Epidemic of Obesity

Mayo Clinic Health Letter, Medical Essay, 1997

Prevalence of Breathlessness with Exertion in Overweight & Obese Individuals

05

10152025303540

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

Perc

ent (

%)

Sin, etal, ArchInternMed, 1996

0

2

4

6

8

10

RPB

(Bor

g sc

ale

0-10

)

Obese withoutBreathlessness(n=8, BMI 36+5)

Obese withBreathlessness(n=8, BMI 37+4)

Rate Your Breathing 0 Nothing at all 0.5 Very, very weak (J ust Noticeable) 1 Very Weak 2 Weak (Light)

3 Moderate

4 Somewhat Strong

5 Strong (Heavy)

6

7 Very Strong

8

9

10 Very, very strong (Almost max) Maximal

Intensity of Breathlessness on Exertion

After 6 min of cycling at 60 W

*

Work Rate (W)

VO2 (

L/m

in)

0

1

2

3

0 20 40 60 80 100 120

.

VO2 (Predicted).

VO2 - Work Rate Relationship .

.VO2 (Observed)

Extreme Obesity

Woman 49 yr 163 cm 154 kg DOE

0

40

80

120

Lean Obese Lean Obese

Cardiovascular Exercise Capacity

Women

VO2 (

%Pr

edic

ted)

.

Men

Obese Without & With Breathlessness

Women

Lean Obese

Lung Volume Subdivisions

Mayo Clinic Health Letter, Medical Essay, 1997

Obese TLC Obese RVObese FRC

MRI at Various Lung Volumes

Flow

(L/s

ec)

Flow

(L/s

ec)

-4

0

4

8

0 1 2 3 4

Volume (L)

Flow-Volume Loop in Extreme Obesity

49 yr 163 cm 154 kg DOE

6 4 2 0

Absolute Volume (L)Volume below TLC (L)

?

LOADLO

AD

Lean Obese

InspiratoryForce

Anterior subcutaneous abdominal fat

Rib cage fat

Visceral fat

Posterior subcutaneous abdominal fat

Theoretical Effects of Chest Wall Obesity

O2 C

ost o

f Bre

athi

ng (m

l/L)

0

1

2

3

4

Obese withoutBreathlessness

n=8, BMI 36+5

Obese withBreathlessness

n=8, BMI 37+4

Work of Breathing

y = 3.5x + 0.21R2 = 0.99

y = 2.0x + 0.19R2 = 0.99

0

100

200

300

400

500

0 20 40 60 80

Obese with breathlessnessObese without breathlessness

VO2

(mL/

min

)

.Rest

Eucapnic Voluntary Hyperpnea

VE (L/min).

y = 3.5x + 0.21R2 = 0.99

y = 2.0x + 0.19R2 = 0.99

0

100

200

300

400

500

0 20 40 60 80

Obese with breathlessnessObese with breathlessnessObese without breathlessnessObese without breathlessness

VO2

(mL/

min

)

. VO2

(mL/

min

)

.Rest

Eucapnic Voluntary Hyperpnea

VE (L/min).VE (L/min).

*

Relationship between Work of Breathing and Breathlessness

0

1

2

3

4

0 2 4 6 8 10RPB (Borg scale 0-10)

O2 C

ost o

f Bre

athi

ng (m

l/L)

y = 0.20x + 1.46R2 = 0.57

Obese with BreathlessnessObese without Breathlessness

Work of Breathing and Fat Distribution

y = 0.59x - 0.42R2 = 0.62

0

1

2

3

4

5

0 2 4 6 8

Anterior Subcutaneous Abdominal Fat (kg)

O2 C

ost o

f Bre

athi

ng (m

l/L) Obese without Breathlessness

Obese with Breathlessness

Obesity of the Chest Wall

Abdominal Fat

Mayo Clinic Health Letter, Medical Essay, 1997

Altered Respiratory Mechanics Increasing Respiratory Impedance

-Low lung volume breathing-Decreased chest wall compliance-Expiratory flow limitation -Increased pulmonary resistance

Obesity

With Dyspnea on ExertionWithout 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

Name: ____________ Date: ________ Test: _________ RPB: ____ STANDARD RESPIRATORY DEBRIEFING: 1. Describe the respiratory sensations you felt when your rating was at its highest. 2. What were you rating? 3. In making your ratings, was there any particular time when you were breathing in, breathing out, or breathing in and out that you were paying attention to? 4. Look over the following symptom list and select (circle) the top 3 descriptors that best describe the respiratory sensations you felt during the exercise.

