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OBESITY and ASTHMA

ı. A. l. l. l. a. e. D. r. j. i. k. m. i. l. i. H. B. a. s. r. t. l. a. k. a. ı. l. OBESITY and ASTHMA. Prof.Dr.Yavuz S.DEMİREL Ankara University Medical School Chest and Allergic Diseases Department. Obesity is an important public health problem worldwide.

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OBESITY and ASTHMA

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  1. ı A l l l a e D r j i k m i l i H B a s r t l a k a ı l OBESITY and ASTHMA Prof.Dr.Yavuz S.DEMİREL Ankara University Medical School Chest and Allergic Diseases Department

  2. Obesity is an important public health problem worldwide. • Cardiovascular disease • Type 2 diabetes • Cancer • Asthma Current Opinion in Pharmacology 2006, 6:1-7

  3. Obesity Trends Among U.S. Adults between 1985 and 2004 • Definitions: • Obesity: having a very high amount of body fat in relation to lean body mass, or Body Mass Index (BMI) of 30 or higher. • Body Mass Index (BMI): a measure of an adult’s weight in relation to his or her height, specifically the adult’s weight in kilograms divided by the square of his or her height in meters.

  4. 1991 Obesity Trends* Among U.S. AdultsBRFSS,1991, 1996, 2004 (*BMI 30, or about 30 lbs overweight for 5’4” person) 1996 2004 No Data <10% 10%–14%15%–19% 20%–24% ≥25%

  5. Cross sectional epidemiologic studies • Studies demonstrating effects of weight loss or weight gain on a variety of asthma • Obesity antedates asthma Current Opinion in Pharmacology 2006, 6:1-7

  6. GERD CO-morbidity Sleep-disordered breathing Endocrine Factors

  7. Epidemiology The first reports of an association between obesity and asthma came from two large surveys in the 1980s. Since then, more than 30 cross-sectional studies have been reported. J Allergy Clin Immunol 2005, 115:897-909

  8. 135.000 Norwegian men and women Followed 21 years The incidence of asthma increased at a rate of 10% and 7% Per unit increase in BMI in men and women, respectively Am J Epidemiol 2004, 160:969-976

  9. Females 40 35 25 20 15 10 5 0 New Persistent 34.0 Astımlı yüzdesi 18.9 11.8 4.3 3.3 4.3 Vücut Kitle İndeksi Association of high body mass index with asthma. In female subjects asthma is more prevalent in overweight and obese individuals. Reproduced with permission from Hancox et al.

  10. Results • These studies report an increased prevalence of asthma in obese children and adolescents. • Is asthma leads to obesity? • Thousands of individuals with follow of periods varying from 2-21 years, reported an increased incidence of asthma. J Allergy Clin Immunol 2005, 115:897-909

  11. 4. In most of the studies have indicated a greater effect of obesity in females than in males. • Obesity appears to increase asthma severity, a lower peak expiratory flow, have more precribed asthma medications and more emergency room visits. • Obese asthmatics are more difficult to control • Allergy 2006:61:79-84 J Allergy Clin Immunol 2005, 115:897-909

  12. A B A, Asthma severity among morbidity obese asthmatic subjects before bariatric surgery. B, Changes in asthma severity after bariatric surgery. Close to 70% of obese asthmatic subjects have moderate-to-severe asthma. Two years after the bariatric surgery, 80% of obese asthmatic subjects have considerably improved their asthma symptoms and control. Reproduced with permission from Obesity Surgery 2004; 14:1381-8

  13. An important gap in our knowledge of the role of comorbidities is the lack of data about the association between asthma and type 2 diabetes. This evidence of arelation between asthma and type 2 diabetes might lead to abetter understanding of the role of obesity in asthma. Current Opinion in Pharmacology 2006, 6:1-7

  14. Relation Between Obesity and Asthma • The basis for this relationship remains to be established. • Relationship between asthma and obesity is an epiphenomenon.

  15. Proposed mechanisms for the relationship between obesity and asthma • Fetal programing • Genetic pleiotropy • COMMON ETIOLOGIES • CO-MORBIDITIES • EFFECTS OF OBESITY ON LUNG MECHANICS • ADİPOKİNLER-TNF- a • Reflu • Sleep disorders • Type II Diabetes • Low FRC • Reduced tidal volume • Leptin adiponectin

  16. Genome-wide scans for asthma have indicated consensus linkage regions on chromosomes 5q, 6p, 11q and 12q, and these regions contain some candidate genes for obesity, including the genes encoding the β2-adrenoceptor, tumor necrosis factor a (TNF- a ) and the glucocorticoid receptor.

