RESUMO
OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. METHODS: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. RESULTS: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). CONCLUSIONS: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.
Assuntos
Pneumopatias , Neoplasias Pulmonares , Linfangioleiomiomatose , Humanos , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/patologia , Estudos Retrospectivos , Pneumopatias/complicações , Biomarcadores , Pulmão , Neoplasias Pulmonares/complicaçõesRESUMO
INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a multisystemic disorder characterized by the proliferation, metastasis, and infiltration of smooth muscle cells in the lung and other tissues. Although LAM is rarely seen in men, it is usually detected in women during the third decade of life. Renal microaneurysms have been reported in patients with LAM, but abdominal aneurysms have not. We describe a patient with a diagnosis of LAM who had an unusual aneurysm in the inferior pancreaticoduodenal artery. CASE PRESENTATION: A 47-year-old Ecuadorian woman self-referred for a routine visit to her family physician. She had a history of allergy to nonsteroidal anti-inflammatory drugs, pneumothorax, bilateral pleurodesis, and LAM since 2007. For her annual follow-up, an ultrasonogram was recommended. The abdominal ultrasonographic report described "a mass with blood flow in the midabdomen." An abdominal computed tomography angiogram was performed and revealed a 2.6-cm aneurysm of the inferior pancreaticoduodenal artery. After diagnosis of arterial aneurysm, she underwent transcatheter arterial embolization and stent placement. She is currently healthy and carries out her activities normally. DISCUSSION: Lymphangioleiomyomatosis is a rare lung disease of unknown etiology. Extrapulmonary manifestations include abdominal aneurysm. This type of lesion should be added to a search for aneurysms in all patients with LAM.
Assuntos
Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Duodeno/irrigação sanguínea , Linfangioleiomiomatose/complicações , Pâncreas/irrigação sanguínea , Tomografia Computadorizada por Raios X , Aneurisma/terapia , Artérias/diagnóstico por imagem , Artérias/cirurgia , Duodeno/diagnóstico por imagem , Duodeno/cirurgia , Embolização Terapêutica/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , StentsRESUMO
Introducción: La linfangioleiomiomatosis Pulmonar (LAM) es una rara y progresiva enfermedad; caracterizada por proliferación excesiva de células musculares lisas a partir de vasos linfáticos, sanguíneos y vías aéreas. En conjunto al anormal crecimiento celular descrito, se aprecia degeneración quística difusa del parénquima pulmonar, lo que puede reflejarse desde cuadros completamente asintomáticos hasta el deterioro severo del intercambio gaseoso con insuficiencia respiratoria fulminante. Descripción del caso: Paciente femenino de 41 años de edad, con cuadro clínico consistente en tos seca ocasional, asociada a dolor leve de características pleuríticas en 'puntada de costado ' derecha. Ante la no mejoría clínica, se indica estudio imagenológico donde se demuestra neumotorax espontáneo derecho. En estudio tomográfico se aprecian además lesiones pulmonares quísticas. El estudio anátomo-patológico demuestra cambios estructurales que se reportan compatibles con LAM. Conclusión: Dada la simplicidad de los síntomas con que la LAM puede debutar, su confirmación diagnóstica se genera en fases avanzadas de la enfermedad, cuando el daño pulmonar importante conlleva a la aparición de factores clínicos con mayor repercusión sobre el estado general de los pacientes por lo que la realización de estudios imagenológicos tempranos gana vital importancia.
Introduction: Pulmonary lymphangioleiomyomatosis (LAM) is a rare and progressive disease; characterized by airway, lymphatic and blood vessels-smooth muscle cells excessive proliferation. Added to the abnormal cell growth, parenchymal cystic degeneration is present, which can be reflected initially as a asymptomatic course and can progress to severe gaseous exchange deterioration and fulminating respiratory insufficiency. Case description: A 41-year-old female patient with a clinical course consisting of occasional dry cough, associated with mild pleuritic pain on the right side of thorax. As no improvement was achieved, thoracic imaging study was performed, where a right pneumothorax was found. Tomography images showed multiple lung cystic lesions. Anatomopathological study reports structural changes compatible with LAM. Conclusion: Given the simplicity of the symptoms that LAM can debut with, its diagnostic confirmation is generated in advanced stages of the disease, when the important pulmonary damage leads to the appearance of clinical factors with greater impact on the general state of patients so early thoracic imaging studies gain vital importance.
