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ABSTRACT |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD. Two survival analyses were performed: (1) a retrospective study, including 400 patients with COPD none of whom had received nutritional therapy; (2) a post hoc analysis of a prospective study, including 203 patients with COPD who had participated in a randomized placebo-controlled trial. There was no overlap between the patient groups. Baseline characteristics of all patients were collected on admission to a pulmonary rehabilitation center in stable clinical condition. In the prospective randomized placebo-controlled trial, the physiologic effects of nutritional therapy alone (n = 71) or in combination with anabolic steroid treatment (n = 67) after 8 wk was studied in patients with COPD prestratified into a depleted group and a nondepleted group. Mortality was assessed as overall mortality. The Cox proportional hazards model was used to quantify the relationship between the baseline variables age, sex, spirometry, arterial blood gases, body mass index (BMI), smoking, and subsequent overall mortality. Additionally, the influence of treatment response on mortality was investigated in the prospective study. The retrospective study revealed that low BMI (p < 0.001), age (p < 0.0001) and low PaO2 (p < 0.05) were significant independent predictors of increased mortality. After stratification of the group into BMI quintiles a threshold value of 25 kg/m2 was identified below which the mortality risk was clearly increased. In the prospective study, weight gain (> 2 kg/8 wk) in depleted and nondepleted patients with COPD, as well as increase in maximal inspiratory mouth pressure during the 8-wk treatment, were significant predictors of survival. On Cox regression analysis weight change entered as a time-dependent covariate remained an independent predictor of mortality in addition to all variables that were entered in the retrospective study. The combined results of the two survival analyses provide evidence to support the hypothesis that body weight has an independent effect on survival in COPD. Moreover the negative effect of low body weight can be reversed by appropriate therapy in some of the patients with COPD.
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INTRODUCTION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Chronic obstructive pulmonary disease (COPD) is an invalidating disorder characterized by aggravating dyspnea, impaired exercise tolerance, and, frequently, weight loss associated with muscle wasting (1). Although weight loss commonly occurs, it is debatable whether this is an epiphenomenon of severe disease or an independent risk factor that should be treated. On the other hand, the relevance of weight loss and muscle wasting for the clinical condition has been clearly demonstrated in recent years by an adverse effect on physical performance (2) and respiratory muscle function (3), independent of the degree of airflow obstruction. Reported prevalence rates of muscle wasting in clinically stable patients range from 20 to 35% (4, 5).
An elevated energy metabolism not adequately met by an increased spontaneous dietary intake underlies weight loss in COPD (6). Several studies have shown that restoration of the energy balance by nutritional support results in a significant increase in body weight, fat-free mass, and respiratory muscle function (7), and even in the immune response (11). Long-term results of weight maintenance or weight gain on morbidity and mortality are not yet available. In retrospective survival studies, however, an inverse relationship between weight loss (12) and a low body weight (13, 14) with survival has been reported.
Here we present two survival studies to further unravel the prognostic significance of body weight changes in patients with COPD. Firstly, we performed a study of patients with moderate to severe COPD to investigate retrospectively the relation between body weight and survival, adjusting for the influence of age, sex, lung function, recent weight loss, and smoking. Thereafter, we performed a post hoc analysis utilizing data of a recently published placebo-controlled randomized nutritional intervention trial (10) to investigate prospectively the effects of treatment and treatment response (i.e., weight gain and improvement of maximal inspiratory mouth pressure) on survival.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Study Design
Retrospective study. Data were collected from patients with COPD admitted to a pulmonary rehabilitation center between January 1, 1986 and January 1, 1990. Patients are referred to this center by their pulmonary physician in a stable clinical condition to participate in an inpatient pulmonary rehabilitation program (mean duration, 10 wk). Patients were eligible for the study if they had COPD according to the American Thoracic Society guidelines (1), FEV1 < 70% of predicted with an increase in FEV1 < 15% of the predicted value after administration of a bronchodilating agonist (400 µg salbutamol). Those with unstable disease or with other confounding disorders such as malignancies, insulin-dependent diabetes mellitus, and thyroid or cardiovascular disease were excluded. None of the patients had received nutritional therapy prior to or during the rehabilitation period.
