ABSTRACT
Though pulmonary rehabilitation can have potent effects on exercise capacity and quality
of life in chronic obstructive pulmonary disease (COPD), not all patients benefit
to the same degree. Enabling patients to achieve higher training intensities may improve
exercise capacity. Adding pharmacological agents to target the abnormal ventilatory
mechanics or skeletal muscle dysfunction may enhance the effects of exercise training.
This review discusses the rationale and clinical evidence supporting the use of pharmacological
adjuncts during the course of pulmonary rehabilitation.
KEYWORDS
COPD - exercise training - bronchodilators - oxygen - helium - anabolic agents
REFERENCES
- 1
Ries A L, Bauldoff G S, Carlin B W et al..
Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice Guidelines.
Chest.
2007;
131(5, Suppl)
4S-42S
- 2
Lacasse Y, Goldstein R, Lasserson T J, Martin S.
Pulmonary rehabilitation for chronic obstructive pulmonary disease.
Cochrane Database Syst Rev.
2006;
(4)
CD003793
- 3
Nici L, Donner C, Wouters E ATS/ERS Pulmonary Rehabilitation Writing Committee et
al.
American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation.
Am J Respir Crit Care Med.
2006;
173
1390-1413
- 4
Griffiths T L, Burr M L, Campbell I A et al..
Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised
controlled trial.
Lancet.
2000;
355
362-368
- 5
Ries A L, Kaplan R M, Myers R, Prewitt L M.
Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized trial.
Am J Respir Crit Care Med.
2003;
167
880-888
- 6
Gimenez M, Servera E, Vergara P, Bach J R, Polu J M.
Endurance training in patients with chronic obstructive pulmonary disease: a comparison
of high versus moderate intensity.
Arch Phys Med Rehabil.
2000;
81
102-109
- 7
Puente-Maestu L, Sánz M L, Sánz P, Ruíz de Oña J M, Rodríguez-Hermosa J L, Whipp B J.
Effects of two types of training on pulmonary and cardiac responses to moderate exercise
in patients with COPD.
Eur Respir J.
2000;
15
1026-1032
- 8
Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner C F, Wasserman K.
Reductions in exercise lactic acidosis and ventilation as a result of exercise training
in patients with obstructive lung disease.
Am Rev Respir Dis.
1991;
143
9-18
- 9
Maltais F, LeBlanc P, Jobin J et al..
Intensity of training and physiologic adaptation in patients with chronic obstructive
pulmonary disease.
Am J Respir Crit Care Med.
1997;
155
555-561
- 10
Ofir D, Laveneziana P, Webb K A, Lam Y M, O’Donnell D E.
Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage
I chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2008;
177
622-629
- 11
O’Donnell D E, Revill S M, Webb K A.
Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2001;
164
770-777
- 12
O’Donnell D E, Webb K A.
Exertional breathlessness in patients with chronic airflow limitation. The role of
lung hyperinflation.
Am Rev Respir Dis.
1993;
148
1351-1357
- 13
O’Donnell D E, Aaron S, Bourbeau J Canadian Thoracic Society et al.
State of the Art Compendium: Canadian Thoracic Society recommendations for the management
of chronic obstructive pulmonary disease.
Can Respir J.
2004;
11(Suppl B)
7B-59B
- 14
Berry M J, Rejeski W J, Adair N E, Ettinger Jr W H, Zaccaro D J, Sevick M A.
A randomized, controlled trial comparing long-term and short-term exercise in patients
with chronic obstructive pulmonary disease.
J Cardiopulm Rehabil.
2003;
23
60-68
- 15
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
207-212
- 16
Wedzicha J A, Bestall J C, Garrod R, Garnham R, Paul E A, Jones P W.
Randomized controlled trial of pulmonary rehabilitation in severe chronic obstructive
pulmonary disease patients, stratified with the MRC dyspnoea scale.
Eur Respir J.
1998;
12
363-369
- 17
O’Donnell D E, Hernandez P, Kaplan A et al..
Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary
disease—2008 update—highlights for primary care.
Can Respir J.