1. My breath does not go in all the way. 2. My breathing requires effort. 3. I feel that I am smothering. 4. I feel hunger for air. 5. My breathing is heavy. 6. I feel out of breath. 7. My chest feels tight. 8. My breathing requires work. 9. I feel that I am suffocating. 10. My chest is constricted. 11. I feel that my breathing is rapid. 12. My breathing is shallow. 13. I feel that I am breathing more. 14. I cannot get enough air. 15. My breath does not go out all the way.

5. Any other sensations?

Mahler, etal, AJRCCM, 1996

Patient Specific Clusters

Mahler, etal, AJRCCM, 1996

Respiratory Sensations in Mild-to-Moderately Obese Women

Cluster Descriptor Obese without Breathlessness Work/Effort [66%] My breathing requires effort (66%) My breathing requires work (33%) Exhalation [33%] My breath does not go out all the way (33%) Inhalation [33%] My breath does not go in all the way (33%) Breathing More [66%] I feel I am breathing more (66%) Heavy [33%] My breathing is heavy (33%) Obese with Breathlessness Work/Effort [66%] My breathing requires effort (33%) My breathing requires work (33%) Suffocating [33%] I feel that I am smothering (33%) Rapid [66%] My breathing is rapid (66%) Breathing more [66%] I feel that I am breathing more (66%) Heavy [66%] My breathing is heavy (66%) Note: () the percentage of patients who selected descriptors as one of ‘best three’ [] the percentage of patients who selected at least one descriptor from this cluster

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, O2 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

Thank You

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.’

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

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

Theoretical Effects of Chest Wall Obesity

?

LOADLO

AD

Lean Obese

InspiratoryForce

0

40

80

120

Lean Obese Lean Obese

Women MenVO

2 (%

Pred

icte

d)

.

y = 3.5x + 0.21R2 = 0.99

y = 2.0x + 0.19R2 = 0.99

0

100

200

300

400

500

0 20 40 60 80

Obese with breathlessness Obese without breathlessness

VO2 (

mL/

min

)

.Rest

Eucapnic Voluntary Hyperpnea

VE (L/min).

Implications of Lung Volume on Airflow

12

-8

-4

0

4

8

0 2 4 6 8Volume (L)

Flow

(L/s

ec)

ERVIC

TLC RV

FRC

0

20

40

60

80

100

Rest MaximalExercise

Workload

0

5

10

15

20

25

30 VO2 (m

l/kg/min)

.

VO2 (

%Pr

ed)

.

VO2 (%Pred)

.

VO2 (ml/kg/min)

.

Addition to Figure 1: Functional Capacity vs Fitness Level

Lung Volume and Gas Distribution

Increased ObesityIncreased Risk of Comorbidities(heart disease, hypertension, etc)

Obesity

Obesity-Related RespiratoryLimitations (O2 cost of breathing)

CardiovascularDeconditioning

Reduced Physical Activity

Exertional Dyspneaand

Exercise Intolerance

Potential Mechanisms of Dyspnea The word ‘dyspnea’ subsumes a variety of unpleasant respiratory perceptions described by terms such as chest tightness, excessive breathing effort, and air hunger (72,117). Work in Dr. Banzett’s laboratories and others has identified at least three separable ‘qualities’ of uncomfortable breathing sensations: ‘Effort or work’, ‘Air hunger’, and ‘Tightness.’

'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 (45,78,82,95). Perceptions of work and effort arise through some combination of respiratory muscle afferents and perceived central neural motor command or 'corollary discharge' (Fig) (63,95). Preliminary studies show that high levels of respiratory work are not as unpleasant or threatening as air hunger. From 1970 until recently, it was widely believed that perception of work/effort was responsible for all dyspnea. The idea that work of breathing is the central feature of all dyspnea (43) is now clearly disproven (30,32,64), but work of breathing can contribute to respiratory discomfort.

‘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 (30,31). Subjects often comment that intense air hunger is a threatening or frightening sensation. Air hunger arises from stimulation of arterial chemoreceptors and other drives to breathe (Fig) (5,32,49,94,132). It is hypothesized that air hunger arises from a copy or ‘corollary discharge’ of brainstem respiratory activity (aka ‘ventilatory drive’) that ascends to the cortex. Such a corollary discharge has been described in the midbrain and thalamus of decorticate cats (41,42,55). Air hunger is associated with activation of paralimbic cortex in humans, an area involved with several unpleasant sensation (33,58).

‘Chest Tightness’ is specific to asthmatic bronchoconstriction (97,116) and may arise from pulmonary afferents (Fig) (36). Tightness will not be directly studied in the present application; however, we will include the descriptor in our dyspnea questionnaires.

