Administration of growth hormone to underweight patients with chronic obstructive pulmonary disease. A prospective, randomized, controlled study.

Patients with chronic obstructive pulmonary disease (COPD) often develop weight loss, which is associated with increased mortality. Recombinant human growth hormone (rhGH) treatment has been proposed to improve nitrogen balance and to increase muscle strength in these patients. The aim of this study was to assess the effects of rhGH administration on the nutritional status, resting metabolism, muscle strength, exercise tolerance, dyspnea, and subjective well-being of underweight patients with stable COPD. Sixteen patients attending a pulmonary rehabilitation program (age: 66 +/- 9 yr; weight: 77 +/- 7% of ideal body weight; FEV1: 39 +/- 13% of predicted) were randomly treated daily with either 0.15 IU/kg rhGH or placebo during 3 wk in a double-blind fashion. Measurements were made at the beginning (DO) and at the end (D21) of treatment and 2 mo later (D81). Body weight was similar in the two groups during the study, but lean body mass was significantly higher in the rhGH group at D21 (p < 0.01) and D81 (p < 0.05). The increase in lean body mass was 2.3 +/- 1.6 kg in the rhGH group and 1.1 +/- 0.9 kg in the control group at D21 and 1.9 +/- 1.6 kg in the rhGH group and 0.7 +/- 2.1 kg in the control group at D81. At D21, the resting energy expenditure was increased in the rhGH group (107.8% of DO, p < 0.001 compared with the control group). At D21 and D81, the changes in maximal respiratory pressures, handgrip strength, maximal exercise capacity, and subjective well-being were similar in the two groups. At D21, the 6-min walking distance decreased in the rhGH group (-13 +/- 31%) and increased in the control group (+10 +/- 14%; p < 0.01). We conclude that the daily administration of 0.15 IU/kg rhGH during 3 wk increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD.

Characterisation of COPD heterogeneity in the ECLIPSE cohort

Background Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations. This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE). Methods We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers. In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography. Results COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function. Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage. The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study. The distribution of these variables within each GOLD stage was wide. Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation. The amount of emphysema increased with GOLD severity. The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage. Some gender differences were also identified. Conclusions The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.

Differences between remaining ability and loss of capacity in maximum aerobic impairment

In the evaluation of exercise intolerance of patients with respiratory diseases the American Medical Association (AMA) and the American Thoracic Society (ATS) have proposed similar classifications for rating aerobic impairment using maximum oxygen uptake (VO2max) normalized for total body weight (ml min-1 kg-1). However, subjects with the same VO2max weight-corrected values may have considerably different losses of aerobic performance (VO2max expressed as % predicted). We have proposed a new, specific method for rating loss of aerobic capacity (VO2max, % predicted) and we have compared the two classifications in a prospective study involving 75 silicotic claimants. Logistic regression analysis showed that the disagreement between rating systems (higher dysfunction by the AMA/ATS classification) was associated with age >50 years (P<0.005) and overweight (P = 0.04). Interestingly, clinical (dyspnea score) and spirometric (FEV1) normality were only associated with the VO2max, % predicted, normal values (P<0.01); therefore, in older and obese subjects the AMA/ATS classification tended to overestimate the aerobic dysfunction. We conclude that in the evaluation of aerobic impairment in patients with respiratory diseases, the loss of aerobic capacity (VO2max, % predicted) should be used instead of the traditional method (remaining aerobic ability, VO2max, in ml min-1 kg-1).

L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs

The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. Sixteen COPD patients (66 ± 7 years) were randomly assigned to L-carnitine (CG) or placebo group (PG) that received either L-carnitine or saline solution (2 g/day, orally) for 6 weeks (forced expiratory volume on first second was 38 ± 16 and 36 ± 12%, respectively). Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions, with 3 sets of 10 loaded inspirations (40%) at maximal inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and six-minute walking test, blood lactate, heart rate, blood pressure, and respiratory muscle strength were determined as baseline and on day 42. Maximal capacity in the incremental exercise test was significantly improved in both groups (P < 0.05). Blood lactate, blood pressure, oxygen saturation, and heart rate at identical exercise levels were lower in CG after training (P < 0.05). Inspiratory muscle strength and walking test tolerance were significantly improved in both groups, but the gains of CG were significantly higher than those of PG (40 ± 14 vs 14 ± 5 cmH2O, and 87 ± 30 vs 34 ± 29 m, respectively; P < 0.05). Blood lactate concentration was significantly lower in CG than in PG (1.6 ± 0.7 vs 2.3 ± 0.7 mM, P < 0.05). The present data suggest that carnitine can improve exercise tolerance and inspiratory muscle strength in COPD patients, as well as reduce lactate production.

