RESUMO
BACKGROUND: Swallowing is a complex process that requires the coordination of muscles in the mouth, pharynx, larynx, and esophagus. Dysphagia occurs when a person has difficulty swallowing. In the case of subjects with respiratory diseases, the presence of oropharyngeal dysphagia potentially increases lung disease exacerbations, which can lead to a rapid decline in lung function. This study aimed to analyze the swallowing of patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients with IPF were evaluated using the Eating Assessment Tool (EAT-10), tongue pressure, the Timed Water Swallow Test (TWST), and the Test of Mastication and Swallowing Solids (TOMASS). The findings were related to dyspnea severity assessed by the modified Medical Research Counsil (mMRC) score; the nutritional status screened with Mini Nutritional Assessment (MNA) tool; and pulmonary function tests, specifically spirometry and measurement of the diffusing capacity for carbon monoxide (DLCO), the maximal inspiratory pressure (PImax), and the maximal expiratory pressure (PEmax). RESULTS: The sample consisted of 34 individuals with IPF. Those who exhibited swallowing modifications scored lower on the MNA than those who did not (9.6 ± 0.76 vs. 11.64 ± 0.41 points; mean difference 1.98 ± 0.81 points; p = 0.02). They also showed poorer lung function when considering the predicted force vital capacity (FVC; 81.5% ± 4.61% vs. 61.87% ± 8.48%; mean difference 19.63% ± 9.02%; p = 0.03). The speed of liquid swallowing was altered in 31of 34 of the evaluated subjects (91.1%). The number of liquid swallows correlated significantly with the forced expiratory volume in 1 s (FEV1)/FVC ratio (r = 0.3; p = 0.02). Solid eating and swallowing assessed with the TOMASS score correlated with lung function. The number of chewing cycles correlated negatively with PImax% predicted (r = -0.4; p = 0.0008) and PEmax% predicted (r = -0.3; p = 0.02). FVC% predicted correlated with increased solid swallowing time (r = -0.3; p = 0.02; power = 0.6). Swallowing solids was also impacted by dyspnea. CONCLUSION: Patients with mild-to-moderate IPF can present feeding adaptations, which can be related to the nutritional status, lung function, and the severity of dyspnea.
Assuntos
Transtornos de Deglutição , Deglutição , Fibrose Pulmonar Idiopática , Língua , Humanos , Masculino , Feminino , Idoso , Fibrose Pulmonar Idiopática/fisiopatologia , Fibrose Pulmonar Idiopática/complicações , Deglutição/fisiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Pessoa de Meia-Idade , Língua/fisiopatologia , Testes de Função Respiratória , Pressão , Estado Nutricional , Pulmão/fisiopatologia , Dispneia/fisiopatologia , Dispneia/etiologia , Avaliação Nutricional , Idoso de 80 Anos ou maisRESUMO
Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: We sought to assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: In a Phase 2, randomized (1:1:1), double-blind, placebo-controlled study (ClinicalTrials.gov ID: NCT03142191), patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in the percentage of predicted FVC (ppFVC) from baseline to Week 24; secondary endpoints included safety. Measurements and Main Results: In total, 112 patients received at least one dose of study drug. The study was terminated early because of a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% confidence interval: -2.1, 4.3; P = 0.50) and 2.2% (400 mg; 95% confidence interval: -1.1, 5.4; P = 0.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 arms than in the placebo arm experienced cough and dyspnea. Conclusions: Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared with placebo. CC-90001 was generally well tolerated, which was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT03142191).
Assuntos
Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/fisiopatologia , Método Duplo-Cego , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , AdultoRESUMO
Se presenta un estudio observacional compasivo de seguimiento de 20 pacientes portadores de Fibrosis Pulmonar Idiopática tratados con Nintedanib, que muestra que Nintedanib es un medicamento en general bien tolerado, sin efectos adversos serios, que otorga una sobrevida más prolongada que la que cabría esperar en pacientes con esta enfermedad.