This is a scale for rating:

BREATHLESSNESS

The number 0 represents no breathlessness. The number 10

represents the strongest or greatest breathlessness that you have ever

experienced. Each minute during the exercise test you will be asked to

point to a number, with your finger, which represents your perceived

level of breathlessness at the time. The number will be repeated out loud

in order to confirm your choice. During the exercise test you may have

an even stronger or greater intensity of breathlessness than you have

previously experienced. You should then point to the word “maximal” if

the severity is greater than 10. You can tell us this number after the

mouthpiece has been removed.

Ventilatory Limitations of Aging

Babb, DeLorey, etal JAP & AJRCCM 1997, 1999, 2000, 2001, 2002, 2003

Ventilatory Limitations of Aging

Babb, DeLorey, etal JAP & AJRCCM 1997, 1999, 2000, 2001, 2002, 2003

Volume (L)2 4

-4

0

4

8

Flow

(L/s

)

Patients with Chronic Airflow Limitation (CAL)

Babb Rodarte etalJAP& MSSE1991, 1992, and 1993

Volume (L)2 4

-4

0

4

8

Flow

(L/s

)

Ventilatory Limitations in Patients with Chronic Airflow Limitation (CAL)

Babb Rodarte etalJAP& MSSE1991, 1992, and 1993

Ventilatory Limitations in Obesity

Babb, DeLorey, etal JAP, Annals Int Med, RespPhysiolNeurobiology, Int J Obes 2002, 2003, 2004, 2005Mayo Clinic Health Letter, Medical Essay, 1997

Lean

Obese

Ventilatory Limitations of Aging

Babb, DeLorey, etal JAP & AJRCCM 1997, 1999, 2000, 2001, 2002, 2003

Ventilatory Limitations of Aging

Babb, DeLorey, etal JAP & AJRCCM 1997, 1999, 2000, 2001, 2002, 2003

Volume (L)2 4

-4

0

4

8

Flow

(L/s

)

Patients with Chronic Airflow Limitation (CAL)

Babb Rodarte etalJAP& MSSE1991, 1992, and 1993

Volume (L)2 4

-4

0

4

8

Flow

(L/s

)

Ventilatory Limitations in Patients with Chronic Airflow Limitation (CAL)

Babb Rodarte etalJAP& MSSE1991, 1992, and 1993

Ventilatory Limitations in Obesity

Babb, DeLorey, etal JAP, Annals Int Med, RespPhysiolNeurobiology, Int J Obes 2002, 2003, 2004, 2005Mayo Clinic Health Letter, Medical Essay, 1997

Lean

Obese

Flow

(L/s

ec)

Flow

(L/s

ec)

-4

0

4

8

0 1 2 3 4

Volume (L)

Flow-Volume Loop in Extreme Obesity

49 yr 163 cm 154 kg DOE

6 4 2 0

Absolute Volume (L)Volume below TLC (L)

-10

-5

0

5

10

4 3 2 1 0Volume (L)

Flow

(L/s

ec)

4 3 2 1 0

FVCExpiration

Inspiration

Exercise

Rest

Exercise Flow-Volume Loops

Flow

(L/s

ec)

-4

0

4

8

0

Volume (L)6 4 2 0

Absolute Volume (L)

49 yr 163 cm 154 kg DOE

Exercise and Breathing Pattern

1208040001

2

3

4

0

20

40

60

200160120804000

40

80

120

160

LOAD (W)

Tida

l Vol

ume

(L)

Freq

uenc

y (b

pm)

V E (L

/min

)

.

VE (L/min)

.

.

-8

-4

0

4

8

12

0 2 4 6 8

VOLUME (L)

Flow

(L/s

)RVTLC

Work Rate (W)

0

1

2

3

0 20 40 60 80 100 120

VO2 (

L/m

in)

.

Figure 1: VO2 - Work Rate Relationship.

Linear relationship, independent of age, sex, or Ht. Predicted maximal work rate and VO2 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

0

20

40

60

80

100

Rest MaximalExercise

Workload

0

5

10

15

20

25

30 VO2 (m

l/kg/min)

.

VO2 (

%Pr

ed)

.

VO2 (%Pred)

.

VO2 (ml/kg/min)

.

Addition to Figure 1: Functional Capacity vs Fitness Level

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 ExertionWithout 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

Rate Your Breathing 0 Nothing at all 0.5 Very, very weak (J ust Noticeable) 1 Very Weak 2 Weak (Light)

3 Moderate

4 Somewhat Strong

5 Strong (Heavy)

6

7 Very Strong

8

9

10 Very, very strong (Almost max) Maximal

Rate Your Breathing 0 Nothing at all 0.5 Very, very weak (J ust Noticeable) 1 Very Weak 2 Weak (Light) 3 Moderate 4 Somewhat Strong 5 Strong (Heavy) 6 7 Very Strong 8 9 10 Very, very strong (Almost max) Maximal