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1.
Isr Med Assoc J ; 22(12): 781-783, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33381952

RESUMO

BACKGROUND: Transbronchial cryobiopsy (TBC) has recently emerged for the assessment of diffuse parenchymal lung disease (DPLD) as a less invasive procedure than surgical lung biopsy. The diagnostic usefulness and safety of TBC is still controversial. OBJECTIVES: To evaluate the safety and diagnostic yield of TBC in a peripheral community medical center. METHODS: We retrospectively reviewed the charts of all patients with DPLD who underwent TBC from January 2015 to January 2020. RESULTS: The study comprised 97 patients. Three samples were taken from each patient with an average diameter of 0.59 cm. The histologic diagnostic yield was 54% (52 of 97 procedures). The most frequent histopathologic diagnoses were usual interstitial pneumonia in 13 patients (13%). Bleeding was observed in 19 cases (19%) and only one patient (1%) had severe bleeding. Pneumothorax developed in seven patients (7%) and one patient (1%) suffered from Interstitial lung disease exacerbation. CONCLUSIONS: TBC was found to be safe; however, the diagnostic yield was rather low compared to other studies, which emphasizes the need for interstitial lung disease centers with expert in this field.


Assuntos
Biópsia/métodos , Broncoscopia/métodos , Doenças Pulmonares Intersticiais/diagnóstico , Feminino , Congelamento , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade
2.
Front Immunol ; 11: 587517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123171

RESUMO

Background and Objectives: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.


Assuntos
Doenças do Tecido Conjuntivo/patologia , Infecções por Coronavirus/patologia , Doenças Pulmonares Intersticiais/patologia , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Betacoronavirus/imunologia , Doenças do Tecido Conjuntivo/imunologia , Infecções por Coronavirus/imunologia , Feminino , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Estudos Prospectivos , Síndrome Respiratória Aguda Grave/imunologia
3.
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
4.
PLoS One ; 15(9): e0239114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956379

RESUMO

BACKGROUND: In recent years, transbronchial cryobiopsy (TBCB) has come to be increasingly used in interventional pulmonology units as it obtains larger and better-quality samples than conventional transbronchial lung biopsy (TBLB) with forceps. No multicenter studies have been performed, however, that analyse and compare TBCB and TBLB safety and yield according to the interstitial lung disease (ILD) classification. OBJECTIVES: We compared the diagnostic yield and safety of TBCB with cryoprobe sampling versus conventional TBLB forceps sampling in the same patient. METHOD: Prospective multicenter clinical study of patients with ILD indicated for lung biopsy. Airway management with orotracheal tube, laryngeal mask and rigid bronchoscope was according to the protocol of each centre. All procedures were performed using fluoroscopy and an occlusion balloon. TBLB was followed by TBCB. Complications were recorded after both TBLB and TBCB. RESULTS: Included were 124 patients from 10 hospitals. Airway management was orotracheal intubation in 74% of cases. Diagnostic yield according to multidisciplinary committee results for TBCB was 47.6% and for TBLB was 19.4% (p<0.0001). Diagnostic yield was higher for TBCB compared to TBLB for two groups: idiopathic interstitial pneumonias (IIPs) and ILD of known cause or association (OR 2.5; 95% CI: 1.4-4.2 and OR 5.8; 95% CI: 2.3-14.3, respectively). Grade 3 (moderate) bleeding after TBCB occurred in 6.5% of patients compared to 0.8% after conventional TBLB. CONCLUSIONS: Diagnostic yield for TBCB was higher than for TBLB, especially for two disease groups: IIPs and ILD of known cause or association. The increased risk of bleeding associated with TBCB confirms the need for safe airway management and prophylactic occlusion-balloon use. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02464592.


Assuntos
Broncoscopia/instrumentação , Criocirurgia/instrumentação , Fluoroscopia/instrumentação , Doenças Pulmonares Intersticiais/diagnóstico , Hemorragia Pós-Operatória/epidemiologia , Idoso , Biópsia/efeitos adversos , Biópsia/instrumentação , Biópsia/métodos , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Broncoscopia/estatística & dados numéricos , Criocirurgia/efeitos adversos , Criocirurgia/métodos , Feminino , Fluoroscopia/efeitos adversos , Fluoroscopia/métodos , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Estudos Prospectivos
5.
J Cancer Res Ther ; 16(4): 919-921, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930141