Comparaison de la performance à l’exercice de patients souffrant d’insuffisance cardiaque sévère à une épreuve d’effort maximal, une épreuve sous-maximale et un test de marche

L’insuffisance cardiaque est une pathologie provoquant une diminution importante des capacités fonctionnelles des patients ainsi qu’une diminution drastique de la qualité de vie. L’évaluation des capacités fonctionnelles est généralement effectuée par une épreuve d’effort maximal. Cependant pour plusieurs patients, cet effort est difficile à compléter. Les objectifs de l’étude présentée dans ce mémoire sont : (1) valider trois méthodes d’évaluation de la capacité fonctionnelle et aérobie des sujets souffrant d’insuffisance cardiaque avec un complexe QRS élargi; (2) chercher à établir le profil des patients démontrant une meilleure tolérance à l’exercice malgré une consommation maximale d’oxygène identique; et (3) démontrer les conséquences de la présence et de la magnitude de l’asynchronisme cardiaque dans la capacité fonctionnelle et la tolérance à l’exercice. Tous les sujets ont été soumis à un test de marche de six minutes, un test d’endurance à charge constante sur tapis roulant et à une épreuve d’effort maximal avec mesure d’échanges gazeux à la bouche. Les résultats ont montré une association significative entre les épreuves maximale et plus spécifiquement sous-maximale. De plus, une meilleure tolérance à l’exercice serait associée significativement à une plus grande masse du ventricule gauche. Finalement, les résultats de notre étude n’ont pas montré d’effet d’un asynchronisme cardiaque sur la performance à l’effort tel qu’évalué par nos protocoles.

Diseño de un programa de rehabilitación pulmonar en la Clínica Universitaria Teletón

Las enfermedades pulmonares crónicas son muy frecuentes en la población mayor de 40 años y es superior en los países con un alto consumo de cigarrillo; han sido durante muchos años consideradas como un problema grave de salud pública, el cual va en aumento de manera acelerada en Colombia y en el mundo debido a su alta incidencia e impacto sobre la calidad de vida de quien la padece y de su familia.La Asociación Colombiana de Neumología y Cirugía de Tórax junto a la Fundación Neumológica Colombiana realizó un estudio acerca de la Prevalencia de la Enfermedad Pulmonar Obstructiva Crónica (EPOC) en Colombia (Prepocol).

Ánálise da capacidade funcional e da distribuição regional da ventilação pulmonar em pacientes com doença de chagas

INTRODUCTION: Cardiac and pulmonary manifestations of the Chagas disease (CD) affect between 20-30% of the infected subjects. The chronic Chagas cardiomyopathy (CCC) has some peculiarities such as arrhythmias and, especially heart failure (HF) and is potentially lethal due to left ventricular dysfunction. How respiratory disorders, patients get progressive loss of functional capacity, which contributes to a poor quality of life related to disease. Measurements of lung volume by the movement of the chest wall surface are an alternative evaluation of lung function and kinematics of complex thoracoabdominal for these patients. OBJECTIVE: evaluate the kinematics of the thoracoabdominal complex through the regional pulmonary volumes and to correlate with functional evaluation of the cardiorrespiratory system in patients with Chagas disease at rest. MATERIALS AND METHODS: a cross-section study with 42 subjects had been divided in 3 groups, 15 composed for patients with CCC, 12 patients with HF of different etiologies and 15 healthful presented control group. An optoelectronic plethysmography (POE), Minnesota questionnaire, six minute walk test, spirometer and manovacuometer was used. RESULTS: It was observed in the 6MWT where group CRL presented greater distance 464,93±44,63m versus Group HF with 399,58± 32,1m (p=0,005) and group CCC 404±68,24m (p=0,015), both the groups presented difference statistics with regard to Group CRL. In the manovacuometer 54,59±19,98; of the group CCC and 42,11±13,52 of group IC found group CRL presented 81,31±15,25 of the predicted versus, presenting in relation to group CRL. In the POE it observed a major contribution in abdominal compartment in patients with IC if compared like CCC and control groups. On the basis of the questionnaire of quality of life of Minessota, verified a low one groups CCC and IC 43,2±15,2 and 44,4±13,1, respectively (p<0,05) when compared with the control group (19,6±17,31). CONCLUSION: it seems that the patients with CCC possess same functional and respiratory characteristics, observed for the POE, 6MWT, manovacuometer and spirometer to the patients of group HF, being able to consider similar interventions for this complementary group as therapeutical of this neglected disease

Relationship of upper-limb and thoracic muscle strength to 6-min walk distance in COPD patients

