ASTHMA and OBESITY

Ömer KALAYCI, MD

Hacettepe Universit School of Medicine

Pediatric Allergy and Asthma Unit

When the world was a simpler place

The rich were fat, the poor were thin and

The wise people thought about how to feed the hungry.

Now, in many places around the world

The rich are thin, th epoor are fat and

The wise people are thinking about how to deal with obesity.

Economist, 13 Aralık 2003

OBESITY

Accumulation of fat to a degree to endanger health

WHO 2006

ClassificationBMI(kg/m²)

wight/ height2

Ayırım noktası

Lean <18.50

     Severe <16.00

     Moderate 16.00 - 16.99

     Mild 17.00 - 18.49

Normal range 18.50 - 24.99

Overweight ≥25.00

     Pre-obese 25.00 - 29.99

     Obese ≥30.00

          Obese class I 30.00 - 34-99

          Obese class II 35.00 - 39.99

          Obese class III ≥40.00

WHO 2006

OBESITY FIGURES

• Year 2005 – 1.6 billion adults (age 15+) overweight– AT least 400 million adult obese– < 5 age 20 million children overweight

• By 2015 – 2.3 billion adults overweight– > 700 million obese.

WHO 2006

ASTHMA AND OBESITY

• Epidemiology

• Physiology

• Immunological-inflammatory

• Experimental

EPIDEMIOLOGY

• Does obesity increase the risk of asthma?

• Does obesity influence the course of asthma?

EPIDEMIOLOGY CROSSSECTIONAL STUDIES

• Obesity in asthmatics – obesity in controls

• High in asthma / no difference between groups• Difference in women / No gender related difference

REsults are not consistentCannot define cause-effect relationship

EPIDEMIOLOGY PROSPECTIVE STUDIES

Overweight, Obesity, and Incident AsthmaA Meta-analysis of Prospective Epidemiologic StudiesAm J Respir Crit Care Med Vol 175. pp 661–666, 2007

• Adults• Primary outcome measure: asthma devlopment• BMI measurement• AT least 1 year follow-up• AT least 70% follow-up • Classification according to standard BMI ranges

Çalışma Nüfus n İzlem (yıl)

OR

Camargo 99 Nurse

Male

Female

0

85,911

4

2.7 (2.3-3.1)

Chen 02 Canada national

Male

Female

9,149 2

1.0

1.9 (1.1-3.4)

Ford 04 NHANES

Male

Female

9,546 10

1.5 (0.9-2.6)

1.4 (1.0-1.9)

Gunnbjrn 04 ECRHS

Male

Female

16,191 7,9

2.1 (1.4-3.2)

1.6 (1.1-2.1)

Huovinen 03 Finnland twin

Male

Female

9,671 9

3.5 (1.6-7.7)

2.3 (0.9-6.1)

Nystad 04 Norway

Male

Female

135,405 21

1.8 (1.4-2.3)

2.0 (1.7-2.4)

Nomieu 03 French

Male

Female

0

67,229

3

2.2 (1.4-3.2)

Total 333,102 8.1 2

1 year point incidence

60

65

70

75

80

85

Baseline 8 week diet 6 month 1 year

Diet n=19 Control n=19

EPIDEMIOLOGYWeight loss

% F

EV

1

Stenius-Aarniala, B. et al. BMJ 2000;320:827-832

8

10

12

14

1618

20

22

24

Baseline 8 weeks diet 6 months 1 year

Diyet n=19 Kontrol n=19

Dy

sp

ne

a v

isu

al s

ca

le

Stenius-Aarniala, B. et al. BMJ 2000;320:827-832

EPIDEMIOLOGYWeight loss

0,0

0,5

1,0

1,5

2,0

2,5

Baseline 8 week diet 6 month 1 year

Bro

nk

od

ilato

r u

se Diyet n=19

Kontrol n=19

Stenius-Aarniala, B. et al. BMJ 2000;320:827-832

EPİDEMİYOLOJİKilo verme

EPIDEMIOLOGY

STUDIES• Cross-sectional• Prospective• Weight loss

RESULTS• Obesity increases the risk of

asthma• Obesity impairs asthma control

FİZYOLOJİ

ERV and FRC decrease fast and shallow breathingTidal vıolume decrease loss of bronchodil effect

