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1.
Allergol Int ; 65(1): 88-95, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26666486

RESUMO

BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) occurs in 10%-30% of patients with RA, and interstitial lung disease (ILD) is associated with increased mortality in up to 10% of patients with RA. The pathogenesis of RA-ILD is virtually unknown. The aim of this study is to investigate the proteins related to UIP pattern by comparing to OP pattern in RA-ILD using proteome analysis of bronchoalveolar lavage fluid (BALF). METHODS: Proteomic differences in BALF were compared between the UIP pattern and OP pattern by examining BALF from 5 patients with the UIP pattern and 7 patients with the OP pattern by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: In individual comparisons of BALF samples, the levels of the protein gelsolin and Ig kappa chain C region were significantly higher in the UIP pattern than in the OP pattern. In contrast, the levels of α-1 antitrypsin, CRP, haptoglobin ß, and surfactant protein A (isoform number 5) were all significantly higher in the OP pattern than in the UIP pattern. Gelsolin was cleaved into two fragments, a C-terminal half and N-terminal half, and the levels of both were significantly higher in the UIP pattern than in the OP pattern. CONCLUSIONS: Fragmented gelsolins may be associated with the pathogenesis of fibrosis in RA-ILD.


Assuntos
Artrite Reumatoide/complicações , Gelsolina/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/metabolismo , Idoso , Sequência de Aminoácidos , Líquido da Lavagem Broncoalveolar/química , Feminino , Gelsolina/química , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteoma , Proteômica/métodos
2.
Respirol Case Rep ; 11(4): e01117, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36910133

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) has been reported as a rare complication of immune checkpoint inhibitors (ICI); however, ICI-related HLH is a life-threatening and comparatively late adverse event. Early diagnosis is critical, and it should be included in the differential diagnosis especially in patients with cytopenia with fever and hyperferritinaemia.

3.
Thorac Cancer ; 13(9): 1267-1275, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35322551

RESUMO

BACKGROUND: A standard treatment regimen for advanced non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) has not been established since most clinical trials exclude such patients because of the high risk of acute exacerbation of ILD. This study aimed to prospectively investigate the efficacy and safety of carboplatin and nab-paclitaxel as a first-line regimen for NSCLC patients with ILD. METHODS: The enrolled patients had treatment-naïve advanced NSCLC with ILD. The patients received 4-6 cycles of carboplatin (area under the curve = 5) on day 1 and nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the completion rate of four or more cycles. Secondary endpoints included toxicity, overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-five patients were enrolled in this study. Nine patients had adenocarcinoma, 11 had squamous cell carcinoma, one had large cell carcinoma, and four had NSCLC, not otherwise specified. The completion rate of ≥4 cycles was 76% (95% confidence interval: 56.2%-88.8%), which met the primary endpoint. The ORR and DCR were 44% and 88%, respectively. The median PFS and OS were 5.8 months and 15.8 months, respectively. Three patients experienced grade ≥2 pneumonitis, and one patient met the acute exacerbation criteria. CONCLUSION: The 4-week modified regimen of carboplatin and nab-paclitaxel showed tolerable toxicity with favorable efficacy in NSCLC patients with ILD. This regimen may be an effective treatment option for patients in real clinical settings.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Viabilidade , Humanos , Doenças Pulmonares Intersticiais/complicações , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel
4.
Artigo em Inglês | MEDLINE | ID: mdl-32476874

RESUMO

Background: Sarcoidosis goes into remission in two-thirds of patients with sarcoidosis, but about 20 % of patients develop pulmonary fibrosis. The mechanisms of pulmonary fibrosis in sarcoidosis and differences in pathogenesis between clinical stages are still unclear. Objectives: The aim of this study was investigating proteins associated with clinical stages by comparing bronchoalveolar lavage fluid (BALF) protein between stage I and stage IV using proteome analysis. Methods: Proteomic differences in BALF were compared between stage I and stage IV by examining BALF from 8 stage I patients and 5 stage IV patients by two-dimensional gel electrophoresis and mass spectrometry. Results: In individual comparisons of BALF samples, the levels of apolipoprotein (Apo) A-I fragment, fibrinogen γ chain, calcyphosine, complement C3, and surfactant protein A were significantly higher in stage I than in stage IV. In contrast, none of the proteins examined significantly higher in stage IV than in stage I. To confirm the results of Apo A-I in the BALF proteome, we performed enzyme-linked immunosorbent assay (ELISA) in a larger group. The concentration of BALF Apo A-I was significantly higher in stage I patients than in stage IV patients (0.70 [0.13-0.89] vs. 0.15 [0.08-0.21] ng/µg protein, p=0.003). Conclusion: The involvement of BALF Apo A-I in sarcoidosis may differ between stage I and stage IV. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 5-15).