2008;
15(Suppl A)
1A-8A
- 18
Celli B R, MacNee W. ATS/ERS Task Force .
Standards for the diagnosis and treatment of patients with COPD: a summary of the
ATS/ERS position paper.
Eur Respir J.
2004;
23
932-946
- 19
Tashkin D P, Celli B, Senn S UPLIFT Study Investigators et al.
A 4-year trial of tiotropium in chronic obstructive pulmonary disease.
N Engl J Med.
2008;
359
1543-1554
- 20
Barr R G, Bourbeau J, Camargo C A, Ram F S.
Inhaled tiotropium for stable chronic obstructive pulmonary disease.
Cochrane Database Syst Rev.
2005;
(2)
CD002876
- 21
Calverley P M, Anderson J A, Celli B TORCH investigators et al.
Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary
disease.
N Engl J Med.
2007;
356
775-789
- 22
Sin D D, McAlister F A, Man S F, Anthonisen N R.
Contemporary management of chronic obstructive pulmonary disease: scientific review.
JAMA.
2003;
290
2301-2312
- 23
Sridhar M, Taylor R, Dawson S, Roberts N J, Partridge M R.
A nurse led intermediate care package in patients who have been hospitalised with
an acute exacerbation of chronic obstructive pulmonary disease.
Thorax.
2008;
63
194-200
- 24
Maltais F, Bourbeau J, Shapiro S Chronic Obstructive Pulmonary Disease Axis of Respiratory
Health Network, Fonds de recherche en santé du Québec et al.
Effects of home-based pulmonary rehabilitation in patients with chronic obstructive
pulmonary disease: a randomized trial.
Ann Intern Med.
2008;
149
869-878
- 25
O’Donnell D E, Voduc N, Fitzpatrick M, Webb K A.
Effect of salmeterol on the ventilatory response to exercise in chronic obstructive
pulmonary disease.
Eur Respir J.
2004;
24
86-94
- 26
Celli B, ZuWallack R, Wang S, Kesten S.
Improvement in resting inspiratory capacity and hyperinflation with tiotropium in
COPD patients with increased static lung volumes.
Chest.
2003;
124
1743-1748
- 27
Casaburi R, Mahler D A, Jones P W et al..
A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary
disease.
Eur Respir J.
2002;
19
217-224
- 28
O’Donnell D E, Flüge T, Gerken F et al..
Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD.
Eur Respir J.
2004;
23
832-840
- 29
Man W D, Mustfa N, Nikoletou D et al..
Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible
COPD.
Thorax.
2004;
59
471-476
- 30
Liesker J J, Van De Velde V, Meysman M et al..
Effects of formoterol (Oxis Turbuhaler) and ipratropium on exercise capacity in patients
with COPD.
Respir Med.
2002;
96
559-566
- 31
Grove A, Lipworth B J, Reid P et al..
Effects of regular salmeterol on lung function and exercise capacity in patients with
chronic obstructive airways disease.
Thorax.
1996;
51
689-693
- 32
Casaburi R, Kukafka D, Cooper C B, Witek Jr T J, Kesten S.
Improvement in exercise tolerance with the combination of tiotropium and pulmonary
rehabilitation in patients with COPD.
Chest.
2005;
127
809-817
- 33
Lindsay M, Lee A, Chan K et al..
Does pulmonary rehabilitation give additional benefit over tiotropium therapy in primary
care management of chronic obstructive pulmonary disease? Randomized controlled clinical
trial in Hong Kong Chinese.
J Clin Pharm Ther.
2005;
30
567-573
- 34
Weiner P, Magadle R, Berar-Yanay N, Davidovich A, Weiner M.
The cumulative effect of long-acting bronchodilators, exercise, and inspiratory muscle
training on the perception of dyspnea in patients with advanced COPD.
Chest.
2000;
118
672-678
- 35
Nocturnal Oxygen Therapy Trial Group .
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease:
a clinical trial.
Ann Intern Med.
1980;
93
391-398
- 36
Report of the Medical Research Council Working Party .
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating
chronic bronchitis and emphysema.
Lancet.
