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(Chest. 2001;119:353-363.)
© 2001 American College of Chest Physicians

Nutritional Intervention in COPD*

A Systematic Overview

Ivone M. Ferreira, MD, PhD; Dina Brooks, PhD, MSc (PT); Yves Lacasse, MD, MSc and Roger S. Goldstein, MB, ChB, FCCP

* From the Departments of Medicine (Drs. Ferreira and Goldstein) and Physical Therapy (Dr. Brooks), the University of Toronto and Respiratory Medicine, West Park Hospital, Toronto, Ontario; and Centre de Pneumologie (Dr. Lacasse), Hopital Laval, Ste-Foy, Quebec, Canada.

Correspondence to: Ivone M. Ferreira, MD, PhD, c/o Dr. Roger Goldstein, West Park Hospital, 82 Buttonwood Ave, Toronto, Canada M6M 215; e-mail: ivoneferreira{at}hotmail.com


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Objective: We conducted a systematic overview of randomized controlled trials (RCTs) to clarify the contribution of nutritional supplementation for patients with stable COPD.

Methods: RCTs were identified from several sources, including the Cochrane Airways Group register of RCTs, a hand search of abstracts presented at international meetings, and consultation with experts. Two reviewers independently selected trials for inclusion, assessed quality, and extracted the data.

Results: Twenty-one reports were classified according to the type, duration of supplementation, and the presence of anabolic substances. High carbohydrate meals were associated with an increase in carbon dioxide production and a decrease in exercise capacity. Short-term crossover studies in which diets of various compositions were administered supported the notion that high carbohydrate loads increase the stress on the ventilatory system. The influence of longer-term supplementation (> 2 weeks) on weight, anthropometry, and exercise capacity varied, without there being a consistent effect. Lean body weight was only occasionally reported and health-related quality of life too rarely to be included as an outcome. The influence of recombinant human growth hormone was disappointing. Anabolic steroids increased body weight and lean body mass, but had little influence on exercise capacity.

Conclusion: This systematic overview in patients with COPD supports the notion that those with marginal ventilatory reserve might benefit from a dietary regimen in which a high percentage of calories are supplied by fat. Although there are reports of the benefits of nutritional repletion, trials of > 2 weeks failed to show consistent benefit on body weight. Evaluating nutritional repletion is hampered by the absence of information regarding body composition, exercise, and health-related quality of life. Growth hormone has not been shown to be useful. Further studies are needed to refine the beneficial effects of anabolic steroids as adjunctive agents together with nutritional support and exercise.

Key Words: anabolic steroids • COPD • growth hormone • nutrition • respiratory rehabilitation • systematic overview


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
A number of individuals with COPD experience involuntary weight loss as their condition progresses.1 Those who do lose weight have more dyspnea and less exercise capacity than those who do not, even when their underlying levels of impairment (airflow obstruction) are similar.2 The loss includes both fat and lean body mass.3 It may occur even in the presence of a dietary intake thought to be adequate for predicted energy requirements.4 Malnourished subjects have worse scores on a respiratory disease-specific quality-of-life questionnaire than do adequately nourished individuals.5 In advanced COPD, severe weight loss is sometimes referred to as pulmonary cachexia.6 Given the negative association between COPD and weight loss,2 7 8 9 a number of clinical trials have examined the influence of nutritional supplementation, alone or with anabolic substances such as steroids or growth hormone (GH), on patients with COPD.

The pathophysiologic mechanisms that result in weight loss for patients with COPD are not well understood. The many hypotheses include inadequate dietary intake, increased resting energy expenditure (REE), diet-induced thermogenesis, systemic inflammation, tissue hypoxia, and medications.1 4 Patients are considered to be underweight if their body weight is <= 90% than their ideal body weight (IBW; 1983 Metropolitan Life Insurance Tables10 ), or if their body mass index (BMI; weight/height squared) is < 20 kg/m2.11 Since weight and height do not provide information on fat or fat-free mass (FFM), the latter is often measured as part of a nutritional evaluation of patients with COPD.3 12