RESUMO

An 84-year-old male had a recurrence after surgical resection against Stage IIIA pulmonary adenocarcinoma and was treated with crizotinib due to harboring the anaplastic lymphoma kinase fusion gene. The patient exhibited crizotinib-induced interstitial lung disease (ILD), and alectinib was administered because of progressive disease. However, ILD appeared in both lungs again after alectinib treatment. This is the first case of ILD, resulting from alectinib administration after crizotinib-induced ILD. We should pay careful attention to patients who are treated with alectinib after crizotinib-induced ILD.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Carbazóis/efeitos adversos , Crizotinibe/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Carbazóis/uso terapêutico , Crizotinibe/uso terapêutico , Humanos , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Piperidinas/uso terapêutico , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico
7.
Medicine (Baltimore) ; 99(30): e21473, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791765

RESUMO

RATIONALE: Lymphoid interstitial pneumonia is a rare benign pulmonary lymphoproliferative disorder usually presenting with a sub-acute or chronic condition and frequently associated with autoimmune disorders, dysgammaglobulinemia, or infections. PATIENT CONCERNS: A 74-year-old woman with no past medical history presented with acute dyspnea, nonproductive cough, hypoxemia (room air PaO2: 48 mmHg) and bilateral alveolar infiltrates with pleural effusion. Antibiotics and diuretics treatments did not induce any improvement. No underlying condition including cardiac insufficiency, autoimmune diseases, immunodeficiency, or infections was found after an extensive evaluation. Bronchoalveolar lavage revealed a lymphocytosis (60%) with negative microbiological findings. High-dose intravenous corticosteroids induced a mild clinical improvement only, which led to perform a surgical lung biopsy revealing a lymphoid interstitial pneumonia with no sign of lymphoma or malignancies. DIAGNOSES: Acute severe idiopathic lymphoid interstitial pneumonia. INTERVENTIONS: Ten days after the surgical lung biopsy, the patient experienced a dramatic worsening leading to invasive mechanical ventilation. Antibiotics and a new course of high-dose intravenous corticosteroids did not induce any improvement, leading to the use of rituximab which was associated with a dramatic clinical and radiological improvement allowing weaning from mechanical ventilation after 10 days. OUTCOMES: Despite the initial response to rituximab, the patient exhibited poor general state and subsequent progressive worsening of respiratory symptoms leading to consider symptomatic palliative treatments. The patient died 4 months after the diagnosis of lymphoid interstitial pneumonia. LESSONS: Idiopathic lymphoid interstitial pneumonia may present as an acute severe respiratory insufficiency with a potential transient response to rituximab.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pulmão/patologia , Rituximab/uso terapêutico , Idoso , Evolução Fatal , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Tomografia Computadorizada por Raios X
8.
J Infect Dis ; 222(10): 1596-1600, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32745172

RESUMO

Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we exposed macaques to high titers of SARS-CoV-2 via combined transmission routes. We observed acute interstitial pneumonia with endotheliitis in the lungs of all infected macaques. All macaques had a significant loss of total lymphocytes during infection, which were restored over time. These data show that SARS-CoV-2 causes a coronavirus disease 2019 (COVID-19)-like disease in macaques. This new model could investigate the interaction between SARS-CoV-2 and the immune system to test therapeutic strategies.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/complicações , Modelos Animais de Doenças , Doenças Pulmonares Intersticiais/complicações , Linfopenia/complicações , Doenças dos Macacos/virologia , Pneumonia Viral/complicações , Animais , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Doenças Pulmonares Intersticiais/patologia , Linfopenia/patologia , Macaca fascicularis , Macaca mulatta , Masculino , Doenças dos Macacos/patologia , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
9.
J Clin Pathol ; 73(11): 762-768, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32843423

