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1.
BMC Pulm Med ; 23(1): 199, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37291485

RESUMO

BACKGROUND: Interstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment. METHODS: This is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence. DISCUSSION: This is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases. TRIAL REGISTRATION NUMBER: UMIN000045149.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Japão , Antifibróticos , Inteligência Artificial , População do Leste Asiático , Estudos Prospectivos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/epidemiologia , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/complicações , Estudos de Coortes , Progressão da Doença
2.
Kyobu Geka ; 74(8): 635-639, 2021 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-34334610

RESUMO

We experienced two cases of primary pulmonary amyloidosis with a localized consolidation. Case 1 is a 80-year-old man, who was found to have an abnormal chest nodular shadow with blurred margin at a medical examination. Chest computed tomography( CT) showed a localized consolidation on the periphery of the upper lobe of the right lung. A CT-guided biopsy was performed. Case 2 is a 66-year-old woman, who was found to have an abnormal chest opacity at a medical examination. Chest CT showed a localized gathering of small nodules in the right lower lobe. Gradual enlargement was noted by follow up CT and the accumulation of fluorodeoxyglucose (FDG) was shown by PET/CT. In consideration of primary lung cancer or malignant lymphoma, right lower lobectomy was performed. Both cases were pathologically diagnosed as pulmonary amyloidosis. Since no findings of amyloid deposits in other organs or of existence of any blood disorders, a diagnosis of primary pulmonary amyloidosis was made.


Assuntos
Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Pneumopatias , Neoplasias Pulmonares , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico por imagem , Amiloidose/cirurgia , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Pneumopatias/diagnóstico por imagem , Pneumopatias/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
3.
Int J Clin Oncol ; 26(1): 78-86, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32965577

RESUMO

BACKGROUND: Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLC patients with poor PS (i.e., PS ≥ 2). METHODS: In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1-49%, ≥ 50%, and unknown. RESULTS: The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups (P < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups (P = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1-49%, hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.99, P = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02-0.71, P = 0.02; unknown, HR 0.30, 95% CI 0.08-1.22, P = 0.09). CONCLUSIONS: NSCLC patients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLC patients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos Imunológicos/uso terapêutico , Apoptose , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estudos Retrospectivos
4.
Respiration ; 83(3): 190-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21555868

RESUMO

BACKGROUND: Serum levels of pneumocyte biomarkers KL-6 and surfactant protein D (SP-D) are useful diagnostic markers for interstitial lung diseases. However, associations of serum KL-6 and SP-D with radiologic findings in nonspecific interstitial pneumonia (NSIP) remain unclear. OBJECTIVES: To determine whether serum levels of KL-6 and SP-D reflect fibrotic and/or inflammatory processes in NSIP, we investigated the correlation between high-resolution computed tomography (HRCT) findings and serum KL-6 and SP-D levels. METHODS: Serum levels of KL-6 and SP-D were measured in 21 patients with biopsy-confirmed NSIP. The radiographic extent of 6 HRCT patterns and total HRCT score, defined as the scored fibrotic index, were assessed. Changes in the levels of serum markers and CT findings during follow-up were also monitored. RESULTS: Serum levels of KL-6 in NSIP positively correlated with the total HRCT score and overall extent of interstitial disease. Serum levels of SP-D in NSIP showed a positive correlation with the area of ground-glass attenuation without traction bronchiectasis and the inflammatory CT pattern, but the levels were inversely correlated with the area of ground-glass attenuation with traction bronchiectasis and the fibrotic CT pattern. The follow-up CT and serum marker changes after treatment showed that percent change of disease extent was reflected in both markers, especially KL-6. Further, the decreased fibrotic pattern correlated with both biomarkers. CONCLUSIONS: The results indicate that serum levels of KL-6 in NSIP reflect the overall extent of interstitial lesions, which include both inflammatory and fibrotic lesions, while the levels of SP-D mainly reflect the extent of inflammatory lesions.


Assuntos
Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Mucina-1/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Adulto , Biomarcadores/sangue , Bronquiectasia/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
5.
Nihon Kokyuki Gakkai Zasshi ; 44(5): 359-67, 2006 May.
Artigo em Japonês | MEDLINE | ID: mdl-16780093

RESUMO

The clinical course of idiopathic pulmonary fibrosis (IPF) is chronic, but some patients with IPF have phases of accelerated deterioration superimposed on the chronic course of their illness, which is referred to as acute exacerbation (Aex) of IPF. To evaluate the clinical feature of Aex of IPF, we analyzed clinical findings of the 112 patients with IPF admitted to our hospital from 1994 to 2004. Of the 112 patients 56 with IPF died during the observation period due to Aex (42.9%), lung cancer (21.4%), chronic respiratory failure (14.3%), and lower respiratory infections (8.9%). Aex of IPF was seen 28 of 112 patients with IPF (25.0%) and 24 patients (85.7%) died with Aex. The median survival time (MST) after the onset of Aex was 0.9 months. The 5-yr survival rate of all patients with IPF was 38.3% and the MST was 3.1 yrs after diagnosis. On the other hand, the 5-yr survival rate and MST was 10.7% and 0.6 yrs in patients with Aex of IPF. We treated the patients with Aex with methylprednisolone pulse therapy in combination with cyclophosphamide or cyclosporine A, which did not significantly improve the outcome of Aex. In conclusion, there is little evidence that currently accepted treatments are effective in Aex of IPF, and further studies are needed to clarify the pathogenesis and contribute to the prevention of Aex.