Prospective study. The prospective study was a post hoc analysis of a randomized placebo-controlled trial (10) of 203 patients that was performed between January 1, 1988 and January 1, 1992. In this study the effects of nutritional support, alone or in combination with anabolic steroids, on body weight, body composition (fat mass and fat-free mass), and physiologic function was investigated for 8 wk. In addition to the above-mentioned selection criteria with respect to COPD and confounding disorders, patients with a body mass index (BMI) > 29 kg/m2 were excluded from the intervention trial. There was no overlap with the patient population that was analyzed in the retrospective study. Patients were prestratified into a depleted and a nondepleted group on the basis of a low body weight and/or a low fat-free mass, such as previously described (10). Nutritional support (n = 71) consisted of a daily high caloric liquid supplement (420 kcal/200 ml: 51% fat, 35% carbohydrate, 14% protein; mixture of Nutridrink, Protifar, Fantomalt [N.V. Nutricia, Zoetermeer, The Netherlands], and oil). Anabolic steroid treatment (n = 67) consisted of four (two-weekly administered) intramuscular injections with nandrolone decanoate (Decadurabolin [N.V. Organon, The Netherlands]; men: 50 mg, women: 25 mg). The placebo group (n = 65) received intramuscular injections with nandrolon decanoate vehicle (arachis oil). Daily nutritional supplementation could not be administered in a double-blind fashion. The study design is schematically displayed in Figure 1.
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Measurements
FEV1 and inspiratory vital capacity (IVC) were measured with a wet spirometer; the highest value of at least three acceptable spirometric maneuvers was used. Prebronchodilator and postbrochodilator FEV1 and IVC were expressed as a percentage of the reference values (15). Arterial blood gases were drawn by puncture of the brachial artery at rest while the subjects breathed room air. PaO2 and PaCO2 were analyzed on a blood gas analyzer (ABL 330; Radiometer, Copenhagen, Denmark). Body height was measured with subjects standing barefoot and determined to the nearest 0.5 cm (Lameris WM 715; Breukelen). Body weight without clothes was measured on a beam scale (SECA, Germany). Respiratory muscle strength was measured as mouth pressure during maximal static inspiratory (PImax) maneuvers from RV using the technique described by Black and Hyatt (16). The best of three reproducible efforts was chosen. Exercise performance was evaluated with a 12-min walk along an indoor corridor 100 m long. All tests were performed in the early afternoon, and no encouragement was given. Walking distance was not evaluated in patients suffering from chronic hypoxemia or with locomotor ailments.
Statistical Analysis
Univariate analysis of survival was performed using the Kaplan-Meier
method (17). A log-rank chi-square test for comparing the survival between groups was used to analyze the association of clinical characteristics at entry with survival. Mortality was assessed as overall mortality
from all causes. A two-sided value of p < 0.05 was considered significant. Patients were stratified into two subgroups by the degree of airflow
obstruction (FEV1 < or 
45%), by the presence of chronic hypoxemia (PaO2 < 7.3 kPa) and by the presence of chronic hypercapnia
(PaCO2 > 6.0 kPa). Kaplan-Meier survival curves were calculated for
four BMI classes based on commonly used criteria of leanness and
obesity (< 20: underweight, 20 to 24: normal; 24 to 29: overweight; > 29:
obese). Because the patients were unequally distributed among these
four groups, an additional stratification into BMI quintiles was performed (I: < 20.5; II: 20.5 to 22.8; III: 22.9 to 25.0; IV: 25.1 to 27.6; V: > 27.6). Patients were further characterized by smoking (current smoking/nonsmoking) and weight history (weight loss > 10% of baseline).
The Cox proportional hazards model was used to quantify the relationship between the baseline variables (age, sex, FEV1, IVC, PaO2, PaCO2, BMI, and smoking) and subsequent overall mortality. The relative risk (RR) corresponding to a risk factor in this model is the exponential of the regression coefficient. Data were analyzed using the SPSS for Windows statistical package (SPSS Inc., Chicago, IL) (18).
Prior to the prospective survival study, treatment response was defined as an increase in body weight > 2 kg (3.5% of baseline) during the 8-wk intervention period, based on previous nutritional intervention studies (8) and subsequently the influence of the treatment response (significant increase in body weight and improvement of PImax as primary outcome measure) on survival was analyzed in an univariate analysis using the Kaplan-Meier method. Subsequently, weight change was entered as a time-dependent covariate in a Cox proportional hazards model adjusting for change in PImax treatment and other possible contributors to overall mortality that were studied in the retrospective analysis.
