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1.
Anticancer Res ; 39(11): 6231-6240, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704852

RESUMO

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Interferon gama/sangue , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Tuberculose Latente/metabolismo , Doenças Pulmonares Intersticiais/etiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Estudos Prospectivos , Linfócitos T/imunologia , Fatores de Tempo
2.
Internist (Berl) ; 60(12): 1251-1269, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31754753

RESUMO

Systemic sclerosis (SSc) is a rare fibrosing rheumatic multi-systemic disease involving many medical specialties. The mortality of SSc is determined by lung fibrosis, pulmonary arterial hypertension and cardiac involvement. With early and intensive treatment, the disease can be stabilized and symptoms relieved. This review summarizes insights into pathophysiology, disease classification, clinical manifestations and successful therapies, as well as recent studies on new immunosuppressant, biological and vasoactive therapies.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/etiologia , Fibrose Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia
3.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(10): 765-770, 2019 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-31594111

RESUMO

Objective: To investigate the clinical significance of detection of myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) in patients with connective tissue disease-associated interstitial lung diseases (CTD-ILD). Methods: Serum samples of 120 patients with CTD-ILD admitted to the Department of Respiratory, Affiliated Drum Tower Hospital of Nanjing University Medical College from December 2016 to April 2018 were collected for analysis. The patients included 45 with polymyositis/dermatomyositis (PM/DM), 36 with Sjogren's syndrome (SS) and 39 with undifferentiated connective tissue disease (UCTD). There were 37 males and 83 females with an average age of (56±11) years. Thirty-two patients with non-CTD-ILD, 10 males and 22 females with an average age of (42±17) years, were enrolled as the control group. Euroline Autoimmune Inflammatory Myopathies 16 Ag kit was used for detecting MSAs and MAAs, and the positive rates of serum MSAs and MAAs were calculated. The antibody distribution and clinical characteristics of different groups were analyzed and compared. Results: Eighty-nine of the 120 patients with CTD-ILD were positive for MSA and/or MAA (74.2%), and the detection rates of MSAs and MAAs were 52.5% (63/120) and 61.7% (74/120) respectively. No myositis antibody was detected in the non-CTD-ILD group. The detection rates of MSAs in PM/DM-ILD group, SS-ILD group and UCTD-ILD group were 75.6% (34/45), 33.3%(12/36) and 43.6%(17/39) respectively. The total detection rate of MSAs in PM/DM group was significantly higher than that in SS group and UCTD group (χ(2)=14.53, 8.95, 0.01). The anti-ARS was the most frequent (50/120, 41.7%). The positive rates of MAAs in the three groups were 64.4%(29/45), 77.8%(28/36), 43.6%(17/39) respectively, and anti-Ro-52 accounted for 60%(72/120), and were highly correlated with MSAs such as anti-Jo-1 antibodies. Conclusion: Myositis antibody profiling should be performed in patients with ILD who were negative for conventional autoimmune antibody testing and had no CTD. In patients with SS-ILD and UCTD-ILD, the myositis antibody spectrum could detect the presence of myositis-specific antibodies and myositis-related antibodies in some patients, and its role in clinical diagnosis and treatment needed further observation.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças Pulmonares Intersticiais/imunologia , Miosite/imunologia , Polimiosite/imunologia , Adulto , Idoso , China/epidemiologia , Doenças do Tecido Conjuntivo/sangue , Dermatomiosite/sangue , Dermatomiosite/complicações , Dermatomiosite/epidemiologia , Dermatomiosite/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/diagnóstico , Miosite/epidemiologia , Polimiosite/complicações , Polimiosite/epidemiologia , Testes Sorológicos
4.
Zhonghua Yi Xue Za Zhi ; 99(38): 2976-2981, 2019 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-31607028