Assuntos
Humanos , Feminino , Adulto , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Pneumotórax/etiologia , Espirometria , Radiografia Torácica , Tomografia Computadorizada por Raios X , Linfangioleiomiomatose/complicações , Sirolimo/uso terapêutico , Cistos/etiologia , Neoplasias Pulmonares/complicaçõesAssuntos
Dispneia/diagnóstico , Neoplasias Renais/diagnóstico , Pulmão/diagnóstico por imagem , Linfangioleiomiomatose/diagnóstico , Pneumotórax/diagnóstico , Adolescente , Dispneia/etiologia , Dispneia/terapia , Serviços Médicos de Emergência , Feminino , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/terapia , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/terapia , Nefrectomia , Pneumotórax/etiologia , Pneumotórax/terapia , Radiografia , Recidiva , ToracostomiaRESUMO
A middle-aged female patient, previously diagnosed with asthma, presented with a large spontaneous left pneumothorax. She had a history of nephrectomy for a ruptured renal angiomyolipoma (AML) with a postoperative spontaneous pneumothorax when she was an adolescent. High-resolution CT chest revealed multiple scattered thin-walled lung parenchyma cysts consistent with lymphangioleiomyomatosis (LAM). Hepatic AMLs and adenoma sebaceum skin lesions were also noted, consistent with an overall diagnosis of tuberous sclerosis. Her acute management included lung re-expansion via chest tube insertion, antibiotics for concurrent chest infection, nebulisation and chest physiotherapy. Since discharge, the patient had only occasional shortness of breath, relieved by bronchodilators. She is considering expanded immunisation as well as enrolment in a clinical trial. Her hepatic AMLs will be monitored via ultrasound for growth. LAM treatment is generally aimed at its complications with lung transplantation reserved for severe disease; however, hormonal therapy and the mTOR inhibitor aim at targeting systemic disease.
Assuntos
Linfangioleiomiomatose/diagnóstico , Pneumotórax/etiologia , Esclerose Tuberosa/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/terapia , Pneumotórax/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Esclerose Tuberosa/complicações , Esclerose Tuberosa/terapiaRESUMO
RATIONALE: Lymphangioleiomyomatosis (LAM) is characterized by exercise performance impairment. Although airflow limitation is common, no previous studies have evaluated the prevalence and impact of dynamic hyperinflation (DH) in LAM. OBJECTIVES: To investigate the dynamic responses during maximal exercise and the prevalence, predictors, and repercussions of DH in LAM. METHODS: Forty-two patients with LAM performed symptom-limited incremental cycle exercise and pulmonary functions tests (PFTs) and were compared with 10 age-matched healthy women. Dyspnea intensity, inspiratory capacity, oxygen saturation, and cardiac, metabolic, and respiratory variables were assessed during exercise. Patients with LAM also performed a 6-minute walk test (6MWT). MEASUREMENTS AND MAIN RESULTS: Patients with LAM had higher baseline dyspnea, poorer quality of life, obstructive pattern, air trapping, and reduced diffusing capacity of carbon monoxide in PFTs. Although they had the same level of regular physical activity, their maximal exercise performance was reduced and was associated with ventilatory limitation, greater desaturation, and dyspnea. The prevalence of DH was high in LAM (55%), even in patients with mild spirometric abnormalities, and was correlated with airflow obstruction, air trapping, and diffusing capacity of carbon monoxide. Compared with the non-DH subgroup, the patients who developed DH had a ventilatory limitation contributing to exercise cessation on cycling and higher desaturation and dyspnea intensity during the 6MWT. CONCLUSIONS: Ventilatory limitation and gas exchange impairment are important causes of exercise limitation in LAM. DH is frequent in LAM, even in patients with mild spirometric abnormalities. DH was associated with the severity of disease, higher dyspnea, and lower oxygen saturation. In the 6MWT, desaturation and dyspnea were greater in patients with DH.