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RESULTS |
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INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Retrospective Study
Patient characteristics are given in Table 1. The study group consisted of 400 patients with COPD with a moderate to severe airflow obstruction, 72% of whom were male. Maintainance medication consisted of beta2-sympathicomimetics (96%), theophyllines (82%), ipratropium bromide (90%), and inhalation corticosteroids (73%); 50% were receiving oral corticosteroids. Mean BMI amounted to 24.0 (4.6) kg/m2 ranging from 12.9 to 41.7 kg/m2. No difference in age, IVC, and resting arterial blood gas determinations were seen between the classes, but FEV1 was significantly lower in the underweight (33 [12]%) and normal weight (36 [11]%) patients compared with the overweight (39 [13]%) and obese patients (45 [14]%). A history of weight loss amounting to > 10% of habitual body weight was reported by 49% of the underweight group, 29% of the normal weight group, 16% of the overweight group, and 0% of the obese group.
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Survival was significantly decreased in both underweight and normal weight patients as compared with overweight and obese patients. (Figure 2, upper panel) (p < 0.0001). A history of weight loss was also significantly related to decreased survival (p < 0.005). Kaplan-Meier plots further indicated a decreased survival in the group with severe airflow obstruction (Figure 2, lower panel) (p = 0.0072) and in the group suffering from chronic hypoxemia (Figure 3, upper panel) (p < 0.0018) or chronic hypercapnia (Figure 3, lower panel) (p < 0.001). The majority of patients were current or ex-smokers. Smoking behavior in this group of patients with severe COPD did not significantly influence survival rates. The results of the Cox proportional hazards model are shown in Table 2. BMI as continuous variable was a significant predictor of survival in addition to age and PaO2. In this model IVC as percentage of predicted, FEV1 as percentage of predicted, PaCO2, sex, and smoking were not selected as independent contributors. Cox regression plots were made to compare BMI quintiles. For all other variables mean values were used in this model. A noteworthy pattern in these plots is shown in Figure 4. The three lower quintiles (BMI < 25 kg/m2) nearly overlapped but were significantly lower than the two upper quintile plots.
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Prospective Study
Baseline physical and lung function characteristics were not significantly different between the treatment groups (i.e., placebo, nutrition, nutrition and anabolic steroids). Short-term treatment results have been reported before (10). In summary, nutritional intervention resulted in a significant increase in weight, fat-free mass, and fat-mass, whereas no significant changes in any of these parameters was seen in the placebo group. Relative to a similar body weight gain as the group receiving nutritional support only, the anabolic steroids group showed a larger increase in fat-free mass and maximal inspiratory mouth pressure without causing adverse side effects.
No significant difference between the treatments on survival was shown (Table 3). On the basis of body weight change > 2 kg/8 wk, 50% of the treated patients were characterized as responders, including 24% of the placebo group. In 62% of the patients an improvement in PImax was shown. Weight gain in depleted and non-depleted patients with COPD was significantly associated with decreased mortality risk (Figure 5, upper panel), and also improvement in PImax during the rehabilitation period was associated with decreased mortality risk (Figure 5, lower panel). Survival was not related to baseline 12-min walking distance or to the change in 12-min walking distance obtained during the rehabilitation program. On multivariate analysis weight gain in depleted and non-depleted patients with COPD was an independent predictor of survival in addition to BMI and age.
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DISCUSSION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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The combined results of the two survival analyses provide further evidence to support the hypothesis that body weight has an independent effect on survival in COPD. Moreover, the negative effect of low body weight can be reversed by appropriate therapy.
Survival data in COPD are limited. Older studies were performed in selected groups of patients and often included too few patients for valid survival analysis (3, 14, 19, 20). Our study was also performed in a selected group of patients, i.e., those eligible for pulmonary rehabilitation, but the setting provided an excellent opportunity to examine our research question with a careful characterization of patients and standardized therapy. Furthermore, the inverse relationship between BMI and survival was found in addition to known single risk factors such as age (20), FEV1 (14, 20, 21), and PaO2 (22) and PaCO2 (21, 22).