A compassionate observational follow-up study of 20 patients with Idiopathic Pulmonary Fibrosis treated with Nintedanib is presented, showing that Nintedanib is a generally well-tolerated drug, with no serious adverse effects, that grants a longer survival in real-life patients.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Inibidores de Proteínas Quinases/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/uso terapêutico , Análise de Sobrevida , Capacidade Vital , Estudos Retrospectivos , Seguimentos , Inibidores de Proteínas Quinases/efeitos adversos , Fibrose Pulmonar Idiopática/fisiopatologia , Indóis/efeitos adversosRESUMO
Idiopathic pulmonary fibrosis (IPF) is a severe interstitial disease with a mean survival of about 2.5-5 years after diagnosis. Its pathophysiology is still a major challenge for science. It is known that angiotensin II (Ang-II) binds AT1 receptor (AT1R) and its overactivation induces fibrosis, inflammation and oxidative stress. In contrast, activation of the Mas receptor (Mas-R) by angiotensin 1-7 opposes the harmful effects induced by Ang-II. Thus, our innovative objective was to analyze, in patients' lung with IPF, the balance between AT1R and Mas-R expression and their possible association with pulmonary spirometric parameters: forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%). One cubic centimeter of lung tissue was obtained from IPF patients (n = 6) and from patients without IPF (n = 6) who underwent bronchial carcinoma resection. Receptor expression was quantified using western blot. AT1R expression was significantly higher (34 %) in patients with IPF (P = 0.006), whereas Mas-R was significantly less expressed (54 %) in these patients' lungs (P = 0.046). There was also a positive correlation between Mas-R expression and FEV1% (r = 0.62, P = 0.03) and FVC% (r = 0.58, P = 0.05). Conversely, AT1R expression was negatively correlated with FEV1% (r = 0.80, P = 0.002) and FVC% (r = 0.74, P = 0.006). In conclusion, our results demonstrated an increased expression of AT1R and reduced expression of Mas-R in the lung of patients with IPF. The dominance of AT1R expression is associated with reduced lung function, highlighting the role of the renin-angiotensin system peptides in the pathophysiology of IPF.
Assuntos
Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proto-Oncogene MasRESUMO
Prediction models for survival at baseline evaluation have been proposed in idiopathic pulmonary fibrosis (IPF) but include diffusion capacity of the lung for carbon monoxide, a test not available in many places. The aim of the present study was to develop a simple new mortality risk scoring system for patients with IPF at initial evaluation without diffusion capacity of the lung for carbon monoxide measurement.A total of 173 patients, 72% males, mean age 70 years, 64% smokers/ex-smokers, were included in a retrospective study. The diagnosis was made by surgical lung biopsy in 40 (23%); in the remaining patients, a usual interstitial pneumonia pattern was present in high-resolution computed tomography. Patients with forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) <0.70 were excluded. Dyspnea was evaluated by magnitude of task on the Mahler scale (Chest 1984). Peripheral oxygen saturation was measured by oximetry at rest and at the end of a 4âminutes step test or a 6-minute walk test.At the end of the follow-up period, 154 (89%) of the patients had died. Based on the univariate Cox proportional-hazards model, survival (P ≤ .10) was related directly to the dyspnea score, presence of cough, lower values of FVC% and FEV1%, lower rest and oxygen desaturation during exercise, and greater FEV1/FVC. By Cox multivariate analysis, the results remained correlated to the survival dyspnea score, FVC%, and exercise peripheral oxygen saturation. A score, using these variables, was developed and was able to discriminate among 3 groups, with high, low, and intermediate survival curves.A prognostic score, taking into account dyspnea, FVC%, and oxygen desaturation during exercise, can estimate survival in IPF.
