Muscle reconditioning in COPD: main interventions and new tendencies

Abstracts

Há algum tempo o condicionamento físico vem sendo parte obrigatória no tratamento de portadores de DPOC. Estes pacientes apresentam comumente intolerância ao exercício de intensidade variável e relacionada à disfunção muscular esquelética. Neste sentido, o exercício físico apresenta-se como ramo mais importante no processo de reabilitação pulmonar. O exercício aeróbio e o treino de força com pesos são fundamentais no incremento de capacidade física e qualidade de vida, principalmente naqueles indivíduos que apresentam as formas moderada ou grave da DPOC. Além disso, espera-se atualmente maior desenvolvimento nas pesquisas em relação à aplicação de estimulação elétrica neuromuscular (EENM) e ao uso criterioso de substâncias ergogênicas tais como esteróides anabolizantes e creatina oral. Tendo em vista as repercussões negativas da disfunção muscular e a importância da reabilitação pulmonar no tratamento da DPOC, esta revisão tem como objetivo reunir informações de estudos relevantes acerca das principais estratégias para o recondicionamento muscular esquelético nestes pacientes nos últimos 15 anos.

Exercício físico; Reabilitação pulmonar; Disfunção muscular

REVIEW ARTICLE

Muscle reconditioning in COPD: main interventions and new tendencies

Recondicionamiento muscular en la enfermedad pulmonar obstructiva crónica (EPOC): principales intervenciones y nuevas tendencias

Victor Zuniga Dourado^I; Irma Godoy^II

^IPhysiotherapist. Master of Science in the program: "Physiopathology in Medical Clinics". Concentration area: "Metabolism and Nutrition" Medical Clinics Department - Botucatu Medical School - Unesp

^IIAssistant Professor of Pneumology Discipline - Botucatu Medical School - Unesp

^{Correspondence}

ABSTRACT

Physical exercises have been a vital part in the treatment of COPD patients since some time ago. These patients frequently present intolerance to exercises of variable intensity related to the skeletal-muscle dysfunction. In this context, the physical exercise is presented as the most important branch in the pulmonary rehabilitation process. The aerobic exercise and the strength training are vital in the increment of the physical capacity and quality of life, especially for individuals who present moderate or acute forms of the COPD. Furthermore, a higher research development is currently expected in relation to the application of neuromuscular electric stimulation (NMEE) and to the judicious use of ergogenic substances such as anabolic steroids and oral creatin. Considering the negative repercussion of the muscle dysfunctions and the importance of the pulmonary rehabilitation in the treatment of COPD, this reviewing has as objective to gather information from relevant studies with regard to the main strategies for the skeletal-muscular reconditioning in patients in the last 15 years.

Key words: Physical exercise. Pulmonary rehabilitation. Muscle dysfunction.

RESUMEN

Hace algún tiempo el condicionamiento físico viene siendo parte obligatoria en el tratamiento de portadores de EPOC. Estos pacientes presentan comúnmente intolerancia al ejercicio de intensidad variable y relacionada a la disfunción muscular esquelética. En este sentido, el ejercicio físico se presenta como la rama más importante en la rehabilitación pulmonar. El ejercicio aeróbico y el entrenamiento de la fuerza con pesas son fundamentales en el incremento de la capacidad física y en la calidad de vida, principalmente en aquellos individuos que presentan las formas moderada y grave de la EPOC. Además, se espera actualmente mayor capacidad de desenvolvimiento en las investigaciones en relación a la aplicación de la estimulación eléctrica neuromuscular (EENM) y al uso criterioso de las sustancias ergogénicas tales como esteroides­ anabólicos y creatina oral. Teniendo en vista las repercusiones negativas de la disfunción muscular en el tratamiento de la EPOC, esta revisión tiene como objetivo reunir informaciones de estudios relevantes a cerca de las principales estrategias para el recondicionamiento muscular esquelético en estos pacientes en los últimos 15 años.