  17. Obese individuals FRC↓ Obese FRC↓ Retractive of the lung paranchyma on the airways decline at low lung volume. AHR ↑ TV ↓ Higher frequency ↑ Bronchial obstruction

  18. OBESITY FRC↓ VT↓ Less Stretch Stiffness Airway shortening BHR

  19. A. Morbidity obese (BMI < 40) B. Non obese (BMI < 30) Airways of a morbidity obese person (A) and of a nonobese person (B), In morbidity obese individuals it is common to observe widening of the bifurcation and a less-defined cartilage ring. BMI, Body mass index.

  20. Absence of a protective effect of deep inhalation to methacholine-induced bronchoconstriction in obese subjects. For a similar dose of methacholine, avoidance of deep inspiration for a 20 minute period before methacholine challenge increased the decrease in FEV1 compared with nonavoidance in nonobese subjects (blue circles, body mass index [BMI] <30; P = .0003), whereas no difference was observed in obese subjects (red circles, body mass index > 30; p> .05).

  21. Fetal Programming The relationship between obesity and asthma could also be the result of fetal programming. Low birth weight is associated with relatively increased body fat later in life. Low–normal gestational age increases the risk for asthma at six years of age , and impaired fetal growth is also a risk factor for adult Nat Immunol 2005, 6:537-539

  22. Female Sex Steroid Hormones Aromatase Adipose tissue estrogenes Androgens • 2 different estrogen receptor • ERα ERβ • Östrojen – basal metabolism ↑ • ERβ

  23. Estrogen and progestorone IL 4 ↑ IL 13↑ periferic bloodmononuclear cells ERs are present on airway smooth muscle.

  24. Sleep Disordered Breathing • Apnea-hypopneas, abnormal gas exchange, snoring and sleep disruption • Children %1-3 • Middle aged %2-40 • Elderly %25 Am J Respir 2004, 169:963

  25. Sleep disordered breathing and asthma share some common risk factors • African American race • Prematurity • Obesity • Allergy • Lower respiratory system infection Hormonal changes Changes in neural tone Reflux Alterations in breathing pattern Altered smooth muscle tone Am J Respir 2004, 169:963 Hypoxemia

  26. ADIPOKINs The term ‘adipokine’ refers to proteins synthesized by and secreted from adipose tissue. These include cytokines, chemokines, hormones involved in energy regulation. The serum concentrations of many adipokines could affect airway function leading to asthma Current Opinion in Pharmacology 2006, 6:1-7

  27. Table Adipokines. TNF-a IL-8 Leptin PAI-1 IL-1 MCP-1 Adiponectin Angiotensinogen IL-6 MIP-1a Resistin Complement B, C3 and D Visfatin (PBEF) Eotaxin VEGF IL-10 IL-1RA IL-1RA, interleukin 1 receptor antagonist; MCP-1, monocyte chemotactic protein 1; MIP-1a, macrophage inflammatory protein 1a;PAI-1, plasminogen activator inhibitor 1; VEGF, vascular endothelial growth factor. Cytokines Chemokines Hormones Other factors

  28. Markers in Obesity Visfatin (PBEF) Eotaxin Adinopectin TNFa Eosinophil recruitment Insulin synthesis Bronchial hyperreactivity

  29. Leptin Ozon-induced Bronchial hyperreactivity (eotaxin release) Leptin TNFa IL6 (Eosinophil recruitment)

  30. Systemic inflammation Leucocyte C reactive protein Pro-inflamatuary cytokines Lipid peroxidation Obezite

  31. High levels of leptin in overweight children with asthma. High levels of serum leptin are present in overweight children, and even higher levels are found in asthmatic overweight children. Reproduced with the permission of Blackwell Publishing from Mai XM, Bottcher MF, Leijon I. Leptin and asthma in overweight children at 12 years of age. Pediatr Allergy Immunol 2004; 15: 523-30

  32. 3 2 Serum Leptin (ng/mL) 1 0 Atopic asthmatics n=78 Nonatopic asthmatics n=24 Controlsn=33 Serum leptin levels of atopic and nonatopic asthmatics and healthy controls. Data represent median values. P values are given for comparison between groups by using the Mann-Whitney U test.

  33. CONCLUSIONS • Asthma and obesity are common conditions, • both are major public health problems. • Obesity increase the risk of asthma • Both disorders share common genetic and • environmental causes • There are mechanical, developmental, • hormonal and immunologic reasons for • their effects

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