Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.

The effect of multiple micronutrient supplementation on left ventricular ejection fraction in patients with chronic stable heart failure: a randomized, placebo-controlled trial:A randomized, placebo-controlled trial

Objectives: This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction (LVEF) in patients with heart failure. Background: Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients. However, there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months. The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography. Secondary endpoints were Minnesota Living With Heart Failure Questionnaire score, 6-min walk test distance, blood concentrations of N-terminal prohormone of brain natriuretic peptide, C-reactive protein, tumor necrosis factor alpha, interleukin-6, interleukin-10, and urinary levels of 8-iso-prostaglandin F2 alpha. Results: Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group, indicating excellent compliance with the intervention. There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline (mean difference: 1.6%, 95% confidence interval: -2.6 to 5.8, p = 0.441). There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups. Conclusions: This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement. (Micronutrient Supplementation in Patients With Heart Failure [MINT-HF]; NCT01005303).

Percutaneous Treatment of Mitral Valve Regurgitation: Initial Experience with the MitraClip Device

INTRODUCTION: Mitral regurgitation (MR) is the most common valvular disease and has recently become the target of a number of percutaneous approaches. The MitraClip is virtually the only device for which there is considerable experience, with more than 20,000 procedures performed worldwide. OBJECTIVE: To describe our initial experience of the percutaneous treatment of MR with the MitraClip device. METHODS: We describe the first six MitraClip cases performed in this institution (mean age 58.5 ± 13.1 years), with functional MR grade 4+ and New York Heart Association (NYHA) heart failure class III or IV (n=3), with a mean follow-up of 290 ± 145 days. RESULTS: Procedural success (MR ≤ 2+) was 100%. Total procedure time was 115.8 ± 23.7 min, with no in-hospital adverse events and discharge between the fourth and eighth day, and consistent improvement in the six-minute walk test (329.8 ± 98.42 vs. 385.33 ± 106.95 m) and in NYHA class (three patients improved by two NYHA classes). During follow-up there were two deaths, in two of the four patients who had been initially considered for heart transplantation. CONCLUSION: In patients with functional MR the MitraClip procedure is safe, with both a high implantation and immediate in-hospital success rate. A longer follow-up suggests that the clinical benefit decreases or disappears completely in patients with more advanced heart disease, namely those denied transplantation or on the heart transplant waiting list.

Contribuição para o estudo da fibromialgia : análise de variáveis de aptidão física, de composição corporal e capacidade funcional

A presente dissertação pretendeu verificar o efeito de um programa de exercício supervisionado versus domiciliário, de intensidade moderada, com a duração de 16 semanas, na aptidão física de pessoas com fibromialgia. Houve necessidade de ajustamento dos objetivos e analisaram-se os dados obtidos no primeiro momento de avaliação, pretendendo-se analisar a relação entre variáveis de aptidão física, contribuindo para a compreensão da aptidão física de pessoas com fibromialgia. Apresentam-se e analisam-se variáveis de aptidão física e os resultados do efeito do exercício a nível de composição corporal, capacidade cardiorrespiratória e capacidade funcional. Neste âmbito realizaram-se 5 estudos. No estudo I analisou-se a precisão de diferentes equações preditivas de consumo de oxigénio, que utilizam a distância caminhada no teste de marcha de 6 minutos e propõe-se uma atualização para a equação específica para esta população. No estudo II observou-se a relação entre o consumo de oxigénio, composição corporal e força muscular. No estudo III avaliou-se a precisão de equações preditivas de composição corporal utilizando pregas adiposas e a densitometria de raio-X de dupla energia como método de referência. No estudo IV verificou-se qual o índice que melhor reflete a composição corporal destas mulheres. No estudo V analisou-se a associação entre a frequência cardíaca de recuperação, após um teste de esforço máximo e o consumo de oxigénio. Os principais resultados reforçam os resultados anteriores de que a população estudada apresenta diminuição da aptidão física, da capacidade funcional e valores de composição corporal indicativos de excesso de peso. Não apresentaram alterações autonómicas e verificou-se que a distância caminhada durante o teste de marcha de 6 minutos, a idade, percentagem de massa gorda e a massa magra apendicular são preditores do VO2 pico. Após a intervenção as participantes apresentaram alterações positivas a nível da aptidão física.

