Catabolic/Anabolic Balance and Muscle Wasting in Patients With COPD

doi:10.1378/chest.124.1.83

Chest

Volume 124, Issue 1, July 2003, Pages 83-89

https://doi.org/10.1378/chest.124.1.83 Get rights and content

Backgroud

The mechanisms leading to muscle wasting in patients with COPD are still uncertain. This study was undertaken to evaluate the relationships among circulating levels of catabolic factors (ie, interleukin [IL]-6 and cortisol), anabolic factors (ie, bioavailable testosterone [Tbio], dehydroepiandrosterone sulfate [DHEAS], and insulin-like growth factor [IGF]-I), and mid-thigh muscle cross-sectional area (MTCSA) in patients with COPD.

Methods

Serum levels of the above factors were measured in 45 men with COPD (mean [± SEM] FEV₁, 43 ± 3% predicted; mean age, 67 ± 1 years) and 16 sedentary healthy men of similar age. MTCSA was quantified using CT scanning. Patients with COPD were subdivided into two groups according to the MTCSA (< 70 or ≥ 70 cm²).

Results

There was a greater prevalence of hypogonadism (ie, Tbio, < 2 nmol/L) in patients with COPD compared to control subjects (22% vs 0%, respectively). Patients with an MTCSA of < 70 cm² had significantly reduced levels of DHEAS compared to those in healthy subjects (p < 0.01). IL-6 levels were significantly higher in both subgroups of COPD patients compared to those in control subjects (p < 0.005). The cortisol/DHEAS, IL-6/DHEAS, IL-6/Tbio, and IL-6/IGF-I ratios were significantly greater in COPD patients with an MTCSA of < 70 cm² compared to those in control subjects (p < 0.05). The cortisol/DHEAS and IL-6/DHEAS ratios were also significantly greater in COPD patients with an MTCSA of < 70 cm² than in COPD patients with an MTCSA of ≥ 70 cm² (p < 0.05). In a stepwise multiple regression analysis, the IL-6/DHEAS ratio explained 20% of the variance in MTCSA (p < 0.005).

Conclusion

Catabolic/anabolic disturbances were found in COPD patients leading to a shift toward catabolism and possibly to the development of peripheral muscle wasting.

Section snippets

Subjects

The study population consisted of 45 men with COPD who were in stable condition, who had participated in our previous study⁶ evaluating the impact of low muscle mass on survival in COPD, and in whom blood was available for the quantification of anabolic and catabolic factors. The diagnosis of COPD was based on smoking history and on pulmonary function test results showing irreversible airflow limitation.²¹ Patients with any active inflammatory diseases as well as any other chronic diseases,

Results

The anthropometric characteristics of both subgroups of patients and control subjects are shown in Table 1. Twenty-seven patients with COPD had an MTCSA of ≥ 70 cm² (86 ± 2 cm²), while the remaining 18 patients had an MTCSA of < 70 cm² (58 ± 2 cm²). For comparison, the mean MTCSA in the 16 healthy individuals was 96 ± 4 cm². Patients with an MTCSA of < 70 cm² had a significantly lower BMI compared to patients with an MTCSA of ≥ 70 cm² and subjects in the control group. The impairment in

Discussion

In this study, peripheral muscle atrophy was associated with disturbances in catabolism and anabolism and not with the level of impairment in lung function. Marked elevations of catabolic/anabolic factor ratios (ie, cortisol/DHEAS, IL-6/Tbio, IL-6/DHEAS, and IL-6/IGF-1), particularly in patients with COPD and low MTCSAs, indicate that there was a shift toward catabolism in COPD patients. Although none of the catabolic or anabolic factors were related to MTCSA, IL-6/DHEAS ratio, which is a

ACKNOWLEDGMENT

The authors acknowledge the contribution of Fernand Bertrand for his assistance in biochemical measurements, and the technical support of Marthe Bélanger, Marie-Josée Breton, and Brigitte Jean in accomplishing this study. The authors also thank Drs. Yves Deshaies and Guy M. Tremblay for their helpful suggestions regarding the manuscript.