Study objectives: This study was developed to investigate the influence of thoracic and upperlimb muscle function on 6-min walk distance (6MWD) in patients with COPD.Design: A prospective, cross-sectional study.Setting: the pulmonary rehabilitation center of a university hospital.Patients: Thirty-eight patients with mild to very severe COPD were evaluated.Measurements and results: Pulmonary function and baseline dyspnea index (BDI) were assessed, handgrip strength, maximal inspiratory pressure (Pimax), and 6MWD were measured, and the one-repetition maximum (1RM) was determined for each of four exercises (bench press, lat pull down, leg extension, and leg press) performed on gymnasium equipment. Quality of life was assessed using the St. George Respiratory Questionnaire (SGRQ). We found statistically significant positive correlations between 6MWD and body weight (r = 0.32; p < 0.05), BDI (r = 0.50; p < 0.01), FEV, (r = 0.33; p < 0.05), PImax (r = 0.53; p < 0.01), and all values of 1RM. A statistically significant negative correlation was observed between 6MWD and dyspnea at the end of the 6-min walk test (r = -0.29; p < 0.05), as well as between 6MWD and the SGRQ activity domain (r = -0.45; p < 0.01) and impact domain (r = -0.34; p < 0.05) and total score (r = -0.40; p < 0.01). Multiple regression analysis selected body weight, BDI, Pimax, and lat pull down IRM as predictive factors for 6MWD (R-2 = 0.589).Conclusions: the results of this study showed the importance of the skeletal musculature of the thorax and upper limbs in submaximal exercise tolerance and could open new perspectives for training programs designed to improve functional activity in COPD patients.

Maior nível de atividade física associa-se a melhor função cognitiva em renais crônicos em hemodiálise

INTRODUÇÃO: Pacientes com doença renal crônica (DRC) apresentam menor tolerância ao exercício e baixa capacidade funcional, o que os torna, via de regra, sedentários. Outra alteração importante encontrada na DRC é a disfunção cognitiva. O sedentarismo tem sido associado à disfunção cognitiva na população geral, porém, poucos estudos avaliaram essa associação na DRC. OBJETIVOS: Verificar associação entre o nível de atividade física e a função cognitiva de pacientes com DRC que realizam hemodiálise (HD). MÉTODOS: Foram avaliados 102 pacientes que realizam HD. Os participantes responderam o Questionário Internacional de Atividade Física, que avalia o nível de atividade física e o Mini Exame do Estado Mental, utilizado para o rastreamento cognitivo. Os pacientes foram divididos em três grupos conforme a classificação do nível de atividade física (GI: ativos/GII: irregularmente ativos/GIII: sedentários). Foi aplicada análise de regressão logística adotando-se como variável desfecho a presença de disfunção cognitiva e preservando como variáveis independentes aquelas com probabilidade estatística de diferença entre os grupos inferior a 0,1. Foi considerado estatisticamente significante o valor de p inferior a 0,05. RESULTADOS: Os grupos foram semelhantes quanto à idade, tempo de HD, escolaridade e tabagismo. Apresentaram diferença estatisticamente significante quanto à raça, índice de massa corporal, presença de diabetes mellitus, doença de base e grau de déficit cognitivo. Quanto aos dados laboratoriais, os grupos diferiram quanto à creatinina, glicemia, hemoglobina e hematócrito. Houve associação entre o nível de atividade física e função cognitiva, mesmo ajustando-se para as variáveis de confusão. CONCLUSÃO: O maior nível de atividade física associou-se a melhor função cognitiva em renais crônicos em HD, independentemente das variáveis de confusão avaliadas.

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.

Differential morphofunctional characteristics and gene expression in fast and slow muscle of rats with monocrotaline-induced heart failure

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

Perfil do nível de atividade física na vida diária de pacientes portadores de DPOC no Brasil

Objective: To evaluate characteristics of physical activities in daily life in COPD patients in Brazil, correlating those Characteristics with physiological variables. Methods: Physical activities in daily life were evaluated in 40 COPD patients (18 males; 66 +/- 8 years of age; FEV(1) = 46 +/- 16 % of predicted; body mass index = 27 +/- 6 kg/m(2)) and 30 healthy age- and gender-matched subjects, using a multiaxial accelerometer-based sensor for 12 h/day on two consecutive days. We also assessed maximal and functional exercise capacity, using the incremental exercise test and the six-minute walk test (6MWT), respectively; MIP and MEP; peripheral muscle force, using the one-repetition maximum test and the handgrip test; quality of life, using the Saint George's Respiratory Questionnaire (SGRQ); functional status, using the London Chest Activity of Daily Living questionnaire; and dyspnea sensation, using the Medical Research Council (MRC) scale. Results: Mean walking time/day was shorter for COPD patients than for the controls (55 +/- 33 vs. 80 +/- 28 min/day; p = 0.001), as movement intensity was lower (1.9 +/- 0.4 vs. 2.3 +/- 0.6 m/s(2); p = 0.004). The COPD patients also tended to spend more time seated (294 +/- 114 vs. 246 +/- 122 min/day, p = 0.08). Walking time/day correlated with the 6MWT (r = 0.42; p = 0.007) and maximal workload (r = 0.41; p = 0.009), as well as with age, MRC scale score and SGRQ activity domain score (-0.31 <= r <= -0.43; p <= 0.05 for all). Conclusions: This sample of Brazilian patients with COPD, although more active than those evaluated in studies conducted in Europe, were less active than were the controls. Walking time/day correlated only moderately with maximal and functional exercise capacity.