Palabras-clave: Ejercicio físico. Rehabilitación pulmonar. Disfunción muscular.

INTRODUCTION

The intolerance to physical exercise is frequent manifestation in patients with COPD^(1,2). This fact had once been attributed to respiratory dysfunctions that these individuals presented; however, it has been currently verified that the peripheral skeletal-muscle dysfunction is important factor for the decrease on the capacity of performing exercise among this population⁽³⁾. In this context, the persistence of this intolerance is observed even after lung transplant, situation in which the improvement of the pulmonary function occurs^(4,5).

The importance of the skeletal muscle dysfunction in the decrease on the capacity of performing exercises in patients with COPD was firstly suggested by Killian et al.⁽⁶⁾. These authors observed that many patients with COPD complained of lower limbs fatigue during maximal effort test without, however, reporting dyspnea as limiting factor of performance.

Considering that the ventilatory function of patients with COPD may be improved only slightly by clinical therapies, the physical conditioning plays important role with the objective of reducing the respiratory demand and the dyspnea feeling⁽⁷⁾. Dourado et al.⁽⁸⁾ found significant correlation between the six-minutes walking test performance and the domains "Activity" and "Impact" of the Saint George Hospital quality of life questionnaire in respiratory diseases. These findings were corroborated through linear multiple regression, suggesting the influence of tolerance on exercise and quality of life of patients with COPD. When compared to other types of treatment such as bronchodilator agents and oral teofiline, the physical exercise is associated to more significant improvements on quality of life and functional capacity⁽⁹⁾.

Currently, there are a large number of useful therapies in the rehabilitation process of individuals with COPD⁽¹⁰⁾. Among them, the following therapies can be mentioned: the oxygenotherapy, the resistive exercises, the anabolic steroids supplementation⁽¹¹⁾, the creatin supplementation and the neuromuscular electric stimulation (NMEE)⁽⁷⁾. However, there are evidences that the physical exercise is the most effective procedure in the pulmonary rehabilitation⁽¹²⁾. Associated to any other type of therapy, the physical exercise may increase significantly the physical capacity and the quality of life of patients with COPD⁽¹¹⁾.

Considering the negative repercussion of the muscle dysfunctions and the importance of the pulmonary rehabilitation in the treatment of COPD, this reviewing has as objective to gather information from relevant studies with regard to the main strategies for the skeletal-muscular reconditioning in these patients in the last 15 years. This work also aims at presenting new therapy tendencies to improve the physical capacity in patients with COPD. The bibliographic research was performed in the database Medline and Journals@Ovid Full Text using terms exercise and COPD.

AEROBIC EXERCISE

The aerobic exercise is recommended for individuals with COPD and its benefits are observed regardless the COPD stage in which patients are found⁽¹³⁾. This type of training increases the concentration of mitochondrial oxidative enzymes, the capillary action of the trained muscles, the anaerobic threshold, the and decreases the phosphate creatin recovery time (PC) resulting in improvements of the exercise capacity⁽¹⁴⁾.

In patients with COPD, the benefits of the aerobic conditioning result in increase on the distance walked in the six-minutes walking test (TC6), improvement on the performance of quality of life questionnaires and in relief of the exercise tolerance⁽¹¹⁾. The training of the lower limbs may be performed in cycle-ergometers or treadmill walking belts or even by means of walking. Pitta⁽¹⁵⁾ compared the lower limbs training isolated in cycle-ergometer to a non-exercised control group and the results showed significant improvement of the , the TC6, the endurance time with constant load in cycle-ergometer, the PImax and the dyspnea feeling on the trained group, suggesting the positive effects of the lower limbs training even in the absence of other important components of the pulmonary rehabilitation process. For the upper limbs, arm ergometer, weights, sticks or elastics can be used^(10,16).

