Metabolism and Nutrition in COPD

Metabolic changes in COPD Metabolic changes in COPD and its clinical implication.and its clinical implication.

Dr. Benjamin J Tanuwihardja, SpP, FCCP.Fakultas Kedokteran-Universitas Kristen Maranatha

Konsultan Balai Pengobatan Penyakit Paru-Paru (BP-4) Bandung

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Pathogenesis of COPDPathogenesis of COPD

NOXIOUS AGENT(tobacco smoke, pollutants, occupational agent)

Genetic factorsRespiratory infectionOther

COPDwww.GOLDCOPD.com


http://www.GOLDCOPD.com


Inflammatory cells and mediators Inflammatory cells and mediators involved in the pathogenesis of COPDinvolved in the pathogenesis of COPD

Adapted from GOLD workshop report 2001

Cells

MacrophagesNeutrophilsCD8+ lymphocytesEosinophilsEpithelial cellsFibroblasts

Mediators

LTB4, IL-8GRO-1αMCP-1MIP -1αGM-CSFEndothelinSubstance P

Proteinases

Neutrophil elastaseMatrix-metalloproteinasesCathepsinsProteinase-3

EffectsMucus secretion, fibrosis, alveolar wall destruction

Oxidative stress



COPDCOPD

Chest X-Ray PA

Pulmonary EmphysemaPulmonary Emphysema(pink puffer)(pink puffer)

Chronic BronchitisChronic Bronchitis(Blue Bloater)(Blue Bloater)



COPDComplications

COPDComplications

SYSTEMICEFFECTSIN COPD

SYSTEMICEFFECTSIN COPD

CARDIOVASCULARDISORDER

CARDIOVASCULARDISORDER

HANDICAP / DISABILITYHANDICAP / DISABILITY

NUTRITIONALDISORDER

NUTRITIONALDISORDER

OsteoporosisEndocrine

disturbances

OsteoporosisEndocrine

disturbances

SYSTEMICINFLAMMATORY

RESPONSE

SYSTEMICINFLAMMATORY

RESPONSE

RESPIRATORYMUSCLE

DYSFUNCTION

RESPIRATORYMUSCLE

DYSFUNCTION

Wouters,EMF. Eur Respir J 2003; 22, Suppl. 46



NUTRITIONAL DISORDER



Malnourished COPD Malnourished COPD patientpatient

Body Mass Index(BMI = weight / height= weight / height22)

Body Mass Index (BMI)

Underweight : BMI < 18.5



Measurement of Nutritional DepletionMeasurement of Nutritional Depletion

l Body Weight <90% IBW (ideal body weight)l BMI (body mass index) = weight/height2 is <20

kg·m-2 or 18.5 kg·m-2

l Fat mass (FM). l Fat -free mass (FFM)

– Bioelectrical impedance (BIA) is a simple method to assess FFM

– Dual-energy X-ray absorptiometry (DEXA) : first measures the bone mass and the soft tissue mass independently, then separates the soft tissue mass into lean tissue mass and FM



DexaDexa scanscan

SkinfoldsSkinfolds

Bioelectrical Bioelectrical impedanceimpedance



Prevalence of FFM depletion in Prevalence of FFM depletion in stable moderatestable moderate--toto--severe COPDsevere COPD

l Outpatients : 20 %l Eligible for pulm. rehabilitation : 35 %l Lung transplant candidates : 45 %

Engelen, MP. Eur Respir J 1994,7:1793– 1797

Schols,AM. Am Rev Respir Dis 1993,147:1151– 1156

Schwebel,C. Eur Respir J 2000,16:1050– 1055



9%26%

10%55%

Underweight Muscle wasting

Underweight Normal muscle mass

Normal weight Muscle wasting

Normal weightNormal muscle mass

Body composition in COPD



Impact of nutritional depletion Impact of nutritional depletion on COPD out comeon COPD out come



Nutritional status and mortality in Nutritional status and mortality in COPDCOPD

l 348 severe COPD patients was studied in a cohort of Canadian men and women followed for 3 to 5 yr

l evaluated for lung function and body weightl In conclusion, low body weight was

associated with respiratory mortality in severe COPD

Gray-Donald,K. Am. J. Respir. Crit. Care Med., 1996,153:961-966.



Prognostic Value of Nutritional Status in COPDPrognostic Value of Nutritional Status in COPD

l Prospective study: whether BMI is an independent predictor of mortality in subjects with COPD from the Copenhagen City Heart Study.

l 1,218 men and 914 women, aged 21 to 89 yr, with airway obstruction defined as an FEV1 / FVC ratio < 0.7

l Spirometric values, BMI, smoking habits, and respiratorysymptoms were assessed at the time of study enrollment, and mortality from COPD and from all causes during 17 yr of follow-up

LANDBO, C. Am. J. Respir. Crit. Care Med., 1999,160:1856-1861



Results Results

l Low BMI is an independent risk factor for mortality in subjects with COPD, andthat the association is strongest in subjects with severe COPD

LANDBO, C. Am. J. Respir. Crit. Care Med., 1999,160:1856-1861

COPDCOPD--related mortality by BMI related mortality by BMI in subjects with mild, moderate in subjects with mild, moderate

and severe COPD.and severe COPD.