Assuntos
Fibrose Pulmonar/complicações , Fibrose Pulmonar/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Fibrose Pulmonar/mortalidade , Insuficiência Respiratória/etiologia , Infecções Respiratórias/etiologia , Taxa de Sobrevida
6.
Clin Diagn Lab Immunol ; 12(1): 206-12, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15643009

RESUMO

Dendritic cells (DCs) are antigen-presenting cells with the ability to induce primary immune responses necessary in innate immunity and adaptive immunity. Osteopontin (OPN) is a secreted acidic phosphoprotein containing an arginine-glycine-aspartate sequence and has been suggested to play an important role in early cellular immune responses. The interaction between DCs and OPN has not been clarified. We hypothesized that there is an important interaction between DCs and OPN, which is an indispensable extracellular matrix component in early cellular immune responses. Human monocyte-derived DCs synthesized OPN especially during the differentiation from monocytes to immature DCs. By blocking of OPN with anti-OPN antibody, cultured DCs became smaller and expressed lower levels of costimulatory molecules and major histocompatibility complex class II antigens than untreated DCs. Furthermore, DCs treated with anti-OPN antibody easily underwent apoptosis. These results suggest that human DCs can produce OPN and that OPN may play a role in the differentiation, maturation, and survival of DCs by autocrine and/or paracrine pathways.


Assuntos
Diferenciação Celular/fisiologia , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Sialoglicoproteínas/metabolismo , Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Citometria de Fluxo , Humanos , Monócitos/citologia , Monócitos/metabolismo , Osteopontina , Células-Tronco/citologia , Células-Tronco/metabolismo
7.
Intern Med ; 42(8): 735-9, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12924503

RESUMO

Castleman's disease is a rare and poorly understood condition involving lymph nodes at various sites, predominantly in the mediastinum. Individuals with this disease often present with lymphadenopathy and general symptoms suggestive of lymphomatous disease, and they are at risk of developing malignant lymphoma. It is thus important to distinguish Castleman's disease from other lymphoproliferative disorders. 67Ga scintigraphy is a non-invasive and practical diagnostic tool for the investigation of patients with lymphoproliferative disorders. However, the value of this technique for the diagnosis of Castleman's disease is not clear. Here, we describe five consecutive patients with various types of Castleman's disease and show that none of these individuals exhibited 67Ga uptake. Our results suggest the potential value of 67Ga scintigraphy in both the diagnosis and management of Castleman's disease.


Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Radioisótopos de Gálio , Compostos Radiofarmacêuticos , Adulto , Hiperplasia do Linfonodo Gigante/classificação , Hiperplasia do Linfonodo Gigante/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia
8.
Intern Med ; 42(2): 182-6, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12636239

RESUMO

Multicentric Castleman's disease (MCD) is an uncommon and often incurable lymphoproliferative disorder. There has been some recent evidence that rare cases of MCD manifest diffuse lung involvement, but the features in these cases are not well characterized. We report just such a biopsy-proven case of MCD with typical laboratory abnormalities including serum interleukin-6 elevation and characteristic high-resolution CT findings. Immunopathologically, the features of the lung tissue resembled those of lymphocytic interstitial pneumonia with predominant infiltration of B cells and plasma cells. In addition, the abnormal appearance of B cells in bronchoalveolar lavage fluid was of diagnostic value. Although MCD is often refractory to treatment including corticosteroid, chemo- and immuno-therapy, we show successful treatment with corticosteroid and cyclophosphamide and 4 years of complete remission.


Assuntos
Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/patologia , Ciclofosfamida/administração & dosagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/patologia , Prednisolona/administração & dosagem , Biópsia por Agulha , Líquido da Lavagem Broncoalveolar/citologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Doenças Raras , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Am J Respir Cell Mol Biol ; 26(6): 671-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12034565

RESUMO

To investigate the contribution of dendritic cells (DC) in a pulmonary granulomatous immune response, C57BL/l6 mice, nonimmunized or immunized with purified protein derivative (PPD) of Mycobacterium bovis, were intravenously injected with PPD-coated Sepharose-4B beads. One and three days later lungs were harvested, granuloma size was measured, and immunolabeled cells in granulomas were counted. On Day 1, granulomas in immunized mice were 3-fold larger and contained more major histocompatibility complex class II+, CD11c+ DCs than nonimmunized mice. By Day 3, these differences had diminished. In all granulomas MHC class II+, CD11c+ DCs were in contact with the beads. By in situ hybridization these DCs expressed interleukin (IL)-12 p40 mRNA. MOMA2+ macrophages were present throughout the granulomas, whereas CD4+ and CD8alpha+ T cells were localized at the granuloma periphery. DCs isolated from granulomatous lungs at Day 1, and from thoracic lymph nodes (LNs) at Days 1 and 3, stimulated PPD-specific T cell proliferation without exogenously added antigen, indicating that they had acquired bead-bound antigen. By Day 3, however, granuloma DCs presented little antigen, suggesting that newly immigrated DC lacked access to antigen or that antigen uptake/processing was inhibited. RNase protection assays of whole-lung mRNA showed increased interferon-gamma, IL-1beta, IL-1 receptor antagonist, IL-6, and macrophage inhibitory factor, but no IL-10 mRNA on Days 1 and 3. These observations support the premise that DCs are key in initiating granulomatous cell-mediated immunity. However, factors generated within the granuloma downregulate the antigen presenting function of DC by Day 3 in this experimental model.


Assuntos
Células Dendríticas/imunologia , Granuloma/imunologia , Pulmão/imunologia , Animais , Sequência de Bases , Citocinas/genética , Primers do DNA , Feminino , Hibridização In Situ , Integrina alfaXbeta2/imunologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética
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