Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms. There is no curative clinical treatment for COPD. In this context, cell-based therapy is a promising therapeutic alternative for COPD. Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD. The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association. METHODS: To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group - patients receiving conventional treatment; BMMC group - patients receiving only BMMC; ADSC group - patients receiving only ADSC, and co-infusion group - patients receiving the concomitant infusion of BMMC and ADSC. Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up. RESULTS: No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion. In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures. Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO). Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life. CONCLUSION: The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD. However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.

Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension.

The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.

Impact of activities in self-esteem of patients in a pulmonary rehabilitation program.

OBJECTIVE: To evaluate self-esteem and self-image of respiratory diseases patients in a Pulmonary Rehabilitation Program, who participated in socialization and physical fitness activities, and of patients who participated only in physical fitness sessions. METHODS: A descriptive cross-sectional exploratory study. Out of a total of 60 patients analyzed, all enrolled in the Pulmonary Rehabilitation Program, 42 participated in at least one of the proposed activities, 10 did not participate in any activity and 8 were excluded (7 were discharged and 1 died). RESULTS: When the two groups were compared, despite the fact that both demonstrated low self-esteem and self-image, the difference between them was relevant (p<0.05) regarding self-esteem, indicating that those who participated in the proposed socialization activities had better self-esteem than the individuals who only did the physical fitness sessions. Regarding self-image, the difference between the groups was not relevant (p>0.05). CONCLUSION: The Pulmonary Rehabilitation Program patients evaluated presented low self-esteem and self-image; however, those carrying out some socialization activity proposed had better self-esteem as compared to the individuals who did only the physical fitness sessions.

Impact of activities in self-esteem of patients in a pulmonary rehabilitation program / Impacto das atividades na autoestima dos pacientes em um programa de reabilitação pulmonar

Objective To evaluate self-esteem and self-image of respiratory diseases patients in a Pulmonary Rehabilitation Program, who participated in socialization and physical fitness activities, and of patients who participated only in physical fitness sessions. Methods A descriptive cross-sectional exploratory study. Out of a total of 60 patients analyzed, all enrolled in the Pulmonary Rehabilitation Program, 42 participated in at least one of the proposed activities, 10 did not participate in any activity and 8 were excluded (7 were discharged and 1 died). Results When the two groups were compared, despite the fact that both demonstrated low self-esteem and self-image, the difference between them was relevant (p<0.05) regarding self-esteem, indicating that those who participated in the proposed socialization activities had better self-esteem than the individuals who only did the physical fitness sessions. Regarding self-image, the difference between the groups was not relevant (p>0.05). Conclusion The Pulmonary Rehabilitation Program patients evaluated presented low self-esteem and self-image; however, those carrying out some socialization activity proposed had better self-esteem as compared to the individuals who did only the physical fitness sessions. .

Objetivo Avaliar a autoestima e a autoimagem de pacientes com doenças respiratórias de um Programa de Reabilitação Pulmonar, que participaram de atividades de socialização e de treinamento físico e de pacientes que participaram apenas de treinamentos físicos. Métodos Estudo exploratório descritivo e transversal. Foram analisados 60 pacientes, todos inclusos em um Programa de Reabilitação Pulmonar. Destes, 42 participaram de pelo menos uma das atividades propostas, 10 não participaram das atividades e 8 foram excluídos (7 tiveram alta e 1 faleceu), não respondendo ao questionário de autoimagem e autoestima. Resultados Quando comparados os dois grupos, apesar de ambos terem apresentado autoestima e autoimagem baixas, a diferença entre eles foi significativa (p<0,05) com relação à autoestima: aqueles que participaram de atividades de socialização propostas pela equipe tiveram autoestima melhor que a dos sujeitos que participam apenas do treinamento físico. Já quanto à autoimagem, a diferença entre os grupos não foi significativa (p>0,05). Conclusão Os pacientes do Programa de Reabilitação Pulmonar avaliados apresentaram baixas autoestima e autoimagem, porém aqueles que realizaram alguma atividade de socialização proposta tiveram a autoestima maior comparada à dos que fizeram apenas o treinamento físico. .

