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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
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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
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 consistent Cannot define cause-effect relationship
EPIDEMIOLOGY PROSPECTIVE STUDIESOverweight, 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
EPIDEMIOLOGYWeight loss 85 80 Diet n=19 Control n=19 75 % FEV1 70 65 60 Baseline 8 week diet 6 month 1 year Stenius-Aarniala, B. et al. BMJ 2000;320:827-832
EPIDEMIOLOGYWeight loss 24 22 20 18 Dyspnea visual scale Diyet n=19 Kontrol n=19 16 14 12 10 8 Baseline 8 weeks diet 6 months 1 year Stenius-Aarniala, B. et al. BMJ 2000;320:827-832
Diyet n=19 Kontrol n=19 EPİDEMİYOLOJİKilo verme 2,5 2,0 1,5 Bronkodilator use 1,0 0,5 0,0 Baseline 8 week diet 6 month 1 year Stenius-Aarniala, B. et al. BMJ 2000;320:827-832
STUDIES Cross-sectional Prospective Weight loss RESULTS Obesity increases the risk of asthma Obesity impairs asthma control EPIDEMIOLOGY
FİZYOLOJİ ERV and FRC decrease fast and shallow breathing Tidal 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 Gaw L s-1 cm H2O-1 0,00 -0,05 -0,10 -0,15 18.5 – 25.0 25.0 – 30.0 > 30.0 BMI kg/m2 PHYSIOLOGY Pulmonary functions n=139 E
18 16 14 12 FEV1 (% decrease) 10 Obese Non-obese Obes Non-obes 8 6 4 2 0 10 100 1 Metacholin μmol PHYSIOLOGY Airway hyperreactivity Non-obese n= 25 BMI: 23.1 (21-28) kg/m2 Obese n= 23 BMI: 37.3 (30-63) kg/m2 Salome, Munoz, King AJRCCM ATS 2005 A562
PHYSIOLOGY Airway hyperreactivity 2,0 BHR developing group (4 years) n=61 Control, n= 244 1,5 OR airway hyperreactivity 1,0 0,5 0,0 -1.5 - -0.2 -0.2 - 0 0 – 0.2 0.2 – 0.4 0.4 – 1.9 BMI annual change A A Litonjua, D Sparrow, J C Celedon, D DeMolles and S T Weiss. Thorax 2002;57;581-585
PHYSIOLOGY OBESITY • Decreased lung volumes • Alterations in airway smooth muscle • Data on airway hyperreactivity are inconsistent
Normal immune functions İmmune aktivation Inflamattory İmmune suppression Optimum nutrition Over nutrition Mal nutrition
OBESITYINFLAMMATORY MEDIATORS • TNF-α • IL-6 • IL-1 • IL-8 • MCP • IL-10 • TGF-β • LEPTİN • CRP • ADİPONEKTİN: decreased increased
Adipocytes Blunts appetite Increases energy expenditure Correaltes with BMI. T cell increased proliferation increased activation Monocyte increased activation Anjiogenesis increase LEPTİN
30,00 25,00 20,00 Serum leptin ng/ml 15,00 10,00 5,00 0,00 After treatment Before treatment Control n=20 ASTHMA n=23 INFLAMMATION ASTIMLI ÇOCUKLARDA SERUM LEPTİN DÜZEYİ Gürkan F et al., Ann Allergy Asthma Immunol. 2004;93:277-80.
Guler N, Kirerleri E, Ones U, Tamay Z, Salmayenli N, Darendeliler F. J Allergy Clin Immunol. 2004;114:254-9.
OBESITY INFLAMMATION WellenKE and Hotamisligil GS. J. Clin. Invest. 2003;112:1785-1788
EXPERIMENTAL 4.5 4.0 3.5 3.0 Saline-PBS Penh 2.5 Leptin-PBS Saline -OVA 2.0 Leptin-Ova 1.5 1.0 0.5 0.0 Saline 0,3 1 3 10 30 Methacholine mg/ml Shore S. et al., JACI 2005;115:103-109
70 60 50 IL-13 pg/ml 40 30 20 10 9 0 8 14 7 12 IL-5 pg/ml 10 6 IL-4 pg/ml Salin 8 5 6 4 Leptin 4 3 2 2 0 1 0 OVA PBS 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 RESULTS Obesity is associated with alterations in pulmonary physiology. Specifity of clinical findings may be low. OBESE ASTHMATICS SHOULD LOSE WEIGHT