The Swiss registry for pulmonary arterial hypertension: the paediatric experience.

Pulmonary arterial hypertension is a rare disease with a poor prognosis. Epidemiological data are scarce, particularly in the paediatric population. A registry was recently developed in order to collect epidemiological data on patients with pulmonary arterial hypertension (PAH) in Switzerland. This is the first description of the paediatric data. Paediatric patients aged 0-18 years with the diagnosis of PAH were enrolled in the registry from 1999 to 2005 with informed consent from their parents. Patient characteristics, PAH aetiology, functional capacity, exercise capacity, treatments and outcome were among the most important data collected. A total of 23 patients (12 male, 11 female) have been thus far included in the registry. Median age at time of diagnosis was 3 years (range 1 month-18 years) and median follow-up was 3.47 years (range 1 day-12.6 years). PAH aetiologies are diagnosed as idiopathic in 8/23 patients (34.8%) and associated with congenital heart diseases in 12/23 (52.2%) or with pulmonary diseases in 3/23 patients (13.0%). Death occurred in 1 patient before treatment was initiated. Single treatments include medications with a calcium channel blocker in 2/23 patients, with bosentan in 10/23, and with inhaled iloprost in 1/23. Combined therapies include bosentan and inhaled iloprost in 7/23 patients, bosentan and sildenafil in 2/23 patients, and bosentan, sildenafil and inhaled iloprost in 2/23 patients. Additional oral anticoagulation is given to 14/23 patients and 8/23 patients are on oxygen therapy. NYHA class at baseline visit was obtained in 22/23 patients (4 NYHA 2, 17 NYHA 3 and 1 NYHA 4). Changes in NYHA class were observed over a 2-year period in 3/22 patients who improved from NYHA 3 to NYHA 2. Initial improvement of 6-minute walk distance was observed in 6/13 patients with a sustained improvement in 4. These preliminary results provide information on the epidemiology of PAH in children in Switzerland and demonstrate that most paediatric patients show stabilisation of the disease under new treatments. This underscores the utility of registries for rare diseases in providing crucial information in the era of new therapies. It may also help to improve the future medical approach.

La qualité de vie et la capacité fonctionnelle chez les patients atteints de fibrillation auriculaire et d'insuffisance cardiaque congestive

De déterminer si une stratégie de contrôle du rythme améliore la qualité de vie et / ou la capacité fonctionnelle par rapport à une stratégie de contrôle de la fréquence cardiaque chez les patients atteints de fibrillation auriculaire et d'insuffisance cardiaque congestive. Méthode: Pour évaluer la qualité de vie, le questionnaire SF-36 a été administré à l'inclusion et à 4 mois chez 749 patients de l’étude AF-CHF. Les paramètres de capacité fonctionnelle évalués ont été la classe fonctionnelle NYHA (1376 patients) et la distance de marche de six minutes (1099 patients). Résultats: Le type du traitement assigné n'a pas eu un impact significatif sur la qualité de vie ou la capacité fonctionnelle. Conclusion: La qualité de vie et la capacité fonctionnelle sont similaires chez les patients randomisés au contrôle du rythme par rapport au contrôle de la fréquence. Les hommes non-obèses avec moins de comorbidités semblent plus susceptibles de s'améliorer.