The activities performed with the upper limbs are related to intense dyspnea because some shoulder muscles are respiratory accessories as well, for example the pectoral and the latissimus dorsi muscles⁽¹⁷⁾. When involved in other activities, their function in the respiration process is decreased and, consequently the work of the diaphragm increases⁽¹⁸⁾. The training for the upper limbs has as objective to increment especially daily activities that are mostly performed with arms and it has already shown benefits in the muscle reconditioning of patients with COPD⁽¹¹⁾.

The aerobic exercise for the lower limbs improves the tolerance to exercise, however, presents small effect with regard to the atrophy and muscle weakness⁽⁵⁾. The lower limbs endurance training benefits have been shown proportional to the intensity in which the exercise is performed; exercises performed between 60 and 80% of the maximal work load (w) present higher endurance increment than exercises performed at low intensities⁽¹⁶⁾. Lower lactate accumulation and CO₂ production, increased quadriceps resistance and evidences of increase on the mitochondrial oxidative capacity after 12 weeks of training are clear signals of muscle adaptation to the aerobic training^(1,14).

Oliveira et al.⁽¹⁹⁾ associated the training of the respiratory muscles (TRM) with 40% of the PImax daily performed in pressure-dependent device to reconditioning general exercises at light intensity performed twice a week. The group submitted to both types of training improved significantly the strength in the respiratory muscles without improvement on the TC6, suggesting the ineffectiveness of the TRM with regard to the improvement of the exercise tolerance in patients with COPD.

The current recommendations for aerobic training include sessions with duration of 20 and 45 minutes and frequency of three to five times a week⁽²⁰⁾. The exercise program should be maintained for at least eight weeks⁽¹⁴⁾.

STRENGTH TRAINING

Considering that the muscle weakness contributes to the exercise intolerance in patients with pulmonary disease, the strength exercise is the rational option in the pulmonary rehabilitation process⁽¹⁶⁾. Currently, there is no sufficient number of studies and, therefore, there is no agreement with regard to the application of the strength training in patients with chronic pulmonary disease⁽⁵⁾.

The decrease on strength in patients with COPD occurs specially in the lower limbs. Gosselink et al.⁽²¹⁾ demonstrated that the decrease on the quadriceps strength is significantly higher than the loss of strength of pectoral muscles or of latissimus dorsi muscle and that, in the upper limbs, the strength reduction is higher in the shoulder proximal muscles⁽³⁾.

Simpson et al.⁽²²⁾ randomized 34 patients with severe COPD in a training group and another non-exercised control group during a eight-weeks program. The training consisted of three series of ten repetitions of three selected exercises performed three times a week. The initial intensity was of 50% of a maximal repetition (1 RM) in the first week, progressively increasing up to 85% of 1 RM in the last training weeks. The maximal voluntary strength increased between 16% and 44% for the trained group and did not change for the control group. No significant alteration on the distance traveled in the TC6 was observed in none of the groups. However, an increment on the quality of life questionnaire performance and on the muscular resistance in the trained group was verified. Troosters et al.⁽²³⁾ analyzed 100 patients with severe COPD and identified values significantly higher in the maximal exercise performance in TC6, in the peripheral muscular strength and in the quality of life among patients who performed six weeks of strength training in relation to those who did not train.

Treatments with muscle hypertrophy objectives do not result in increases on the endurance⁽²⁴⁾, in other words, they do not further aerobic gains, once variables such as and anaerobic threshold do not change significantly⁽¹³⁾ and, therefore, the strength work should be associated to exercise programs that reserve part of their time to the acquisition of aerobic resistance⁽⁵⁾.

The strength training prescriptions for individuals with COPD are not yet well defined; however, the training proposed by most researchers on this topic includes: two or three training days per week, one to three repetition series for each muscle group selected, eight to twelve repetitions, interval from two to three minutes between series; intensity of 50 to 85% of 1 RM and intensity adjustment each three or four weeks⁽⁵⁾.

