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Nutritional support and treatment

Nutritional support and treatment. Annemie Schols Department of Respiratory Medicine. COPD: heterogeneous disease. Blue bloater. Pink puffer. COPD: systemic disease. ?. Celli B and Barnes P, ERJ 2009. Systemic inflammation TNF α = ‘cachectin’.

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Nutritional support and treatment

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  1. Nutritional support and treatment Annemie Schols Department of Respiratory Medicine

  2. COPD: heterogeneous disease Blue bloater Pink puffer

  3. COPD: systemic disease ? Celli B and Barnes P, ERJ 2009

  4. Systemic inflammation TNFα = ‘cachectin’ CACHEXIA Disability and decreased health status

  5. Cardiovascular disease risk Systemic inflammation OBESITY

  6. Malnutrition & obesity: body mass index

  7. BMI does not tell it all fat-free mass fat mass

  8. Hidden muscle wasting in COPD HIdden muscle wasting Cachexia adjusted for age, gender, smoking, lung function Schols A, AJCN, 2005; Schols A, ERJ, 2009

  9. Ageing and body composition ↓ in muscle mass: “sarcopenia”

  10. Fat mass versus distribution of adipose tissue

  11. Obesity paradox in advanced COPD COPD related mortality Landbo C, et al. AJRCCM 1997

  12. Obese Normal weight Dyspnea (Borg scale) FEV1 49% FEV1 49% Ventilation (Liters/min) Ora et al., Am J Respir Crit Care Med 2009 Exercise capacity in moderate to severe disease

  13. Potential beneficial effects of obesity on lung volumes in COPD Ora et al., Am J Respir Crit Care Med 2009

  14. Nutritional intervention in advanced COPD Energy balance (muscle) protein balance Weight loss: ↑ ↑ Muscle atrophy: ↔ ↑ (Visceral) fat expansion: ↓ ? -/↑ Enhance efficacy of exercise training: stimulate oxidative metabolism Limit diet induced ventilatory stress: caloric load versus carbohydrate load

  15. Weight loss ≈ negative energy balance Hyperinflation? Reversible after ‘pulmonary’ intervention • - Lung volume reduction surgery • Non-invasive ventilation Reduced cost of breathing Increased food intake by reduced dyspnea Takayama T, et al. Chest. 2003

  16. Weight loss ≈ negative energy balance Decreased mechanical efficiency? Physical activity induced energy expenditure Plantar flexion reps in MRI  PCr Layec et al. AJP 2011 Baarends et al. AJRCCM 1997

  17. Nutritional intervention • Study Design (RCT) • Patients: n=66; FEV1: 31%, 69 yr, weight losing • Duration: 6 months + 6 months follow-up • Home-based • Intervention: Control: usual care • Treatment: dietary counseling and food fortification • Results (intention to treat analysis) • ↑ in energy & protein intake • ↑ body weight • FM: ↑ in (T) and ↓ in (P) • FFM - in (T) and ↓ in (P) • → No difference in muscle strength Weekes CE, et al. Thorax. 2009

  18. Nutrition as adjunct to walking exercise • Study Design (RCT) • Patients: n=85; FEV1: 35%; normal and underweight out-patients • Duration: 7 weeks • Intervention: Treatment: Exercise + nutrition (600 kcal) Control: Exercise + placebo nutrition (100 kcal) • Exercise: Walking and low impact conditioning exercisesNutrition: CH (60%) / protein (20%); ± 600 kcal • Elevated energy expenditure balanced • by supplemental nutrition. • No enhancing effect on FFM. Steiner MC, et al. Thorax. 2003;58:745-51.