RESUMO

Objective: To explore the expression and clinical significance of chemokine ligand 18 (CCL18) in Bronchoalveolar Lavage Fluid (BALF) of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: From January 2016 to June 2017, BALF of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD group), patients with dermatomyositis-associated interstitial lung disease (DM-ILD group), and patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD group) of Peking University People's Hospital were collected. According to the prognosis of each group of patients during hospitalization, they were divided into the discharged and the died. Besides, 30 patients without ILD served as a control group. Levels of CCL18 in BALF of all patients were tested by enzyme linked immunosorbent assay (ELISA). Cells in BALF of RA-ILD group, DM-ILD group and pSS-ILD group were collected and analyzed by absolute different cell counts. Results of high-resolution CT (HRCT) of these three groups were scored. In addition, the area under the curve (AUC) of CCL18 in predicting mortality during hospitalization was calculated. Results: A total of 38 patients with RA-ILD, 54 patients with DM-ILD, and 35 patients with pSS-ILD were enrolled. Levels of CCL18 of those discharged patients of RA-ILD, DM-ILD, and pSS-ILD groups were 8.27(3.62, 14.36), 11.04 (5.86, 17.38), 5.25(2.68, 8.21) µg/L, respectively, which were all significantly higher than that of the control group [2.54(1.26, 3.66) µg/L, all P<0.05]. Furthermore, levels of CCL18 of those deceased patients of RA-ILD and DM-ILD groups were 18.28 (13.82, 22.39), 18.81 (16.29, 22.90) µg/L, which were significantly higher than that of the discharged patients of same group (all P<0.05). Levels of CCL18 were positively correlated with lymphocyte percentage in BALF of RA-ILD, DM-ILD and pSS-ILD groups (r=0.4356, 0.4029, 0.3939, respectively, all P<0.05). Besides, levels of CCL18 were significantly correlated with HRCT scores of RA-ILD and DM-ILD groups (r=0.4242, 0.3319, respectively, both P<0.05). Areas under the curve (AUCs) of CCL18 to predict mortality during hospitalization of RA-ILD and DM-ILD groups were 0.860, 0.851, respectively. Conclusions: Levels of CCL18 are elevated in BALF of CTD-ILD patients, and may be correlated with the severity and prognosis during hospitalization. CCL18 might be served as an indicator of the severity and prognosis of CTD-ILD.


Assuntos
Doenças do Tecido Conjuntivo , Dermatomiosite , Doenças Pulmonares Intersticiais , Líquido da Lavagem Broncoalveolar , Quimiocinas , Quimiocinas CC , Doenças do Tecido Conjuntivo/metabolismo , Humanos , Doenças Pulmonares Intersticiais/etiologia
5.
Clin Exp Rheumatol ; 37 Suppl 119(4): 115-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573469

RESUMO

OBJECTIVES: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%. Recently, nintedanib has been reported to exert anti-fibrotic activity on systemic sclerosis (scleroderma, SSc) skin fibroblasts and to diminish skin and lung fibrosis in mouse models. The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD). METHODS: Study was performed using lung fibroblasts (LF) isolated from five patients with SSc-ILD and from three control subjects. RESULTS: Nintedanib inhibited LF proliferation and migration in a concentration- and time-dependent manner. The proliferation rate of LF stimulated with PDGF in the presence of nintedanib was reduced 1.9-fold within 24 h as compared to cells stimulated with PDGF alone. Migration of SSc-ILD LF incubated with 100 nM nintedanib was reduced from 62.8±12.5% to 39.1±9.0% in the presence of PDGF and from 38.2±7.9% to 26.6±7.2% in serum-free medium. Nintedanib attenuated PDGF-induced Ca2+ efflux, reduced α-SMA promoter activity and α-SMA protein expression. Furthermore, nintedanib blocked PDGF-induced differentiation of normal LF to myofibroblasts, reduced production of collagen and fibronectin, and decreased contractility of SSc-ILD LF in both floating and fixed collagen gels. CONCLUSIONS: Our data demonstrate significant antifibrotic efficacy of nintedanib in SSc-ILD LF suggesting that nintedanib has the potential not only to prevent but also to reverse the increased activity of LF consequently attenuating excessive lung fibrosis observed in SSc-ILD.


Assuntos
Fibrose Pulmonar Idiopática , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais , Inibidores de Proteínas Quinases/uso terapêutico , Escleroderma Sistêmico , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/etiologia , Pulmão/citologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações
6.
Medicine (Baltimore) ; 98(38): e17088, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567944

