SINDROME METABOLICA E BPCO SINDROME METABOLICA E BPCO

AAlessia Verduri - Leonardo M. Fabbrilessia Verduri - Leonardo M. Fabbri

Clinica Clinica di Malattie dell’Apparato Respiratorio

Università degli Studi di Modena e Reggio Emilia

Direttore Prof. Leonardo M. Fabbri

CORSO DI FORMAZIONE PER PERSONALE MEDICO DI NYCOMED

Modena, 6-7/8-9 Settembre 2011

DEFINITIONS

Definition of COPD

COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients.

Its pulmonary component is characterized by airflow limitationthat is not fully reversible.

The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung tonoxious particles or gases.

METABOLIC SYNDROMEMETABOLIC SYNDROME

…is a complex disorder and an emerging clinical challenge, recognised clinically by the findings of abdominal obesity, atherogenic dyslipidaemia, hypertension and insulin resistance…

Grundy SM, et al. Circulation 2005; 112: 2735-52

The Metabolic SyndromeThe Metabolic Syndrome IDF 2006

Obesity and Body Mass Index (BMI)Obesity and Body Mass Index (BMI)

Body Mass Index (BMI) provides a more accurate measure of obesity than does weight alone

BMI = (kg)/(m)2

EPIDEMIOLOGY

Courtesy of M. Porta

Obesity Trends* Among U.S. AdultsBRFSS, 1985

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14% 15%–19% 20%-24% 25%

Obesity Trends* Among U.S. AdultsBRFSS, 1995

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14% 15%–19% 20%-24% 25%

Obesity Trends* Among U.S. AdultsBRFSS, 2000

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14% 15%–19% 20%-24% 25%

No Data <10% 10%–14% 15%–19% 20%-24% 25%

Source: Behavioral Risk Factor Surveillance System, CDC

(*BMI 30, or about 30 lbs overweight for 5’4” person)

Obesity Trends* Among U.S. Adults BRFSS, 2003

5-yrs mortality5-yrs mortality

The present study analysed data from 20,296 subjects aged >45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).

5-yrs mortality and presence of

no, 1 ,2 or 3 comorbidities

(diabetes, hypertension,

CVD)

Cause of death on treatment

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Cardio-vascular

Pulmonary Cancer Other Unknown

Deaths (%)

Placebo SFC

Calverley et al. NEJM 2007

For every 10% decrease in FEVFor every 10% decrease in FEV11, ,

cardiovascular mortality increases by cardiovascular mortality increases by approximately 28% and non-fatal coronary approximately 28% and non-fatal coronary

event increases by approximately 20% in mild event increases by approximately 20% in mild to moderate COPDto moderate COPD

Anthonisen Anthonisen et al. Am J Respir Crit Care Med 2002et al. Am J Respir Crit Care Med 2002

Cardiovascular mortality in COPDCardiovascular mortality in COPD

Emphysema severity is associated with arterial Emphysema severity is associated with arterial stiffness in patients with COPDstiffness in patients with COPD

Similar pathophysiological processes may be involved Similar pathophysiological processes may be involved in both lung and arterial tissuein both lung and arterial tissue

Further studies are now required to identify the Further studies are now required to identify the mechanism underlying this newly described mechanism underlying this newly described

associationassociation

MacNee W et al. MacNee W et al. AJRCCM 2007; AJRCCM 2007; 176:1208-1214176:1208-1214

ARTERIAL STIFFNESS IS INDEPENDENTLY ARTERIAL STIFFNESS IS INDEPENDENTLY ASSOCIATED WITH EMPHYSEMA SEVERITY IN ASSOCIATED WITH EMPHYSEMA SEVERITY IN

PATIENTS WITH CHRONIC OBSTRUCTIVE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASEPULMONARY DISEASE

Lancet 2007; 370:797-99

PHYSIOPATHOLOGY: link between MS and COPD

Martinis M et al. Exp. Mol. Pathol. 2006;80(3):219-227.

MuscleWeakness / Wasting

Metabolic Syndrome Type 2 diabetes

Osteoporosis

CRPCardiovascular

Events Liver

?LocalInflammation

TNF IL-6

Fabbri LM et al. Fabbri LM et al. Eur Respir J 2008Eur Respir J 2008

Courtesy of M. Porta

Pathogenesis of MS

Grundy SM. J Clin Endocrinol Metab 2007;92:399-404

INSULIN RESISTANCE AND INFLAMMATION - A INSULIN RESISTANCE AND INFLAMMATION - A FURTHER SYSTEMIC COMPLICATION OF COPDFURTHER SYSTEMIC COMPLICATION OF COPD

Bolton CE et al. COPD. 2007;4:121-6Bolton CE et al. COPD. 2007;4:121-6

This study demonstrates greater insulin This study demonstrates greater insulin resistance in non-hypoxaemic patients with resistance in non-hypoxaemic patients with

COPD compared with healthy subjects, COPD compared with healthy subjects, which was related to systemic which was related to systemic

inflammation. This relationship may inflammation. This relationship may indicate a contributory factor in the excess indicate a contributory factor in the excess risk of cardiovascular disease and type II risk of cardiovascular disease and type II

diabetes in COPD. diabetes in COPD.