A recent meta-analysis13 of studies on nutritional supplementation in COPD identified nine randomized controlled trials (RCTs) in which nutritional supplementation was compared with usual clinical care. Nutritional supplementation was defined as caloric supplementation for at least 2 weeks. For each of the outcomes studied (anthropometric measures, pulmonary function, respiratory muscle strength, and functional exercise capacity), the effect of nutritional support was homogeneously small.13

The effect of nutritional support in the management of patients with COPD continues to be of interest. In this overview, we reviewed prospective RCTs that provided information regarding the influence of nutritional support. We have included studies addressing the immediate effects of a meal, short-term (< 2 weeks) supplementation, supplementation of > 2 weeks, and supplementation by adjunctive treatments such as anabolic steroids and GH.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Search Strategy
The following strategies were used to uncover relevant publications from the English-language medical literature. RCTs were identified with assistance from the Cochrane Airways Group registry of RCTs in COPD. We also searched MEDLINE (National Library of Medicine from 1966 to 1999), EMBASE, and CINAHL (Cumulated Index to Nursing and Allied Health from 1982 to 1999) for original articles published in all languages. The following terms were used to uncover trials related to nutritional support in COPD: Nutrit*, Malnutrit*, Undernourish*, Weight loss, Food, Feed, Diet*, Lean Body Mass, BMI, Depletion, Anabolic, Androgen, Male hormone, Sex hormone, and Growth hormone. Trials were identified by the following strategy: placebo*, trial, random*, double blind, single blind, controlled study, and comparative study. Also, references from existing reviews and abstracts presented at international meetings (American Thoracic Society, American College of Chest Physicians from 1980 to 1998, and European Respiratory Society from 1987 to 1998) were hand searched for potentially relevant citations. Authors of all included papers were asked to advise regarding any other relevant studies published in the last 10 years, unpublished or in progress.

Inclusion Criteria
Two reviewers (I.M.F. and D.B.) independently selected trials for inclusion in the review according to prior agreement regarding definitions and interventions. Disagreement was solved after consultation with a third reviewer (Y.L.). To be selected, trials had to include stable patients among whom at least 75% had COPD characterized by a FEV1 of < 70% predicted, and < 15% reversibility after bronchodilator therapy.

Nutritional Supplementation
We required that subjects had been allocated to receive either (1) oral, enteral, or parenteral nutritional intervention; or (2) placebo, their usual diet, or other treatment regimens such as anabolic substances. Studies involving patients with COPD undergoing treatment in the ICU were excluded.

Outcomes
The primary outcomes consisted of anthropometric measures (body weight, lean body mass, BMI) and functional exercise capacity (timed walk test, submaximal or graded exercise). Other measures included pulmonary mechanics (lung volumes, respiratory muscle function), peripheral muscle function, and health-related quality of life (HRQL).

Data Extraction and Analysis
The data and trial quality information were extracted independently by two reviewers (I.M.F., D.B.). The methodologic quality of the trials was assessed using a validated instrument.14 This instrument contained items that assessed whether a study was truly randomized, whether the study was described as blinded, and whether the study provided detailed information regarding dropouts and withdrawals. The study was scored within a range of 0 to 5, in which a score of > 2 represented a higher-quality study and a score of < 2 represented a study of lower quality. Any missing data were requested from the primary study investigators. Once the reviewers had reached agreement regarding the quality score, the articles were classified and grouped according to type and length of supplementation. Those studies dealing with supplementation of > 2 weeks were grouped separately.13


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
A total of 272 abstracts were identified. After the two primary reviewers assessed the abstracts, the number was reduced to 55 reports ({kappa}, 0.89; 95% confidence interval, 0.82 to 0.96) on nutrition and COPD. When reviewed in detail, 21 reports were included. Both reviewers agreed on all except four reports ({kappa}, 0.94; 95% confidence interval, 0.85 to 1.0), which were therefore sent to a third reviewer (Y.L.) for arbitration. Reasons for excluding studies included the following: uncontrolled study,8 15 16 17 18 19 no randomization,20 21 investigations into weight loss without nutritional support,22 23 24 25 26 27 28 29 30 31 32 nutritional assessment without nutritional support,2 33 34 35 36 37 38 39 40 41 subjects not meeting eligibility criteria,42 43 44 45 and a second report of the same trial.