1981;
1
681-686
- 37
Bradley J M, Lasserson T, Elborn S, Macmahon J, O’Neill B.
A systematic review of randomized controlled trials examining the short-term benefit
of ambulatory oxygen in COPD.
Chest.
2007;
131
278-285
- 38
Somfay A, Pórszász J, Lee S M, Casaburi R.
Effect of hyperoxia on gas exchange and lactate kinetics following exercise onset
in nonhypoxemic COPD patients.
Chest.
2002;
121
393-400
- 39
Somfay A, Porszasz J, Lee S M, Casaburi R.
Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic
COPD patients.
Eur Respir J.
2001;
18
77-84
- 40
O’Donnell D E, D’Arsigny C, Webb K A.
Effects of hyperoxia on ventilatory limitation during exercise in advanced chronic
obstructive pulmonary disease.
Am J Respir Crit Care Med.
2001;
163
892-898
- 41
O’Donnell D E, Bain D J, Webb K A.
Factors contributing to relief of exertional breathlessness during hyperoxia in chronic
airflow limitation.
Am J Respir Crit Care Med.
1997;
155
530-535
- 42
Libby D M, Briscoe W A, King T K.
Relief of hypoxia-related bronchoconstriction by breathing 30 per cent oxygen.
Am Rev Respir Dis.
1981;
123
171-175
- 43
Emtner M, Porszasz J, Burns M, Somfay A, Casaburi R.
Benefits of supplemental oxygen in exercise training in nonhypoxemic chronic obstructive
pulmonary disease patients.
Am J Respir Crit Care Med.
2003;
168
1034-1042
- 44
Wadell K, Henriksson-Larsén K, Lundgren R.
Physical training with and without oxygen in patients with chronic obstructive pulmonary
disease and exercise-induced hypoxaemia.
J Rehabil Med.
2001;
33
200-205
- 45
Rooyackers J M, Dekhuijzen P N, Van Herwaarden C L, Folgering H T.
Training with supplemental oxygen in patients with COPD and hypoxaemia at peak exercise.
Eur Respir J.
1997;
10
1278-1284
- 46
Garrod R, Paul E A, Wedzicha J A.
Supplemental oxygen during pulmonary rehabilitation in patients with COPD with exercise
hypoxaemia.
Thorax.
2000;
55
539-543
- 47
Fichter J, Fleckenstein J, Stahl C, Sybrecht G W.
Effect of oxygen (FI02: 0.35) on the aerobic capacity in patients with COPD [in German].
Pneumologie.
1999;
53
121-126
- 48
Nonoyama M L, Brooks D, Lacasse Y, Guyatt G H, Goldstein R S.
Oxygen therapy during exercise training in chronic obstructive pulmonary disease.
Cochrane Database Syst Rev.
2007;
(2)
CD005372
- 49
Lacasse Y, Lecours R, Pelletier C, Bégin R, Maltais F.
Randomised trial of ambulatory oxygen in oxygen-dependent COPD.
Eur Respir J.
2005;
25
1032-1038
- 50
Nonoyama M L, Brooks D, Guyatt G H, Goldstein R S.
Effect of oxygen on health quality of life in patients with chronic obstructive pulmonary
disease with transient exertional hypoxemia.
Am J Respir Crit Care Med.
2007;
176
343-349
- 51
Eaton T, Garrett J E, Young P et al..
Ambulatory oxygen improves quality of life of COPD patients: a randomised controlled
study.
Eur Respir J.
2002;
20
306-312
- 52 Lumb A B. Nunn's Applied Respiratory Physiology. 6th ed. Philadelphia; Elsevier
Butterworth Heinemann 2005
- 53
Eves N D, Petersen S R, Haykowsky M J, Wong E Y, Jones R L.
Helium-hyperoxia, exercise, and respiratory mechanics in chronic obstructive pulmonary
disease.
Am J Respir Crit Care Med.
2006;
174
763-771
- 54
Palange P, Valli G, Onorati P et al..
Effect of heliox on lung dynamic hyperinflation, dyspnea, and exercise endurance capacity
in COPD patients.
J Appl Physiol.