Shore and Fredberg JACI 2005;115:925-7

FİZYOLOJİ

Beuther, Weiss, Sutherland AJRCCM 2006;174:112–119

-0,15

-0,10

-0,05

0,00

0,05

0,10

0,15

18.5 – 25.0 25.0 – 30.0 > 30.0

BMI kg/m2

Gaw

L s

-1 c

m H

2O-1

PHYSIOLOGYPulmonary functions

n=139 E

0

2

4

6

810

12

14

16

18

10 1 100

FE

V1

(% d

ecre

ase)

ObesNon-obesObeseNon-obese

Metacholin μmol

Obese n= 23 BMI: 37.3 (30-63) kg/m2

Non-obese n= 25 BMI: 23.1 (21-28) kg/m2

Salome, Munoz, King AJRCCM ATS 2005 A562

PHYSIOLOGYAirway hyperreactivity

0,0

0,5

1,0

1,5

2,0

BMI annual change

-1.5 - -0.2 -0.2 - 0 0 – 0.2 0.2 – 0.4 0.4 – 1.9

OR

airw

ay h

yper

reac

tivity

PHYSIOLOGYAirway hyperreactivity

A A Litonjua, D Sparrow, J C Celedon, D DeMolles and S T Weiss. Thorax 2002;57;581-585

BHR developing group (4 years) n=61Control, n= 244

PHYSIOLOGY

OBESITY

• Decreased lung volumes

• Alterations in airway smooth muscle

• Data on airway hyperreactivity are inconsistent

Normal immunefunctions

Optimum nutrition

İmmune aktivation Inflamattory

Over nutrition

İmmune suppression

Malnutrition

OBESITYINFLAMMATORY MEDIATORS

• TNF-α• IL-6• IL-1• IL-8• MCP• IL-10• TGF-β• LEPTİN • CRP• ADİPONEKTİN: decreased

increased

LEPTİN

• Adipocytes• Blunts appetite• Increases energy

expenditure• Correaltes with BMI.

• T cell– increased proliferation– increased activation

• Monocyte– increased activation

Anjiogenesis– increase

0,00

5,00

10,00

15,00

20,00

25,00

30,00

Before treatment

Aftertreatment

ASTHMAn=23

Controln=20

Ser

um le

ptin

ng/

ml

INFLAMMATIONASTIMLI ÇOCUKLARDA SERUM LEPTİN DÜZEYİ

Gürkan F et al., Ann Allergy Asthma Immunol. 2004;93:277-80.

Asthma

N=102

Control

N=33

GEnder

Girl

Boy

37

65

14

19

AGe

Girl

Boy

6.0±3.5

5.4±3.0

6.3 ±3.7

6.1±3.5

6.8±3.0

5.7±3.8

>0.05

BMI

Girl

Boy

17.5±2.9

16.9±2.8

17.9±2.9

17.0±3.0

17.0±3.0

17.0±2.9

>0.05

Leptin (ng/ml)

Girl

Boy

3.5 (2.1-7.2)

4.7 (2.7-7.2)

3.1 (2.0-7.5)

2.3 (1.3-4.7)

2.7 (2.2-12.2)

1.5 (1.1-3.2)

0.008

>0.05

0.003

Guler N, Kirerleri E, Ones U, Tamay Z, Salmayenli N, Darendeliler F. J Allergy Clin Immunol. 2004;114:254-9.

Wellen KE and Hotamisligil GS. J. Clin. Invest. 2003;112:1785-1788

OBESITY INFLAMMATION

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Saline 0,3 1 3 10 30

Saline-PBS

Leptin-PBS

Saline -OVA

Leptin-Ova

Pen

h

Methacholine mg/ml

Shore S. et al., JACI 2005;115:103-109

EXPERIMENTAL

0

10

20

30

40

50

60

70

IL-1

3 p

g/m

l

0

2

4

6

8

10

12

14

IL-4

pg

/ml

0

1

2

3

4

5

6

7

8

9

IL-5

pg

/ml

PBS OVA

Salin

Leptin

Shore S. Et al., JACI 2005;115:103-109

OTHER FACTORS

• Sex hormones - estrogen

• Genetic markers

ASTHMA AND OBESITY

• Epidemiology

• Physiology

• Immunological-inflammatory

• Experimental

CLINICAL RESULTSObesity is associated with alterations in

pulmonary physiology.

Specifity of clinical findings may be low.

OBESE ASTHMATICS SHOULD LOSE WEIGHT