Assuntos
Tolerância ao Exercício , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Dispneia/diagnóstico , Dispneia/etiologia , Dispneia/fisiopatologia , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Feminino , Volume Expiratório Forçado , Humanos , Capacidade Inspiratória , Esforço Físico , Testes de Função Respiratória/métodos , Testes de Função Respiratória/estatística & dados numéricosRESUMO
A Linfangioleiomiomatose (LAM) é uma doença sistêmica rara, de etiologia desconhecida, que afeta quase exclusivamente mulheres em idade reprodutiva. Caracterizada pela proliferação atípica de células musculares lisas em diversos órgãos, especialmente pulmão, que leva ao desenvolvimento de um distúrbio ventilatório obstrutivo, de caráter progressivo, com hiperinsuflação pulmonar e diminuição da difusão de monóxido de carbono, devido aos inúmeros cistos que formados no parênquima pulmonar. A manifestação clínica mais comumé o pneumotórax. O fator hormonal tem sido exposto como coadjuvante no desenvolvimento da doença, já que esta atinge quase que exclusivamente indivíduos do sexo feminino e se intensifica durante a gestação. Pesquisas recentes verificaram ao corrência de mutações genéticas e presença de lesões que estão associadas à doença Esclerose Tuberosa; porém, há necessidadede mais estudos para afirmar essa correlação. O presente relatorefere-se a paciente do sexo feminino, 45 anos de idade, brasileira,leucoderma, com diagnóstico de Linfangioleiomiomatose que compareceu ao ambulatório de Odontologia do Instituto do Coração do Hospital das Clínicas (FMUSP), encaminhada pelo Departamento de Pneumologia, para avaliação odontológica pré-operatória de transplante pulmonar. Paciente contactuante,com dispneia e uso contínuo de cateter de oxigênio, apresentando em cadeira de rodas para mínimo esforço físico. Higiene oral insatisfatória evidenciada pela presença de tártaro, raiz residual inaproveitável e lesões cariosas. Sabe-se que a infecção está entre as maiores causas de perda do órgão recebido pelo transplantado e, por isso, a atuação do cirurgião-dentista é de suma importância para prevenir quadros sistêmicos infecciosos decorrentes de focos bucais, pré e pós-transplante.
The Lymphangioleiomyomatosis (LAM) is a rare systemic disease of unknown etiology that affects mainly women atreproductive age. Characterized by an atypical proliferation of smooth muscle cells in various organs, especially in thelungs, which leads to the development of obstructive lung disease, a progressive character, with hyperinflation anddecreased lung diffusion of carbon monoxide due to the numerous cysts that are formed in the lung parenchyma.The most common clinical manifestation is pneumothorax. The hormonal factor has been exposed as an adjuvant in thedevelopment of the disease since it affects almost exclusively women and intensifies during pregnancy. Recent researches verified the occurrence of mutations and genetic lesions thatare associated with the disease Tuberous Sclerosis, but further studies are necessary in order to affirm this correlation. This report refers to a female patient, 45 years of age, Brazilian, leukoderma, diagnosed with Lymphangioleiomyomatosis who attended the outpatient clinic of Dentistry from the Heart Institute, Hospital das Clínicas (FMUSP) forwarded by the Department of Pulmonology, for a lung transplantpreoperative dental evaluation. Patient with dyspnea and continuous use of oxygen catheter, performing in a wheelchair for minimal physical effort. Poor oral hygiene evidenced by the presence of tartar, root caries and residual unusable. It is known that infection is among the biggest causes of loss of the transplanted organ by the receiver and, therefore, the role of the dentist is very important to prevent systemic frameworks infectious foci resulting from oral pre-andpost-transplant.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Odontologia , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/diagnóstico , PneumologiaRESUMO
BACKGROUND: Lymphangioleiomyomatosis (LAM) is characterised by progressive airway obstruction and hypoxaemia in young women. Although sleep may trigger hypoxaemia in patients with airway obstruction, it has not been previously investigated in patients with LAM. METHODS: Consecutive women with lung biopsy proven LAM and absence of hypoxaemia while awake were evaluated with pulmonary function test, echocardiography, 6-min walk test, overnight full polysomnography, and Short Form 36 health-related quality-of-life questionnaire. RESULTS: Twenty-five patients with (mean±SD) age 45±10 years, SpO(2) awake 95%±2, forced expiratory volume in the first second (median-interquartile) FEV(1)(% predicted) 77 (47-90) and carbonic monoxide diffusion capacity, DL(CO) (%) 55 (34-74) were evaluated. Six-minute walk test distance and minimum SpO(2) (median-interquartile) were, respectively, 447m (411-503) and 90% (82-94). Median-interquartile apnoea-hypopnoea index was in the normal range 2 (1-5). Fourteen patients (56%) had nocturnal hypoxaemia (10% total sleep time with SpO(2) <90%), and the median sleep time spent with SpO(2) <90% was 136 (13-201)min. Sleep time spent with SpO(2) <90% correlated with the residual volume/total lung capacity ratio (r(s)=0.5, p: 0.02), DL(CO) (r(s)=-0.7, p: 0.001), FEV(1) (r(s)=-0.6, p: 0.002). Multivariate linear regression model showed that RV/TLC ratio was the most important functional variable related to sleep hypoxaemia. CONCLUSION: Significant hypoxaemia during sleep is common in LAM patients with normal SpO(2) while awake, especially among those with some degree of hyperinflation in lung function tests.