Comparison between the 6-minute walk tests performed in patients with chronic obstructive pulmonary disease at different altitudes / Comparação entre os testes de caminhada de 6 minutos realizados em pacientes com doença pulmonar obstrutiva crônica em diferentes altitudes

Objective To evaluate the influence of the altitude on the 6-minute walking test in patients with moderate to severe pulmonary disease. Methods Twenty-nine patients performed the 6-minute walk test at a pulmonary rehabilitation clinic in Santo André (above sea level), in São Paulo State, and at the Enseada Beach, in Guarujá (at sea level), also in São Paulo State. Of these 29 patients, 8 did the test both on hard sand and on asphalt to analyze if there were differences in performance during the tests. Data such as heart rate, oxygen saturation, test distance, and Borg scale were compared. Results We found no statistical difference in relation to oxygen saturation at rest before the beginning of the walking test in Santo André 94.67±2.26% and at sea level 95.56±2% (p=0.71). The minimum saturation measured during the test was 87.27±6.54% in Santo André and 89.10±5.41% in Guarujá (p=0.098). There were no differences in the performed distance between the different kinds of terrains; the distance on sand was 387.75±5.02m and on asphalt it was 375.00±6.54m (p=0.654). Regarding oxygen saturation during walking, the pulse oximetry on sand was 95.12±1.80% and on asphalt it was 96.87±1.64% (p=1.05). Conclusion Altitude did not affect the performance of the walking test in patients with moderate to severe pulmonary disease and the results were similar in both cases, on sand and on asphalt. .

Objetivo Avaliar a influência da altitude no teste de caminhada de 6 minutos em pacientes com doença pulmonar moderada a grave. Métodos Vinte e nove pacientes realizaram o teste de caminhada de 6 minutos em um ambulatório de reabilitação pulmonar, na cidade de Santo André (acima do nível do mar), em São Paulo, e na praia da Enseada no Guarujá (ao nível do mar), também em São Paulo. Destes, oito pacientes realizaram tanto na areia batida como no asfalto, para avaliar a existência de alguma alteração no desempenho durante o teste. Dados como frequência cardíaca, saturação de oxigênio, distância do teste e escala de Borg foram comparados. Resultados Não encontramos diferença estatística em relação à saturação de oxigênio em repouso antes do início do teste de caminhada em Santo André 94,67±2,26% e ao nível do mar 95,56±2% (p=0,71). A saturação mínima obtida durante os testes foi de 87,27±6,54%, em Santo André, e de 89,10±5,41%, no Guarujá (p=0,098). Não houve diferença na distância percorrida e nos diferentes tipos de piso; a distância na areia foi de 387,75±5,02m e 375,00±40,88m no asfalto (p=0,654). Quanto à saturação durante a caminhada, a oximetria de pulso na areia foi de 95,12±1,80% e no asfalto foi de 96,87±1,64% (p=1,05), ou seja, o teste foi reprodutível em ambos os solos. Conclusão A altitude não influenciou o desempenho do teste de caminhada realizado por pacientes com doença pulmonar moderada a grave, sendo reprodutível tanto acima quanto ao nível do mar, mesmo ...

Selectins and platelet-derived growth factor (PDGF) in schistosomiasis-associated pulmonary hypertension.

PURPOSE: The aim of this study was to evaluate the expression profiles of the relevant selectins and PDGF in schistosomiasis-associated pulmonary hypertension. METHODOLOGY: Patients with three distinct clinical profiles were enrolled in the study: IPAH(n = 11), schistosomiasis-associated PH (Sch-PH))(n = 13), and schistosomiasis without PH (Sch) (n = 13). Healthy volunteers, were recruited as a control group(n = 13). Echocardiography was performed in all groups, and the PH patients underwent right heart catheterization. Plasma soluble adhesion molecules E- and P-Selectin, PDGF-AB, PDGF-BB were determined by ELISA. RESULTS: E-selectin was significantly increased in the IPAH group compared with the other groups [the control, Sch + PH and Sch groups) (p < 0.001) (Fig. 2)]. P-selectin was lower in Sch (20.2 + 8.9 × 103 pg/mL) as compared to the control, (43 16.8 × 103 pg/mL), IPAH (35.8 7.8 × 103 pg/mL), and Sch + PH (36.8 ± 15.7 × 103 pg/mL) (p = 0.005) groups. Serum PDGF-BB levels were higher in the control group (8.9 ± 4.8 × 103 pg/mL) compared with the IPAH (3.7 ± 2.17 × 103 pg/mL), Sch + PH (5.2 ± 3.7 × 103 pg/mL) and Sch (2.4 ± 1.7 × 103 pg/mL) groups (p < 0.05). PDGF-AB levels were also higher in the control group (25.6 ± 8.6 × 103 pg/mL), compared with the other three groups, being the Sch group the one with lower serum levels of this marker (11.4 ± 8.6 × 103 pg/mL) (p = 0.006). CONCLUSIONS: In conclusion, vascular inflammation in schistosomiasis, with or without PH, is different from IPAH suggesting distinct pathophysiological mechanisms associated with the development of pulmonary hypertension.