COMBINED TRAINING

Bernard et al.⁽²⁵⁾ compared the classic aerobic training in cycle-ergometer to this modality associated to weightlifting strength training and concluded that the association resulted in no significant differences in relation to the , TC6 and to the quality of life indicatives when compared to the aerobic training alone. However, they observed that the strength training resulted in less intense dyspnea if compared to the cycle exercise and, consequently more tolerated by patients. When the aerobic training is compared to the strength training alone, the effects are similar in both modalities, except with regard to the that respond better to the aerobic training⁽²⁶⁾.

Dourado et al.⁽²⁷⁾ randomized 15 patients with COPD from light to severe in a 36-sessions program of strength training alone with three series of 8-12 RM in bodybuilding machines with intensity ranging from 50 to 80% of 1 RM (n = 8) or combined (two series of 8-12 repetitions with 50-80% of 1 RM) with light aerobic exercise involving free walking and reconditioning general exercises with dumbbell (n = 7). The groups were submitted to evaluation of pulmonary function, strength and muscular resistance, exercise maximal capacity (), aerobic resistance with constant load in treadmill, TC6, quality of life and dyspnea feeling. A significant improvement on the muscular resistance and TC6 was observed in both groups with no statistical difference between them. However, the quadriceps muscle resistance, the aerobic resistance with constant load in treadmill and the quality of life score improved significantly only for the strength training group alone. These findings suggest the improvement on the muscle strength and capacity of performing exercises in both training regimen. However, the strength training alone showed higher association with the improvement on the quadriceps muscle resistance, aerobic resistance in test with constant load in treadmill and quality of life in these patients with COPD when compared to the combined training with light aerobic exercise.

When the total aerobic training protocol is divided into treadmill, cycle-ergometer and arm ergometer and compared to strength training alone, the effects are similar with relation to the functional capacity and to the quality of life in both modalities⁽²⁶⁾.

NEW TENDENCIES

Androgen administration

The muscle growth depends on the adequate hormonal supply and the reduction on the amount of anabolic hormones causes muscular deficiency⁽⁴⁾. The effects of the anabolic hormones supplementation on the musculature of patients with COPD have only recently been evaluated⁽¹¹⁾.

In men, the aspects of higher concernment with regard to the androgen administration are hyperplasia and prostate cancer, reduced levels of HDL cholesterol and eventual toxicity⁽⁴⁾. Although hyperplasia and prostate cancer are uncommon in individuals with reduced hormonal levels, the testosterone therapy seems not to induce the development of these diseases⁽²⁸⁾. Besides, the testosterone administration in aged individuals with hormonal deficiency does not affect significantly the HDL cholesterol levels⁽²⁹⁾.

Among the main risk deriving from the androgen administration in women, virilization, skin reactions, side effects in plasmatic lipids and changes of behavior must be mentioned⁽⁴⁾. The androgen-prolonged therapy may increase risks of cardiovascular events due to the decrease on the HDL cholesterol. With regard to the correlation of the androgen supplement and breast cancer, the literature present data not much consistent⁽⁴⁾.

Schols et al.⁽³⁰⁾ were the first authors to evaluate the effects of the anabolizant steroid therapy in patients with COPD in a large dimension randomized study, controlled and placebo group involving 203 patients. The patients were divided into two groups as follows: The first group was composed of patients with weight loss (< 90% of the ideal weight) and loss of lean body mass (< 67% of the ideal weight for men and < 63% for women) and the second group without alterations of these parameters. Later, the patients were randomized into three groups: the first group (P) of patients who received placebo and supplementary nutrition (N = 420 Kcal); the second group (N) of patients who received only supplementary nutrition and the third group (N + A) of patients who received supplementary nutrition + intramuscular nandrolone every two weeks (1 ml for men and 0.5 ml for women). When submitted to an 8-weeks general physical exercise program the three groups increased significantly PImax at the first four weeks, however, from the fourth to the eighth weeks, only group N + A remained presenting significant increase in relation to the control group. With regard to the 12-minutes walking test, all groups improved significantly with no statistical difference between them at the end of the 8 weeks.

