia. Objective: To describe a possible new phenotype of rapidly non IPF progressive fibrosing with an IPF-like outcome. Methods: Three previously fit and well patients who developed a rapidly progressive ILD and died within 6 to 7 months from the initial development of respiratory symptoms. Results: Unlike what is currently known, our patients developed a severe fibrosing ILD with an IPF-like outcome despite a) being younger than the average patient with IPF, b) having received a non-IPF MDT diagnosis, c) having a non-UIP pattern on HRCT. Moreover and similarly to IPF, they failed to respond to immunosuppressive treatment which is the preferred treatment option in these cases. Conclusion: We believe that patients who present with similar characteristics should be considered as likely to develop a phenotype of rapidly progressive ILD and be treated with antifibrotic medications instead of immunosuppressive ones according to the favourable treatment response to antifibrotic therapy observed in clinical trials of patients with progressive fibrosing ILDs. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 231-233).


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Pulmão/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Adulto , Antibacterianos/uso terapêutico , Progressão da Doença , Evolução Fatal , Volume Expiratório Forçado , Humanos , Imunossupressores/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Falha de Tratamento , Capacidade Vital
12.
Sheng Li Xue Bao ; 72(5): 597-604, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33106830

RESUMO

Pulmonary fibrosis is a chronic, diffuse, interstitial lung disease involving the pulmonary interstitium, alveoli, and bronchioles caused by various causes. There is no effective treatment. Currently, exogenous bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation has attracted much attention as a new stem cell therapy in the treatment of pulmonary fibrosis. Less attention has been paid to the functional status of endogenous BM-MSCs during pulmonary fibrosis. Based on summary on the anti-pulmonary fibrosis effect of BM-MSCs and its mechanism, this review further discusses the abnormal changes of bone marrow function in animals with pulmonary fibrosis and the role of glutamate NMDA receptor overactivation in mediating the functional inhibition of endogenous BM-MSCs induced by pulmonary fibrosis. This will provide potential ideas for finding effective treatments for pulmonary fibrosis.


Assuntos
Células-Tronco Mesenquimais , Fibrose Pulmonar , Animais , Medula Óssea , Células da Medula Óssea , Transdução de Sinais
13.
Respir Res ; 21(1): 286, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126869

RESUMO

It has been recently hypothesized that infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to fibrotic sequelae in patients recovering from coronavirus disease 2019 (COVID-19). In this observational study, hospitalized patients with COVID-19 had a HRCT of the chest performed to detect the extension of fibrotic abnormalities via Hounsfield Units (HU). At follow-up, the lung density significantly improved in both lungs and in each lobe of all patients, being in the normal range (- 950 to - 700 HU). This study provides preliminary evidence that hospitalized patients with mild-to-moderate forms of COVID-19 are not at risk of developing pulmonary fibrosis.


Assuntos
Infecções por Coronavirus/complicações , Progressão da Doença , Pneumonia Viral/complicações , Fibrose Pulmonar/diagnóstico por imagem , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/terapia , Idoso , Estudos de Coortes , Terapia Combinada , Intervalos de Confiança , Infecções por Coronavirus/diagnóstico , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Estudos Prospectivos , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/patologia , Radiografia Torácica/métodos , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico
14.
Signal Transduct Target Ther ; 5(1): 235, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037188

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to respiratory illness and multi-organ failure in critically ill patients. Although the virus-induced lung damage and inflammatory cytokine storm are believed to be directly associated with coronavirus disease 2019 (COVID-19) clinical manifestations, the underlying mechanisms of virus-triggered inflammatory responses are currently unknown. Here we report that SARS-CoV-2 infection activates caspase-8 to trigger cell apoptosis and inflammatory cytokine processing in the lung epithelial cells. The processed inflammatory cytokines are released through the virus-induced necroptosis pathway. Virus-induced apoptosis, necroptosis, and inflammation activation were also observed in the lung sections of SARS-CoV-2-infected HFH4-hACE2 transgenic mouse model, a valid model for studying SARS-CoV-2 pathogenesis. Furthermore, analysis of the postmortem lung sections of fatal COVID-19 patients revealed not only apoptosis and necroptosis but also massive inflammatory cell infiltration, necrotic cell debris, and pulmonary interstitial fibrosis, typical of immune pathogenesis in the lung. The SARS-CoV-2 infection triggered a dual mode of cell death pathways and caspase-8-dependent inflammatory responses may lead to the lung damage in the COVID-19 patients. These discoveries might assist the development of therapeutic strategies to treat COVID-19.