Assuntos
Monóxido de Carbono/metabolismo , Fibrose Pulmonar Idiopática/mortalidade , Pulmão/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Testes de Função Respiratória , Estudos Retrospectivos , Medição de RiscoRESUMO
La fibrosis pulmonar idiopática (FPI) es una forma específica de neumonía intersticial idiopática, de tipo fibrosante crónica y progresiva, con patrón radiológico y/o histológico de neumonía intersticial usual (NIU). Su patogenia es compleja, el modelo más aceptado actualmente es basado en las células epiteliales alveolares, aberrantemente activadas que conducen a la proliferación de fibroblastos y su diferenciación a miofibroblastos que depositan matriz extracelular y destruyen irreversiblemente la arquitectura pulmonar. No existe un claro factor inicial que explique la activación y posterior mantención del mecanismo de la fibrosis. El factor de crecimiento transformante beta (TGF-β) liberado por las células epiteliales alveolares se ha implicado como unos de los principales conductores de la inducción y proliferación de fibroblastos alterados que persiste mucho tiempo después de la estimulación inicial, lo que explicaría en gran parte el comportamiento clínico progresivo y crónico.
Idiopathic pulmonary fibrosis (IPF) is a specific form of idiopathic interstitial pneumonia, of chronic and progressive fibrosing type, with radiological and / or histological pattern of usual interstitial pneumonia (UIP). Its pathogenesis is complex, the most accepted model currently is based on the fact that the alveolar epithelial cells, aberrantly activated, lead to the proliferation of fibroblasts and their differentiation to myofibroblasts that deposit extracellular matrix and irreversibly destroy the pulmonary architecture. There is no clear initial trigger that explains the activation and subsequent maintenance of the fibrosis mechanism. The transforming growth factor beta (TGF-β), released by the alveolar epithelial cells, has been implicated as one of the main drivers of the induction and proliferation of altered fibroblasts that persists long after the initial stimulation, which would largely explain progressive and chronic clinical behavior.
Assuntos
Humanos , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/fisiopatologia , Fibrose Pulmonar Idiopática/epidemiologia , Fatores de Risco , Fator de Crescimento Transformador beta , Matriz Extracelular , Células Epiteliais AlveolaresRESUMO
La fibrosis pulmonar idiopática (FPI) se ha clasificado en enfermedad leve o temprana-moderada-severa o Avanzada, sin puntos de corte en parámetros clínicos, funcionales o imagenológicos. No existe aún consenso en cual es el principal parámetro que se debe medir. Si bien las variables funcionales como la capacidad vital forzada (CVF), capacidad de difusión de monóxido de carbono (DLCO) y test de caminata de 6 minutos se han utilizado de forma rutinaria en la practica clínica y en los principales estudios clínicos de tratamiento muchas veces no son representativos de la evolución clínica. Por lo anterior se han desarrollado, índices o puntajes compuestos como la escala GAP (Gender-Age-Physiology) que podrían ser útiles en el seguimiento de los pacientes.
Idiopathic pulmonary fibrosis (IPF) has been classified as mild or early - moderate - severe or advanced disease, with no cut-off points in clinical, functional or imaging parameters. There is no consensus yet on which is the main parameter to be measured although the functional variables such as forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO) and 6-minute walk test, have been routinely used in clinical practice and in the main clinical studies of treatment, are often not representative of the clinical evolution. Therefore, composite indices or scores such as the GAP (Gender-Age-Physiology) scale have been developed that could be useful in the follow-up of patients.
Assuntos
Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/fisiopatologia , Testes de Função Respiratória/métodos , Evolução Clínica , Medição de Risco , Tosse/etiologia , Dispneia/etiologiaRESUMO
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an unclear pathogenic mechanism. Components of the renin-angiotensin system (RAS) have a role in the pathogenesis of IPF, specifically, the aspartyl protease renin acts as a profibrotic factor in the lung. However, the concentration of the RAS components renin and soluble (pro)renin receptor (sPRR) have not been previously evaluated neither in serum nor in bronchoalveolar lavage fluid (BAL) of patients with IPF or chronic Hypersensitivity pneumonitis (cHP), a disease which may be confused with IPF. METHODS: The serum levels of renin [IPF patients (n = 70), cHP patients (n = 83), and controls (n = 26)] and sPRR [IPF (n = 28), cHP (37), and controls (n = 20)] were measured by ELISA. Renin was also quantified in BALs of IPF patients and controls by Western blot. RESULTS: We found that the levels of renin were higher in serum samples from IPF patients when compared with cHP patients and controls. Furthermore, BALs from IPF patients had more renin than BALs from controls. Unlike renin, the serum levels of sPRR were lower in IPF and cHP patients than in control individuals. CONCLUSIONS: The high levels of renin in sera and BALs of IPF patients suggest that renin might play a major role in the pathogenesis of IPF. Results from BAL confirm that renin is produced locally in the lung. Serum levels of renin could be used to differentiate IPF from cHP.