RESUMO

An international consensus for rheumatoid arthritis (RA) patients at risk of developing interstitial lung disease (ILD) is still lacking. The aims of study were to evaluate: the prevalence of ILD involvement in RA over high-resolution computed tomography (HRCT); the relationships between pulmonary function tests (PFTs), patient-centered measurements, and ILD; and the potential risk factors contributing to RA-ILD patients.Data regarding the clinical characteristics (age, sex, age at onset of RA), laboratory findings (rheumatoid factor [RF] and anti-citrullinated protein antibodies [ACPA]), respiratory functional assessment (forced vital capacity [FVC] and carbon monoxide diffusion capacity [DLCO]), patient-centred measures of dyspnea (PCMD), Health Assessment Questionnaire-Disability Index (HAQ-DI), and HRCT have collected retrospectively. HRCT abnormalities were evaluated using a conventional visual reader-based score (CoVR) and a computer-aided method (CaM). The relationships between the 2 HRCT scores-PFTs and PCMD-were calculated using Pearson correlation. The area under the receiving-operating characteristic (AUC-ROC) curve was calculated to determine the discriminatory performance of measurements between patients with and without ILD. The multivariate regression model was used to evaluate the association force between ILD and RA characteristics.In all, 151 patients (45 males and 106 females, mean age 53.4 ±â€Š7.6 years) were included. ILD had been detected in 29 patients out of 151 (19.2%). Usual interstitial pneumonia was the most common HRCT. RA-ILD patients were older, and older at RA onset (both P < .01), with a higher HAQ-DI (P < .05) than patients without ILD. ACPA positivity and titer were higher in the RA-ILD group (P = .02). Extent and severity of ILD, and total CoVR and CaM score closely related to DLCO and PCMD (both P < .0001). A reduced DLCO was the most sensitive test for predicting the presence of ILD on HRCT (AUC-ROC 0.811 ±â€Š0.037). Advanced age (P < .0001), age at RA onset (P = .025), ACPA titer (P = .004), and smoking (P = .008) were independent explanatory variables of HRCT damage in multivariate analysis.The RA-ILD is associated with age and older age of RA onset, smoking, and ACPA titer. DLCO seems to be the most sensitive parameter to predict ILD on HRCT, followed by PCMD.


Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais/epidemiologia , Fatores Etários , Idoso , Feminino , Humanos , Itália/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Curva ROC , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Tomografia Computadorizada por Raios X
8.
BMJ Case Rep ; 12(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420429

RESUMO

Sweet's syndrome is an acute febrile neutrophilic dermatosis with classical clinical features. Systemic manifestations in Sweet's syndrome including fever, arthralgia, myalgia and ocular involvement are common. Pulmonary involvement is a rare manifestation that has been reported previously in 34 cases and can be fatal if left untreated. We report a striking case of Sweet's syndrome with respiratory failure secondary to bilateral pulmonary interstitial infiltrates, which rapidly responded to intravenous corticosteroid therapy. This case is an important reminder of the systemic manifestations of Sweet's syndrome and highlights the value of collaboration between different medical specialities to optimise patient management and outcomes.


Assuntos
Doenças Pulmonares Intersticiais/etiologia , Insuficiência Respiratória/etiologia , Síndrome de Sweet/complicações , Idoso de 80 Anos ou mais , Humanos , Masculino
9.
Clin Exp Rheumatol ; 37 Suppl 118(3): 249-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464665

RESUMO

OBJECTIVES: Interstitial lung disease is a life-threatening complication of many systemic autoimmune diseases with diverse clinical and histopathological features. Among them, lymphocytic interstitial pneumonia (LIP) is mainly associated with primary Sjögren's syndrome (pSS). A case of a middle-aged man with LIP, anti-Ro/La, anti-Scl70 autoantibodies and overlapping histopathological features of pSS and systemic sclerosis (SSc) is presented and discussed. METHODS: A 65-year-old man complaining for easy fatigue and dry cough was evaluated. Physical examination revealed bibasilar crackles on auscultation. Imaging tests showed areas of centrilobular nodules with tree-in-bud sign on the medial lobe of the right lung. Pulmonary function tests demonstrated small airways disease. Laboratory evaluation revealed elevated ESR and CRP, ANA titre >1/320, positive Ro52, Ro60 and La autoantibodies but also, weakly positive anti Scl70 autoantibody. RESULTS: Right lobe lung biopsy showed diffuse fibrosis with altered alveolar architecture and diffuse infiltration of alveolar septa by lymphocytes and mast cells. Ectopic germinal centres were disclosed, adjacent to the small bronchi causing lumen obstruction and validated after the demonstration of CD23 expression, specific for follicular dendritic cells. Biopsy of minor salivary glands revealed intense periductal fibrosis with limited round cell infiltrates, not fulfilling the histopathological criteria for pSS. The diagnosis of LIP was established and the patient received corticosteroids with poor response. Subsequently he was treated with rituximab with satisfactory results. CONCLUSIONS: This case with LIP and disease-specific autoantibodies for pSS and SSc teaches the complexity and overlapping nature of both diseases, extending from autoimmune epithelitis with ectopic germinal centres to fibrosis-related SSc. It points out the significance of the affected tissue biopsy, which may uncover the different disease phenotypes. To this end, treatment with anti-CD20, acting at the crossroads of the pathogenetic mechanisms of both diseases may serve as a first choice therapy.