References (37)

R Mostert et al.
Tissue depletion and health related quality of life in patients with chronic obstructive pulmonary disease
Respir Med
(2000)
SD Anker et al.
Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting
J Am Coll Cardiol
(1997)
J Niebauer et al.
Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation
J Am Coll Cardiol
(1998)
K Tsuji et al.
Specific binding and effects of dehydroepiandrosterone sulfate (DHEA-S) on skeletal muscle cells: possible implication for DHEA-S replacement therapy in patients with myotonic dystrophy
Life Sci
(1999)
American Thoracic Society/European Respiratory Society
Skeletal muscle dysfunction in chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(1999)
F Whittom et al.
Histochemical and morphological characteristics of the vastus lateralis muscle in COPD patients: comparison with normal subjects and effects of exercise training
Med Sci Sports Exerc
(1998)
S Bernard et al.
Peripheral muscle weakness in patients with chronic obstructive pulmonary disease
Am J Respir Crit Care Med
(1998)
AL Hamilton et al.
Muscle strength, symptom intensity and exercise capacity in patients with cardiorespiratory disorders
Am J Respir Crit Care Med
(1995)
K Marquis et al.
Mid-thigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with COPD
Am J Respir Crit Care Med
(2002)
S Bernard et al.
Aerobic and strength training in patients with COPD
Am J Respir Crit Care Med
(1999)

AMWJ Schols et al.

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)

HE Turner et al.

Gonadal function in men with chronic illness

Clin Endocrinol (Oxf)

(1997)

DP Kotler

Cachexia

Ann Intern Med

(2000)

M Buck et al.

Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants

EMBO J

(1996)

AMWJ Schols et al.

Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease

Thorax

(1996)

B Levine et al.

Elevated circulating levels of tumor necrosis factor in severe chronic heart failure

N Engl J Med

(1990)

AA Ionescu et al.

Bone density, body composition, and inflammatory status in cystic fibrosis

Am J Respir Crit Care Med

(2000)

SW Lamberts et al.

The endocrinology of aging

Science

(1997)

Cited by (185)