Weight Loss Is a Reversible Factor in Weight Loss Is a Reversible Factor in the Prognosis of COPDthe Prognosis of COPD

l (1) a retrospective study, 400 patients with COPD none of whom had received nutritional therapy; done in theNetherlands.

l (2) a prospective study, 203 patients with COPD who had participated in a randomized placebo-controlled trial.

l The results:l body weight has an independent effect on survival in COPDl the negative effect of low body weight can be reversed

by appropriate therapy in some of the patients with COPD

SCHOLS,AMWJ. Am. J. Respir. Crit. Care Med., 1998, 157: 1791-1797



Survival was significantly decreased in both underweight and normal weight patients as compared with overweight and obese patients. (p < 0.0001).



FEV1 was significantly lower in the underweight and normal weight patients compared with the overweight and obese patients



Nutritional support consisted of a daily high caloric liquid supplement and combinedwith Anabolic steroid treatment consisted of four injections with Decadurabolin



Respiratory muscle strength was measured as mouth pressure during maximal static inspiratory (PImax) maneuvers from RV



Treatment with Growth Treatment with Growth Hormone Hormone

l Growth hormone (rhGH) treatment has been proposed to improve nitrogen balance and to increase muscle strength in COPD

l Randomized placebo control studyl the daily administration of 0.15 IU/kg rhGH during 3 wk

increases lean body mass but does not improve muscle strength or exercise tolerance in underweight patients with COPD.

BURDET, L. Am. J. Respir. Crit. Care Med., 1997, 156: 1800-1806



MegestrolMegestrol Acetate Stimulates Weight Gain Acetate Stimulates Weight Gain and Ventilation in Underweight COPD Pts.and Ventilation in Underweight COPD Pts.

l Prospective, double-blind, randomized, placebo-controlled trial conducted on an outpatient basis at 18 sites

l Underweight (< 95% ideal body weight) COPD patients > 40 years old

l MA, 800 mg/d oral suspension, or placebo at a 1:1 ratio for 8 weeks

l Of 145 randomized patients (63% men), 128 patients completed the trial

Weisberg,J. Chest. 2002;121:1070-1078



Body weight ± 1 SE in each group at each Body weight ± 1 SE in each group at each assessment is shownassessment is shown

Weisberg,J. Chest. 2002;121:1070-1078



PaCOPaCO22 Values in Values in HypercapnicHypercapnic PatientsPatients**

0.020-0.3-4.5Change from baseline50.3 (7.2)44.8 (6.3)Week 8

0.026-1.3-4.6Change from baseline49.3 (5.5)44.7 (6.0)Week 4

0.1650.4-4.4Change from baseline51.0 (12.2)44.9 (6.5)Week 250.6 (5.2)49.3 (3.5)Baseline

p ValuePlacebo Group (n = 12)

MA Group (n = 15)

PaCO2 Values, mm Hg

Weisberg,J. Chest. 2002;121:1070-1078



PaOPaO22 Values in Hypoxic PatientsValues in Hypoxic Patients**

0.1762.75.7Change from baseline61.2 (11.5)66.5 (11.3)Week 8

0.0052.39.9Change from baseline60.8 (9.9)70.7 (14.1)Week 4

0.0062.37.7Change from baseline60.8 (9.9)68.5 (10.7)Week 258.5 (8.3)60.8 (6.6)Baseline

p ValuePlacebo Group (n = 29)

MA Group (n = 35)

PaO2 Values, mm Hg

Weisberg,J. Chest. 2002;121:1070-1078



Nutritional Support for Nutritional Support for Individuals With COPDIndividuals With COPD

( A Meta( A Meta--analysis)analysis)

l From 272 references, 9 RCTs were ultimately included.Six articles were considered as high quality.

l Only 2 studies were double blinded.l Conclusion: Nutritional support had no effect

on improving anthropometric measures, lung function, or functional exercise capacity amongpatients with stable COPD.

Ferreira,I.M. Chest. 2000;117:672-678



SYSTEMIC INFLAMMATIONIN COPD

Oudijk,EJD. Eur Respir J 2003; 22: Suppl. 46, 5s-13s



Chronic inflammation in the lungChronic inflammation in the lung

Sensory nerves

Cigarette smoke

Alveolar macrophage

Neutrophil

Inhibited byα1-antitrypsin

Neutrophil elastaseAnd other proteolytic enzymes

Mucus secretion(chronic bronchitis)

Alveolar wall destruction(emphysema)

Cytokines and chemotactic factors(TNFα, IL-8, LTB4, etc)

LUNGS

-–



Crapo,J. 1st ERS lung Science Conference, Taormina, 2003.

Oxidative stress as an initiator of cytokine

release and cell damage.



muscle wastingimpairment

health status

exercise intolerancedyspneadisability

handicap

skeletal muscle dysfunction

respiratory musclefunction

inflammation

lung impairment



è spill over from lungs?èenhanced by hypoxia?

inflammation

Elevated circulating levels of:

- TNFα, sTNF-R55, sTNF-R75- IL-8, IL-6, sIL-6R- acute phase proteins



Inflammation in the airways Inflammation in the airways lead to systemic effects.lead to systemic effects.

Local / lung Systemic effects

Acute

Chronic

Damage of lung tissue / COPD

Leucocytes activation in PB

Cytokines TNF α

Muscle wasting

Weight loss

↓ Prognosis

Ouddijk,EJD. Systemic inflammation in COPD Eur Respir J 2003;22:Suppl. 46, 5s-13s

Effect of smoke

ROS

Mø, PMN



Model for disease progression in COPDModel for disease progression in COPD

Switch to chronicitySubclinical Clinical

Reversible inflammation

Irreversible inflammation

Mononuclear cells

PMN PMN

Systemic response

Oudijk,EJD. Eur Respir J 2003; 22: Suppl. 46, 5s-13s

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Metabolism and Nutrition in COPD

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