L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs

The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. Sixteen COPD patients (66 ± 7 years) were randomly assigned to L-carnitine (CG) or placebo group (PG) that received either L-carnitine or saline solution (2 g/day, orally) for 6 weeks (forced expiratory volume on first second was 38 ± 16 and 36 ± 12%, respectively). Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions, with 3 sets of 10 loaded inspirations (40%) at maximal inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and six-minute walking test, blood lactate, heart rate, blood pressure, and respiratory muscle strength were determined as baseline and on day 42. Maximal capacity in the incremental exercise test was significantly improved in both groups (P < 0.05). Blood lactate, blood pressure, oxygen saturation, and heart rate at identical exercise levels were lower in CG after training (P < 0.05). Inspiratory muscle strength and walking test tolerance were significantly improved in both groups, but the gains of CG were significantly higher than those of PG (40 ± 14 vs 14 ± 5 cmH2O, and 87 ± 30 vs 34 ± 29 m, respectively; P < 0.05). Blood lactate concentration was significantly lower in CG than in PG (1.6 ± 0.7 vs 2.3 ± 0.7 mM, P < 0.05). The present data suggest that carnitine can improve exercise tolerance and inspiratory muscle strength in COPD patients, as well as reduce lactate production.

Correlações entre os níveis de L-carnitina plasmática, o estado nutricional e a função ventilatória de portadores de doença pulmonar obstrutiva crônica

OBJETIVO: Avaliar os níveis de L-carnitina livre no plasma, o estado nutricional, a função pulmonar e a tolerância ao exercício em pacientes com doença pulmonar obstrutiva crônica e verificar as correlações entre a composição corporal e as frações de L-carnitina no plasma. MÉTODOS: Quarenta pacientes entre 66,2±9 anos, com diagnóstico clínico de doença pulmonar obstrutiva crônica, foram divididos em dois grupos: G1, com índice de massa corporal menor que 20kg/m², e G2, com índice de massa corporal maior que 20kg/m². Foram mensurados os parâmetros espirométricos, a tolerância ao exercício no teste de caminhada, a força muscular respiratória, a composição corporal por meio da impedância bioelétrica e as dosagens da L-carnitina plasmática, através de amostras de sangue. RESULTADOS: Foram observados menores valores das variáveis espirométricas (p<0,01), da força muscular respiratória e dos níveis de L-carnitina nos pacientes do G1; porém, não houve diferença entre os grupos quanto à capacidade de realizar exercício físico dinâmico de baixa intensidade. Correlações significativas entre o percentual de gordura e os níveis de L-carnitina plasmática foram observadas nos pacientes (r=0,53 com p<0,002); sendo que, nos pacientes com índice de massa corporal menor que 18kg/m², essa relação aumentou (r<0,73 com p<0,01). CONCLUSÃO: Na doença pulmonar obstrutiva crônica, a desnutrição está associada tanto aos prejuízos da função pulmonar e da força muscular respiratória, quanto aos baixos níveis de L-Carnitina plasmática.

Vagal control of heart rate and cardiac shunts in reptiles: Relation to metabolic state

The vagus is clearly of primary importance in the regulation of reptilian cardiorespiratory systems. Vagal control of pulmonary blood flow and cardiac shunts provides reptiles with an additional means of regulating arterial oxygen levels that is not present in endothermic vertebrates (birds and mammals). Within a given species, there exists a clear correlation between withdrawal of vagal tone on the cardiovascular system and elevated metabolic rate. Undisturbed and resting reptiles are normally characterised by high vagal tone, low pulmonary blood flow and large right-left (R-L) cardiac shunts. The low oxygen levels that result from the large R-L shunt may serve to regulate metabolism. However, when metabolism is increased by temperature, exercise or digestion, the R-L cardiac shunt is reduced, which serves to increase oxygen delivery. This response is partially elicit ed by reduction of vagal tone. Interspecies comparisons reveal a similar pattern. Thus, species that are able to sustain the highest metabolic rates possess the highest degree of anatomical ventricular separation and, therefore, less cardiac shunting. It is interesting to note that when cardiac shunts occur in mammals, due for example to developmental defects, they are associated with reduced maximal metabolic rates and impaired exercise tolerance. It appears, therefore, that full separation of ventricular blood flows was a prerequisite for the evolution of high aerobic metabolic rates and exercise stamina in mammals and birds.