RESUMO

The aim of this review is to explain why the term 'desquamative interstitial pneumonia' (DIP) should be discarded and replaced with modern terminology. Reason 1: DIP is a misnomer. Within a few years after the term was coined, it was shown that the airspace cells in DIP are macrophages not desquamated pneumocytes. Reason 2: As a result of overly simplistic and poorly defined histologic criteria, DIP is currently a mixed bag of smoking-related diseases and unrelated processes in never-smokers. Reason 3: DIP obfuscates the modern concept that smoking causes some forms of parenchymal lung disease. Despite the fact that >80% of cases of DIP are caused by smoking, it is currently classified as a 'smoking-related idiopathic interstitial pneumonia', an oxymoron. Reason 4: The premise that the presence of numerous macrophages within airspaces defines an entity creates problematic histologic overlap with other lung diseases that may feature prominent airspace macrophages. Reason 5: DIP is outdated. It was coined in 1965, when many entities in interstitial lung disease had not been described, smoking-related interstitial lung disease was an unknown concept, computed tomograms of the chest had not been introduced and immunohistochemistry was unavailable. We suggest a way forward, which includes eliminating the term DIP and separating smoking-related lung abnormalities (including accumulation of pigmented airspace macrophages) from cases characterised by numerous non-pigmented macrophages in never-smokers. The laudable goal of smoking cessation is not served well by muddying the relationship between smoking and lung disease with inaccurate, outdated terminology.


Assuntos
Doenças Pulmonares Intersticiais/patologia , Fumar/patologia , Terminologia como Assunto , Humanos , Imuno-Histoquímica , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Macrófagos/patologia , Abandono do Hábito de Fumar , Tórax/patologia
10.
J Comput Assist Tomogr ; 44(5): 667-672, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32842066

RESUMO

OBJECTIVE: The aim of the study was to compare the prevalence of diffuse pulmonary ossification (DPO) in idiopathic pulmonary fibrosis (IPF), systemic sclerosis (SSc)-related interstitial lung disease (ILD), and chronic hypersensitivity pneumonitis (HP). METHODS: High-resolution computed tomography (HRCT) from 71 IPF, 67 SSc-ILD, and 75 HP cases were independently evaluated by 2 thoracic radiologists blinded to patient data. Studies were assessed for the presence of DPO, HRCT scanning pattern, stigmata of granulomatous infection, and honeycombing. RESULTS: The prevalence of DPO was significantly higher in cases of IPF and SSc compared with HP, although there was no significant difference in prevalence between the IPF and SSc groups, even when accounting for the presence of prior granulomatous infection. Interobserver agreement for the presence of DPO was substantial. CONCLUSIONS: Although prevalence DPO on HRCT varies between some forms of ILD, the use of DPO to influence characterization of ILD should be considered with caution.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Ossificação Heterotópica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/patologia , Escleroderma Sistêmico/complicações , Adulto Jovem
11.
J Comput Assist Tomogr ; 44(5): 656-666, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32842067

RESUMO

The aim of this work is to review interstitial lung fibrosis Imaging Reporting and Data System (ILF-RADS) that was designed for reporting of interstitial lung fibrosis (ILF). Findings include pulmonary and extrapulmonary findings and is subsequently designed into 4 categories. Pulmonary findings included lung volume, reticulations, traction bronchiectasis, honeycomb, nodules, cysts, ground glass, consolidation, mosaic attenuation and emphysema, and distribution of pulmonary lesions; axial (central, peripheral and diffuse), and zonal distribution (upper, middle, and lower zones). Complications in the form of acute infection, acute exacerbation, and malignancy were also assessed. Extrapulmonary findings included mediastinal, pleural, tracheal, and bone or soft tissue lesions. The lexicon of usual interstitial pneumonia (UIP) was classified into 4 categories designated as belonging in 1 of 4 categories. Lexicon of ILF-RADS-1 (typical UIP), ILF-RADS-2 (possible UIP), ILF-RADS-3 (indeterminate for UIP), and ILF-RADS-4 (inconsistent with UIP).


Assuntos
Doenças Pulmonares Intersticiais , Sistemas de Informação em Radiologia , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Radiologistas
12.
Science ; 369(6505): 818-823, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32616673

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Canal Anal/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Subpopulações de Linfócitos B/imunologia , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Interações entre Hospedeiro e Microrganismos , Imunidade Celular , Imunidade Humoral , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/virologia , Macaca mulatta , Nasofaringe/virologia , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Recidiva , Subpopulações de Linfócitos T/imunologia , Carga Viral , Replicação Viral
13.
Expert Rev Clin Immunol ; 16(8): 751-770, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32722946