Vandenbergh and coworkers (12) had highlighted already in 1968 a relation between weight loss and mortality in patients with end stage COPD (12). Five-year survival in the weight losing patients was 50% relative to 80% in the weight stable patients. More recently, Wilson and coworkers (13), utilizing data of the National Institutes of Health Intermittent Positive Pressure Breathing Trial (13), studied retrospectively the influence of body weight on survival in 779 male patients with COPD (PaO2 > 7.3 kPa; FEV1 < 60%). A borderline significant association (p = 0.055) was seen between body weight (expressed as a percentage of ideal weight) and survival, in a Cox proportional hazards model, after adjusting for age, postbronchodilator %FEV1, %TLC, exercise capacity, and heart rate. It is of interest to note that the strongest relation between body weight and survival was found in men with moderate airflow obstruction.
In contrast to the present study the most significant predictor besides age in the IPPB-trial (13) was postbronchodilator FEV1, which may be related to a higher ratio between post/pre FEV1 in this study compared with the present study. Furthermore, patients suffering from chronic hypoxemia, which was an independent risk factor in the present study, were excluded from the IPPB trial. More recently, Gray-Donald and coworkers (14) studied the role of the BMI in the prognosis of patients with severe COPD in a cohort of Canadian men and women, including those with hypoxemia, recruited for a clinical trial of negative pressure ventilation. In the total cohort, low BMI and use of home oxygen were independently associated with reduced survival.
When Cox regression plots were drawn to compare BMI quintiles adjusted for age, sex, FEV1, IVC, PaO2, PaCO2, and smoking a striking finding in our retrospective analysis was that below the 3th quintile (BMI < 25.0 kg/m2) the relative risk was clearly increased, but that the 3 lower quintiles nearly overlapped. In the study by Wilson and coworkers (13) survival was also remarkably longer in overweight to obese patients with COPD, body weight > 110% of predicted (ranging from 111 to 210%) compared with the normal weight group (ranging from 90 to 110%). This discrepancy could not be attributed to differences in spirometry or arterial blood gas determinations between the two groups. The present study did not discriminate for the type of disease. In an earlier study, Engelen and coworkers (6) showed a significant relationship between BMI and emphysema based on measurement of DLCO. Limited data are available on the prognostic value of DLCO adjusted for spirometry, arterial blood gas measurements, and BMI. In the survival study by Vandenbergh and coworkers (12), no difference in DLCO was shown between weight-stable and weight-losing patients and also no significant drop of DLCO in the follow-up of the weight-losing patients. In a sub-group of hospitalized patients with COPD, Gray-Donald and coworkers found that low diffusing capacity was a significant predictor of respiratory mortality in addition to elevated PaCO2, low BMI, and low PImax.
At present the rationale for treatment modalities aimed at an increase in body weight in COPD is based on the observed relationship between weight loss, muscle wasting, and muscle weakness (2, 3) independent of the irreversible FEV1, as well as the findings that respiratory muscle weakness and dyspnea are closely related. In three randomized controlled nutritional intervention trials (8) a clear short-term effect of nutritional supplementation has been shown on body weight, fat-free mass, and respiratory and peripheral skeletal muscle function, and in one of them also on exercise performance. The unique large size of the present study population allowed us to investigate post hoc the effects of the treatments as well as the treatment response on survival. As may be expected in view of the short intervention duration (8 wk) and the fact that the placebo group was also encouraged to optimize their diet resulting in 24% "responders," no differential effect of either of the treatments on survival was shown. Treatment response, i.e., both weight gain as well as improvement of respiratory muscle strength, however, were significantly related to survival. After adjusting for the significant influence of BMI on mortality, weight gain remained a significant predictor, but PImax did not. This is not surprising since muscle function is related to muscle mass and muscle metabolism. Independent of muscle mass, we have recently shown alterations in cellular energy metabolism in muscle biopsies of patients with clinically stable COPD in resting condition. Chronic or intermittent hypoxemia could be an important trigger of these metabolic alterations. Although the treatment duration relative to the follow-up period was short, it is conceivable that treatment response could have had longer-lasting implications since during the intervention study, independent of the received treatment, this was the first time that the patients were informed about the role of appropriate nutrition in their disease and how to adapt their dietary habits. Similarly, most patients were for the first time confronted with the beneficial effects of exercise on disability and handicap associated with their disease.