Comparison between the 6-minute walk tests performed in patients with chronic obstructive pulmonary disease at different altitudes.

OBJECTIVE: To evaluate the influence of the altitude on the 6-minute walking test in patients with moderate to severe pulmonary disease. METHODS: Twenty-nine patients performed the 6-minute walk test at a pulmonary rehabilitation clinic in Santo André (above sea level), in São Paulo State, and at the Enseada Beach, in Guarujá (at sea level), also in São Paulo State. Of these 29 patients, 8 did the test both on hard sand and on asphalt to analyze if there were differences in performance during the tests. Data such as heart rate, oxygen saturation, test distance, and Borg scale were compared. RESULTS: We found no statistical difference in relation to oxygen saturation at rest before the beginning of the walking test in Santo André 94.67±2.26% and at sea level 95.56±2% (p=0.71). The minimum saturation measured during the test was 87.27±6.54% in Santo André and 89.10±5.41% in Guarujá (p=0.098). There were no differences in the performed distance between the different kinds of terrains; the distance on sand was 387.75±5.02m and on asphalt it was 375.00±6.54m (p=0.654). Regarding oxygen saturation during walking, the pulse oximetry on sand was 95.12±1.80% and on asphalt it was 96.87±1.64% (p=1.05). CONCLUSION: Altitude did not affect the performance of the walking test in patients with moderate to severe pulmonary disease and the results were similar in both cases, on sand and on asphalt.

Efeitos da reabilitação pulmonar em pacientes fumantes e ex-fumantes com doença pulmonar obstrutiva crônica / Pulmonary rehabilitation in current smokers and ex-smokers chronic obstructive pulmonary disease patients

Introdução: O carcinoma colorretal é uma das neoplasias mais incidentes nos países ocidentais. É controverso se os níveis séricos e a imunoexpressão tecidual do marcador tumoral CA 19-9 estão relacionados com o comprometimento linfonodal e com a invasão linfática no carcinoma colorretal. Casuística e métodos: Em 45 pacientes com carcinoma colorretal operados, o nível de CA19-9 pré-operatório e a imunoexpressão do CA19-9 no tecido neoplásico foram analisados. Valores de CA19-9 ≥ 37 UI/ml foram considerados aumentados. As amostras do tecido com carcinoma colorretal foram submetidas ao estudo imunoistoquímico, com anticorpo monoclonal anti-CA19-9. A intensidade de expressão do CA19-9 na neoplasia foi semiquantificada em leve (+/+++), moderada (++/+++), intensa (+++/+++) ou ausente. Foram comparados os níveis séricos e a imunoexpressão tecidual do marcador CA19-9 com o comprometimento linfonodal e a invasão linfática. Resultados: O nível sérico e a imunoexpressão tecidual do CA19-9 não se relacionaram significantemente com o comprometimento linfonodal (p = 0,49 e p = 0,45, respectivamente) ou com a invasão linfática (p = 0,12 e p = 0,74, respectivamente). Conclusões: O nível sérico e a imunoexpressão tecidual do CA19-9 não refletem o comprometimento linfonodal e a presença de invasão linfática no carcinoma colorretal.

Introduction: Colorectal carcinoma is one of the most common tumors in Western countries. It is controversial whether serum and tissue immunohistochemical expression of tumor marker CA 19-9 are associated with lymph node involvement or lymphatic invasion in colorectal carcinoma. Methods: In 45 patients with colorectal carcinoma operated, the preoperative serum levels and immunoexpression of CA19-9 in tumor tissues were performed. Values of CA19-9 ≥ 37 UI/ml were considered increased. Tissue samples with colorectal carcinoma were subjected to the immunohistochemistry study, with monoclonal antibody anti-CA19-9. The severity of CA19-9 expression in the tumor was semiquantified as mild (+/+++), moderate (++/+++), intense(+++/+++), or absent. We compared the serum levels and the tissue immunoexpression of CA19-9 marker with lymph node and lymphatic invasion. Results: Serum level and tissue immunoexpression of CA19-9 did not correlate significantly with lymph node involvement (p = 0.49 and p = 0.45,respectively) or with lymphatic invasion (p = 0.12 and p = 0.74, respectively). Conclusions: The serum level and tissue immunoexpression of CA19-9 do not reflect the presence of lymph node involvement and the presence of lymphatic invasion in colorectal carcinoma.

Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy: Is schistosomiasis hypertension an important confounding factor?

INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male). The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR) of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001). Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for pulmonary thromboendarterectomy had a hemodynamically severe status and had elevated brain natriuretic peptide serum levels. There was a predominance of females in our cohort, and the prevalence of hematological disorders and schistosomiasis was low (less than 10%).

Clinical and haemodynamic evaluation of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy: Is schistosomiasis hypertension an important confounding factor?

INTRODUCTION: Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described. OBJECTIVES: To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil. METHODS: From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels. RESULTS: Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male). The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR) of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001). Brain natriuretic peptide serum levels were elevated in 19 of 27 patients. CONCLUSIONS: In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for pulmonary thromboendarterectomy had a hemodynamically severe status and had elevated brain natriuretic peptide serum levels. There was a predominance of females in our cohort, and the prevalence of hematological disorders and schistosomiasis was low (less than 10 percent).

Cardiopulmonary manifestations of hepatosplenic schistosomiasis.

BACKGROUND: Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. METHODS AND RESULTS: All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). CONCLUSIONS: Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease.

Avaliação do comprometimento da função do endotélio em pacientes com hipertensão arterial pulmonar idiopática e em esquistossomóticos / Endothelial dysfunction in patients with pulmonary arterial hypertension and schistosomiasis

INTRODUÇÃO: Existem várias doenças que evoluem com hipertensão pulmonar (HP), entre elas a Hipertensão Arterial Pulmonar Idiopática (HAPI) e a Esquistossomose. Acredita-se que um dos principais fatores desencadeantes da HP esteja relacionado com a disfunção endotelial. OBJETIVOS: 1. Avaliar a disfunção endotelial de pacientes com HAPI e esquistossomóticos com e sem HAP usando os marcadores plasmáticos Endotelina-1, Selectina E, VEGF, PDGFAB e PDGF-BB; 2.Avaliar se pacientes com HAP associada à esquistossomose possuem o mesmo grau de disfunção endotelial que pacientes com esquistossomose sem HAP. METODOLOGIA: Foram formados 4 grupos distintos: Controle (n=13), HAPI (n=11), pacientes com esquistossomose e HP (ESQ+HP) (n=13) e pacientes com esquistossomose sem HP (ESQ)(n=13). Os pacientes foram submetidos a avaliação clínica (caracterizados quanto a gravidade), funcional (realizaram ecocardiograma com medida de pressão sistólica de ventrículo direito, ultrassonografia abdominal quando indicada e exames para excluir outras doenças) e laboratorial (entre eles, contagem de leucócitos, plaquetas e dosagem de BNP). A avaliação hemodinâmica foi realizada nos pacientes com HP. Para a análise da disfunção endotelial, foram coletados 40 mL de sangue de todos os indivíduos para a dosagem de Endotelina-1, Selectina E, VEGF, PDGF-AB e PDGF-BB. RESULTADOS: Observou-se que os grupos não se diferiram quanto a idade, houve um predomínio do sexo feminino e os grupos controle e ESQ apresentaram valores de PSVD menores do que os grupos com HP (controles: 23,4±4,6, ESQ: 29,5±8,5, HAPI: 79,8±26,4 e ESQ+HP: 75,2±15,3 mmHg). As medidas hemodinâmicas foram semelhantes em ambos os grupos com HAP. Quanto aos marcadores da função endotelial, o grupo controle apresentou valores séricos de PDGF-BB mais aumentados (8,9±4,8x 103 pg/mL, p<0,001) que os grupos HAPI, ESQ+HP, ESQ (3,7±2,1; 5,2±3 ; 2,4±1,7 x 103 pg/mL, respectivamente). O grupo HAPI apresentou valores mais elevados...