RESUMO

INTRODUCTION: Main clinical manifestations of SARS-CoV-2 infection are characterized by fever, dyspnea, and interstitial pneumonia, frequently evolving in acute respiratory distress syndrome (ARDS). AREAS COVERED: Features of coronavirus disease 2019 (COVID-19) presents some common points with interstitial lung disease (ILD) both idiopathic and related to rheumatoid arthritis (RA), typically characterized by a chronic progression over time and possibly complicated by acute exacerbation (AE). The study of common pathogenetic mechanisms, such as the involvement of toll-like receptor 4, could contribute to the knowledge and treatment of idiopathic and RA-ILD. Moreover, hyperinflammation, mainly characterized by increase of effector T-cells and inflammatory cytokines, and activation of coagulation cascade, observed in COVID-19 related ARDS have been already shown in patients with AE of idiopathic and RA-ILD. A literature search was performed in PubMed, Embase, Scopus, and Web of Science, together with a manual search in COVID-resource centers of the main journals. EXPERT OPINION: Despite the uncertainty about pathogenetic aspects about COVID-19- pneumonia, it could be a possible model for other forms of ILD and AE. The great amount of data from studies on COVID-19 could be helpful in proposing safe therapeutic approaches for RA-ILD, in understanding pathogenesis of usual interstitial pneumonia and to develop new therapeutic strategies for AE.


Assuntos
Artrite Reumatoide/patologia , Infecções por Coronavirus/patologia , Doenças Pulmonares Intersticiais/patologia , Pneumonia Viral/patologia , Artrite Reumatoide/terapia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Progressão da Doença , Humanos , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/terapia , Pulmão/patologia , Doenças Pulmonares Intersticiais/terapia , Pandemias , Pneumonia Viral/terapia , Exacerbação dos Sintomas , Receptor 4 Toll-Like/metabolismo
14.
J Vet Diagn Invest ; 32(4): 621-625, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32687009

RESUMO

A 22-y-old American Quarter Horse gelding was presented with a history of chronic progressive respiratory problems and a diffuse pulmonary nodular pattern in thoracic radiographs. The horse was euthanized, and 4 formalin-fixed samples of lung were submitted for histopathology. There were multifocal areas of marked thickening of alveolar septa as a result of proliferation of myofibroblasts embedded in fibromyxoid matrix (interpreted as "Masson bodies"), focal areas of fibrosis, and numerous papillary projections of connective tissue into bronchioles. A diagnosis of organizing pneumonia was reached. No etiology was found for this lesion. It is important to consider causes of chronic interstitial pneumonia with fibrosis in horses other than equid herpesvirus 5, such as complicated viral or bacterial pneumonia or chronic toxicoses.


Assuntos
Doenças dos Cavalos/diagnóstico , Doenças Pulmonares Intersticiais/veterinária , Pneumonia/veterinária , Animais , Evolução Fatal , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/patologia , Cavalos , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pneumonia/diagnóstico , Pneumonia/etiologia , Pneumonia/patologia
15.
Presse Med ; 49(3): 104039, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32650042

RESUMO

Lung involvement is one of the most common clinical features in ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we detail the five main presentations of pulmonary involvement in AAV: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis, interstitial lung disease (ILD) and asthma with their clinical, radiological and therapeutic characteristics. The prevalence of these manifestations is variable according to the subtype of AAV, necrotizing granulomatous inflammation and tracheobronchial inflammation being defining features of GPA whereas ILD is primarily seen in patients with MPA, especially in association with ANCA directed against myeloperoxydase (MPO-ANCA), and asthma is characteristic of EGPA. Despite recent progresses in the diagnosis and management of these conditions, several questions remain and are discussed here, including local treatments for subglottic stenosis, the uncertain efficacy of plasma exchanges for alveolar hemorrhage, the potential role of antifibrotic agents in ILD associated with MPA, and the use of novel anti-IL-5 strategies in EGPA.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Doenças Pulmonares Intersticiais/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Asma/etiologia , Asma/patologia , Asma/terapia , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/patologia , Síndrome de Churg-Strauss/terapia , Granuloma/etiologia , Granuloma/patologia , Granuloma/terapia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Inflamação/etiologia , Inflamação/patologia , Inflamação/terapia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/terapia , Poliangiite Microscópica/complicações , Poliangiite Microscópica/patologia , Poliangiite Microscópica/terapia , Necrose/etiologia , Necrose/patologia , Necrose/terapia
16.
Medicine (Baltimore) ; 99(28): e20930, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664089