Reports were classified according to the type, duration of supplementation, and presence of anabolic substances (Table 1 ).


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  		Table 1. RCTs of Nutritional Support in COPD Grouped by Type and Duration of Intervention

 
Immediate Effects of a Meal
The four studies47 48 49 50 that focused on the effects of a meal with different carbohydrate (CHO) and fat composition all cited indexes of metabolism and exercise performance (Table 2 ). Each of the studies used a randomized crossover design. The protocols differed slightly, with three of the studies including a control group and the fourth evaluating a moderate- vs a high-fat content. Immediately following a meal high in CHO, carbon dioxide production (CO2) and respiratory quotient (RQ) increased and exercise capacity decreased.47 48 50 The increased CO2 and ventilatory requirement was more marked following ingestion of a high CHO load compared with a high fat load.47 48 50 When a high-fat meal was compared with a moderate-fat meal, the former was associated with a measurable delay in gastric emptying.49 Such a delay might, by extending the time of abdominal distension, impact on the position and mobility of the diaphragm as well as the lower thorax, which would have a negative impact among individuals in whom respiratory function was already compromised.


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  		Table 2. Summary of Studies That Examined the Immediate Effects (Before and After) of Meals With Different Percentages of CHO and Fat*

 
There are several possible mechanisms by which high-CHO diets influence ventilation and exercise capacity. The absorption and metabolism of food results in an increase in CO2 output. Given the close linkages between CO2 output and ventilation, ingestion of high-CHO foods increases the ventilatory requirement.47 In normal subjects, the increased CO2 is easily eliminated by increasing alveolar ventilation. In patient with COPD, such increases may contribute to the increase in dyspnea, a decrease in exercise tolerance, and an increase in PaCO2.47 48 50 It has been suggested that the increase in ventilation is greatest following CHO compared with fat or protein.47 48 50 This suggestion is based on theoretical considerations that under ideal conditions, the oxidation of fat produces less CO2 per unit of calories than does CHO. Ideal conditions, however, assume that all dietary calories are used for energy and not for lean body mass or fat accretion.49 They do not account for the simultaneous ingestion of other macronutrients (as in normal feeding), or for the possible effect of macronutrients on gastric emptying, rate of digestion, absorption, and metabolic utilization.49

Although the increase in CO2 might aggravate those in respiratory failure, in stable patients its effect was small and may be of little clinical significance.49 Food ingestion may then be more likely related to the load on the diaphragm than the composition of the meal.51 Of note, postprandial exercise was consistently reduced in each of these studies.

Short-term Effects (<= 2 Weeks)
Studies in which subjects were offered short-term supplementation containing different percentages of fat and CHO52 53 54 are summarized in Table 3 . Two reports used a similar design.52 54 Ambulatory malnourished patients with emphysema and malnourished patients without lung disease received hypercaloric diets high in either fat or CHO for a week, then crossing over to the other limb in a randomized design. In the third study,53 hypercapnic subjects were given low-, medium-, or high-CHO diets for 5 days each in a randomized double-blind trial. One of the studies54 measured the influence of diet on submaximal exercise at a level comparable to daily activities (12 W and 24 W). The findings by Angellilo et al53 and Goldstein et al54 are consistent with studies of immediate effects of a meal, showing that a high-fat diet places a lower demand on the respiratory system than a diet high in CHO. Goldstein et al54 noted small but consistent decreases in CO2 (112 ± 9 to 95 ± 6 mL/min/m2), RQ (1.0 ± 0.02 to 0.86 ± 0.02), minute ventilation (E; 4.7 ± 0.1 to 4.0 ± 0.3 L/min/m2), and tidal volume (VT; 241 ± 15 to 193 ± 25 mL/m2) with the higher fat content. These changes were mirrored among a control group of malnourished subjects who did not have COPD. During exercise, both ventilation and inspiratory flow (VT/inspiratory time) was greater in the high-CHO group. Exercise efficiency increased with refeeding, with further increases among those switching from low-fat to high-fat diets. Weight gain occurred in both groups. Measures of nitrogen and energy relationships in subjects who were malnourished (weight loss of 13 to 15% in the previous year, reduced creatinine/height index)52 suggest that patients with emphysema are hypermetabolic but in contrast to other patients are not hypercatabolic nor do they show a preference for fat oxidation. Improved nutritional status with both diets was reflected by a positive nitrogen balance after 2 weeks, as well as comparable improvements in weight, arm circumference, and total iron-binding capacity. Such changes were accompanied by improvements in respiratory muscle strength and in peripheral muscle endurance (quadriceps, hamstring, and handgrip).52 CHO oxidation was higher in COPD, irrespective of diet. The route of administration (parenteral vs oral) had no effect on any of the measured metabolic parameters.52 When energy and protein intake were supplied in proportion to energy expenditure (1.7 x REE), energy balance and nitrogen balance were similar in CHO or fat diets.


