lll session - nutritional support in respiratory diseases ... · lll session - nutritional support...

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