2004;
97
1637-1642
- 55
Marciniuk D D, Butcher S J, Reid J K et al..
The effects of helium-hyperoxia on 6-min walking distance in COPD: a randomized, controlled
trial.
Chest.
2007;
131
1659-1665
- 56
Johnson J E, Gavin D J, Adams-Dramiga S.
Effects of training with heliox and noninvasive positive pressure ventilation on exercise
ability in patients with severe COPD.
Chest.
2002;
122
464-472
- 57
Eves N D, Sandmeyer L C, Wong E Y et al..
Helium-hyperoxia: a novel intervention to improve the benefits of pulmonary rehabilitation
for patients with COPD.
Chest.
2009;
135
609-618
- 58
Engelen M P, Schols A M, Baken W C, Wesseling G J, Wouters E F.
Nutritional depletion in relation to respiratory and peripheral skeletal muscle function
in out-patients with COPD.
Eur Respir J.
1994;
7
1793-1797
- 59
Laaban J P, Kouchakji B, Dore M F, Orvoen-Frija E, David P, Rochemaure J.
Nutritional status of patients with chronic obstructive pulmonary disease and acute
respiratory failure.
Chest.
1993;
103
1362-1368
- 60
Gosker H R, Lencer N H, Franssen F M, van der Vusse G J, Wouters E F, Schols A M.
Striking similarities in systemic factors contributing to decreased exercise capacity
in patients with severe chronic heart failure or COPD.
Chest.
2003;
123
1416-1424
- 61
Schols A M, Soeters P B, Dingemans A M, Mostert R, Frantzen P J, Wouters E F.
Prevalence and characteristics of nutritional depletion in patients with stable COPD
eligible for pulmonary rehabilitation.
Am Rev Respir Dis.
1993;
147
1151-1156
- 62
Wilson D O, Rogers R M, Wright E C, Anthonisen N R. The National Institutes of Health
Intermittent Positive-Pressure Breathing Trial .
Body weight in chronic obstructive pulmonary disease.
Am Rev Respir Dis.
1989;
139
1435-1438
- 63
Kobayashi A, Yoneda T, Yoshikawa M et al..
The relation of fat-free mass to maximum exercise performance in patients with chronic
obstructive pulmonary disease.
Lung.
2000;
178
119-127
- 64
Mostert R, Goris A, Weling-Scheepers C, Wouters E F, Schols A M.
Tissue depletion and health related quality of life in patients with chronic obstructive
pulmonary disease.
Respir Med.
2000;
94
859-867
- 65
Nishimura Y, Tsutsumi M, Nakata H, Tsunenari T, Maeda H, Yokoyama M.
Relationship between respiratory muscle strength and lean body mass in men with COPD.
Chest.
1995;
107
1232-1236
- 66
Sahebjami H, Doers J T, Render M L, Bond T L.
Anthropometric and pulmonary function test profiles of outpatients with stable chronic
obstructive pulmonary disease.
Am J Med.
1993;
94
469-474
- 67
Skeletal muscle dysfunction in chronic obstructive pulmonary disease. A statement
of the American Thoracic Society and European Respiratory Society.
Am J Respir Crit Care Med.
1999;
159(4 Pt 2)
S1-S40
- 68
Allaire J, Maltais F, Doyon J F et al..
Peripheral muscle endurance and the oxidative profile of the quadriceps in patients
with COPD.
Thorax.
2004;
59
673-678
- 69
Couillard A, Maltais F, Saey D et al..
Exercise-induced quadriceps oxidative stress and peripheral muscle dysfunction in
patients with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2003;
167
1664-1669
- 70
Gosker H R, van Mameren H, van Dijk P J et al..
Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic
obstructive pulmonary disease.
Eur Respir J.
2002;
19
617-625
- 71
Agustí A G, Sauleda J, Miralles C et al..
Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2002;
166
485-489
- 72
Koechlin C, Couillard A, Cristol J P et al..
Does systemic inflammation trigger local exercise-induced oxidative stress in COPD?.
Eur Respir J.
2004;
23
538-544
- 73
Koechlin C, Couillard A, Simar D et al..