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  		Table 3. Summary of Studies That Examined the Effects of Meals With Different Percentages of CHO and Fat for a Duration of < 2 Weeks

 
Angelillo and colleagues53 also reported that the low-CHO, high-fat diet reduced CO2 and RQ compared with the high-CHO diet. They also noted a small but significant increase in PaCO2 (from 47.5 ± 1.4 to 49.2 ± 1.6 mm Hg) as the CHO content increased from low to moderate. Although the overall mean caloric intake over 15 days was thought to be slightly higher than the measured requirements, these authors report that their subjects experienced weight loss (values not provided) that may be an important clinical limitation to this approach.

Supplementation for > 2 Weeks
The results of nutritional supplementation beyond 2 weeks have varied (M. C. DeLetter, RN, PhD; unpublished data; January 1999).55 56 57 58 59 60 61 62 63 Although nonsystematic reviews have concluded that an increase in energy intake > 1.5 of the REE, or an increase of 30% will result in weight gain,4 64 these reviews were often based on trials that were not randomized or controlled.4 64

The main findings from RCTs (M. C. DeLetter, RN, PhD; unpublished data; January 1999),55 56 57 58 59 60 61 62 63 in which nutritional supplementation was maintained for at least 2 weeks identified no consistent effects on weight, anthropometric measures, or pulmonary function. Nine of these trials have been summarized in a previous meta-analysis.13 Adding 2 additional trials to the previous 9 trials, the 11 trials included 327 subjects randomized fairly equally between control and study groups. Most of the trials involved small numbers of subjects (< 30 subjects in all but two trials), with one trial in particular accounting for 135 subjects.63 Those who received nutritional supplementation gained just under 2 kg (1.87 ± 1.06 kg [SD]), whereas the weight of those in the control groups remained the same (- 0.03 ± 0.70). As with any intervention study, the issue of how the intervention was delivered is an important one. In eight of the trials, subjects received their nutritional intervention as outpatients, one trial included both inpatient and outpatient phases, and two trials were conducted with inpatients only. Supervision varied from daily dietary supervision to written instructions supported by two weekly visits to the patient’s home by a nurse. Some subjects were asked to keep daily records of their dietary intake, whereas others were supported by family members who were incorporated into the protocol and given written instructions as to how they could supervise the nutritional supplementation. Although measures of REE were not always provided, a good approximation was made using the Moore-Angellilo equation (11.5 x body weight + 952),64 given that most if not all subjects were male. Comparing the approximate REE with the prescribed nutritional protocols, the subjects (both nutritionally depleted and nondepleted) did receive the recommended caloric intake for weight gain (1.5 x REE). Although some did gain weight, it was due to a change in fat mass.16 58 63 Nutritional support alone was insufficient to promote significant overall weight gain in trials of individuals with COPD. However, lean body mass, the preferred measure of a positive energy balance, was reported in only two trials, and HRQL was reported too rarely even to be included as an outcome. Only one protocol included exercise as part of the overall management of COPD.63