RESUMO

Surgical lung biopsy is regarded as the golden standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). Here, we attempted to show the diagnostic accuracy of multidisciplinary classifications based on transbronchial pathology including transbronchial lung cryobiopsy (TBLC) , bronchoalveolar lavage fluid (BALF) and endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA).Patients with suspected interstitial lung diseases admitted from June 1, 2016 to December 31, 2018 were involved. Patients with known causes of interstitial lung diseases and typical idiopathic pulmonary fibrosis diagnosed through clinical, radiological information were excluded. Patients with atypical idiopathic pulmonary fibrosis and possible IIPs accepted transbronchial pathological evaluation. Initial multidisciplinary diagnosis (MDD) classifications were made depending on clinical, radiological and transbronchial pathological information by a multidisciplinary team (MDT). The final MDD classifications were confirmed by subsequent therapeutic effects. All patients were followed up for at least 6 months.A total of 70 patients were finally involved. The samples of lung parenchyma extracted through TBLC were enough for confirmation of pathological diagnoses in 68.6% (48/70) cases. Samples of 6 cases were extracted by EBUS-TBNA. Bacteriological diagnoses were positive in 1 case by BALF. Pathological diagnoses of 77.1% (54/70) cases were achieved through TBLC, EBUS-TBNA and BALF. During the follow up study, the pulmonary lesions of 60% patients were improved, 11.43% were relapsed when glucocorticoid was reduced to small dose or withdrawal, 14.29% were leveled off and 8.57% were progressed. The diagnoses of 4 patients with progressed clinical feature were revised. As a result, 94.3% initial MDD classifications based on transbronchial pathology were consistent with the final MDD, and the difference of diagnostic yield wasn't significant between initial and final MDD (Z = -1.414, P = .157).Classifications of IIPs based on transbronchial pathology were useful and quite agreed with final MDD.


Assuntos
Broncoscopia/métodos , Pneumonias Intersticiais Idiopáticas/classificação , Pneumonias Intersticiais Idiopáticas/patologia , Biópsia Guiada por Imagem/métodos , Idoso , Biópsia/tendências , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia/efeitos adversos , Broncoscopia/tendências , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Comunicação Interdisciplinar , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Tomografia Computadorizada por Raios X/métodos
17.
J Crit Care ; 59: 149-155, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32674001

RESUMO

PURPOSE: Pathological data of critical ill COVID-19 patients is essential in the search for optimal treatment options. MATERIAL AND METHODS: We performed postmortem needle core lung biopsies in seven patients with COVID-19 related ARDS. Clinical, radiological and microbiological characteristics are reported together with histopathological findings. MEASUREMENT AND MAIN RESULTS: Patients age ranged from 58 to 83 years, five males and two females were included. Time from hospital admission to death ranged from 12 to 36 days, with a mean of 20 ventilated days. ICU stay was complicated by pulmonary embolism in five patients and positive galactomannan on bronchoalveolar lavage fluid in six patients, suggesting COVID-19 associated pulmonary aspergillosis. Chest CT in all patients showed ground glass opacities, commonly progressing to nondependent consolidations. We observed four distinct histopathological patterns: acute fibrinous and organizing pneumonia, diffuse alveolar damage, fibrosis and, in four out of seven patients an organizing pneumonia. None of the biopsy specimens showed any signs of invasive aspergillosis. CONCLUSIONS: In this case series common late histopathology in critically ill COVID patients is not classic DAD but heterogeneous with predominant pattern of organizing pneumonia. Postmortem biopsy investigations in critically COVID-19 patients with probable COVID-19 associated pulmonary aspergillosis obtained no evidence for invasive aspergillosis.


Assuntos
Infecções por Coronavirus/patologia , Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Pneumonia Viral/patologia , Aspergilose Pulmonar/patologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Betacoronavirus , Biópsia , Biópsia com Agulha de Grande Calibre , Líquido da Lavagem Broncoalveolar/química , Coinfecção , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Estado Terminal , Feminino , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Mananas/metabolismo , Pessoa de Meia-Idade , Pandemias , Fenótipo , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/diagnóstico por imagem , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/etiologia , Tomografia Computadorizada por Raios X
18.
PLoS One ; 15(7): e0236346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726327