Does oxidative stress alter quadriceps endurance in chronic obstructive pulmonary
disease?.
Am J Respir Crit Care Med.
2004;
169
1022-1027
- 74
Maltais F, LeBlanc P, Whittom F et al..
Oxidative enzyme activities of the vastus lateralis muscle and the functional status
in patients with COPD.
Thorax.
2000;
55
848-853
- 75
Whittom F, Jobin J, Simard P M et al..
Histochemical and morphological characteristics of the vastus lateralis muscle in
patients with chronic obstructive pulmonary disease.
Med Sci Sports Exerc.
1998;
30
1467-1474
- 76
Maltais F, Jobin J, Sullivan M J et al..
Metabolic and hemodynamic responses of lower limb during exercise in patients with
COPD.
J Appl Physiol.
1998;
84
1573-1580
- 77
Maltais F, Simard A 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
288-293
- 78
Gosselink R, Troosters T, Decramer M.
Peripheral muscle weakness contributes to exercise limitation in COPD.
Am J Respir Crit Care Med.
1996;
153
976-980
- 79
Saey D, Debigare R, LeBlanc P et al..
Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients
with chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2003;
168
425-430
- 80
Killian K J, Leblanc P, Martin D H, Summers E, Jones N L, Campbell E J.
Exercise capacity and ventilatory, circulatory, and symptom limitation in patients
with chronic airflow limitation.
Am Rev Respir Dis.
1992;
146
935-940
- 81
Mador M J, Kufel T J, Pineda L A, Sharma G K.
Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive
pulmonary disease.
Am J Respir Crit Care Med.
2000;
161
118-123
- 82
Sala E, Roca J, Marrades R M et al..
Effects of endurance training on skeletal muscle bioenergetics in chronic obstructive
pulmonary disease.
Am J Respir Crit Care Med.
1999;
159
1726-1734
- 83
Maltais F, LeBlanc P, Simard C et al..
Skeletal muscle adaptation to endurance training in patients with chronic obstructive
pulmonary disease.
Am J Respir Crit Care Med.
1996;
154(2 Pt 1)
442-447
- 84
Schols A.
Nutritional modulation as part of the integrated management of chronic obstructive
pulmonary disease.
Proc Nutr Soc.
2003;
62
783-791
- 85
Schols A M, Soeters P B, Mostert R, Saris W H, Wouters E F.
Energy balance in chronic obstructive pulmonary disease.
Am Rev Respir Dis.
1991;
143
1248-1252
- 86
Ferreira I M, Brooks D, Lacasse Y, Goldstein R S, White J.
Nutritional supplementation for stable chronic obstructive pulmonary disease.
Cochrane Database Syst Rev.
2005;
(2)
CD000998
- 87
Steiner M C, Barton R L, Singh S J, Morgan M D.
Nutritional enhancement of exercise performance in chronic obstructive pulmonary disease:
a randomised controlled trial.
Thorax.
2003;
58
745-751
- 88
Broekhuizen R, Creutzberg E C, Weling-Scheepers C A, Wouters E F, Schols A M.
Optimizing oral nutritional drink supplementation in patients with chronic obstructive
pulmonary disease.
Br J Nutr.
2005;
93
965-971
- 89
Bhasin S, Woodhouse L, Casaburi R et al..
Testosterone dose-response relationships in healthy young men.
Am J Physiol Endocrinol Metab.
2001;
281
E1172-E1181
- 90
Bhasin S, Storer T W, Berman N et al..
The effects of supraphysiologic doses of testosterone on muscle size and strength
in normal men.
N Engl J Med.
1996;
335
1-7
- 91
Harman S M, Metter E J, Tobin J D, Pearson J, Blackman M R. Baltimore Longitudinal
Study of Aging .
Longitudinal effects of aging on serum total and free testosterone levels in healthy
men.
J Clin Endocrinol Metab.
2001;
86
724-731
- 92
Amory J K, Watts N B, Easley K A et al..
Exogenous testosterone or testosterone with finasteride increases bone mineral density
in older men with low serum testosterone.
