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ESPEN Congress Leipzig 2013
LLL Session - Nutritional support in respiratory diseases
Mechanisms and consequences of body composition abnormalities in chronic respiratory diseases
A. Schols (NL)
Body composition abnormalities in COPD Mechanisms and consequences
Annemie Schols Department of Respiratory Medicine
Murray CJ, NEJM 2013
Disease burden of COPD
• Persistent airflow obstruction
• Musculoskeletal abnormalities and cardiovascular comorbidity
• Symptoms: dyspnea and exercise impairment
• Limited effects of the mainstay pharmacological therapies: bronchodilators and anti-inflammatories
COPD
COPD: heterogenous disease
Pink puffer
Blue bloater
Airflow obstruction (FEV1) Respiratory failure (PaO2, PaCO2)
Engelen Clin Nutr 1999
Body composition by DEXA-scan
weight: ↓ ↔
Fat mass ↓ ↑
Fat-free mass ↓↓ ↓
trunk ↓ ↔
extremities ↓ ↓
Bone mineral content ↓↓ ↓
Weight loss & underweight more prevalent in emphysema
Muscle atrophy also in chronic bronchitis
Body composition, disease severity and survival
HIdden muscle wasting Cachexia
Schols A, AJCN, 2005; Schols A, ERJ, 2009
adjusted for age, gender, smoking, lung function
Cachexia HIdden muscle wasting
Pathophysiology of wasting in COPD
Whole body energy balance versus protein balance
Muscle energy metabolism and protein turnover
Energy balance Energy intake Energy output REE Thermic effect of food Physical activity
Resting energy expenditure in COPD
Increased REE is related to increased whole body protein turnover and enhanced systemic inflammation in particular during acute exacerbations Not different between emphysematous and bronchitic phenotype
EMPHYSEMA
Inflammation oxidative stress hypoxia
WEIGHT LOSS MUSCLE WASTING
COPD cachexia
Weight gain after lung reduction surgery is associated with improved lung function and ventilatory efficiency
Kim, AJRCCM 2012
Ferreira et al, 2012
Dietary intervention
Muscle maintenance & functional improvement → exercise
Endurance exercise - increase in functional performance + QoL - increase in muscle aerobic capacity Resistance exercise/neuromuscular electrical stimulation - increase in muscle mass and strength - less load on ventilatory system
cycling & local muscle exercise
Increased exercise induced energy requirements
Decreased efficiency: muscle fibre type shift
Altered substrate metabolism
Franssen et al. Metabolism 2011
Mitochondrial dysfunction m
ito
ch
on
dria
l fu
ncti
on
Rabinovich, Eur Respir J 2007 ~ confirmed by Picard 2008 & Puente-Maestu 2009
oxidative
stress Muscle atrophy
NF-kB
Disturbed regulation of nutrient sensing metabolic pathways
Remels et al. Eur Respir J 2007; FASEB J 2010; BBA 2013
Natanek et al. Eur Respir J 2012
NF-kB
Disturbed regulation of nutrient sensing metabolic pathways
Remels et al. Eur Respir J 2007; FASEB J 2010; BBA 2013
Natanek et al. Eur Respir J 2012; Broekhuizen R Thorax 2006
Poly unsaturated fatty acids
EMPHYSEMA
MUSCLE oxidative phenotype
Inflammation oxidative stress hypoxia
MUSCLE ATROPHY
↑ respiratory muscle ↓ lower limb muscle
Muscle maintenance
Muscle wasting in clinically stable COPD
• Indirect evidence for increased muscle protein degradation rate - Increased myofibrillar turnover - activation of markers of ubiquitin proteasome pathway
• No information about muscle protein synthesis rate • But:
- Compensatory increase in muscle protein synthesis signalling - Good post prandial whole protein synthetic response
Engelen M. Am. J. Clin. Nutr. 2007
Jonker R, Clin Nutr 2013.
0
100
endogeneous
feeding
1500
2000
2500
3000
3500
4000
Control COPD
Whole body protein synthesis
Nn
mo
l/kg
FFM
/min
*
Enhanced post prandial protein synthesis in ‘sarcopenic’ COPD patients
Q: Increased protein requirements in COPD or need for more targeted intervention in cachectic patients?
Convergence of putative muscle wasting triggers during severe acute exacerbations
Graat-Verboom et al., Respir Med 2009
Osteoporosis and body composition in patients with COPD
→ Common denominators
COPD anno 2013 Frequent comorbidities in patients eligible for rehabilitation
Disease triggers or lifestyle induced? Vanfleteren et al, Am J Respir Crit Care Med 2013
Clusters of comorbidities in 213 COPD patients
Vanfleteren et al, Am J Respir Crit Care Med 2013
The ‘metabolic obese’ normal weight COPD patient
Preservation of fat mass & fat-redistribution
A B
C D
Healthy person COPD patient
↑ Visceral fat
Systemic inflammation
Van den Borst, AJCN 2012 Van den Borst, AJCN 2012 Van den Borst, AJCN 2012
Van den Borst, AJCN 2012
Van den Borst, AJRCCM 2012
Central fat & peripheral muscle
Partners in crime in COPD
Body composition assessment is essential for optimizing nutritional and metabolic care of COPD patients