Despite the positive overall results of nutritional support on body weight and body composition in our clinical trial, there was also a high proportion of "nonresponse" similar to that of other studies. Knowledge of the pathogenesis of weight loss and muscle wasting is essential for an optimal implementation and interpretation of nutritional and metabolic therapy. It is clearly established (23) that a substantial proportion of patients with moderate to severe COPD exhibit an elevated resting metabolic rate. Furthermore, Baarends and coworkers (24) recently showed, using the doubly labeled water method, that independent of resting metabolic rate, total energy expenditure is increased in COPD. Careful analysis of the available nutritional intervention studies in view of our recent data on total daily energy expenditure in COPD, suggests that nonresponse to nutritional therapy may have been partly due to inadequate judgment of energy expenditure or patient's inability to ingest the required energy intake. Theoretically, noncompliance of the treatment could also have contributed to nonresponse. However, patients were included in an in-patient pulmonary rehabilitation program allowing good control. The movement therapist monitored the training of the patients and the nurses closely monitored if the patients were eating there daily meals and if and how much they were taking from the daily liquid nutritional supplement.
Another possible explanation could be the presence of alterations in intermediary metabolism superposed on the elevated energy metabolism. Recently, we showed that a subset of patients with COPD with elevated resting metabolic rate displayed elevated levels of acute phase proteins and soluble TNF-receptors in peripheral blood (25). These patients were further characterized by depletion of fat-free mass, independent of the BMI. In line with these findings, Di Francia and coworkers (26) and de Godoy and coworkers (27) recently reported a significant relation between weight loss and TNF. From the combined results of these previous reports and the present study, it is hypothesized that tissue depletion in patients with COPD may be related in part to a systemic catabolic response induced by inflammation, which cannot completely be reversed by nutritional support only. Further studies are indicated to confirm this hypothesis and to identify further characteristics of nonresponders.
In conclusion, the present survival analyses provide further evidence to support the hypothesis that body weight has an independent effect on survival in COPD. Moreover, the negative effect of low body weight can be reversed by appropriate therapy.
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Footnotes |
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Correspondence and requests for reprints should be addressed to Dr. A. M. W. J. Schols, Department of Pulmonology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
(Received in original form May 7, 1997 and in revised form February 10, 1998).
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References |
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ABSTRACT
INTRODUCTION
METHODS
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DISCUSSION
REFERENCES
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1. American Thoracic Society. 1987. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma (ATS statement). Am. Rev. Respir. Dis. 134: 239-243 .
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5. Engelen, M. P. K. J., A. M. W. J. Schols, W. C. Baken, G. J. Wesseling, and E. F. M. Wouters. 1994. Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in an out-patient population with chronic obstructive pulmonary disease. Eur. Respir. J. 7: 1793-1797 [Abstract].
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W. M. Chatila, B. M. Thomashow, O. A. Minai, G. J. Criner, and B. J. Make Comorbidities in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2008; 5(4): 549 - 555. [Abstract] [Full Text] [PDF]
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A. M. Kuzma, Y. Meli, C. Meldrum, P. Jellen, M. Butler-Lebair, D. Koczen-Doyle, P. Rising, K. Stavrolakes, and F. Brogan Multidisciplinary Care of the Patient with Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2008; 5(4): 567 - 571. [Abstract] [Full Text] [PDF]
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P. D. Wagner Possible mechanisms underlying the development of cachexia in COPD Eur. Respir. J., March 1, 2008; 31(3): 492 - 501. [Abstract] [Full Text] [PDF]