Cardiovascular fitness and cardiovascular risk factors among obese men and women aged 58 years and older, in Portugal

Background: A better physical fitness may have survival advantages in adults. Aim: To analyze the relationship between cardiorespiratory fitness and cardiovascular risk factors among obese subjects aged 58 years and older. Material and Methods: Cardiorespiratory fitness using the six-minute walk test, body composition by dual-energy x-ray absorptiometry and blood pressure were measured in a non-representative sample of 76 obese Portuguese subjects aged 58 to 87 years (55 women). Participants were stratified in tertiles of walking capacity according to the six-minute walk test. Results: Six minutes walk test results were negatively correlated with percentage body fat (r = -0.28; p = 0.012) and systolic blood pressure (r = -0.23; p = 0.045). Participants located in the lowest tertile for the six minutes walk test had an odds ratio of 4.34 (95% confidence intervals: 1.02-18.43) for elevated blood pressure. Conclusions: A lower six minutes walk test result is associated with a higher risk for high blood pressure. (Rev Med Chile 2012; 140: 1164-1169).

O índice BODE reflete o nível de atividade física na vida diária de pacientes com DPOC?

Objectives: To study the relationship between the level of physical activity in daily life and disease severity assessed by the BODE index in patients with chronic obstructive pulmonary disease (COPD). Methods: Sixty-seven patients with COPD (36 men) with forced expiratory volume in the first second (FEV(1)) of 39 (27-47)% predicted and age of 66 (61-72) years old were evaluated by spirometry, dyspnea levels (measured by the Medical Research Council scale, MRC) and by the 6-minute walking test (6MWT). The BODE index was calculated based on the body mass index (weight/height(2)), FEV(1), MRC and 6MWT, and then the patients were divided in four quartiles according to their scores (Quartile I: 0 to 2 points, n=15; Quartile II: 3 to 4 points, n=20; Quartile III: 5 to 6 points, n=23; Quartile IV: 7 to 10 points, n=9). Two activity monitors (DynaPort (R) and SenseWear (R)) were used to evaluate the level of physical activity in daily life. The Kruskal-Wallis test (Dunns's post-hoc test), the Mann-Whitney test and the Spearman Correlation Coefficient were used for statistical analysis. Results: There were modest correlation between the BODE index and the time spent walking per day, the total daily energy expenditure and the time spent in moderate and vigorous activities per day (-0.32 <= r <=- 0.47; p <= 0.01 for all variables). When comparing the pooled quartiles I+II with III+IV, there were significant difference between the time spent walking per day, the total daily energy expenditure and the time spent in moderate activities per day (p <= 0.05). Conclusion: The level of physical activity in daily life has a modest correlation with the classification of COPD severity assessed by the BODE index, reflecting only differences between patients with classified as mild-moderate and severe-very severe COPD.

Step Counting and Energy Expenditure Estimation in Patients With Chronic Obstructive Pulmonary Disease and Healthy Elderly: Accuracy of 2 Motion Sensors

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exercício físico de baixa intensidade na dpoc: comparação dos programas solo e aquático

Physical Exercise (PE) is a necessary component in the management in COPD patients, where respiratory symptoms are associated with reduced functional capacity. Even with the increase in the number of studies that have been published and the therapeutics success using aquatic therapy approach, studies using PE in water in COPD patients are so few. Objective: the aim of this present study was to analyze the effects of low intensity water exercise in COPD patients, developed in two different places aquatic and ground. Methods: This is a randomized clinical trial study, 42 patients with moderate to very severe DPOC were recruited for the study, mean age of 63,2  10,9 years old. Randomized in 3 groups: Control Group (CG), Land Group (LG) and Water Group (WG). The PE protocol was performed in a period of 8 weeks, with frequency of 3 times per week. The CG participated in an educational program. All the patients were assessed twice through spirometry, respiratory muscular strength, the 6-min walk test, the quality of life (SF-36 and SGRQ), the LCADL, the MRC, the BODE index and the upper limbs (UP) incremental test. Results: There was a significant difference after the approaches in DP6 from the WG (p=0,02); in VEF1 in LG (p=0,00) and WG (p=0,01); in MIP in LG (p=0,01) and WG (p=0,02); in MEP in LG (p=0,02) and WG (p=0,01); the MRC decreases in WG (p=0,00). there was an increase of the weight supported by the UP in LG (p=0,00) and WG (p=0,01). The LG showed an increase of the quality of life represented by the SGRQ total score (p=0,00). The BODE index decreased in LG (p=0,00) and WG (p=0,01). In LCDAL, the LG showed a decrease. Conclusion: This data in this present study suggest that both approaches of low intensity exercise showed to be beneficial in moderate to very severe COPD patients. The WG showed additional benefits in physical function, pointing to a new therapeutic modality for COPD patients