INTRODUCTION: There are several diseases that cause Pulmonary hypertension (PH), such as Idiopathic Pulmonary Arterial Hypertension and Schistosomiasis. The mechanisms that lead to PH are thought to be related to endothelial dysfunction. OBJECTIVES: To evaluate endothelial dysfunction, using plasma markers such as Endothelin-1(ET-1), E-Selectin, VEGF, PDGF-AB and -BB, in patients with idiopathic pulmonary arterial hypertension (IPAH) and schistosomiasis patients with or without PH; and to evaluate if schistosomiasis groups have endothelial dysfunction in the same degree. METHODOLOGY: Patients were divided in 4 different groups: Patients with IPAH (n=11), Patients with PH associated to Schistosomiasis (SchPH)(n=13), Patients with Schistosomiasis without PH (Sch)(n=13) and Controls(n=13). PAH patients were classified according to severity. All groups were submitted to echocardiography and right ventricule systolic pressure(RVSP) was measured. Abdominal ultrassonography was used to rule in or rule out schistosomiasis diagnosis. PH patients went through haemodynamics evaluation and all patients had laboratorial assessment (leucocytes and platelet count and BNP levels) Soluble adhesion molecules such as E-Selectin, VEGF, PDGF-AB, PDGF-BB e ET-1 were determined by ELISA. Leucocytes and platelet counts as well as BNP levels were also evaluated. Results: Subjects did not differ according to age and there was a higher proportion of female patients. Controls and Sch subjects had lower RVSP compared to PH groups (Sch: 23.4±4.6, controls: 29.5±8.5, IPAH: 79.8±26.4 and Sch+HP: 75.2±15.3 mmHg). Haemodynamics data did not differ in PH patients. In IPAH group, E-selectin was elevated (61.5±24,2x103pg/mL) compared to controls, Sch+HP and Sch (14.5±12.2; 23.9±15.3; 21.4±18 x103pg/mL, respectively, p=0,005). PDGF-BB was decreased in IPAH, Sch+HP, Sch (3.7±2.1; 5.2±3; 2.4±1.7x103pg/mL, respectively) compared to controls (8.9±4.8x 103 pg/mL, p<0.001). PDGF-AB was elevated...

NT-proBNP as a tool to stratify disease severity in pulmonary arterial hypertension.

The recent development of treatment modalities for patients with idiopathic pulmonary arterial hypertension has been based on the evaluation of many different markers such as functional capacity, addressed by NYHA classification, six-minute walk test (6MWT) and hemodynamic parameters. The aim of this study was to evaluate the correlation of N-terminal fragment (NT-proBNP) with other markers in IPAH and its potential for patient stratification. We studied 42 IPAH patients consecutively evaluated through right heart catheterization in the absence of any specific treatment for pulmonary hypertension. Blood samples, clinical evaluation and 6MWF distance were collected at baseline. The levels of NT-proBNP showed a high correlation with hemodynamic parameters, such as pulmonary vascular resistance (r=0.80, P<0.001). A significant difference was found among patients with different functional classes, addressed by NYHA classification (P< 0.02 for all groups comparison). The discriminant analysis reinforced the ability of NT-proBNP to stratify patients according to NYHA functional class. Compared to the other variables studied (hemodynamics and 6MWT), NT-proBNP had the lowest level of overlap in the stratification of IPAH patients. We conclude that NT-proBNP differs among the different functional classes and correlates with other measures of disease severity, although its role in predicting survival still needs to be addressed.

Tadalafil para o tratamento da hipertensão arterial pulmonar idiopática / Tadalafil as treatment for idiopathic pulmonary arterial hypertension

O uso de inibidores de fosfodiesterase, mais especificamente o sildenafil, no tratamento da hipertensão arterial pulmonar mostrou bons resultados, indicados por melhora dos parâmetros hemodinâmicos e da capacidade funcional. Poucos estudos existem a respeito dos efeitos de seus análogos como o tadalafil. O presente caso refere-se a uma paciente com hipertensão arterial pulmonar idiopática em classe funcional IV (NYHA) com resposta significativa ao uso de tadalafil.

Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.

[Clinical characteristics of pulmonary hypertension patients in two reference centers in the city of Sao Paulo]. / Características clínicas dos pacientes com hipertensão pulmonar em dois centros de referência em São Paulo.

