1. R Rodriguez-Roisin, MD UNIVERSITAT DE BARCELONA OBESIDAD SEVERA Y PULMÓN: EFECTOS DE LA CIRUGÍA BARIÁTRICA

2.  Why?  Pre-Operative Findings  One Year Later...  Summary Agenda

3.  Why?  Pre-Operative Findings  One Year Later...  Summary Agenda

4. BODE MASS INDEX (BMI) = WEIGHT/HEIGHT 2 18.5 – 24.9 25 – 29.9 30– 34.9 35– 39.9 ≥ 40 NORMALOVERWEIGHTOBESITY IOBESITY IIOBESITY III Obesity: Definition (BMI) & prevalence Yanovski SZ & Yanovski JA. NEJM 2011;364:987-9

5. Leptin, IL-6, TNFα, C-RP Obesity, systemic inflammation & lung

6. Arismendi E et al. PLoS ONE 2014;9:e107859

8. Vanfleteren LEGW et al. AJRCCM 2013;187:728-35

9. Obesity treatment Eckel RH. NEJM 2007;356:2176-83

10. Bariatric surgery for severe obesity DeMaria EJ. NEJM 2008;358:1941-50

11. Beuther D et al. AJRCCM 2006;74:112-9 Severe obesity & lung function Lung volume reduction in the lower regions due to excessive unopposed intra-abdominal pressure is likely the principal mechanism of arterial blood gases abnormalities induced by ventilation-perfusion (V A /Q) imbalance

12. Leptin, IL-6, TNFα, CRP Hypothesis The contention was that very severe obesity:  is associated with impaired pulmonary gas exchange, more specifically ventilation- perfusion (V A /Q) ratio and pulmonary vascular abnormalities.  bariatric surgery reduces body mass index and systemic inflammation and improves pulmonary gas exchange defects. Rivas E et al. Chest 2014 (In Press)

13.  To use the multiple inert gas elimination technique in morbidly obese individuals, before and after bariatric surgery.  To characterize pulmonary gas exchange abnormalities while breathing ambient air and 100% oxygen. Objective Rivas E et al. Chest 2014 (In Press)

14.  Why?  Pre-Operative Findings  One Year Later...  Summary Agenda

15. CONTROLOBESE (n, 8)(n, 19) Age, yrs50±351±2 BMI, kg/m 2 25±1 *45±1 * Waist Circumference, cm82±5 *125±2 * Waist-to-Hip Ratio0.83±0.030.90±0.01 Former Smokers, n02 Pack-years017±3 AHI, events/h010±2 Metabolic Syndrome, n07 Clinical characteristics Rivas E et al. Chest 2014 (In Press)

16. ERV & serum biomarkers 0 35 70 Leptin, ng/mL < 0.001 CONTROLOBESE 0 3.0 6.0 9.0 12.0 CRP, mg/L < 0.001 CONTROLOBESE Adiponectin, μg/mL CONTROLOBESE 0.05 0 5 15 25 ERV, % pred CONTROLOBESE < 0.001 0 25 50 75 100 125

17. Arterial blood gases (ambient air) mmHg 0 50 100 87±1 76±3 37±1 39±1 18±1 27±2 PaO 2 AaPO 2 PaCO 2 < 0.001 NS CONTROL OBESE Rivas E et al. Chest 2014 (In Press)

18. PaO 2 PaCO 2 Arterial blood gases (air vs 100% O 2 ) 0 50 100 150 450 650 mmHg 76±3 39±1 519 21%100% PaO 2 PaCO 2 * * Rivas E et al. Chest 2014 (In Press)

19. 100%21% Blood Flow Dispersion (Log SDQ) Shunt & V A /Q mismatching Shunt, %Q T  21% 100% < 0.01 0 5 10 15 0.00 0.50 1.00 NS Rivas E et al. Chest 2014 (In Press)

20. r, – 0.63 p < 0.05 Response to 100% oxygen Rivas E et al. Chest 2014 (In Press)

23. Aghamohammadzadeh R et al. JACC 2013;62:128–35 Obesity & perivascular adipose tissue

24.  Why?  Pre-Operative Findings  One Year Later...  Summary Agenda

25. BMI decreased from 45 to 31 kg/m 2 Excess Weight Loss: 79 % ERV & serum biomarkers Rivas E et al. Chest 2014 (In Press)

26. BMI decreased from 45 to 31 kg/m 2 Excess Weight Loss: 79 % ERV & serum biomarkers 125 < 0.001 ERV, % pred BEFOREAFTER 0 25 50 75 100 0 3.0 6.0 9.0 12.0 CRP, mg/L BEFOREAFTER < 0.001 0 35 70 Leptin, ng/mL BEFOREAFTER < 0.001 0 5 15 25 Adiponectin, μg/mL < 0.005 BEFORE AFTER

27. Arterial blood gases (ambient air) mmHg 100 0 50 89±2 27±2 40±1 15±2 76±3 39±1 PaCO 2 AaPO 2 PaO 2 BEFORE AFTER < 0.001 NS Rivas E et al. Chest 2014 (In Press)

28. Arterial blood gases (air vs 100% O 2 ) 0 50 100 150 450 650 Arterial PO 2, mmHg 76±3 39±1 < 0.001 † 21%100% * * † 89±2 76±3 519 583 BEFORE AFTER Rivas E et al. Chest 2014 (In Press)

29. * 21% Blood Flow Dispersion (Log SDQ) Shunt, %Q T  < 0.01 * 21% Shunt & V A /Q mismatching < 0.01 † 100% 0 5 10 15 0.00 0.50 1.00 † BEFORE AFTER Rivas E et al. Chest 2014 (In Press)

30.  r, – 0.63 p < 0.05 BEFORE Change in Log SDQ 15.0 Change in Shunt,%Q T  0.001.00 -5.0 0.0 5.0 10.0 AFTER r, – 0.45 p, NS Change in Shunt,%Q T Change in Log SDQ 0.001.00 -5.0 0.0 5.0 10.0 15.0 Response to 100% oxygen Rivas E et al. Chest 2014 (In Press)

31. Δ BMI, Kg/m 2 Rho, – 0.72 p < 0.01 Δ FRC, L -20-15-10-5 0 1 2 Δ BMI, Kg/m 2 Δ Log SDQ Rho, 0.54 p < 0.01 0 1 -20-15-10-5 Pre- & post-operative correlations

32. Aghamohammadzadeh R et al. JACC 2013;62:128–35 Obesity & perivascular adipose tissue

33.  Why?  Pre-Operative Findings  One Year Later...  Summary Agenda

34. Summary (1) Morbidly obese subjects have mild- to-moderate arterial hypoxemia induced by mild-to-moderate shunt and mildly broadened pulmonary blood flow dispersion Rivas E et al. Chest 2014 (In Press)

35. Summary (2) Functional reabsorption atelectasis, without reversion of hypoxic pulmonary vasoconstriction is induced by oxygen breathing. This is consistent with alveolar denitrogenation and weaker pulmonary vessels possibly related to endothelial dysfunction Rivas E et al. Chest 2014 (In Press)

36. Summary (3) These gas exchange disturbances appear to be related to underlying excess body weight, reduced expiratory reserve volume and chronic systemic inflammation Rivas E et al. Chest 2014 (In Press)

37. Summary (4) After bariatric surgery, pulmonary gas exchange defects are considerably improved but not completely restored. These abnormalities concur with residual obesity and systemic inflammation Rivas E et al. Chest 2014 (In Press)

38. Muchas Gracias !!!!