Assuntos
Apoptose/imunologia , Betacoronavirus/patogenicidade , Caspase 8/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Necroptose/imunologia , Pneumonia Viral/imunologia , Fibrose Pulmonar/imunologia , Animais , Caspase 8/genética , Linhagem Celular Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-7/genética , Interleucina-7/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/virologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
J Toxicol Sci ; 45(10): 611-617, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33012729

RESUMO

Acute paraquat poisoning (APP) is a serious public health problem with a high mortality rate and there is no specific antidote for APP in clinical. Early haemoperfusion (HP) treatment is effective in APP rescue. In this study, we compared the influence of routine HP and continuous HP on the survival rate and the treatment of pulmonary fibrosis in mild and moderate APP patients. Eighty-two cases of mild and moderate APP patients who were admitted to our hospital from January of 2017 to December of 2018 were selected. All patients were randomly divided into a routine haemoperfusion (HP) group (n = 40) and a continuous haemoperfusion (CHP) group (n = 42). Compared with the HP group, the 28-day survival rate of mild and moderate APP patients was elevated in the CHP group. Blood N-terminal procollagen Ш propeptide (PIIINP) levels in APP patients were positively related with paraquat (PQ) concentration (r = 0.309, P = 0.000). There were statistically significant differences in the levels of PIIINP, Collage TypeIV (CIV), transforming growth factor-beta 1 (TGF-ß1), malondialdehyde (MDA), superoxide dismutase (SOD) activity and sequential organ failure assessment (SOFA) score between the two groups both on the third and seventh days after treatment, and the treatment effect of the CHP group on pulmonary fibrosis in APP patients was better than that of the HP group. In conclusion, CHP treatment had a significant therapeutic effect on mild and moderate APP patients, which could effectively improve the survival rate and relieve pulmonary fibrosis.


Assuntos
Hemoperfusão/métodos , Paraquat/envenenamento , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/terapia , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Fibrose Pulmonar/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
Medicine (Baltimore) ; 99(35): e21804, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871900

RESUMO

INTRODUCTION: Pneumonia is one of the most important characteristics of coronavirus disease 2019 (COVID-19) and imaging findings of COVID-19 pneumonia are diverse and change over disease course. However, the detailed clinical course of organizing pneumonia (OP) caused by COVID-19 has not been clarified. PATIENT CONCERNS: A 60-year-old man and a 61-year-old woman diagnosed with mild COVID-19 were admitted to our hospital. Their respiratory symptoms were deteriorating even after initiating treatment with antiviral drugs. DIAGNOSIS: Chest X-rays and computed tomography scan showed a rapid progression of linear consolidation with reversed halo sign, distributed in subpleural and peri-bronchial regions. They also presented with pulmonary fibrosis findings, including traction bronchiectasis and marked lung volume reduction. They were diagnosed with rapidly progressing OP. INTERVENTIONS: They were treated with systemic corticosteroids. OUTCOMES: The patients' imaging findings and respiratory conditions improved rapidly without any adverse effects. CONCLUSION: Physicians should carefully monitor patients with COVID-19, as they can develop rapidly progressive and fibrotic OP, which respond to corticosteroids.


Assuntos
Infecções por Coronavirus , Pulmão , Pandemias , Pneumonia Viral , Prednisolona/administração & dosagem , Fibrose Pulmonar , Antivirais/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/administração & dosagem , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Lancet Respir Med ; 8(9): 925-934, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32890499

RESUMO

Within the spectrum of fibrosing interstitial lung diseases (ILDs) is a subset of patients who have inexorable progression of pulmonary fibrosis despite treatment, which is known as the progressive fibrotic phenotype. Although the concept of progressive fibrosing ILD has been applied largely to patients with idiopathic pulmonary fibrosis (IPF), there is now an increasing focus on irreversible progressive fibrosis in a proportion of patients with a range of underlying ILD diagnoses. Evidence has emerged to support a possible role for antifibrotic therapy in these patients. In this Position Paper, we discuss the importance of retaining diagnostic scrutiny within the multidisciplinary team and suggest a multidomain definition for progressive fibrosis. We consider the potential role of antifibrotic drugs as second-line therapy in the treatment algorithm for patients with progressive non-IPF ILD. We highlight risk factors that might predispose individuals to developing progressive fibrosis. Finally, we discuss key uncertainties and future directions for research and clinical practice.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Pesquisa Biomédica , Progressão da Doença , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/patologia , Fibrose Pulmonar/tratamento farmacológico , Pesquisa
18.
J Proteome Res ; 19(11): 4327-4338, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32883081

RESUMO

The COVID-19 pandemic rapidly became a worldwide healthcare emergency affecting millions of people, with poor outcomes for patients with chronic conditions and enormous pressure on healthcare systems. Pulmonary fibrosis (PF) has been cited as a risk factor for a more severe evolution of COVID-19, primarily because its acute exacerbations are already associated with high mortality. We reviewed the available literature on biochemical, pathophysiological, and pharmacological mechanisms of PF and COVID-19 in an attempt to foresee the particular risk of infection and possible evolution of PF patients if infected with SARS-COV-2. We also analyzed the possible role of medication and risk factors (such as smoking) in the disease's evolution and clinical course. We found out that there is a complexity of interactions between coexisting idiopathic pulmonary fibrosis/interstitial lung disease (ILD) and COVID-19 disease. Also, patients recovering from severe COVID-19 disease are at serious risk of developing PF. Smokers seem to have, in theory, a chance for a better outcome if they develop a severe form of COVID-19 but statistically are at much higher risk of dying if they become critically ill.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Fibrose Pulmonar , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fibrose Pulmonar/complicações , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/fisiopatologia , Fatores de Risco , Fumar
19.
PLoS One ; 15(9): e0239066, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941486

