1. Epidemic of Obesity Mayo Clinic Health Letter, Medical Essay, 1997

2. Prevalence of Breathlessness with Exertion in Overweight & Obese Individuals 0 5 10 15 20 25 30 35 40 NHANES III, 28% of Overweight Adults, 27 < BMI < 31 (~ 19 Million) NHANES III, 36% of Obese, BMI > 31 (~ 22 Million) 33% of M-to-M Obese, 30 < BMI < 43 Percent (%) Sin, etal, ArchInternMed, 1996

3. 0 2 4 6 8 10 RPB (Borg scale 0-10) Obese without Breathlessness (n=8, BMI 36+5) Obese with Breathlessness (n=8, BMI 37+4) Intensity of Breathlessness on Exertion After 6 min of cycling at 60 W *

4. Work Rate (W) VO 2 (L/min) 0 1 2 3 020406080100120. VO 2 (Predicted). VO 2 - Work Rate Relationship.. VO 2 (Observed) Extreme Obesity Woman 49 yr 163 cm 154 kg DOE

5. 0 40 80 120 Lean ObeseLeanObese Cardiovascular Exercise Capacity Women VO 2 (%Predicted). Men Obese Without & With Breathlessness Women

6. Lean Obese Lung Volume Subdivisions Mayo Clinic Health Letter, Medical Essay, 1997

7. Obese TLC Obese RVObese FRC MRI at Various Lung Volumes

8. Flow (L/sec) -4 0 4 8 01234 Volume (L) Flow-Volume Loop in Extreme Obesity 49 yr 163 cm 154 kg DOE 6420 Absolute Volume (L) Volume below TLC (L)

9. ? LOAD LeanObese Inspiratory Force Anterior subcutaneous abdominal fat Rib cage fat Visceral fat Posterior subcutaneous abdominal fat Theoretical Effects of Chest Wall Obesity

10. O 2 Cost of Breathing (ml/L) 0 1 2 3 4 Obese without Breathlessness n=8, BMI 36+5 Obese with Breathlessness n=8, BMI 37+4 Work of Breathing *

11. Relationship between Work of Breathing and Breathlessness 0 1 2 3 4 0246810 RPB (Borg scale 0-10) O 2 Cost of Breathing (ml/L) y = 0.20x + 1.46 R 2 = 0.57 Obese with Breathlessness Obese without Breathlessness

12. Work of Breathing and Fat Distribution y = 0.59x - 0.42 R 2 = 0.62 0 1 2 3 4 5 02468 Anterior Subcutaneous Abdominal Fat (kg) O 2 Cost of Breathing (ml/L) Obese without Breathlessness Obese with Breathlessness

13. Obesity of the Chest Wall

14. Abdominal Fat Mayo Clinic Health Letter, Medical Essay, 1997

15. Altered Respiratory Mechanics Increasing Respiratory Impedance -Low lung volume breathing -Decreased chest wall compliance -Expiratory flow limitation -Increased pulmonary resistance Obesity With Dyspnea on Exertion Without Dyspnea on Exertion Effort/Work Corollary discharge from cortical motor centers + Respiratory Mechanoreceptor feedback Air Hunger Corollary discharge from respiratory motor activity in brainstem respiratory centers + Chemoreceptor feedback -Increased oxygen cost of breathing and increased abdominal fat distribution Potential Mechanisms of Dyspnea during Exercise Chest Tightness Pulmonary receptor feedback

17. Mahler, etal, AJRCCM, 1996

18. Patient Specific Clusters Mahler, etal, AJRCCM, 1996

19. Respiratory Sensations in Mild-to- Moderately Obese Women

20. Summary 1. Dyspnea on exertion is prevalent in mild-to-moderate obesity 2. Shortness of breath on exertion does not appear to be associated with CV deconditioning 3. There are significant obesity-related changes in respiratory mechanics at rest and during exercise in mild-to-moderate obesity 4. Shortness of breath on exertion appears to be associated with an increased work of breathing and abdominal fat distribution 5. Obesity-related changes in respiratory mechanics, O 2 cost of breathing, and abdominal fat distribution appear to change respiratory muscle efferent and afferent signals and these changes give rise to the primary sensation of work or effort to breathe

21. Thank You

22. Potential Mechanisms of Dyspnea ‘Effort or work’ of breathing is perceived when the work of breathing is increased by high minute ventilation (rate or tidal volume) or in the lab by external impedance to inspiration. ‘Air hunger’ is the conscious perception of the urge to breathe. It is described as ‘not getting enough air,’ ‘uncomfortable urge to breathe,’ and is the sensation felt at the end of a long breath hold. Subjects often comment that intense air hunger is a threatening or frightening sensation. ‘Chest tightness’ is specific to asthmatic bronchoconstriction. The word ‘dyspnea’ subsumes a variety of unpleasant respiratory perceptions described by terms such as chest tightness, excessive breathing effort, and air hunger. At least three separable ‘qualities’ of uncomfortable breathing sensations have been identified in the laboratory termed ‘Effort or work,’ ‘Air hunger,’ and ‘Tightness.’