In this study⁽³⁰⁾, the group of patients with nutritional deficit and the group without nutritional deficit both gained weight; however, the weight gain was higher in undernourished patients. However, the individuals who received anabolizant therapy obtained weight gain due to the increase of the mass free of fat with no adiposity alteration while patients who received complementary nutrition alone presented no alteration on the mass free of fat, being adiposity the responsible for the weight gain. Therefore, in this study, the nandrolone therapy was able to improve the nutritional status of patients with COPD, being important perspective in this matter.

Ferreira et al.⁽³¹⁾ evaluated the influence of the steroid oral administration on BMI, anthropometric measures, respiratory muscular strength and exercise capacity in 23 undernourished patients with COPD and with PImax < 60% of the predicted value. For the group studied, 250 mg of intramuscular testosterone and 12 mg of oral stanozolol were administrated every day during 27 weeks. For the control group, only placebo was administrated. Both groups participated in the inspiratory muscular training from week 1 to week 27 and cycle-ergometer exercises during weeks 18 to 27. The group that received anabolic steroids increased body weight while control group lost weight. The BMI, the percentile of fat-free mass and the arm circumference presented results significantly better in the group of study if compared to the control group. However, no significant difference in PImax, TC6 and in the exercise maximal capacity was observed. Furthermore, no adverse effect caused by the oral administration of anabolic steroids was observed.

The short-duration therapy with anabolic steroids may be an additional intervention for the improvement of the body composition and the exercise tolerance in diseases that present chronic loss of lean body mass as the case of COPD, especially due to the antagonistic effects in relation to the muscle and bone losses typical of the glycocorticoid therapy. Although, the short-duration well-controlled anabolizant therapy presented no adverse effect in patients with COPD so far⁽³²⁾.

Neuromuscular electric stimulation

The neuromuscular electric stimulation (NMEE) is already usually used in the rehabilitation of patients with neuromuscular and orthopedic diseases and, more recently, it has been used in the skeletal-muscle dysfunction as in the case of the chronic cardiac insufficiency⁽⁷⁾.

Neder et al.⁽³³⁾ randomized 15 patients with severe COPD as follows: 9 patients in the 6-weeks of domiciliary NMEE group and 6 patients in the control group. The quadriceps strength and resistance, the physical capacity and the quality of life were evaluated. Significant improvements of the muscular function, exercise tolerance and the dyspnea component of the quality of life questionnaire (CRQ) were verified in the group studied.

Therefore, The NMEE was useful especially in patients who presented severe COPD and relevant muscle-skeletal dysfunction. The benefits of this type of therapy may be particularly evident in patients with relevant dyspnea, unable to be submitted even to extremely light physical activities. In this type of patient, the NMEE may soften the effects of the muscular dysfunction, making the participation in pulmonary rehabilitation programs involving physical conditioning possible⁽⁷⁾.

Creatin supplementation

The simplest and rapid method to obtain energy involves the ATP-CP: CP + ADP Þ ^{kinase creatin} ATP + C system⁽¹⁴⁾. However, the muscle cells are able to store only small amounts of CP and, therefore, the amount of energy produced by the ATP-CP system is limited. This system supplies energy for muscular contraction at the beginning of a given exercise and in high-intensity exercises and of duration shorter than 5 seconds⁽¹⁴⁾.

The CP depletion may limit the performance of high-intensity short duration exercises. With regard to patients with COPD, due to the CP depletion be even higher than in control individuasl⁽³⁴⁾, these activities represent, for example, the ascending of one step in a stair or walking in higher velocity than the usual⁽⁷⁾.

The creatin supplementation may increase the lean body mass, the time required for the muscular fatigue, improve the performance in sprint activities and increase muscular strength⁽³⁵⁾.

In aged individuals, Gotshalk et al.⁽³⁶⁾ found results that indicate positive effects in the muscular performance in men between 59 and 73 years of age submitted to creatin administration. The benefits of the creatin supplementation are expressed as the higher ability in developing daily activities. In short, the creatin administration during a short period (7 days) results in increase on muscular strength and power in aged individuals with no adverse effect.