RESUMO

BACKGROUND: Combined pulmonary fibrosis with emphysema (CPFE) is a clinically meaningful syndrome characterized by coexisting upper-lobe emphysema and lower-lobe interstitial fibrosis. However, ambiguous diagnostic criteria and, particularly, the absence of objective methods to quantify emphysematous/fibrotic lesions in patients with CPFE confound the interpretation of the pathophysiology of this syndrome. We analyzed the relationship between objectively quantified computed tomography (CT) measurements and the results of pulmonary function testing (PFT) and clinical events in CPFE patients. MATERIALS AND METHODS: We enrolled 46 CPFE patients who underwent CT and PFT. The extent of emphysematous lesions was obtained by calculating the percent of low attenuation area (%LAA). The extent of fibrotic lesions was calculated as the percent of high attenuation area (%HAA). %LAA and %HAA values were combined to yield the percent of abnormal area (%AA). We assessed the relationships between CT parameters and other clinical indices, including PFT results. Multivariate analysis was performed to examine the association between the CT parameters and clinical events. RESULTS: A greater negative correlation with percent predicted diffusing capacity of the lung for carbon monoxide (DLCO %predicted) existed for %AA (r = -0.73, p < 0.001) than for %LAA or %HAA alone. The %HAA value was inversely correlated with percent predicted forced vital capacity (r = -0.48, p < 0.001), percent predicted total lung capacity (r = -0.48, p < 0.01), and DLCO %predicted (r = -0.47, p < 0.01). Multivariate logistic regression analysis found that %AA showed the strongest association with hospitalization events (odds ratio = 1.20, 95% confidence interval = 1.01-1.54, p = 0.029). CONCLUSION: Quantitative CT measurements reflected deterioration in pulmonary function and were associated with hospitalization in patients with CPFE. This approach could serve as a useful method to determine the extent of lung morphology, pathophysiology, and the clinical course of patients with CPFE.


Assuntos
Pulmão/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Feminino , Humanos , Pulmão/fisiopatologia , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Enfisema Pulmonar/complicações , Enfisema Pulmonar/fisiopatologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Testes de Função Respiratória
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 216-222, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981275

RESUMO

Objective: To observe whether the mechanism of small dose capsaicin (Cap) against pulmonary fibrosis in mouse is mediated by agitating transient receptor potential vanilloid 1 (TRPV1). Methods: A total of 60 BALB/c mice were randomly divided into control (CON) group, bleomycin (BLM)group, Cap (0.5, 1,2 mg/kg) groups and Cap (2 mg/kg) plus SB-452533 (2.5 mg/kg) group. C57BL/6 mice were intratracheally injected with 3.5 mg/kg BLM to induce pulmonary fibrosis model. Animals for drugs treatment received daily drug via subcutaneous injection for 21 days. The morphological changes and collagen deposition in lung tissues were analysed by HE staining, Masson staining and immunohistochemistry. The concentration of calcitonin gene-related peptide (CGRP) in plasma was determined by ELISA. The mRNA and (or) proteins levels of α-CGRP, ß-CGRP, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), vimentin, alpha smooth muscle actin (α-SMA), TRPV1, p-ERK1/2 and eukaryotic initiation factor 3a (eIF3a) were detected by qPCR and (or) Western blot. Results: Compared with the BLM group, small dose Cap significantly reduced bleomycin-induced pulmonary fibrosis in mice and obviously reversed alveolar epithelial cells epithelial-mesenchymal transition (EMT) (the expression of E-cadherin and ZO-1 were increased(P<0.05 or P<0.01)and the expression of α-SMA and Vimentin were decreased (P<0.05 or P<0.01) after drugs treatment for 21 day, concomitantly with the increase the expressions of TRPV1 and CGRP (P<0.05 or P<0.01), and inhibiting ERK1/2 phosphorylation and eIF3a expression (P<0.05 or P<0.01). These effects of small dose Cap were abolished in the presence of TRPV1 receptor antagonist SB-452533. Conclusion: The results suggest that small dose Cap can reverse alveolar epithelial cells EMT and alleviate bleomycin-induced pulmonary fibrosis in mice by inhibiting ERK1/2/eIF3asignaling pathway, which is related to agitating TRPV1 receptor and releasing of CGRP.


Assuntos
Células Epiteliais Alveolares , Capsaicina , Transição Epitelial-Mesenquimal , Fibrose Pulmonar , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Antipruriginosos/farmacologia , Antipruriginosos/uso terapêutico , Bleomicina/toxicidade , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Distribuição Aleatória , Fator de Crescimento Transformador beta1
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