Anabolic Steroids and GH
Anabolic Steroids:
Studies in which either anabolic steroid63 65 or GH66 67 were administered are summarized in Table 4 . All the studies of hormonal supplementation recruited patients referred for respiratory rehabilitation. Whereas the exact program details vary, patients were engaged in exercises such as treadmill, cycle, swimming, or walking. The largest study63 began with 217 male or female subjects who were stratified into depleted and nondepleted groups at baseline according to body weight (< 90% IBW) or FFM (< 67% in men and < 63% in women). Those who were depleted had lower inspiratory pressures and lower 12-min walking distances than those who were not. The REEs throughout the study were lower in the depleted vs the nondepleted groups (range, 1,170 to 1,189 kcal depleted vs 1,555 to 1,580 kcal nondepleted). The weight gains were similar between those who received nutrition alone or those who received nutrition plus anabolic steroids, although those who were depleted (malnourished) gained more than those who were not depleted (2.9 ± 2.9 kg in nutrition vs 2.4 ± 2.2 kg in nutrition and anabolic steroid) or nourished (1.1 ± 2.4 kg in nutrition vs 1.2 ± 2.7 kg in nutrition and anabolic steroid). Moreover, patients who had combined therapy (nutrition plus anabolic steroid) showed a greater increase in FFM compared to those who received only nutritional supplements in whom the weight gain was predominantly due to an expansion of fat mass. A small increase in maximal inspiratory pressure (PImax; 10.2 ± 1.9 kPa) was noted in only the combined nutrition plus anabolic steroid group. This change was not significantly different from the group who received only nutritional supplementation. Both groups improved their 12-min walk distance, although over a third of patients were too disabled to participate in a walking test. No side effect was reported even in female patients, who received half of the dose of that given to male patients.63


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  		Table 4. Summary of Studies That Examined the Effects of Anabolic Steroids or GH*

 
Ferreira et al65 recruited 23 malnourished (depleted) men (BMI < 20 kg/m2) with COPD in whom respiratory muscle strength was reduced to < 60% predicted. Synthetically derived testosterone (stanozolol) or placebo was administered for 6 months. Weight improved in the treatment vs the control group (1.8 ± 0.5 kg vs 0.4 ± 0.2 kg, respectively). BMI, lean body mass, arm muscle circumference (AMC), and thigh circumference also improved in the study group. Despite some involvement in inspiratory muscle training (weeks 9 to 27) and cycle ergometry (weeks 18 to 27), the two groups did not differ in respiratory muscle strength or exercise capacity after 6 months. It is of importance to note that in neither of the above studies were any harmful effects noted, despite careful monitoring of a variety of biochemical and functional indexes.

GH:
Burdet and colleagues66 administered recombinant human GH (rhGH) or placebo in a 3-week, double-blind, randomized trial to 16 subjects (14 male and 2 female) with COPD who were participating in a pulmonary rehabilitation program, provided their baseline body weight was < 90% IBW. Lean body mass increased (2.3 ± 1.6 kg in the rhGH group and 1.1 ± 0.9 kg in control subjects) after 21 days, being sustained 2 months after cessation of rhGH administration. There was no effect on respiratory muscle strength, peripheral muscle strength, maximal power during incremental exercise, or sensation of dyspnea. REE increased by 7.8% (p < 0.01) in the study group at the end of 3 weeks, being identical to the control group 2 months later. Caloric intake did not change with rhGH, and there was no influence on body weight. The two groups had similar pulmonary function and exercise characteristics at baseline and throughout the study, with a trivial change in 6-min walk test in the study group, which was unlikely to be clinically important (13 ± 31%).

A similar protocol was reported by Casaburi et al67 in abstract form. Training was extended for 6 weeks among 29 subjects with moderately severe COPD who were randomized to receive GH plus training (12 subjects), GH plus placebo (12 subjects), or placebo alone (5 subjects). Levels of insulin-like growth factor were low initially and increased markedly from 110 ± 62 to 213 ± 81 ng/mL in the study group only. GH administration was associated with an increase in lean body mass of 6.4 ± 5.6% in the GH group compared with no change in the placebo group. Although muscle cross-sectional area increased 6.1 ± 2.5% in the study group vs 2.0 ± 2.5% in control subjects, this change was not associated with any improvement in exercise capacity tolerance by incremental or constant work-rate measures. No significant difference was noted in HRQL measure (measure not specified).