5.
Respir Investig ; 54(6): 454-461, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27886857

RESUMO

BACKGROUND: Chronic bird-related hypersensitivity pneumonitis (BRHP) is often misdiagnosed as other interstitial lung diseases. While the utility of the inhalation provocation test (IPT) has been reported, the test is not commonly performed. In this study, we aimed to identify significant clinical variables associated with positive inhalation provocation test results in subjects suspected of having chronic BRHP. This would help clinicians decide whether to perform IPT in patients suspected of having chronic BRHP in real-life practice. METHODS: We retrospectively evaluated 107 patients who underwent the IPT for suspected chronic BRHP. We used the IPT as the gold standard diagnostic tool for chronic BRHP. RESULTS: Specific antibodies against pigeon dropping extract were documented in 52% of the IPT-positive patients but also in 38% of the IPT-negative patients (p=0.172). By using the logistic regression model, three significant predictors of IPT results were identified as follows: (1) a history of raising birds (odds ratio [OR] 3.112), (2) exposure to birds from the surrounding environment (OR 7.321), (3) white blood cell count (×102/µl; OR 0.959). CONCLUSIONS: This study demonstrates that current or past exposure to avian antigens is a positive predictor of positive IPT results in patients suspected of having chronic BRHP.


Assuntos
Pulmão do Criador de Aves/diagnóstico , Testes de Provocação Brônquica/métodos , Idoso , Animais , Antígenos , Pulmão do Criador de Aves/imunologia , Aves/imunologia , Doença Crônica , Feminino , Humanos , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
6.
PLoS One ; 10(9): e0137978, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26367130

RESUMO

Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL)-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif) ligand 5 (CXCL5) in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.


Assuntos
Pulmão do Criador de Aves/imunologia , Columbidae , Granuloma do Sistema Respiratório/imunologia , Interleucina-17/imunologia , Infiltração de Neutrófilos , Neutrófilos/imunologia , Animais , Pulmão do Criador de Aves/genética , Pulmão do Criador de Aves/patologia , Quimiocina CXCL5/genética , Quimiocina CXCL5/imunologia , Modelos Animais de Doenças , Granuloma do Sistema Respiratório/genética , Granuloma do Sistema Respiratório/patologia , Humanos , Interleucina-17/genética , Pulmão/imunologia , Pulmão/patologia , Camundongos , Neutrófilos/patologia
7.
Respir Investig ; 53(1): 13-21, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25542599

RESUMO

BACKGROUND: The reaction of specific antibodies and sensitized lymphocytes to antigens is important in hypersensitivity pneumonitis (HP). However, there are no known studies evaluating the utility of the lymphocyte proliferation test (LPT) or specific antibodies to avian antigens in diagnosing bird-related HP. In this study, we examined the sensitivity and specificity of these two tests. METHODS: Patients with acute bird-related HP (n=10), chronic bird-related HP (n=35), acute summer-type HP (n=14), and other interstitial pneumonia (IP) (n=76) were evaluated. The optimal cutoff values were determined by receiver operating curve (ROC) analyses of specific antibodies in serum and bronchoalveolar lavage fluid (BALF), and by conducting the LPT on mononuclear cells in peripheral blood and BALF. RESULTS: The sensitivity and specificity of the antibodies were 80-100% and 92-100% in acute bird-related HP, and 26-79% and 73-93% in chronic bird-related HP, respectively. The sensitivity and specificity of the LPT were 50-100% and 100% in acute bird-related HP, and 46% and 91% in chronic bird-related HP, respectively. CONCLUSIONS: Specific antibodies and the LPT are quite useful for diagnosing acute bird-related HP. The presence of specific antibodies in BALF and the results of LPT with peripheral blood mononuclear cells are particularly useful for diagnosing chronic bird-related HP.


Assuntos
Anticorpos/análise , Anticorpos/sangue , Antígenos/imunologia , Pulmão do Criador de Aves/diagnóstico , Pulmão do Criador de Aves/imunologia , Aves/imunologia , Testes Imunológicos/métodos , Doença Aguda , Adulto , Idoso , Animais , Biomarcadores/análise , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/imunologia , Doença Crônica , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
8.
Clin Rheumatol ; 33(2): 287-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24357324

RESUMO

A 47-year-old Japanese woman developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) complicated by a rare combination of aortitis and hypertrophic pachymeningitis. Despite the therapy with prednisolone and cyclophosphamide, the aortitis was not ameliorated. However, after cyclophosphamide was replaced with intravenous tocilizumab, the aortitis was improved, and the prednisolone dose was successfully tapered to 4 mg/day without elevation in C-reactive protein and myeloperoxidase ANCA (MPO-ANCA) levels. Several studies have reported that tocilizumab is effective for aortitis associated with Takayasu's arteritis and giant cell arteritis. On the other hand, we succeeded to improve the aortitis in AAV with monthly administration of tocilizumab. Moreover, we successfully controlled disease activity and enabled the tapering of prednisolone to 4 mg/day without relapses of AAV symptoms and elevated MPO-ANCA levels. It indicates that tocilizumab may be therapeutically beneficial for not only aortitis but also AAV itself. In conclusion, tocilizumab was effective in treating glucocorticoid- and cyclophosphamide-resistant AAV-associated aortitis. This is the first report demonstrating the successful treatment of AAV-associated aortitis using tocilizumab.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Aortite/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Anticorpos Anticitoplasma de Neutrófilos/sangue , Proteína C-Reativa/metabolismo , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Resultado do Tratamento
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