Sindrome Metabolica

ObesitàBMI >30mg/kg2

Girovita: M>102

F>88cm

Resistenza insulinica

Aumento di colesterolo e

trigliceridi

Ipertensione

Diabete mellito tipo 2 GeneticaSindrome delle

apnee ostruttive del sonno

IpossiemiaSEDENTARIETA‘

Fumo

Sindrome disfunzionalerestrittiva

Courtesy of Muller BComplicazioni secondarie

Schematic representaion of how smoking might add to several mechanisms linking obesity to CV disease. Red arrows indicate an effect of smoking.

Fabbri ERJ 2008; 31:204-12

RESULTS: 43% of COPD pts and 21% of control participants presented 3 or more determinants of the metabolic syndrome.

Gifford AH et al. CHEST 2010;138;704-15

Peppard PE et al. JAMA 2000;284:3015-21

• The increasing prevalence of type 2 diabetes may be attributed to the epidemic of obesity

• Excess weight is an important factor for OSA • OSA may be a novel risk factor for type 2 diabetes and/or

the chronic hyperglycemia may promote OSA• Evidence links OSA to alterations in glucose tolerance,

insulin resistance and type 2 diabetes (intermittent hypoxia, sleep fragmentation and sleep loss)

• OSA has also been linked to metabolic syndrome• CPAP treatment has beneficial effect on visceral adiposity

Eterogeneità della BPCOFEV1=35%MRC=3/4PaO2=66

6MWT=230BMI = 34SCORE=7

FEV1=33%MRC=2/4PaO2=57

6MWT=400BMI = 21 SCORE=6

PHYSICAL ACTIVITIES IN DAILY LIFE IN COPD PHYSICAL ACTIVITIES IN DAILY LIFE IN COPD

Malnutrition and COPD: phenotypes

0 6 12 18 24 30 36 42 480.0

0.2

0.4

0.6

0.8

1.0

Su

rviv

al

Follow-up, months

BMI > 29 Kg/m2

BMI 24-29 Kg/m2

BMI 20-24 Kg/m2

BMI < 20 Kg/m2

Weight loss is a prognosticfactor in COPD

Schols et al. AJRCCM 1998; 157: 1791-7

Mechanism of inflammatory bone lossMechanism of inflammatory bone loss

Takayanagi , J Mol Medicine 2005; Takayanagi , J Mol Medicine 2005; 83:170-983:170-9

Mechanisms of Skeletal MuscleAtrophy in Patients with COPD or CHF

Padeletti- LeJemtel . International Journal of Cardiology, 2008Padeletti- LeJemtel . International Journal of Cardiology, 2008

LeJemtel et al. JACC, 2007

PROGRESSION OF CHF AND COPD

LeJemtel et al. JACC, 2007

THERAPY

Recommendations for treatment

Primary intervention Healthy lifestyle that includes: • Calorie restriction (5-10% loss of body weight in the first year)• Moderate increase in physical activity (role of pulmonary

rehabilitation)• Change in dietary composition

Secondary intervention• In people for whom lifestyle change is not enough and who are

considered to be at high risk for CVD, drug therapy may be required to treat the metabolic syndrome.

• Individual components of MS should be treated.

Pulmonary rehabilitation in chronic Pulmonary rehabilitation in chronic obstructive pulmonary diseaseobstructive pulmonary disease

Troosters et al Am J Respir Crit Care Med. 2005 Jul 1;172(1):19-38Troosters et al Am J Respir Crit Care Med. 2005 Jul 1;172(1):19-38

Today the question is no longer "should patients with Today the question is no longer "should patients with chronic obstructive lung disease receive pulmonary chronic obstructive lung disease receive pulmonary rehabilitation?" but rather "how should pulmonary rehabilitation?" but rather "how should pulmonary rehabilitation be delivered to patients with COPD?" rehabilitation be delivered to patients with COPD?"

CONCLUSIONS• Metabolic syndrome (MS) and manifest diabetes are more

frequent in COPD population.

• A chronic systemic low-grade inflammation and a common complex pathogenetic pathway provide a link between COPD and MS.

• The cluster of cardiometabolic abnormalities may confer an additional CV risk in COPD patients.

• Physical activity and pulmonary rehabilitation along with change in dietary composition may be the way forward for effective management of these comorbidities.

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