OBJECTIVES: Describe the clinical profile of PH patients from two pulmonary hypertension centers. METHODS: Retrospective chart analysis. RESULTS: One hundred and twenty three PH patients were included in the study; 62% of these presented functional class III or IV (NYHA). Mean right ventricle systolic pressure (RVSP) was 83.48+/-24.61 mmHg. There was no correlation between functional class and RVSP. About 50% of the patients were diagnosed as IPAH; 30% as pulmonary hypertension associated to schistosomiasis; 10% as PH associated to connective tissue diseases. Mean time of dyspnea until diagnosis was variable with no correlation with functional class (p>0.05). No difference was found in the clinical presentation in spite of the diverse etiologies. CONCLUSION: Based upon our findings, we stressed the need for an active investigation of PH patients prior to administration of any therapeutic alternative. We emphasized that a better understanding of PH related to schistosomiasis is needed due to the high prevalence of this condition among PH patients as shown in the Brazilian population.

Hipertensão pulmonar na doença tromboembólica crônica / Pulmonary hypertension in chronic thromboembolic disease

Hipertensão pulmonar crônica tromboembólica é observada em até 3,8 por cento dos pacientes que sobreviveram a embolia pulmonar aguda. O desenvolvimento da técnica da tromboendarterectomia possibilitou a melhora significativa da sobrevida dos pacientes portadores de hipertensão pulmonar tromboembólica, com resolução do quadro hipertensivo na maioria dos pacientes operados. Nos últimos anos, tornou-se possível a definição de critérios mais claros para a indicação cirúrgica, assim como de marcadores de prognóstico, o que determinou significativa diminuição do risco cirúrgico associado ao procedimento. Atualmente tratamento médico com drogas está sendo feito em pacientes em que a tromboendarterectomia não apresentou bons resultados ou foi contra-indicada.

Características clínicas dos pacientes com hipertensão pulmonar em dois centros de referência em São Paulo / Clinical characteristics of pulmonary hypertension patients in two reference centers in the city of Sao Paulo

OBJETIVOS: Descrever as características clínicas dos pacientes com hipertensão pulmonar de dois centros de referência para tratamento de HP no país. MÉTODOS: Análise retrospectiva de prontuários. RESULTADOS: Foram incluídos no estudo 123 pacientes com diagnóstico de HP; 62 por cento destes apresentavam classe funcional III e IV (NYHA). A média da pressão sistólica do ventrículo direito (PSVD) encontrada nos pacientes estudados foi de 83,48±24,61 mmHg. Não houve correlação entre a classe funcional dos pacientes e o valor da PSVD. Cerca de 50 por cento dos pacientes tinham o diagnóstico de HAPI, 30 por cento tinham doença associada à esquistossomose e 10 por cento tinham HP associada a doença do tecido conectivo. O tempo de dispnéia até o diagnóstico foi variável e não houve correlação com a classe funcional dos pacientes (p>0,05). Apesar das diferentes etiologias, os pacientes apresentaram características semelhantes. CONCLUSÃO: Baseando-se em nossos achados, reforça-se a necessidade de investigação ativa para o diagnóstico definitivo antes da instituição de quaisquer alternativas terapêuticas para o tratamento da hipertensão pulmonar. Ressalta-se, ainda, a necessidade de um maior entendimento da hipertensão pulmonar associada à esquistossomose, em virtude da prevalência desse diagnóstico em nosso meio.

Tadalafil as treatment for idiopathic pulmonary arterial hypertension.

Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.

Estudo da hiper-responsividade brônquica em pacientes portadores de refluxo gastroesofágico / Bronchial hyperreactivity in patients with gastroesophageal reflux disease

OBJETIVO: O intuito deste trabalho foi evidenciar a existência desse reflexo vagal, através de uma broncoprovocação, em pacientes portadores de refluxo gastroesofágico. MÉTODOS: Onze pacientes com endoscopia sem evidências de refluxo gastroesofágico ou hérnia hiatal (grupo controle) e dez pacientes com hérnia hiatal ou refluxo gastroesofágico foram submetidos à broncoprovocação com carbacol. RESULTADOS: O teste foi positivo em 5 dos pacientes com hérnia hiatal ou refluxo gastroesofágico (50 por cento), e em 3 do grupo controle (27 por cento) (p = 0,64). CONCLUSÃO: A hipótese de que as vias aéreas de pacientes com refluxo gastroesofágico sem sintomas asmatiformes anteriores possam ser mais responsivas do que as de pacientes sem refluxo gastroesofágico permanece não comprovada.