As with studies of anabolic steroids, GH has been associated with a number of undesirable side effects (salt and water retention, impairment of glucose metabolism, etc68 ), none of which were noted in the above two studies.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
How nutrients influence ventilation and metabolism at rest and during low levels of activity among patients with COPD could assist in our understanding of how to minimize dyspnea on exertion and maximize energy reserves. Underweight patients with COPD are more dyspneic than normal-weight patients, and although the origins of dyspnea in COPD are multifactorial, changes in diffusing capacity as well as in respiratory muscle strength may contribute to its intensity.69 Patients with COPD clearly have a distinct pattern of energy metabolism and fuel oxidation that differs from malnourished patients without lung disease. The higher REE in COPD is associated with a significantly higher oxidation of CHO, irrespective of diet. This increased CHO oxidation may relate to a decrease in respiratory efficiency and an increase in the work of breathing, in turn resulting in the use of glucose as the primary fuel for respiratory muscle function.54 When the elevated energy metabolism is not adequately met by an increased spontaneous dietary intake, weight loss occurs.51 70

It is likely that weight loss in COPD results from both a failure of the adaptive response to undernutrition and an inadequate dietary intake for the energy expenditure.71 Given the relationship between weight loss and tumor necrosis factor, several reports have postulated a contributory role of systemic inflammation to this catabolic response similar to the cachexia syndromes associated with heart failure and cystic fibrosis.72 73 74 Restoration of energy balance (positive nitrogen balance) by improved nutritional status following short-term supplementation is supported by weight gain, an increase in FFM, respiratory muscle function, and even in the immune response.59 Thus, short-term nutritional support may be an important clinical modality, as both skeletal and respiratory muscle strength improves in malnourished patients with lung disease.

Attention to the therapeutic implications of weight loss is relatively recent. Previously, this change was considered to be part of the terminal phase of COPD and therefore irreversible. The clinical importance of depletion of fat and muscle mass has been highlighted by the prevalence rates of 20% in stable outpatients and 50% in hospitalized patients with acute respiratory failure.1 In a article regarding the prognostic implications of body weight changes in COPD, Schols et al70 constructed two survival curves for such individuals. The first reflected a retrospective review of 400 rehabilitation patients with COPD, none of whom had been given nutritional supplementation. She noted that a low BMI, age, and PaO2 were significant independent predictors of mortality. When subjects were classified into quintiles based on BMI, a threshold value of 25 kg/m2 was identified, below which the mortality was clearly increased. Weight change entered as a time-dependant covariate remained an independent predictor of mortality in addition to all variables that were entered. The second survival curve was based on a post hoc analysis of the prospective RCT reviewed above (203 patients who received nutritional support alone or with anabolic steroids for an 8-week period). Among these subjects, weight gain of > 2 kg in 8 weeks in both depleted and nondepleted individuals as well as an increase in PImax were significant predictors of survival. Given the short treatment duration relative to follow-up, it is possible that a group of patients exist whose weight loss is more easily reversible following dietary counseling. The combined results of the two survival analyses further support the hypothesis that body weight has an independent effect on survival in COPD.70 The challenge is to identify an approach that will effectively influence FFM.

Nutritional supplementation is clearly feasible, especially in a rehabilitation unit63 where close supervision allows good control over caloric intake. Another advantage is that supplementation may be modified to be delivered to avoid a drop in the normal dietary intake as has been reported previously.57 It is also possible that the gain in FFM may be enhanced by the active participation in a respiratory rehabilitation program especially if the latter includes a substantial component of peripheral muscle training. Unfortunately, despite the encouraging results of short-term (< 2 weeks) studies, RCTs of nutritional support for > 2 weeks (16 days to 12 weeks) failed to show a consistent effect on weight. The absence of detailed information regarding body composition detracts from a clearer understanding of the influence of such nutritional support, as does the variable subject supervision. If nutritional supplements were associated with side effects such as bloating, fullness, or dyspnea, the subjects might well have been tempted to reduce the supplement or to reduce their usual nutritional intake, thus lessening their overall caloric intake. Whether or not the failure to reach a substantial gain in weight reflected a failure to provide sufficient nutritional support rather than a failure of the intervention is likely to be a subject of ongoing discussion. In a article75 characterizing those who responded poorly (< 2% weight gain) to 8 weeks of nutritional supplementation, the authors noted that nonresponse was associated with aging, relative anorexia, and an elevated systemic inflammatory response. Improved nutritional effectiveness will be contingent on a better understanding of the complex multifactorial metabolic issues associated with COPD.76