RESUMO

INTRODUCTION: Interstitial lung diseases (ILDs) include a wide variety of chronic progressive pulmonary diseases characterized by lung inflammation, fibrosis and hypoxemia and can progress to respiratory failure and even death. ILDs are associated with varying degrees of quality of life impairments in affected people. Studies on the quality of life in patients with ILDs are still limited, and there are few studies with long-term follow-up periods in these patients. METHODS: Data from patients who were clinically diagnosed with ILDs in the Respiratory Department, Beijing Chaoyang Hospital, Capital Medical University from January 2017 to February 2018 were collected. Clinical status and HRQoL were assessed at baseline and subsequently at 6- and 12-month intervals with the LCQ, mMRC, HADS, SF-36, and SGRQ. Multivariate linear regression was used to evaluate the determinants of the decline in HRQoL. RESULTS: A total of 139 patients with idiopathic interstitial pneumonia (IIP) and 30 with connective tissue disease-associated ILD (CTD-ILD) were enrolled, 140 of whom completed the follow-up. The mean age was 63.7 years, and 92 patients were men. At baseline, the decline in HRQoL assessed by the SF-36 and SGRQ was significantly associated with the mMRC, LCQ and HADS depression score. In the follow-up, changes in FVC%, DLco%, mMRC and LCQ were significantly associated with changes in HRQoL. CONCLUSIONS: HRQoL in both IIP and CTD-ILD patients deteriorates to varying degrees, and the trend suggests that poor HRQoL in these patients is associated with many determinants, primarily dyspnea, cough and depression. Improving HRQoL is the main aim when treating patients living with ILDs.


Assuntos
Doenças do Tecido Conjuntivo/epidemiologia , Pneumonias Intersticiais Idiopáticas/epidemiologia , Fibrose Pulmonar Idiopática/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Idoso , China/epidemiologia , Doenças do Tecido Conjuntivo/patologia , Tosse/epidemiologia , Tosse/patologia , Dispneia/epidemiologia , Dispneia/patologia , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/patologia , Fibrose Pulmonar Idiopática/patologia , Doenças Pulmonares Intersticiais/classificação , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória , Fatores de Risco
19.
Cell ; 182(1): 50-58.e8, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516571

RESUMO

COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Camundongos Transgênicos , Pneumonia Viral/patologia , Animais , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/virologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos/genética , Pandemias , Peptidil Dipeptidase A/genética , Tropismo Viral , Perda de Peso
20.
Br J Radiol ; 93(1113): 20190121, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32584606

RESUMO

OBJECTIVE: To analyse delayed contrast dynamics of fibrotic lesions in interstitial lung disease (ILD) using five dimensional (5D) MRI and to correlate contrast dynamics with disease severity. METHODS: 20 patients (mean age: 71 years; M:F, 13:7), with chronic fibrosing ILD: n = 12 idiopathic pulmonary fibrosis (IPF) and n = 8 non-IPF, underwent thin-section multislice CT as part of the standard diagnostic workup and additionally MRI of the lung. 2 min after contrast injection, a radial gradient echo sequence with golden-angle spacing was acquired during 5 min of free-breathing, followed by 5D image reconstruction. Disease was categorized as severe or non-severe according to CT morphological regional severity. For each patient, 10 lesions were analysed. RESULTS: IPF lesions showed later peak enhancement compared to non-IPF (severe: p = 0.01, non-severe: p = 0.003). Severe lesions showed later peak enhancement compared to non-severe lesions, in non-IPF (p = 0.04), but not in IPF (p = 0.35). There was a tendency towards higher accumulation and washout rates in IPF compared to non-IPF in non-severe disease. Severe lesions had lower washout rate than non-severe ones in both IPF (p = 0.003) and non-IPF (p = 0.005). Continuous contrast agent accumulation, without washout, was found only in IPF lesions. CONCLUSIONS: Contrast agent dynamics are influenced by type and severity of pulmonary fibrosis, which might enable a more thorough characterisation of disease burden. The regional impairment is of particular interest in the context of antifibrotic treatments and was characterised using a non-invasive, non-irradiating, free-breathing method. ADVANCES IN KNOWLEDGE: Delayed contrast enhancement patterns allow the assessment of regional lung impairment which could represent different disease stages or phenotypes in ILD.


Assuntos
Meios de Contraste/farmacocinética , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Compostos Organometálicos/farmacocinética , Fibrose Pulmonar/diagnóstico por imagem , Idoso , Doenças do Tecido Conjuntivo , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/metabolismo , Pneumonias Intersticiais Idiopáticas/patologia , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Processamento de Imagem Assistida por Computador/métodos , Doenças Pulmonares Intersticiais/metabolismo , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Projetos Piloto , Análise de Componente Principal , Estudos Prospectivos , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Respiração , Índice de Gravidade de Doença , Fatores de Tempo , Capacidade Vital
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