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M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers Eur. Respir. J., February 1, 2008; 31(2): 416 - 469. [Abstract] [Full Text] [PDF]
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 M. Poulain, M. Doucet, V. Drapeau, G. Fournier, A. Tremblay, P. Poirier, and F. Maltais Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease Chronic Respiratory Disease, February 1, 2008; 5(1): 35 - 41. [Abstract] [PDF]
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 J. L. J. van der Velden, A. M. W. J. Schols, J. Willems, M. C. J. M. Kelders, and R. C. J. Langen Glycogen Synthase Kinase 3 Suppresses Myogenic Differentiation through Negative Regulation of NFATc3 J. Biol. Chem., January 4, 2008; 283(1): 358 - 366. [Abstract] [Full Text] [PDF]
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 P. Vaughan, I. F. Oey, M. C. Steiner, M. D.L. Morgan, and D. A. Waller A prospective analysis of the inter-relationship between lung volume reduction surgery and body mass index Eur. J. Cardiothorac. Surg., December 1, 2007; 32(6): 839 - 842. [Abstract] [Full Text] [PDF]
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C. G. Cote, V. Pinto-Plata, K. Kasprzyk, L. J. Dordelly, and B. R. Celli The 6-Min Walk Distance, Peak Oxygen Uptake, and Mortality in COPD Chest, December 1, 2007; 132(6): 1778 - 1785. [Abstract] [Full Text] [PDF]
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Dr. R. Jones Too little, too late the patients' perspective on education for COPD Chronic Respiratory Disease, November 1, 2007; 4(4): 189 - 190. [PDF]
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 J. Tkac, S. F. P. Man, and D. D. Sin Review: Systemic consequences of COPD Therapeutic Advances in Respiratory Disease, October 1, 2007; 1(1): 47 - 59. [Abstract] [PDF]
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A. Agusti Systemic Effects of Chronic Obstructive Pulmonary Disease: What We Know and What We Don't Know (but Should) Proceedings of the ATS, October 1, 2007; 4(7): 522 - 525. [Abstract] [Full Text] [PDF]
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 M. S. Azarisman, M. A. Fauzi, M. P. A. Faizal, Z. Azami, A. M. Roslina, and H. Roslan The SAFE (SGRQ score, air-flow limitation and exercise tolerance) Index: a new composite score for the stratification of severity in chronic obstructive pulmonary disease Postgrad. Med. J., July 1, 2007; 83(981): 492 - 497. [Abstract] [Full Text] [PDF]
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 F. Chi and T. Canada Effects of {omega}-3 Polyunsaturated Fatty Acids on Inflammatory Markers in Chronic Obstructive Pulmonary Disease Nutr Clin Pract, October 1, 2006; 21(5): 533 - 534. [Abstract] [Full Text] [PDF]
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B. R. Celli Roger S. Mitchell Lecture. Chronic Obstructive Pulmonary Disease Phenotypes and Their Clinical Relevance Proceedings of the ATS, August 1, 2006; 3(6): 461 - 465. [Abstract] [Full Text] [PDF]
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A. Agusti Thomas A. Neff Lecture. Chronic Obstructive Pulmonary Disease: A Systemic Disease Proceedings of the ATS, August 1, 2006; 3(6): 478 - 481. [Full Text] [PDF]
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A. Mallampalli Nutritional Management of the Patient With Chronic Obstructive Pulmonary Disease Nutr Clin Pract, December 1, 2004; 19(6): 550 - 556. [Abstract] [Full Text] [PDF]
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Z J McKeough,, J A Alison, M S Bayfield, and P. Bye Reduction in resting energy expenditure following lung volume reduction surgery in subjects with chronic obstructive pulmonary disease Chronic Respiratory Disease, October 1, 2004; 1(4): 197 - 202. [Abstract] [PDF]
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 A Agusti, M Morla, J Sauleda, C Saus, and X Busquets NF-{kappa}B activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight Thorax, June 1, 2004; 59(6): 483 - 487. [Abstract] [Full Text] [PDF]
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T J Ringbaekl, K Viskuml, and P Lange BMI and oral glucocorticoids as predictors of prognosis in COPD patients on long-term oxygen therapy Chronic Respiratory Disease, April 1, 2004; 1(2): 71 - 78. [Abstract] [PDF]
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E. C Creutzberg Factors associated with prognosis in COPD: influence of body composition and systemic corticosteroid use on morbidity and mortality Chronic Respiratory Disease, April 1, 2004; 1(2): 79 - 81. [PDF]
