ABSTRACT
RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.
ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/administration & dosage , Aspartate Aminotransferases/analysis , Time Factors , Vomiting/chemically induced , Algorithms , Brazil , Vital Capacity/drug effects , Reproducibility of Results , Treatment Outcome , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Diarrhea/chemically induced , Drug Tolerance , Chemical and Drug Induced Liver Injury/etiology , Transaminases/analysis , Indoles/adverse effects , Nausea/chemically inducedABSTRACT
BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.
Subject(s)
Humans , Biomarkers/analysis , Latent Tuberculosis/diagnosis , Latent Tuberculosis/immunology , Flow Cytometry , Case-Control Studies , Prospective Studies , Interferon-gamma Release Tests , Neutrophils/immunologyABSTRACT
Na avaliação funcional respiratória, alguns pacientes que irão submeter-se a prova de função respiratória (PFR) apresentam deformidades da coluna vertebral. Estes pacientes podem, ocasionalmente, possuir grandes angulações da coluna, acarretando diminuição da sua estatura. Com isto, serão determinados valores menores do teórico previstos, na PFR... Conseguimos valores da relação envergadura/altura diferentes da literatura de Hepper: 1,06 para homens e 1,03 para mulheres, com significância estatística (p < 0,001). Verificamos que os valores da relação/altura sentada e envergadura/distância ombro-sacro para homens eram 2,04 e 1,96 e para mulheres de 2,99 e 2,90, respectivamente. A diferença do valor encontrado da relação envergadura/altura deve-se à constituição antropométrica das populações comparadas (Hepper - brancos da América do Norte e neste trabalho - brasileiros. Há necessidade de corrigir a altura em pacientes com doença do esqueleto axial, pelos valores das relações encontradas deste estudo, para que não ocorra diminuição dos valores do teórica previsto na PFR.