J Clin Endocrinol Metab.
2004;
89
503-510
- 93
Kenny A M, Prestwood K M, Gruman C A, Marcello K M, Raisz L G.
Effects of transdermal testosterone on bone and muscle in older men with low bioavailable
testosterone levels.
J Gerontol A Biol Sci Med Sci.
2001;
56
M266-M272
- 94
Snyder P J, Peachey H, Hannoush P et al..
Effect of testosterone treatment on body composition and muscle strength in men over
65 years of age.
J Clin Endocrinol Metab.
1999;
84
2647-2653
- 95
Kamischke A, Kemper D E, Castel M A et al..
Testosterone levels in men with chronic obstructive pulmonary disease with or without
glucocorticoid therapy.
Eur Respir J.
1998;
11
41-45
- 96
Forbes G B, Halloran E.
The adult decline in lean body mass.
Hum Biol.
1976;
48
161-173
- 97
Murray M P, Gardner G M, Mollinger L A, Sepic S B.
Strength of isometric and isokinetic contractions: knee muscles of men aged 20 to
86.
Phys Ther.
1980;
60
412-419
- 98
Riggs B L, Wahner H W, Seeman E et al..
Changes in bone mineral density of the proximal femur and spine with aging: differences
between the postmenopausal and senile osteoporosis syndromes.
J Clin Invest.
1982;
70
716-723
- 99
Cabasso A.
Peliosis hepatis in a young adult bodybuilder.
Med Sci Sports Exerc.
1994;
26
2-4
- 100 Snyder P J.
Androgens. In: Brunton LL, Lazo JS, Parker KL Goodman and Gilman’s The Pharmacological Basis
of Therapeutics. 11th ed. New York, NY; McGraw-Hill 2006: 1573-1586
- 101
Drinka P J, Jochen A L, Cuisinier M, Bloom R, Rudman I, Rudman D.
Polycythemia as a complication of testosterone replacement therapy in nursing home
men with low testosterone levels.
J Am Geriatr Soc.
1995;
43
899-901
- 102
Casaburi R, Bhasin S, Cosentino L et al..
Effects of testosterone and resistance training in men with chronic obstructive pulmonary
disease.
Am J Respir Crit Care Med.
2004;
170
870-878
- 103
Creutzberg E C, Wouters E F, Mostert R, Pluymers R J, Schols A M.
A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind,
placebo-controlled, randomized trial.
Chest.
2003;
124
1733-1742
- 104
Ferreira I M, Verreschi I T, Nery L E et al..
The influence of 6 months of oral anabolic steroids on body mass and respiratory muscles
in undernourished COPD patients.
Chest.
1998;
114
19-28
- 105
Schols A M, Soeters P B, Mostert R, Pluymers R J, Wouters E F.
Physiologic effects of nutritional support and anabolic steroids in patients with
chronic obstructive pulmonary disease: a placebo-controlled randomized trial.
Am J Respir Crit Care Med.
1995;
152(4 Pt 1)
1268-1274
- 106
Greenhaff P L.
Creatine and its application as an ergogenic aid.
Int J Sport Nutr.
1995;
5(Suppl)
S100-S110
- 107
Harris R C, Söderlund K, Hultman E.
Elevation of creatine in resting and exercised muscle of normal subjects by creatine
supplementation.
Clin Sci (Lond).
1992;
83
367-374
- 108
Nissen S L, Sharp R L.
Effect of dietary supplements on lean mass and strength gains with resistance exercise:
a meta-analysis.
J Appl Physiol.
2003;
94
651-659
- 109
Brose A, Parise G, Tarnopolsky M A.
Creatine supplementation enhances isometric strength and body composition improvements
following strength exercise training in older adults.
J Gerontol A Biol Sci Med Sci.
2003;
58
11-19
- 110
Chrusch M J, Chilibeck P D, Chad K E, Davison K S, Burke D G.
Creatine supplementation combined with resistance training in older men.
Med Sci Sports Exerc.
2001;
33
2111-2117
- 111
Branch J D.
Effect of creatine supplementation on body composition and performance: a meta-analysis.
