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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2019.tde-09122019-163223
Document
Author
Full name
Glaucia Itamaro Heiden
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Baldi, Bruno Guedes (President)
Fernandes, Caio Julio Cesar dos Santos
Ramos, Roberta Pulcheri
Rodrigues, Silvia Carla Sousa
Title in Portuguese
Avaliação dos mecanismos determinantes de limitação ao esforço e da capacidade de exercício em pacientes com histiocitose pulmonar de células de Langerhans
Keywords in Portuguese
Doenças pulmonares intersticiais
Hipertensão pulmonar
Histiocitose de células de Langerhans
Qualidade de vida
Teste de esforço
Testes de função respiratória
Abstract in Portuguese
Introdução: A histiocitose pulmonar de células de Langerhans (HPCL) é uma doença cística difusa, associada ao tabagismo e que determina redução da capacidade de exercício. Os mecanismos aventados para menor capacidade de exercício são limitação ventilatória, limitação cardiocirculatória, incluindo aquela sugestiva de hipertensão pulmonar (HP), hiperinsuflação dinâmica (HD) e distúrbio de troca gasosa. Objetivos: Avaliar os mecanismos de limitação ao esforço, capacidade de exercício, prevalência de HP e características clínicas, funcionais e hemodinâmicas em pacientes com HPCL. Além disso, avaliar os fatores preditores de limitação ao esforço e de HP. Métodos: Em um estudo transversal, 35 pacientes com HPCL foram submetidos à avaliação clínica, ecocardiograma transtorácico, teste de caminhada de seis minutos, testes de função pulmonar e teste cardiopulmonar de exercício (TCPE) incremental em esteira com avaliação de HD. Os pacientes, com capacidade de difusão do monóxido de carbono (DLCO) menor que 40% do predito e/ou ecocardiograma transtorácico com velocidade de regurgitação tricúspide (VRT) maior que 2,5 m/s e/ou achados indiretos de HP, foram submetidos ao cateterismo cardíaco direito (CCD) para a confirmação de HP pela medida da pressão média de artéria pulmonar (PAPm). Resultados: Trinta e cinco pacientes foram incluídos (68% mulheres, com idade de 47 ± 11 anos, 91% com história de tabagismo e índice basal de dispneia de 8 ± 3). No TCPE, limitação ventilatória, cardiocirculatória e sugestiva de HP ocorreram respectivamente em 58%, 63% e 29% dos casos, sendo multifatorial em 71% dos pacientes. O consumo máximo de oxigênio (O2 pico) foi de 73 ± 19% do predito, sendo reduzido em 70% dos pacientes. Ocorreu HD no TCPE em 68% dos pacientes. Volume expiratório forçado no primeiro segundo (VEF1), relação entre volume residual e capacidade pulmonar total (VR/CPT) e DLCO foram, respectivamente, 64 ± 22% do predito, 44 ± 11 e 56 ± 21% do predito. Ocorreram redução da DLCO, obstrução, e aprisionamento aéreo, respectivamente, em 80%, 77% e 37% dos pacientes. A VRT foi 3,0 (2,4 - 3,2) m/s. Dezoito pacientes foram submetidos ao CCD, com PAPm de 32 ± 12 mmHg. A prevalência de HP na amostra de HPCL foi de 41% (IC95% = 24 - 59%), sendo pré-capilar em 85% dos casos. A PAPm correlacionou-se com VEF1, DLCO, O2 % do O2 pico no limiar anaeróbico no TCPE e VRT no ecocardiograma. VEF1 e DLCO apresentaram boa acurácia para predizer uma redução da capacidade de exercício. Conclusão: A limitação ao exercício é multifatorial e frequente nos pacientes com HPCL. Os mecanismos mais prevalentes incluem limitações ventilatória, cardiocirculatória e sugestiva de HP. Hipertensão pulmonar também é frequente na HPCL, predominantemente pré-capilar
Title in English
Evaluation of the mechanisms determinants of exercise limitation and the exercise capacity in patients with pulmonary Langerhans cell histiocytosis
Keywords in English
Exercise test
Interstitial lung diseases
Langerhans cell histiocytosis
Lung function tests
Pulmonary hypertension
Quality of life
Abstract in English
Introduction: Pulmonary Langerhans cell histiocytosis (PLCH) is a smokingrelated diffuse cystic disease, which determines reduced exercise capacity. The speculated mechanisms of exercise limitation in PLCH include ventilatory limitation, dynamic hyperinflation (DH), cardiocirculatory limitation that encompasses pulmonary hypertension (PH) and impaired gas exchange. Objectives: To evaluate the mechanisms of exercise limitation and to define the exercise capacity, the prevalence of PH and clinical, functional and hemodynamic characteristics in patients with PLCH. In addition, to evaluate the predictors of effort limitation and PH. Methods: In a cross-sectional study, 35 patients with PLCH underwent clinical evaluation, transthoracic echocardiography, six-minute walk test, pulmonary function tests, and incremental treadmill cardiopulmonary exercise test (CPET) with evaluation of DH. Those patients with carbon monoxide diffusion capacity (DLCO) less than 40% of predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity (TRV) greater than 2.5 m/s and/or with indirect PH signs underwent right heart catheterisation (RHC) to confirm the diagnosis of PH based on the mean pulmonary artery pressure (mPAP). Results: Thirtyfive patients were included (68% were women, with 47 ± 11 years old, 91% were current or ex- smokers and with baseline dyspnea index of 8 ± 3). At CPET, ventilatory limitation, cardiocirculatory limitation and impairment suggestive of PH occurred in 58%, 63%, and 29% of patients, respectively. The limitation was multifactorial in 71% of cases. The maximum oxygen consumption ( O2 peak) was 73 ± 19% of predicted, and was reduced in 70% of patients. Dynamic hyperinflation occurred in 68% of patients. Forced expiratory volume in the first second (FEV1), residual volume and total lung capacity ratio (RV/TLC) and DLCO were 64 ± 22% of predicted, 44 ± 11 and 56 ± 21% of predicted, respectively. Reduction in DLCO, an obstructive pattern, and air trapping occurred in 80%, 77% and 37% of patients, respectively. The TRV was 3.0 (2.4 - 3.2) m / s. Eighteen patients underwent CCD, and the mPAP obtained was 32 ± 12 mmHg. The prevalence of PH was 41% (CI95% = 24 - 59%), with pre-capillary pattern in 85% of cases. There was a correlation between mPAP and FEV1, DLCO, O2% of O2 peak at the anaerobic threshold in the CPET and TRV in echocardiogram. FEV1 and DLCO presented good accuracy to predict reduction of exercise capacity. Conclusion: Exercise limitation is multifactorial and frequent in patients with PLCH. The most prevalent mechanisms include ventilatory, cardiocirculatory and suggestive of PH limitations. Pulmonary hypertension is also common in PLCH, predominantly pre-capillary
 
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Publishing Date
2019-12-10
 
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