Neuroendocrine stress hormones associated with short-term exposure to nitrogen dioxide and fine particulate matter in individuals with and without chronic obstructive pulmonary disease: A panel study in Beijing, China
2022, Environmental Pollution
Citation Excerpt :
Because both patients with COPD and non-COPD participants were enrolled and followed up simultaneously in this panel study, we were able to compare their neuroendocrine responses to pollutant exposure. There were no significant differences in basal stress hormone levels between COPD and non-COPD participants (Table 2), which is consistent with previous studies (Debigaré et al., 2003; Karadag et al., 2008). In stratified analyses, we identified significant associations between air pollutant exposure and stress hormones in both subgroups (Fig. 3).
Air pollution is a major trigger of chronic obstructive pulmonary disease (COPD). Dysregulation of the neuroendocrine hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes is essential in progression of COPD. However, it is not clear whether air pollution exposure is associated with neuroendocrine responses in individuals with and without COPD. Based on a panel study of 51 stable COPD patients and 78 non-COPD participants with 384 clinical visits, we measured the morning serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, norepinephrine, and epinephrine as indicators of stress hormones released from the HPA and SAM axes. Ambient nitrogen dioxide (NO₂), fine particulate matter (PM_2.5), and meteorological conditions were continuously monitored at the station from 2 weeks before the start of clinical visits. Linear mixed-effects models were used to estimate associations between differences in stress hormones following an average of 1–14-day exposures to NO₂ and PM_2.5. The average 1 day air pollutant levels prior to the clinical visits were 24.4 ± 14.0 ppb for NO₂ and 55.6 ± 41.5 μg/m³ for PM_2.5. We observed significant increases in CRH, ACTH, and norepinephrine, and decreases in cortisol and epinephrine with interquartile range increase in the average NO₂ and PM_2.5 concentrations in all participants. In the stratified analyses, we identified significant between-group difference in epinephrine following NO₂ exposure in individuals with and without COPD. These results may suggest the susceptibility of COPD patients to the neuroendocrine responses associated with short-term air pollution exposure.
Weighing on Our Minds: Baseline BMI and Weight Loss as Predictors of Interstitial Lung Disease Outcome
2022, Chest
Testosterone and chronic obstructive pulmonary disease
2020, Revue des Maladies Respiratoires
Au cours de la bronchopneumopathie chronique obstructive (BPCO), la diminution de l’indice de masse maigre (IMM) serait associée à la baisse de la testostéronémie.
Déterminer la relation entre la testostéronémie et les paramètres fonctionnels respiratoires au cours de la BPCO.
Étude transversale réalisée au CHU La Rabta (septembre 2017–août 2018), ayant inclus 95 patients BPCO de sexe masculin. N’ont pas été inclus les patients ayant des comorbidités ou sous traitement pouvant interférer avec la sécrétion gonadique. Les patients ont eu des prélèvements sanguins (testostérone, FSH, LH, prolactine, CRP, gaz du sang artériels), une pléthysmographie, un test de marche de six minutes (TM6) et une impédancemétrie.
L’âge moyen était de 63,78 ± 8,90 ans. La moyenne de la testostéronémie était de 20,87 ± 8,60 nmol/L. Elle était normale chez tous les patients. Une corrélation positive significative a été retrouvée entre le VEMS (p = 0,001), la CVF (p = 0,005), le rapport VEMS/CVF (p = 0,001), l’IMM (p = 0,021), le périmètre brachial (p = 0,024) et la testostéronémie. Cependant, la testostéronémie n’était pas corrélée à la distance parcourue au TM6, aux taux d’hormones de l’axe gonadotrope et à la CRP.
Bien que la testostéronémie soit corrélée à la fonction respiratoire et à la masse maigre, l’impact d’une administration d’androgènes sur l’amélioration du pronostic reste à prouver.
Testosterone level has been shown to be associated with respiratory function and loss of lean body mass in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the relationship between testosterone level and functional respiratory parameters during COPD.
We conducted a cross-sectional study that included 95 male patients with stable COPD. Functional tests (body plethysmography, six-minute walk test (6MWT), arterial blood gas) were performed in all patients and serum levels of testosterone, prolactin, FSH, LH and C-reactive protein were determined. Lean body mass was measured using bioelectric impedance.
The average age was 63.78 ± 8.90 years. COPD was classified as stage 3 in 38% of cases and stage 4 in 11% of cases, group C in 10% of cases and group D in 18% of cases. The average testosterone was 20.87 ± 8.60 nmol/L. A significant positive correlation was found between FEV1 (P = 0.005), FVC (P = 0.005), FEV1/FVC ratio (P = 0.001), lean mass index (P = 0.021), and testosterone. However, testosterone was not correlated with 6MWT or blood gas parameters. Similarly, it was not correlated with FSH, LH, prolactin and C-reactive protein.
This study found that serum testosterone level was associated with lung function and lean mass during COPD. Further investigations are required to better evaluate the relationship between COPD and serum testosterone levels and the effect of androgen substitution in lung function.
Resveratrol and metabolic health in COPD: A proof-of-concept randomized controlled trial
2020, Clinical Nutrition
Patients with COPD are often characterized by disturbed metabolic health which is reflected in altered body composition. Current studies in healthy subjects suggest that resveratrol improves metabolic health by enhancing muscle mitochondrial function and adipose tissue morphology. The primary objective was to investigate the effect of four weeks resveratrol supplementation on muscle mitochondrial function in patients with COPD. Secondary objectives were to investigate the effect of resveratrol on adipose tissue inflammatory and metabolic gene expression, systemic inflammation and body composition in patients with COPD.
In a double-blind randomized placebo-controlled proof-of-concept study, 21 COPD patients (FEV₁: 53 ± 15% predicted; age: 67 ± 9 years and BMI: 24.5 ± 3.3 kg/m²) received resveratrol (150 mg/day) or placebo for four weeks. Before and after intervention, blood samples, quadriceps muscle and subcutaneous abdominal fat biopsies were obtained for metabolic and inflammatory profiling. Body composition was assessed by dual energy X-ray absorptiometry.
Muscle mitochondrial biogenesis regulators AMPK, SIRT1 and PGC-1α as well as mitochondrial respiration, Oxphos complexes, oxidative enzyme activities and kynurenine aminotransferases were not improved by resveratrol. Plasma high-sensitive C-reactive protein and kynurenine did not change after resveratrol supplementation. Adipose tissue inflammatory markers were unaffected by resveratrol, while markers of glycolysis and lipolysis were significantly increased compared to placebo supplementation. Body weight decreased after resveratrol supplementation (resveratrol −0.95 ± 1.01 kg vs placebo −0.16 ± 0.66 kg, p = 0.049) due to a reduction in lean mass (resveratrol −1.79 ± 1.67 kg vs 0.37 ± 0.86 kg, p = 0.026).
We do not confirm previously reported positive effects of resveratrol on skeletal muscle mitochondrial function in patients with COPD, but show an unexpected decline in lean mass.
Clinicaltrials.gov NCT02245932.
Psychoactive medications in chronic obstructive pulmonary disease patients: From prevalence to effects on motor command and strength
2019, Respiratory Medicine
Citation Excerpt :
This muscle weakness is a major issue as it has been associated with the increased use of health resources [3,4] and, more critically, it is a strong independent predictor of patient survival [5]. While, the muscle weakness was originally attributed to a peripheral muscle dysfunction due to reduced muscle mass, chronic inflammation and oxidative stress [2,6,7], a reduced motor command has been evidenced by decreased primary motor cortex activation in patients during both maximal and submaximal voluntary contractions, even without marked muscle atrophy [8–10]. Nevertheless, the pathways involved in this impaired motor drive remain unclear.
In chronic-obstructive pulmonary disease (COPD) patients, the peripheral muscle weakness is partly due to reduced motor command. The psychoactive medications, which are often prescribed in COPD, are mainly inhibitory and thus may contribute to motor command reduction. The aims were to characterize and quantify the use of these drugs and determine their effects on cortical excitability and inhibition and thus on motor command and muscle weakness in these patients.
First, a prevalence study was conducted on 421 COPD patients. Second, cortical excitability, inhibition and voluntary activation were assessed in 40 patients (15 under psychoactive medications vs. 25 controls) by transcranial magnetic stimulation of the rectus femoris. Quadriceps maximal isometric strength was also assessed.
About 48% of the patients were taking psychoactive medication. Benzodiazepines (21%) and antidepressants (13.5%) were the most prescribed. Patients with medications tended to be younger and isolated (p < 0.05). They also showed impaired cortical inhibition and decreased cortical excitability (+36%, p = 0.02). Voluntary activation was reduced (−3.6%, p = 0.04) but quadriceps strength was comparable between groups.
Psychoactive medications are prevalent in COPD patients. Patients under these medications exhibited brain impairment and reduced motor command. Paradoxically, voluntary strength was unaltered.
Balancing potential energy and entropy: the foundations of lifestylopathy and homeostasis
2024, Journal of Public Health and Emergency