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 B. R. Celli, C. G. Cote, J. M. Marin, C. Casanova, M. Montes de Oca, R. A. Mendez, V. Pinto Plata, and H. J. Cabral The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity Index in Chronic Obstructive Pulmonary Disease N. Engl. J. Med., March 4, 2004; 350(10): 1005 - 1012. [Abstract] [Full Text] [PDF]
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E.F.M. Wouters Introduction: systemic effects in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 1s - 1s. [Full Text] [PDF]
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H. Andreassen and J. Vestbo Chronic obstructive pulmonary disease as a systemic disease: an epidemiological perspective Eur. Respir. J., November 2, 2003; 22(46_suppl): 2s - 4s. [Abstract] [Full Text] [PDF]
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R.T. Jagoe and M.P.K.J. Engelen Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 52s - 63s. [Abstract] [Full Text] [PDF]
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A.A. Ionescu and E. Schoon Osteoporosis in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 64s - 75s. [Abstract] [Full Text] [PDF]
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A.M.W.J. Schols Nutritional and metabolic modulation in chronic obstructive pulmonary disease management Eur. Respir. J., November 2, 2003; 22(46_suppl): 81s - 86s. [Abstract] [Full Text] [PDF]
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E F M Wouters Eat well to get well Thorax, September 1, 2003; 58(9): 739 - 740. [Full Text] [PDF]
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T. Oga, K. Nishimura, M. Tsukino, S. Sato, and T. Hajiro Analysis of the Factors Related to Mortality in Chronic Obstructive Pulmonary Disease: Role of Exercise Capacity and Health Status Am. J. Respir. Crit. Care Med., February 15, 2003; 167(4): 544 - 549. [Abstract] [Full Text] [PDF]
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P. A. Meyer, D. M. Mannino, S. C. Redd, and D. R. Olson Characteristics of Adults Dying With COPD Chest, December 1, 2002; 122(6): 2003 - 2008. [Abstract] [Full Text] [PDF]
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 M. A. Medow, H. G. Weed, and D. E. Schuller Simple Predictors of Survival in Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, November 1, 2002; 128(11): 1282 - 1286. [Abstract] [Full Text] [PDF]
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K. Marquis, R. Debigare, Y. Lacasse, P. LeBlanc, J. Jobin, G. Carrier, and F. Maltais Midthigh Muscle Cross-Sectional Area Is a Better Predictor of Mortality than Body Mass Index in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., September 15, 2002; 166(6): 809 - 813. [Abstract] [Full Text]
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A. G. N. Agusti, J. Sauleda, C. Miralles, C. Gomez, B. Togores, E. Sala, S. Batle, and X. Busquets Skeletal Muscle Apoptosis and Weight Loss in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., August 15, 2002; 166(4): 485 - 489. [Abstract] [Full Text] [PDF]
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S.-s. Yeh, B. DeGuzman, and T. Kramer Reversal of COPD-Associated Weight Loss Using the Anabolic Agent Oxandrolone* Chest, August 1, 2002; 122(2): 421 - 428. [Abstract] [Full Text] [PDF]
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T. L. Petty COPD in Perspective* Chest, May 1, 2002; 121 (2009): 116S - 120S. [Abstract] [Full Text] [PDF]
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E. F. M. Wouters, E. C. Creutzberg, and A. M. W. J. Schols Systemic Effects in COPD* Chest, May 1, 2002; 121 (2009): 127S - 130S. [Abstract] [Full Text] [PDF]
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M. I. Polkey Muscle Metabolism and Exercise Tolerance in COPD* Chest, May 1, 2002; 121 (2009): 131S - 135S. [Abstract] [Full Text] [PDF]
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J. Weisberg, J. Wanger, J. Olson, B. Streit, C. Fogarty, T. Martin, and R. Casaburi Megestrol Acetate Stimulates Weight Gain and Ventilation in Underweight COPD Patients* Chest, April 1, 2002; 121(4): 1070 - 1078. [Abstract] [Full Text] [PDF]
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R. I. Harik-Khan, J. L. Fleg, and R. A. Wise Body Mass Index and the Risk of COPD Chest, February 1, 2002; 121(2): 370 - 376. [Abstract] [Full Text] [PDF]
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S. Basaria, J. T. Wahlstrom, and A. S. Dobs Anabolic-Androgenic Steroid Therapy in the Treatment of Chronic Diseases J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5108 - 5117. [Abstract] [Full Text] [PDF]
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R. DEBIGARE, C. H. COTE, and F. MALTAIS Peripheral Muscle Wasting in Chronic Obstructive Pulmonary Disease . Clinical Relevance and Mechanisms Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1712 - 1717. [Full Text] [PDF]