23. To examine the basic mechanism of breathing discomfort (dyspnea) in obesity, we will use a debriefing session and a modified dyspnea questionnaire of qualitative respiratory sensation descriptors to investigate the qualities of respiratory sensations and the mechanisms of breathing discomfort in obese subjects during exertion. We propose that the mechanism of this breathing discomfort is related to changes in respiratory muscle efferent and afferent signals associated with the increased oxygen cost of breathing, which is in turn associated with altered respiratory mechanics and fat distribution, and that these changes give rise to the primary sensation of work or effort to breathe rather than the sensations of air hunger or chest tightness. These techniques have not been attempted in obese subjects. Study Details

24. Potential Applications for Identifying Types of Respiratory Sensation Establish a specific diagnosis (e.g., a pts selection of descriptors may direct diagnostic testing) To determine quality of discomfort ask the pt to note two to three statements that best describe dyspnea (similar to asking for characteristics and qualities of chest) In pt with two concurrent diseases, selected descriptors may help identify which condition is the cause of dyspnea (e.g., ‘tightness of asthma from ‘work’ of COPD) Distinguish progression of underlying disease from CV deconditioning secondary to disease process Descriptor questionnaire may also be used to evaluate mechanisms whereby a specific intervention relieves dyspnea (e.g., asthma tightness from airways as well as work effort of Raw) Mahler etal AJRCCM, 1996

26. Theoretical Effects of Chest Wall Obesity ? LOAD LeanObese Inspiratory Force

27. 0 40 80 120 LeanObeseLeanObese Women Men VO 2 (%Predicted).

28. y = 3.5x + 0.21 R 2 = 0.99 y = 2.0x + 0.19 R 2 = 0.99 0 100 200 300 400 500 020406080 Obese with breathlessness Obese without breathlessness VO 2 ( mL/min ). Rest Eucapnic Voluntary Hyperpnea V E (L/min).

29. Implications of Lung Volume on Airflow 12 -8 -4 0 4 8 02468 Volume (L) Flow (L/sec) ERV IC TLCRV FRC

30. 0 20 40 60 80 100 Rest Maximal Exercise Workload 0 5 10 15 20 25 30 VO 2 (ml/kg/min). VO 2 (%Pred).. VO 2 (ml/kg/min). Addition to Figure 1: Functional Capacity vs Fitness Level

31. Lung Volume and Gas Distribution

41. Ventilatory Limitations in ObesityVentilatory Limitations in Obesity Babb, DeLorey, etal JAP, Annals Int Med, RespPhysiolNeurobiology, Int J Obes 2002, 2003, 2004, 2005 Mayo Clinic Health Letter, Medical Essay, 1997 Mayo Clinic Health Letter, Medical Essay, 1997 LeanLean ObeseObese

42. Ventilatory Limitations in ObesityVentilatory Limitations in Obesity Mayo Clinic Health Letter, Medical Essay, 1997 Mayo Clinic Health Letter, Medical Essay, 1997 LeanLean ObeseObese

43. Flow (L/sec) -4 0 4 8 01234 Volume (L) Flow-Volume Loop in Extreme Obesity 49 yr 163 cm 154 kg DOE 6420 Absolute Volume (L) Volume below TLC (L)

44. -10 -5 0 5 10 43210 Volume (L) Flow (L/sec) 43210 FVC Expiration Inspiration Exercise Rest Exercise Flow-Volume Loops

45. Flow (L/sec) -4 0 4 8 0 Volume (L) 6420 Absolute Volume (L) 49 yr 163 cm 154 kg DOE

46. Exercise and Breathing Pattern 120804000 1 2 3 4 0 20 40 60 20016012080400 0 80 120 160 LOAD (W) Tidal Volume (L) Frequency (bpm) V E (L/min)... -8 -4 0 4 8 12 02468 VOLUME (L) Flow (L/s) RV TLC

47. Work Rate (W) 0 1 2 3 020406080100120 VO 2 (L/min). Figure 1: VO 2 - Work Rate Relationship. Linear relationship, independent of age, sex, or Ht. Predicted maximal work rate and VO 2 displayed Predicted Response Plot response side-by-side to predicted normal response Observed Considerably more information is learned from CPET about CV fxn and Gx when the external work is known - cycle is better for this reason

48. 0 20 40 60 80 100 Rest Maximal Exercise Workload 0 5 10 15 20 25 30 VO 2 (ml/kg/min). VO 2 (%Pred).. VO 2 (ml/kg/min). Addition to Figure 1: Functional Capacity vs Fitness Level

49. Altered Respiratory Mechanics Increasing Respiratory Impedance -Low lung volume breathing -Decreased chest wall compliance -Expiratory flow limitation -Increased pulmonary resistance Potential Mechanisms of Dyspnea during Exercise Obesity With Dyspnea on Exertion Without Dyspnea on Exertion Effort/Work Corollary discharge from cortical motor centers + Respiratory Mechanoreceptor feedback Air Hunger Corollary discharge from respiratory motor activity in brainstem respiratory centers + Chemoreceptor feedback Chest Tightness Pulmonary receptor feedback -Increased oxygen cost of breathing and increased abdominal fat distribution