  19. Anabolic response of nutrition & whole body exercise • Study Design (RCT • Patients Treatment: n= 64, 65±9 yrs; FEV1: 35 (5)% Historical controls: n=28, 65±7 yrs • Duration 8 weeks, in-patient rehabilitation • Intervention - exercise + nutritional supplements: 600 kcal • - exercise only (5 days/week; moderate intensity)Nutrition Cabohydrate & protein rich • Results • Increases in body weight, FFM, PIMax, handgrip, Peak work load, QoL Creutzberg E, Nutrition 2003; 19:120-7

  20. Protein quantity and quality • Quantity • > 1.5 g/kg body weight/day to increase muscle mass • Quality • Type of protein (soy, casein, whey) • Digestibility • Essentialaminoacidscomposition • Signallingproperties of specificaminoacids (e.g. leucine) • ↓ plasma branched chain amino acids, i.e. leucine in muscle wasting Op den Kamp, COCNMC 2009

  21. * Whole body protein synthesis 4000 3500 Nnmol/kg FFM/min 3000 2500 2000 1500 100 0 Soy Soy Postabs Postabs Soy+BCAA Soy+BCAA Control COPD endogeneous feeding Enhanced protein synthesis after BCAA enrichment in COPD Acute experiment Engelen MPKKJ et al. Am. J. Clin. Nutr. 2007.

  22. Branched chain amino acids (BCAA) during rehabilitation • Study Design (RCT) • Patients: n=28, active weight loss; FEV1: 42 (3)% • Duration: 12 weeks • Intervention: Treatment: exercise + BCAA supplementation (2 x 200 ml) Control: exercise • Results • Weigth gain in 92% of BCAA groups versus 15% in control • FFM gain in 69% of BCAA and 15% of control • → More studies are needed. Baldi S, et al. Intern. J of COPD 2010

  23. Suboptimal anabolic response after nutrition & exercise Weight gain Baseline systemic Inflammatory profile: TNF receptors ΔFFM (kg) ** * +3.1 >5% >5% ** +1.5 * 2-5% >5% -0.9 <2% Baseline body composition Acute phase proteins

  24. Nutrition including n-3 PUFA as adjunct to exercise • Study Design (RCT) • Patients n= 32, 77±7 yrs; FEV1: 55 (5)%; BMI: 18.4 kg/m2 • Duration 12 weeks; home based • Design - treatment: nutriton & low intensity exercise & education • - controls: education • Nutrition - 400 kcal; 60% CH, 25% fat, 15% protein; 0.6 g n-3 PUFA + vit A • Results • Increases in body weight, FFM, FM, PIMax, QF, 6MWD, QoL • Decreased in hsCRP, IL-8, TNFα Sugawara et al. Respir Med 2010

  25. (n-3/n-6) PUFA supplementation as adjunct to exercise and nutrition • Study Design (RCT • Patients: n=102, FEV1: 37 (3)% • Duration: 8 weeks, in-patient • Intervention: Treatment: (n-3/n-6) capsules+rehab; 3.4 g (n-3+n-6); 2.6 g (n-3); 1.4 g (EPA+DHA) • Control: placebo capsules + rehab • Protein-energy supplementation upon indication in both treatment arms • Results • Improvement in muscle mass & muscle strength after (nutritional) rehabilitation • No effect on markers of systemic inflammation Broekhuizen R, et al. Thorax. 2005;61:17-22.

  26. Muscle pathology in COPD type I II shift ↑ metabolic stress (energy metabolism) ↑ oxidative stress substrate metabolism (carbohydrate/fat) ↓ muscle endurance

  27. Substrate metabolismIncreased glucose metabolism Franssen. Metabolism 2010

  28. Molecular regulation of oxidative metabolism

  29. Decreased expression levels of regulatory proteins of (fat) oxidative muscle metabolism in COPD cachexia Remels AH, et al. Eur Resp J. 2007

  30. PUFA influences regulation of oxidative metabolism PPAR transcriptional activity PUFA rosiglitazone poly unsaturated fatty acids

  31. PUFA as adjunct to exercise and nutrition • Study Design (RCT • Patients: n=102, FEV1: 37 (3)% • Duration: 8 weeks, in-patient • Intervention: Treatment: (n-3/n-6) capsules+rehabilitation; 1.8 g active FA • Control: placebo capsules + rehabilitation • Results • Enhanced improvement in exercise capacity by PUFA • Activation of regulators of fatty acid metabolism (PPARs, PGC1, TFAM) Broekhuizen R, et al. Thorax. 2006;61:17-22.