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British Thoracic Society Standards of Care Subcomm Pulmonary rehabilitation Thorax, November 1, 2001; 56(11): 827 - 834. [Full Text] [PDF]
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 G. Akner and T. Cederholm Treatment of protein-energy malnutrition in chronic nonmalignant disorders Am. J. Clinical Nutrition, July 1, 2001; 74(1): 6 - 24. [Abstract] [Full Text] [PDF]
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J. P. Finnerty, I. Keeping, I. Bullough, and J. Jones The Effectiveness of Outpatient Pulmonary Rehabilitation in Chronic Lung Disease : A Randomized Controlled Trial Chest, June 1, 2001; 119(6): 1705 - 1710. [Abstract] [Full Text] [PDF]
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 R. C. J. LANGEN, A. M. W. J. SCHOLS, M. C. J. M. KELDERS, E. F. M. WOUTERS, and Y. M. W. JANSSEN-HEININGER Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-{kappa}B FASEB J, May 1, 2001; 15(7): 1169 - 1180. [Abstract] [Full Text] [PDF]
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M. A. van Bokhorst-de van der Schueren, J. J Quak, B M. E von Blomberg-van der Flier, D. J Kuik, S. I Langendoen, G. B Snow, C. J Green, and P. A. van Leeuwen Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients Am. J. Clinical Nutrition, February 1, 2001; 73(2): 323 - 332. [Abstract] [Full Text] [PDF]
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I. M. Ferreira, D. Brooks, Y. Lacasse, and R. S. Goldstein Nutritional Intervention in COPD : A Systematic Overview Chest, February 1, 2001; 119(2): 353 - 363. [Abstract] [Full Text] [PDF]
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L. Ezzell and G. L Jensen Malnutrition in chronic obstructive pulmonary disease Am. J. Clinical Nutrition, December 1, 2000; 72(6): 1415 - 1416. [Full Text] [PDF]
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E. C. CREUTZBERG, E. F. M. WOUTERS, I. M. L. VANDERHOVEN-AUGUSTIN, M. A. DENTENER, and A. M. W. J. SCHOLS Disturbances in Leptin Metabolism Are Related to Energy Imbalance during Acute Exacerbations of Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1239 - 1245. [Abstract] [Full Text] [PDF]
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M. P. K. J. ENGELEN, N. E. P. DEUTZ, E. F. M. WOUTERS, and A. M. W. J. SCHOLS Enhanced Levels of Whole-body Protein Turnover in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1488 - 1492. [Abstract] [Full Text] [PDF]
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J. B. Bowen, J. J. Votto, R. S. Thrall, M. C. Haggerty, R. Stockdale-Woolley, T. Bandyopadhyay, and R. L. ZuWallack Functional Status and Survival Following Pulmonary Rehabilitation Chest, September 1, 2000; 118(3): 697 - 703. [Abstract] [Full Text] [PDF]
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P. J. Barnes Chronic Obstructive Pulmonary Disease N. Engl. J. Med., July 27, 2000; 343(4): 269 - 280. [Full Text] [PDF]
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P M A CALVERLEY Supplementary oxygen therapy in COPD: is it really useful? Thorax, July 1, 2000; 55(7): 537 - 538. [Full Text]
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P. M. A. Calverley COPD : Early Detection and Intervention Chest, May 1, 2000; 117 (2009): 365S - 371S. [Abstract] [Full Text] [PDF]
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I. M. Ferreira, D. Brooks, Y. Lacasse, and R. S. Goldstein Nutritional Support for Individuals With COPD: A Meta-analysis Chest, March 1, 2000; 117(3): 672 - 678. [Abstract] [Full Text] [PDF]
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E. C. CREUTZBERG, A. M. W. J. SCHOLS, C. A. P. M. WELING-SCHEEPERS, W. A. BUURMAN, and E. F. M. WOUTERS Characterization of Nonresponse to High Caloric Oral Nutritional Therapy in Depleted Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): 745 - 752. [Abstract] [Full Text] [PDF]
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B. R. Celli The Importance of Spirometry in COPD and Asthma : Effect on Approach to Management Chest, February 1, 2000; 117 (2009): 15S - 19S. [Abstract] [Full Text] [PDF]
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C. LANDBO, E. PRESCOTT, P. LANGE, J. VESTBO, and T. P. ALMDAL Prognostic Value of Nutritional Status in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 1856 - 1861. [Abstract] [Full Text]
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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., April 1, 1999; 159(4): S2 - 40. [Full Text] [PDF]
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