There are no published researches in the evaluation of the creatin supplementation effects as part of the pulmonary rehabilitation so far. The use of creatin in patients with COPD is not indicated until enlightening results are published in literature⁽⁷⁾.

FINAL CONSIDERATIONS

Undoubtedly, the most effective components of the pulmonary rehabilitation are those related to physical activity as the aerobic exercises, peripheral and respiratory resistive exercises, besides the association of both modalities. Currently, the scientific community is interested in developing coadjuvant therapies with the objective of maximizing the effects of physical conditioning programs. In this context, the anabolic steroids therapy starts being evaluated and the NMEE and the creatin therapy, so far incipient, open new perspectives with regard to strategies for the skeletal-muscle reconditioning in patients with COPD.

REFERENCES

Received in 27/9/03. 2^nd version received in 27/4/04. Approved in 7/6/04

All the authors declared there is not any potential conflict of interests regarding this article.

• 1. Maltais F, Simard A, Simard C, Jobin J, Desgagnés P, Leblanc P. Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit Care Med 1996;153:288-93.
• 2. Debigaré R, Côté CH, Maltais F. Peripheral muscle wasting in chronic obstructive pulmonary disease - Clinical relevance and mechanisms. Am J Respir Crit Care Med 2001;164:1712-7.
• 3. Gosselink R, Troosters T, Decramer M. Distribution of muscle weakness in patients with stable chronic obstructive pulmonary disease. J Cardiopulm Rehabil 2000;20:353-60.
• 4. Casaburi R. Skeletal muscle dysfunction in chronic obstructive pulmonary disease. Med Sci Sports Exerc 2001;33:S662-70.
• 5. Storer TW. Exercise in chronic obstructive pulmonary disease: resistance exercise prescription. Med Sci Sports Exerc 2001;33:S680-6.
• 6. Killian KJ, Leblanc P, Martin DH, Summers E, Jones NL, Campbell EJM. Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation. Am J Respir Crit Care Med 1992;146:935-40.
• 7. Neder JA. Estratégias emergentes para o recondicionamento muscular esquelético na DPOC. In: Fernandes ALG, Mendes ESPS, Terra Filho M, editores. Pneumologia: atualização e reciclagem. São Paulo: Atheneu, 2001;1-13.
• 8. Dourado VZ, Antunes LCO, Carvalho LR, Godoy I. Influência de características gerais na qualidade de vida de pacientes com doença pulmonar obstrutiva crônica. J Bras Pneumol 2004;30:207-14.
• 9. Lacasse Y, Brosseau L, Milne S, Martin S, Wong E, Guyatt GH, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease (Cochrane Review). In: The Cochrane Library, Issue 1. Oxford: Update Software, 2004.
• 10. Sociedade Brasileira de Pneumologia e Tisiologia. I Consenso Brasileiro de Doença Pulmonar Obstrutiva Crônica (DPOC). J Pneumol 2000;26:S1-52.
• 11. American Thoracic Society-European Respiratory Society. Skeletal muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:S1-28.
• 12. Cooper CB. Exercise in chronic obstructive pulmonary disease: limitations and rehabilitation. Med Sci Sports Exerc 2001;33:S643-6.
• ¹³
  Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease updated. National Institutes of Health and National Heart, Lung, and Blood Institute 2003;1-95.
• 14. Powers SK, Howley ET. Fisiologia do exercício: teoria e aplicação ao condicionamento e ao desempenho. 3^a ed. São Paulo: Manole, 2000.
• 15. Pitta FO. Efeitos do treinamento de membros inferiores com cicloergometria em portadores de doença pulmonar obstrutiva crônica (DPOC) moderada e grave. (Dissertação). Botucatu: Faculdade de Medicina, Universidade Estadual Paulista.