Fatores associados à diferença clinicamente significativa da qualidade de vida relacionada à saúde após condicionamento físico em pacientes com DPOC

OBJETIVO: Investigar os fatores associados à diferença clinicamente significativa da qualidade de vida (DCSQV) após condicionamento físico em pacientes com DPOC. MÉTODOS: Trinta e cinco pacientes foram submetidos a 12 semanas de condicionamento físico, envolvendo treinamento de força e exercício aeróbio leve. Composição corporal, teste incremental e de endurance em esteira, teste de caminhada de seis minutos, força muscular periférica, PImáx, baseline dyspnea index (BDI) e Saint George's Respiratory Questionnaire (SGRQ) foram avaliados antes e após o treinamento, e suas alterações (Δ) foram calculadas. A DCSQV foi definida como a redução > 4% no escore total do SGRQ. Os pacientes que responderam ao treinamento, apresentando DCSQV, foram alocados no grupo respondedores (R; n = 24), e os demais pacientes foram alocados no grupo não-respondedores (NR; n = 11). RESULTADOS: Os seguintes resultados foram significativamente maiores no grupo R que no grupo NR (p < 0,05): VEF1 (1,48 ± 0,54 L vs. 1,04 ± 0,34 L), VEF1/CVF (47,9 ± 11,7% vs. 35,5 ± 10,7%), PaO2 (74,1 ± 9,7 mmHg vs. 65,0 ± 8,9mmHg) e ΔBDI [mediana (interquartil); 2,0 (0,0-3,5) vs. 0,0 (0,0-1,0)]. Houve correlação significativa (p < 0,01) de ΔSGRQ-sintomas (r = 0,44), ΔSGRQ-atividade (r = 0,62) e ΔSGRQ-total (r = 0,60) com ΔBDI. Após regressão logística, apenas ΔBDI foi selecionado como determinante da DCSQV. CONCLUSÕES: A DCSQV após o condicionamento físico está associada principalmente à redução da dispneia nos pacientes com DPOC. Portanto, são necessárias estratégias de tratamento visando interromper o ciclo dispneia-sedentarismo-dispneia nesses pacientes.

Effect of three exercise programs on patients with chronic obstructive pulmonary disease

We compared the effect of three different exercise programs on patients with chronic obstructive pulmonary disease including strength training at 50_80% of one-repetition maximum (1-RM) (ST; N = 11), low-intensity general training (LGT; N = 13), or combined training groups (CT; N = 11). Body composition, muscle strength, treadmill endurance test (TEnd), 6-min walk test (6MWT), Saint George's Respiratory Questionnaire (SGRQ), and baseline dyspnea (BDI) were assessed prior to and after the training programs (12 weeks). The training modalities showed similar improvements (P > 0.05) in SGRQ-total (ST = 13 ± 14%; CT = 12 ± 14%; LGT = 11 ± 10%), BDI (ST = 1.8 ± 4; CT = 1.8 ± 3; LGT = 1 ± 2), 6MWT (ST = 43 ± 51 m; CT = 48 ± 50 m; LGT = 31 ± 75 m), and TEnd (ST = 11 ± 20 min; CT = 11 ± 11 min; LGT = 7 ± 5 min). In the ST and CT groups, an additional improvement in 1-RM values was shown (P < 0.05) compared to the LGT group (ST = 10 ± 6 to 57 ± 36 kg; CT = 6 ± 2 to 38 ± 16 kg; LGT = 1 ± 2 to 16 ± 12 kg). The addition of strength training to our current training program increased muscle strength; however, it produced no additional improvement in walking endurance, dyspnea or quality of life. A simple combined training program provides benefits without increasing the duration of the training sessions.