View all citing articles on Scopus

: Dr. Debigaré was a recipient of a PhD training award of the Fonds de la Recherche en Santé du Québec. Dr. Maltais is a research scholar of the Fonds de la Recherche en Santé du Québec. This research has been supported by Canadian Institutes of Health Research grant No. 36331.

View full text

Chest

Clinical InvestigationsCopdCatabolic/Anabolic Balance and Muscle Wasting in Patients With COPD

Backgroud

Methods

Results

Conclusion

Section snippets

Subjects

Results

Discussion

ACKNOWLEDGMENT

Respir Med

J Am Coll Cardiol

J Am Coll Cardiol

Life Sci

Skeletal muscle dysfunction in chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Histochemical and morphological characteristics of the vastus lateralis muscle in COPD patients: comparison with normal subjects and effects of exercise training

Med Sci Sports Exerc

Peripheral muscle weakness in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Muscle strength, symptom intensity and exercise capacity in patients with cardiorespiratory disorders

Am J Respir Crit Care Med

Mid-thigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with COPD

Am J Respir Crit Care Med

Aerobic and strength training in patients with COPD

Am J Respir Crit Care Med

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

Gonadal function in men with chronic illness

Clin Endocrinol (Oxf)

Cachexia

Ann Intern Med

Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants

EMBO J

Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease

Thorax

Elevated circulating levels of tumor necrosis factor in severe chronic heart failure

N Engl J Med

Bone density, body composition, and inflammatory status in cystic fibrosis

Am J Respir Crit Care Med

The endocrinology of aging

Science

Clinical Investigations
Copd
Catabolic/Anabolic Balance and Muscle Wasting in Patients With COPD