• 16. American Thoracic Society Statement. Pulmonary rehabilitation. Am J Respir Crit Care Med 1999;159:1666-82.
• 17. Orozco-Levi M, Gea J, Sauleda J, Corominas JM, Minguella M, Aran X, et al. Structure of the latissimus dorsi muscle and respiratory function. J Appl Physiol 1995;78:1132-9.
• 18. Martinez FJ, Couser JI, Celli BR. Respiratory response to arm elevation in patients with chronic airflow obstruction. Am Rev Respir Dis 1991;143:476-80.
• 19. Oliveira LC, Gobette VL, Maio F, Sugisaki C, Godoy I. Treinamento dos músculos respiratórios associado a exercícios de recondicionamento geral em pacientes com doença pulmonar obstrutiva crônica. Rev Bras Fisiot 1999;3:61-7.
• 20. Cooper CB. Exercise in chronic obstructive pulmonary disease: aerobic exercise prescription. Med Sci Sports Exerc 2001;33:S671-9.
• 21. Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am J Respir Crit Care Med 1996;153:976-80.
• 22. Simpson K, Killian K, Mccartney N, Stubbing DG, Jones NL. Randomized controlled trial of weightlifting exercise in patients with chronic airflow limitation. Thorax 1992;47:70-5.
• 23. Troosters T, Gosselink R, Decramer M. Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial. Am J Med 2000;109:207-12.
• 24. Steiner MC, Morgan MDL. Enhancing physical performance in chronic obstructive pulmonary disease. Thorax 2001;56:73-7.
• 25. Bernard S, Whittom F, Leblanc P, Jobin J, Belleau R, Bérubé C, et al. Aerobic and strength training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:896-01.
• 26. Spruit MA, Gosselink R, Troosters T, De Paepe K, Decramer M. Resistance versus endurance training in patients with COPD and peripheral muscle weakness. Eur Respir J 2002;19:1072-8.
• 27. Dourado VZ, Antunes LCO, Tani SE, Gonsalves RS, Godoy I. Strength training alone or combined with low intensity endurance training in patients with chronic obstructive pulmonary disease. In: Proceedings of the ERS annual congress: 2004 sep 4-8; Glasgow. Scotland: Unpublished.
• 28. Treuth MS, Ryan AS, Pratley LA. Effects of strength training on total and regional body composition in older men. J Appl Physiol 1994;77:614-24.
• 29. Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992;75:1092-8.
• 30. Schols AMWJ, Soeters PB, Mostert R, Pluymers RJ, Wouters EFM. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:1268-74.
• 31. Ferreira IM, Verreschi IT, Nery LE. The influence of 6 months of oral anabolic steroids on body mass and respiratory muscles in undernourished COPD patients. Chest 1998;114:19-28.
• 32. Creutzberg E. Anabolic steroids in acute and chronic disease. In: Wouters EFM, Schols AMWJ, editors. Nutrition and metabolism in chronic respiratory disease. European Respiratory Monograph 2003;8:163-77.
• 33. Neder JA, Sword D, Ward SA, Mackey E, Cochrane LM, Clark CJ. Home based neuromuscular electrical stimulation as a new rehabilitative strategy for severely disabled patients with chronic obstructive pulmonary disease (COPD). Thorax 2002;57:333-7.
• 34. Sala E, Roca J, Marrades RM, Alonso J, De Suso JMG, Moreno A, et al. Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1726-34.
• 35. Izquierdo M, Ibañez J, González-Badillo JJ, Gorostiaga EM. Effects of creatine supplementation on muscle power, endurance, and sprint performance. Med Sci Sports Exerc 2002;34:332-43.
• 36. Gotshalk LA, Volek JS, Staron RS, Denegar CR, Hagerman FC, Kraemer WJ. Creatine supplementation improves muscular performance in older men. Med Sci Sports Exerc 2002;34:537-43.

Publication Dates

• Publication in this collection
  09 Nov 2004
• Date of issue
  Aug 2004

History

• Accepted
  07 June 2004
• Reviewed
  27 Apr 2004
• Received
  27 Sept 2003