Influência da massa magra corporal nas repercussões cardiopulmonares durante o teste de caminhada de seis minutos em pacientes com DPOC

OBJETIVO: A massa magra corporal (MMC) tem sido associada à mortalidade em pacientes com DPOC, mas seu impacto na limitação funcional é pouco conhecido. O objetivo deste trabalho foi analisar as variáveis cardiopulmonares em pacientes com DPOC, com ou sem depleção da MMC, antes e após a realização do teste de caminhada de seis minutos (TC6). MÉTODOS: Foram avaliados pacientes com DPOC, 36 sem depleção de MMC e 32 com depleção de MMC. Todos os pacientes foram submetidos à avaliação clínica, espirometria, avaliação da composição da massa corpórea e TC6 e responderam a questionários de qualidade de vida e de percepção de dispnéia. RESULTADOS: Não foram observadas diferenças significativas na gravidade de obstrução das vias aéreas, na percepção da dispnéia e na qualidade de vida entre os grupos. A distância percorrida no TC6 foi similar nos pacientes com DPOC com e sem depleção de MMC (470,3 ± 68,5 m vs. 448,2 ± 89,2 m). Entretanto, durante a realização do teste, os pacientes com depleção de MMC apresentaram aumento significativamente maior na diferença entre os valores final e basal da frequência cardíaca e do índice da escala de Borg para cansaço dos membros inferiores. A distância percorrida no TC6 apresentou correlação significativa positiva com o VEF1 (r = 0,381; p = 0,01). CONCLUSÕES: Não houve influência da depleção da MMC na capacidade funcional de exercício e na qualidade de vida dos pacientes estudados. Entretanto, os pacientes com depleção de MMC apresentam sintomas de fadiga dos membros inferiores mais acentuados durante o TC6, o que reforça a importância da avaliação e tratamento das manifestações sistêmicas da DPOC.

Relationship between disease severity and quality of life in patients with chronic obstructive pulmonary disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Versão em português do Chronic Respiratory Questionnaire: estudo da validade e reprodutibilidade

OBJETIVO: Verificar a validade e a reprodutibilidade de uma versão em português do Chronic Respiratory Questionnaire (CRQ) em pacientes com DPOC. MÉTODOS: A versão em português do CRQ (fornecida pela Universidade de McMaster, detentora dos direitos do questionário) foi aplicada a 50 pacientes portadores de DPOC (32 homens; 70 ± 8 anos; VEF1 = 47 ± 18% predito) em dois momentos, com intervalo de uma semana. O CRQ tem quatro domínios (dispneia, fadiga, função emocional e autocontrole) e foi aplicado em formato de entrevista. O Saint George's Respiratory Questionnaire (SGRQ), já validado em português, foi utilizado como o critério de validação. A espirometria e o teste da caminhada de seis minutos (TC6) foram realizados para a análise das correlações com os valores do CRQ. RESULTADOS: Não foram observadas diferenças significativas entre a aplicação e a reaplicação do CRQ (p > 0.05 para todos os domínios). O coeficiente de correlação intraclasse entre a aplicação e a reaplicação foi de 0,98; 0,97; 0,98 e 0,95 para os domínios dispneia, fadiga, função emocional e autocontrole, respectivamente. O coeficiente alfa de Cronbach foi 0,91. Os domínios do CRQ se correlacionaram significativamente com os domínios do SGRQ (-0.30 < r < -0.67; p < 0,05). Não houve correlação entre as variáveis espirométricas e os domínios do CRQ e nem entre esses domínios e o TC6, exceto para o domínio fadiga (r = 0,30; p = 0,04). CONCLUSÕES: A versão em português do CRQ demonstrou ser reprodutível e válida em pacientes brasileiros portadores de DPOC.