Assuntos
Alveolite Alérgica Extrínseca/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Receptores de Superfície Celular/sangue , Renina/metabolismo , ATPases Vacuolares Próton-Translocadoras/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alveolite Alérgica Extrínseca/fisiopatologia , Western Blotting , Líquido da Lavagem Broncoalveolar/química , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismo , Capacidade de Difusão Pulmonar , Capacidade Vital , Adulto JovemRESUMO
Resumen La fibrosis pulmonar es una enfermedad progresiva y de mal pronóstico por lo que el trasplante pulmonar sigue siendo una opción para pacientes bien seleccionados. Objetivo: Evaluar resultados y sobrevida de pacientes con fibrosis pulmonar trasplantados a 8 años de inicio del programa de trasplante. Métodos: Estudio descriptivo de trasplantados de pulmón por fibrosis pulmonar desde agosto de 2010 a julio de 2018. Resultados: De un total de 76 trasplantes, un 68,4% han sido en pacientes con fibrosis pulmonar. La principal indicación fue fibrosis pulmonar idiopática (75%). El puntaje de priorización pulmonar (LAS) promedio fue de 53 y un 32% cumplía con criterios de urgencia. La edad promedio fue 55 años, y se usó técnica unipulmonar en un 98%. La principal complicación quirúrgica fue la estenosis bronquial (7,6%). De las complicaciones médicas precoces destacaron 26 episodios infecciosos y 6 rechazos celulares agudos. La principal complicación tardía fue la disfunción crónica de injerto. Los resultados funcionales promedio pre trasplante, a 1 y 3 años fueron: CVF de 49%, 71% y 70% del valor teórico. Un 40% ha fallecido en el período de seguimiento. La principal causa de mortalidad el primer año post trasplante fueron las infecciones. La sobrevida a 1, 3 y 5 años fue de 86,2%, 65,2% y 59,8% respectivamente. Conclusiones: En trasplante monopulmonar es una opción de tratamiento en estos pacientes, con una sobrevida de 59% a 5 años. Un tercio se trasplanta con criterios de urgencia, siendo las infecciones la principal complicación precoz y la disfunción crónica de injerto la complicación tardía más frecuente.
Pulmonary fibrosis is a progressive disease with a bad prognosis. This situation makes rise lung transplant as a therapeutic option among carefully selected patients. Objective: Evaluate the results and survival rates of patients with pulmonary fibrosis that were transplanted through an 8 years period of follow-up, from the beginning of our transplant program. Methods: Descriptive study of the transplanted patients diagnosed with pulmonary fibrosis from august 2010 to july 2018. Results: Out of 76 transplants, 68.4% were due to pulmonary fibrosis, among these, the main diagnosis was idiopathic pulmonary fibrosis (75%). The average lung allocation score (LAS) was 53 and 32% of them had urgency criteria. Patients ' age averaged 55 years-old and 98% of them underwent a single lung transplant. Early medical complications were seen in 26 patients with infectious episodes and 6 with acute rejection. The main late complication was chronic allograft dysfunction. The main surgical complication was bronchial stenosis (7.6%). In comparison to its base line reference values FVC means pre transplant and 1 and 3 years post-transplant were 49%, 70% and 71% respectively. A 40% of patients died during follow up period. Infections were the main cause of mortality during the first year. Survival rates at 1st 3rd and 5th year were 86,2%; 65.2% and 59.8% respectively. Conclusions: Single lung transplant is a therapeutic option for patients with interstitial lung disease with a 59% survival rate in 5 years, 1/3 fulfilled urgency criteria at the transplant time. The infections were the main early complication and chronic graft dysfunction was the main late complication.