Early studies of anabolic substances to assist patients with wasting from nonrespiratory causes were limited by the outcome measures used and by the lack of distinction between malnourished and well-nourished individuals. Nutritional support alone may be insufficient in promoting substantial weight gain within the context of promoting FFM as opposed to fat mass.16 58 63 The mechanism by which anabolic steroids may be beneficial was not the topic of any of the RCTs reviewed. However, their influence on anabolic protein receptors and their inhibition of catabolism via glucocorticoid receptors77 may be especially useful as both free and bound testosterone decrease with age, and this decrease may be more pronounced in chronic conditions such as COPD.68 78

Potential side effects related with prolonged use of anabolic steroids are bile retention and gynecomastia in persons with previous liver damage, virilization in women, reduction in high-density lipoprotein, and alteration in glucose metabolism.68 There is no conclusive evidence linking malignancy to the use of anabolic steroids; however, these drugs stimulate the growth of already proven breast and prostatic cancer in men. An association with colonic and prostatic cancer has also been claimed, but never proven.68

Although GH can have a large effect on body composition, including lipolysis, protein anabolism, and muscle growth, either directly or through an insulin-like growth-factor hormone,68 the studies by Burdet et al66 and Casaburi et al,67 in keeping with other (uncontrolled) studies,17 79 80 showed improvements in lean body mass with no effect on peripheral or respiratory muscle strength or exercise capacity. The absence of any change in HRQL was also important, although disease-specific measures were not used. Potential side effects of GH include local reaction, salt and water retention, impairment of glucose metabolism, symptoms of carpal tunnel syndrome, gynecomastia,68 increase of oxygen consumption (O2) and CO2, and decrease in exercise performance.66 GHs are also expensive and available only by injection.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
Nutritional depletion in COPD is common and has a negative impact on respiratory as well as skeletal muscle function, contributing to the morbidity and mortality of this condition.1 2 3 4 5 6 7 8 9 It is therefore valuable to include management strategies that increase energy balance in order to increase weight and FFM. Although most patients tolerate CHO loads, diet content and volume per meal may have to be modified for patients with severe dyspnea or hypercapnia. Although short-term studies of nutritional supplementation have reported a positive nitrogen balance, weight gain, and improved muscle function, nutritional support for > 2 weeks did not show a significant effect size in any of the main outcomes measured.13 Information regarding the influence of nutritional support on functional exercise capacity and HRQL would be helpful. GH studies have not been positive. Anabolic agents do result in weight gain and an increase in FFM. Their role as adjuncts together with nutritional support and exercise training remains to be further defined. Alternative approaches to increasing appetite and caloric intake are to be encouraged. A more precise understanding of the pathophysiology of weight loss and the alterations in cellular metabolism will assist with identifying the nutritional approaches most likely to be successful for those with COPD.


   Acknowledgements
 
We thank the authors of the original articles who provided data beyond that included in their published articles. We also thank the staff of the Cochrane "Airways Group" (Stephen Milan, Anna Bara, Jane Davis, and Professor Paul Jones) for their invaluable support and assistance.


   Footnotes
 
Abbreviations: AMC = arm muscle circumference; BMI = body mass index; CHO = carbohydrate; FFM = fat-free mass; GH = growth hormone; HRQL = health-related quality of life; IBW = ideal body weight; PImax = maximal inspiratory pressure; RCT = randomized controlled trial; REE = resting energy expenditure; rhGH = recombinant human growth hormone; RQ = respiratory quotient; CO2 = carbon dioxide production; E = minute ventilation; O2 = oxygen consumption; VT = tidal volume

This study was made possible due funding from FAPESP–Fundacao de Amparo a pesquisa do Estado de Sao Paulo, Brazil (IMF), Canadian Lung Association/MRC/Glaxo Welcome Postdoctoral fellowship (DB), and West Park Hospital Foundation.

Received for publication February 29, 2000. Accepted for publication September 7, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

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