Assuntos
Doenças Pulmonares Intersticiais , Síndrome de Sjogren , Idoso , Anticorpos Antinucleares , Autoanticorpos , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Glândulas Salivares Menores , Síndrome de Sjogren/complicações
10.
Braz J Med Biol Res ; 52(8): e8513, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365695

RESUMO

Phenotypic differences have been described between patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and SSc-associated pulmonary hypertension, including performance differences in the 6-min walk test (6MWT). Moreover, the correlations between the 6MWT and traditional pulmonary function tests (PFTs) are weak, indicating the need to search for new parameters that explain exercise performance. Thus, our objective was to evaluate the impact of ventilation distribution heterogeneity assessed by the nitrogen single-breath washout (N2SBW) test and peripheral muscle dysfunction on the exercise capacity in patients with SSc-ILD and limited involvement of the pulmonary parenchyma. In this cross-sectional study, 20 women with SSc-ILD and 20 matched controls underwent PFTs (including spirometry, diffusing capacity for carbon monoxide (DLco), and the N2SBW test) and performed the 6MWT and knee isometric dynamometry. The 6-min walking distance (6MWD, % predicted) was strongly correlated with the phase III slope of the single-breath nitrogen washout (phase III slopeN2SBW) (r=-0.753, P<0.0001) and reasonably correlated with the forced vital capacity (FVC) (r=0.466, P=0.008) and DLco (r=0.398, P=0.011). The peripheral oxygen saturation (SpO2) during exercise was not significantly correlated with any of the pulmonary or muscle function parameters. The phase III slopeN2SBW was the only predictive variable for the 6MWD, whereas quadriceps strength and FVC/DLco were predictive variables for SpO2. Ventilation distribution heterogeneity is one factor that contributes to a lower 6MWD in SSc-ILD patients. In addition, muscle dysfunction and abnormal lung diffusion at least partly explain the decreased SpO2 of these patients.


Assuntos
Tolerância ao Exercício/fisiologia , Hipertensão Pulmonar/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiologia , Testes de Função Respiratória/métodos , Escleroderma Sistêmico/complicações , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Medidas de Volume Pulmonar/métodos , Pessoa de Meia-Idade , Ventilação Pulmonar , Doença de Raynaud/complicações , Tomografia Computadorizada por Raios X/métodos , Capacidade Vital/fisiologia , Teste de Caminhada/métodos
11.
Medicine (Baltimore) ; 98(29): e16423, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335694

RESUMO

To test whether texture analysis (TA) can discriminate between Systemic Sclerosis (SSc) and non-SSc patients in computed tomography (CT) with different radiation doses and reconstruction algorithms.In this IRB-approved retrospective study, 85 CT scans at different radiation doses [49 standard dose CT (SDCT) with a volume CT dose index (CTDIvol) of 4.86 ±â€Š2.1 mGy and 36 low-dose (LDCT) with a CTDIvol of 2.5 ±â€Š1.5 mGy] were selected; 61 patients had Ssc ("cases"), and 24 patients had no SSc ("controls"). CT scans were reconstructed with filtered-back projection (FBP) and with sinogram-affirmed iterative reconstruction (SAFIRE) algorithms. 304 TA features were extracted from each manually drawn region-of-interest at 6 pre-defined levels: at the midpoint between lung apices and tracheal carina, at the level of the tracheal carina, and 4 between the carina and pleural recesses. Each TA feature was averaged between these 6 pre-defined levels and was used as input in the machine learning algorithm artificial neural network (ANN) with backpropagation (MultilayerPerceptron) for differentiating between SSc and non-SSc patients.Results were compared regarding correctly/incorrectly classified instances and ROC-AUCs.ANN correctly classified individuals in 93.8% (AUC = 0.981) of FBP-LDCT, in 78.5% (AUC = 0.859) of FBP-SDCT, in 91.1% (AUC = 0.922) of SAFIRE3-LDCT and 75.7% (AUC = 0.815) of SAFIRE3-SDCT, in 88.1% (AUC = 0.929) of SAFIRE5-LDCT and 74% (AUC = 0.815) of SAFIRE5-SDCT.Quantitative TA-based discrimination of CT of SSc patients is possible showing highest discriminatory power in FBP-LDCT images.