Int J Sport Nutr Exerc Metab.
2003;
13
198-226
- 112
Andrews R, Greenhaff P, Curtis S, Perry A, Cowley A J.
The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive
heart failure.
Eur Heart J.
1998;
19
617-622
- 113
Jacobs P L, Mahoney E T, Cohn K A, Sheradsky L F, Green B A.
Oral creatine supplementation enhances upper extremity work capacity in persons with
cervical-level spinal cord injury.
Arch Phys Med Rehabil.
2002;
83
19-23
- 114
Tarnopolsky M A, Roy B D, MacDonald J R.
A randomized, controlled trial of creatine monohydrate in patients with mitochondrial
cytopathies.
Muscle Nerve.
1997;
20
1502-1509
- 115
Vorgerd M, Grehl T, Jager M et al..
Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled
crossover trial.
Arch Neurol.
2000;
57
956-963
- 116
Fiaccadori E, Del Canale S, Vitali P, Coffrini E, Ronda N, Guariglia A.
Skeletal muscle energetics, acid-base equilibrium and lactate metabolism in patients
with severe hypercapnia and hypoxemia.
Chest.
1987;
92
883-887
- 117
Fuld J P, Kilduff L P, Neder J A et al..
Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary
disease.
Thorax.
2005;
60
531-537
- 118
Faager G, Söderlund K, Sköld C M, Rundgren S, Tollbäck A, Jakobsson P.
Creatine supplementation and physical training in patients with COPD: a double blind,
placebo-controlled study.
Int J Chron Obstruct Pulmon Dis.
2006;
1
445-453
- 119
Deacon S J, Vincent E E, Greenhaff P L et al..
Randomized controlled trial of dietary creatine as an adjunct therapy to physical
training in chronic obstructive pulmonary disease.
Am J Respir Crit Care Med.
2008;
178
233-239
- 120
Rodríguez-Arnao J, Jabbar A, Fulcher K, Besser G M, Ross R J.
Effects of growth hormone replacement on physical performance and body composition
in GH deficient adults.
Clin Endocrinol (Oxf).
1999;
51
53-60
- 121
Salomon F, Cuneo R C, Hesp R, Sönksen P H.
The effects of treatment with recombinant human growth hormone on body composition
and metabolism in adults with growth hormone deficiency.
N Engl J Med.
1989;
321
1797-1803
- 122
Pape G S, Friedman M, Underwood L E, Clemmons D R.
The effect of growth hormone on weight gain and pulmonary function in patients with
chronic obstructive lung disease.
Chest.
1991;
99
1495-1500
- 123
Burdet L, de Muralt B, Schutz Y, Pichard C, Fitting J W.
Administration of growth hormone to underweight patients with chronic obstructive
pulmonary disease: a prospective, randomized, controlled study.
Am J Respir Crit Care Med.
1997;
156
1800-1806
- 124
Shahar E, Folsom A R, Melnick S L Atherosclerosis Risk in Communities Study Investigators
et al.
Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary
disease.
N Engl J Med.
1994;
331
228-233
- 125
Agustí A, Morlá M, Sauleda J, Saus C, Busquets X.
NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD
and low body weight.
Thorax.
2004;
59
483-487
- 126
Moses A W, Slater C, Preston T, Barber M D, Fearon K C.
Reduced total energy expenditure and physical activity in cachectic patients with
pancreatic cancer can be modulated by an energy and protein dense oral supplement
enriched with n-3 fatty acids.
Br J Cancer.
2004;
90
996-1002
- 127
Aguilaniu B, Flore P, Perrault H, Page J E, Payan E, Lacour J R.
Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty
acid diet.
Eur J Appl Physiol Occup Physiol.
1995;
72
44-50
- 128
Broekhuizen R, Wouters E F, Creutzberg E C, Weling-Scheepers C A, Schols A M.
Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary
disease.
Thorax.
2005;
60
376-382
Roger GoldsteinM.D.
West Park Healthcare Centre
82 Buttonwood Ave., Toronto, ON, M6M 2J5 Canada
Email: rgoldstein@westpark.org