  32. Enhanced improvement in exercise capacity Peak exercise capacity Exercise endurance time Broekhuizen Thorax 2006

  33. Studies on nutritional modulation of skeletal muscle metabolism and function with inconclusive results • Glutamate/glutamine: • Rationale • Decreasedmuscleglutamateassociatedwithdecreasedmuscleglutathioneandearlylactic acidosis in COPD (Engelen MP, AJRCCM 2000) • Acute experiments • No acute effect of glutamateingestion on skeletalmusclesubstratemetabolismandmuscle performance in COPD (Rutten E, ClinNutr 2008) • No effect of glutaminsupplementation on exerciseinducedoxidativemetabolism (Marwood, Respir. Phsyiol. Neurobiol. 2011)

  34. Studies on nutritional modulation of skeletal muscle metabolism and function with inconclusive results • Creatine • Rationale • Rapid dephosphorylation of creatine andattentuatedphosphoresynthesis in COPD • Randomizedcontrolled trials • Increase in FFM, peripheralmusclestrengthandenduranceafter creatine supplementation but no effect on exercisecapacity (Fuld J, Thorax 2005) • No enhancing effect of creatine supplementationduring a rehabilitation program includingresistanceexercise (Deacon, AJRCCM 2008) • No enhancing effect of creatine supplementationduring a rehabilitationprogramme on endurance shuttle walk performance (Faager G, Int J COPD 2006)

  35. Multimodal intervention in very severe respiratory disease IRAD-2 study • Study Design (RCT) • Patients: n=122, chronic respiratory failure (FEV1: 30%; PaO2: 7.7 kPa); FFMI<25 percentile • Duration: 12 weeks + 12 months follow-up • Home-based • Intervention: 1: education • 2: education + exercise + nutrition+ oral testosterone Pison, et al. Thorax 2011

  36. Improved muscle mass, function and survival follow-up int. Pison, et al. Thorax 2011

  37. Muscle weakness and (hidden) wasting in less advanced COPD Quadriceps muscle weakness Body composition Schols, et al. Am J Clin Nutr. 2006 Seymour J, et al, ERJ 2010

  38. Nutrition as adjunct to exercisein less advanced disease Study design (RCT) Patients: FEV1:60 (16)% + Wmax<70% Duration: 4 month intervention + 20 month maintenance Intervention:all: low intensity exercise, education, coping, stop smoking wastedsub-group: additional nutrition interventionNutrition: 3 x 125 ml; carbohydrate and protein rich; ± 600 kcal Control: usual Care Results Significant difference in exercise capacity and quality of life that sustained after 2-yrs No improvement in muscle function (muscle strength normal in non- wasted group but decreased in wasted group) Van Wetering CR, et al. Thorax. 2010 Hoogendoorn M, et al. Eur Resp J. 2010

  39. Post-hoc analysis:Largest improvement in muscle wasted patients Fat free mass Leg muscle strength p = 0.02 p = 0.03 Van Wetering CR, et al. JAMDA 2010

  40. 6 minute walking distanceMaintenance of walking speed ! Van Wetering CR, et al. JAMDA 2010

  41. COST ANALYSIS: 24 monthsLower hospital admission costs in the wasted intervention group Costs (€) * INTERCOM wasting Usual Care wasting INTERCOM: n = 3 hospitalizations; 2 patients; mean 12 days/hosp Usual care: n= 21 hospitalizations; 10 patients; mean 10 days/hosp Van Wetering CR, et al. JAMDA 2010

  42. Osteoporosis in patients with COPD Graat-Verboom et al., Respir Med 2009

  43. Low vitamin D status in patients with COPD Vitamin D supplementation? Janssens, ERJ 2010

  44. (Systemic inflammation) Nutritional support and treatment CACHEXIA and muscle atrophy Improved health status and survival

  45. Nutritional support and treatment Cardiovascular disease risk reduction? Systemic inflammation OBESITY

  46. Obesity in mild to moderate disease All-cause mortality Landbo et al., Am J Respir Crit Care Med 1999

  47. Causes of death in COPD Mannino et al., Respir Med 2006

  48. Increased cardiovascular risk in COPD Smoking Obesity (western diet & sedentarism) Systemic impairment → Lifestyle or susceptible metabolic phenotype?

  49. Obesity Ouchi et al., Nat Rev Immunol 2011

  50. Fat tissue as source of systemic inflammation COPD: (FEV1: 59%) van den Borst B et al. Am J Clin Nutr 2011

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