Assuntos
Doenças Pulmonares Intersticiais , Pulmão/diagnóstico por imagem , Escleroderma Sistêmico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Algoritmos , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico
13.
Respir Res ; 20(1): 154, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307466

RESUMO

BACKGROUND: Acute exacerbation of interstitial pneumonia (AE-IP) is a serious complication of pulmonary surgery in patients with IP. However, little is known about AE-IP after non-pulmonary surgery. The aim of this study was to determine the frequency of AE-IP after non-pulmonary surgery and identify its risk factors. METHODS: One hundred and fifty-one patients with IP who underwent pulmonary surgery and 291 who underwent non-pulmonary surgery were retrospectively investigated. RESULTS: AE-IP developed in 5 (3.3%) of the 151 patients in the pulmonary surgery group and 4 (1.4%) of the 291 in the non-pulmonary surgery group; the difference was not statistically significant. A logistic regression model showed that serum C-reactive protein (CRP) was a predictor of AE-IP in the non-pulmonary surgery group (odds ratio 1.187, 95% confidence interval 1.073-1.344, P = 0.002). CONCLUSIONS: This is the first study to compare the frequency of AE-IP after pulmonary surgery with that after non-pulmonary surgery performed under the same conditions. The results suggest that the frequency of AE-IP after non-pulmonary surgery is similar to that after pulmonary surgery. A high preoperative C-reactive protein level is a potential risk factor for AE-IP after non-pulmonary surgery.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Doença Aguda , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Radiol Med ; 124(10): 989-999, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267321

RESUMO

Lung ultrasound (LUS) achieved an intriguing role in the management of pulmonary involvement in patients affected by connective tissues diseases (CTDs). Few studies have been performed to support its usefulness in the evaluation of the presence and the severity of interstitial lung disease (ILD), relating it to the information obtained with chest high-resolution computed tomography (HRCT). These results open up new fields of research in order to demonstrate the utility of LUS as screening tool to evaluate ILD in CTD. The aim of this review is to provide the "state of the art" of the role of LUS in the management of ILD associated with CTD.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Reumáticas/diagnóstico por imagem , Ultrassonografia/métodos , Diagnóstico Diferencial , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Reumáticas/complicações
15.
BMC Pulm Med ; 19(1): 120, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272428

RESUMO

BACKGROUND: Patients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF). METHODS: ILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study. RESULTS: Out of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002-1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955-0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366-3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192-0.984 (IPAF vs IPF), respectively) showed significant association. CONCLUSIONS: Compared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.


Assuntos
Autoimunidade , Doenças do Tecido Conjuntivo/complicações , Fibrose Pulmonar Idiopática/mortalidade , Doenças Pulmonares Intersticiais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças do Tecido Conjuntivo/imunologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , República da Coreia/epidemiologia , Análise de Sobrevida , Tomografia Computadorizada por Raios X
16.
BMC Pulm Med ; 19(1): 111, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221137

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. METHODS: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. RESULTS: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. CONCLUSIONS: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.


Assuntos
Artrite Reumatoide/complicações , Auscultação/instrumentação , Doenças Pulmonares Intersticiais/diagnóstico , Sons Respiratórios/diagnóstico , Idoso , Algoritmos , Feminino , Humanos , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos
17.
Respir Investig ; 57(4): 321-324, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31080050

