RESUMO
Authors present a pilot study of the development of innovative flow cytometry-based assay with a potential for use in tuberculosis diagnostics. Currently available tests do not provide robust discrimination between latent tuberculosis infection (TBI) and tuberculosis disease (TB). The desired application is to distinguish between the two conditions by evaluating the production of a combination of three cytokines: IL-2 (interleukin-2), IFNÉ£ (interferon gamma) and TNFÉ (tumor necrosis factor alpha) in CD4+ and CD8+ T cells. The study was conducted on 68 participants, divided into two arms according to age (paediatric and adults). Each arm was further split into three categories (non-infection (NI), TBI, TB) based on the immune reaction to Mycobacterium tuberculosis (M.tb) after a close contact with pulmonary TB. Each blood sample was stimulated with specific M.tb antigens present in QuantiFERON tubes (TB1 and TB2). We inferred TBI or TB based on the predominant cytokine response of the CD4+ and/or CD8+ T cells. Significant differences were detected between the NI, TBI and the TB groups in TB1 in the CD4+TNFÉ+parameter in children. Along with IL-2, TNFÉ seems to be the most promising diagnostic marker in both CD4+and CD8+ T cells. However, more detailed analyses on larger cohorts are needed to confirm the observed tendencies.
Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Citometria de Fluxo , Interferon gama , Interleucina-2 , Tuberculose Latente , Mycobacterium tuberculosis , Humanos , Criança , Tuberculose Latente/diagnóstico , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Citometria de Fluxo/métodos , Adulto , Mycobacterium tuberculosis/imunologia , Linfócitos T CD8-Positivos/imunologia , Masculino , Feminino , Linfócitos T CD4-Positivos/imunologia , Interleucina-2/sangue , Projetos Piloto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Interferon gama/sangue , Interferon gama/imunologia , Pré-Escolar , Citocinas/sangue , Citocinas/metabolismo , Biomarcadores/sangue , Fator de Necrose Tumoral alfa/sangue , Diagnóstico Diferencial , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/sangue , Valor Preditivo dos Testes , Antígenos de Bactérias/imunologia , Testes de Liberação de Interferon-gama/métodos , IdosoRESUMO
INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT). RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.
Assuntos
Antifibróticos , Substituição de Medicamentos , Fibrose Pulmonar Idiopática , Sistema de Registros , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Antifibróticos/uso terapêutico , Capacidade Vital , Progressão da Doença , Piridonas/uso terapêutico , IndóisRESUMO
There are limited data on referral rates and the number of patients with idiopathic pulmonary fibrosis (IPF) who are eligible for lung transplantation. The aim of the present study was to assess adherence to the consensus of the International Society for Heart and Lung Transplantation (ISHLT) for the referral of patients with IPF among Czech interstitial lung disease (ILD) centers. Czech patients who were diagnosed with IPF between 1999 and 2021 (n = 1584) and who were less than 65 years old at the time of diagnosis were retrospectively selected from the Czech Republic of the European Multipartner Idiopathic Pulmonary Fibrosis Registry (EMPIRE). Nonsmokers and ex-smokers with a body mass index (BMI) of <32 kg/m2 (n = 404) were included for further analyses. Patients with a history of cancer <5 years from the time of IPF diagnosis, patients with alcohol abuse, and patients with an accumulation of vascular comorbidities were excluded. The trajectory of individual patients was verified at the relevant ILD center. From the database of transplant patients (1999-12/2021, n = 541), all patients who underwent transplantation for pulmonary fibrosis (n = 186) were selected, and the diagnosis of IPF was subsequently verified from the patient's medical records (n = 67). A total of 304 IPF patients were eligible for lung transplantation. Ninety-six patients were referred to the transplant center, 50% (n = 49) of whom were referred for lung transplantation. Thirty percent of potentially eligible patients not referred to the transplant center were considered to have too many comorbidities by the reporting physician, 19% of IPF patients denied lung transplantation, and 17% were not referred due to age. Among Czech patients with IPF, there may be a larger pool of potential lung transplant candidates than has been reported to the transplant center to date.
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Fibrose Pulmonar Idiopática , Transplante de Pulmão , Encaminhamento e Consulta , Humanos , Fibrose Pulmonar Idiopática/cirurgia , Transplante de Pulmão/estatística & dados numéricos , República Tcheca , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Feminino , Masculino , Estudos Retrospectivos , Fidelidade a Diretrizes/estatística & dados numéricos , Doenças Pulmonares Intersticiais/cirurgia , Sistema de Registros , Adulto , IdosoRESUMO
BACKGROUND: Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. AIMS: To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. METHODS: Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. RESULTS: There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). CONCLUSION: CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Quimiocinas , Biomarcadores , Quimiocina CCL8 , Quimiocina CCL2 , Quimiocina CXCL12RESUMO
Enormous progress has been made on the epic journey towards implementation of lung cancer screening in Europe. A breakthrough for lung health has been achieved with the EU proposal for a Council recommendation on cancer screening. https://bit.ly/3J4O0Jb.