RESUMO

Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications after hematopoietic stem cell transplantation (HSCT). Pleuroparenchymal fibroelastosis (PPFE) is a LONIPC, but its etiology remains elusive. Chronic graft-versus-host disease (cGVHD) and alkylating agents used for conditioning have been considered possible causes of PPFE. Therefore, to investigate the primary cause of PPFE in allogeneic HSCT, we compared three secondary PPFE groups, namely, the post-lung-transplantation, post-autologous-HSCT or chemotherapy-alone, and post-allogeneic-HSCT groups, and focused on the coexistence of bronchiolitis obliterans (BO), a typical phenotype of cGVHD. We found a trend towards higher rates of PPFE with BO in the post-allogeneic-HSCT and post-lung-transplantation groups (71% and 90%, respectively) than in the post-autologous-HSCT or chemotherapy-alone group (25%). The incidence of BO following allogeneic HSCT is reportedly <10%. If PPFE in the post-allogeneic-HSCT group has no association with BO and is induced by alkylating agents rather than cGVHD, the incidence of BO in PPFE in this group is estimated to be <10%, which is inconsistent with our data (71%). Thus, this study suggests that PPFE following allogeneic HSCT could be mainly induced by cGVHD because the majority of cases are associated with BO, a typical phenotype of cGVHD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pleurais/etiologia , Complicações Pós-Operatórias/etiologia , Alquilantes/efeitos adversos , Aloenxertos , Bronquiolite Obliterante/complicações , Doença Crônica , Tecido Elástico/patologia , Doença Enxerto-Hospedeiro/complicações , Humanos , Doenças Pulmonares Intersticiais/patologia , Tecido Parenquimatoso/patologia , Doenças Pleurais/patologia , Complicações Pós-Operatórias/patologia
18.
Immunobiology ; 224(4): 551-559, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31072629

RESUMO

An early diagnosis of interstitial lung disease (ILD) is important for guiding treatments of rheumatoid arthritis (RA)-associated ILD (RA-ILD) in clinical settings. The non-canonical Wnt signaling representative ligand Wnt5a was recently found to involve in idiopathic pulmonary fibrosis (IPF) and pathogenesis of RA. The goal of this study was to examine the clinical relevance of Wnt5a in RA-ILD. In this report, the clinical relevance of plasma Wnt5a protein was evaluated in 40 RA-ILD patients and 41 non-ILD RA cohorts. The results showed an elevated Wnt5a protein in plasmas of RA-ILD patients compared with non-ILD RA patients (p < 0.01), which was positively correlated with the plasma level of rheumatoid factor (RF). Of note, more abundant Wnt5a was also found in patients with usual interstitial pneumonia (UIP) than those with nonspecific interstitial pneumonia (NSIP) and other ILD patterns. More importantly, the disease severity was correlated with the circulating Wnt5a as ascertained by high-resolution computed tomography (HRCT)-UIP scores. The multiple-factor non-conditional logistic regression analysis further revealed that the age, RA duration, smoking and plasma Wnt5a were risk factors with clinical significance for RA-ILD. Interestingly, more Wnt5a-positive patients were identified in RA-ILD smokers relative to RA-ILD never-smokers, and longer smoking duration was strongly correlated with Wnt5a in RA-ILD patients. In consistence, ROC curve also suggested that the Wnt5a was a potential candidate biomarker for identifying patients with RA-UIP. These results demonstrate that the circulating Wnt5a may be a risk factor and potential biomarker for identifying UIP and accessing the severity and progression of ILD in RA patients.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Proteína Wnt-5a/sangue , Biomarcadores , Progressão da Doença , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Curva ROC , Radiografia Torácica , Fatores de Risco , Tomografia Computadorizada por Raios X
19.
N Engl J Med ; 380(26): 2518-2528, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31112379

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).


Assuntos
Inibidores Enzimáticos/uso terapêutico , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Escleroderma Sistêmico/complicações , Administração Oral , Adulto , Diarreia/induzido quimicamente , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico , Capacidade Vital
20.
Pan Afr Med J ; 32: 40, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31143345

RESUMO

Anti-synthetase syndrome (ASS) is an inflammatory myopathy commonly associated with pulmonary involvement, especially parenchymal (diffuse infiltrative pneumonitis). Extrathoracic manifestations associated with pulmonary involvement can give an indication to the diagnosis: myalgias, polyarthralgias, Raynaud's syndrome, erythematous palmar hyperkeratosis with fissures and fever. Given the suggestive clinical and radiological picture, the presence of aminoacyl-transfer RNA (tRNA) synthetase antibodies enables to confirm, in particular, Anti Jo-1 antibody activity. Pulmonary involvement is a major prognostic factor, hence the indication for intensive immunosuppressive therapy based on corticosteroids, immunosuppressive medications or the association among them. A better awareness about this disorder revealed by pulmonary manifestations could enable early and adequate management and to improve patient's prognosis.


Assuntos
Imunossupressores/administração & dosagem , Doenças Pulmonares Intersticiais/etiologia , Miosite/diagnóstico , Corticosteroides/administração & dosagem , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Miosite/tratamento farmacológico , Miosite/imunologia , Prognóstico
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