Resperation and Stress

Harnessing the Therapeutic Power of Breathing

To Lower Blood Pressure & Reduce StressApril 2006

Judy Chodirker, MHSc

Manager, Scientific Affairs

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Agenda

Overview

Respiratory Pacing & the Physiological Mechanism of Action

Clinical Studies Highlights

Professional Programs

Questions? Feedback?

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FDA-Cleared, Hypertension Treatment Device

Clinically proven therapeutic breathing device Sustained blood pressure reductions within 8 weeks No side effects, no drug interactions Seven clinical trials published in peer-reviewed journals Relaxing, pleasant and easy to use

“We found that RESPeRATE was very helpful to many of our patients who experience shallow breathing. And patients, some of whom don’t have high blood pressure, say it simply helps them relax. We use it for patients to take home as a means of reinforcing our biofeedback work with them.”

Leonard Schwartzburd, PhD Clinical Psychologist & Director of the Clinical Institute of

Behavioral Medicine Berkeley, California

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RESPeRATE: FDA Indication for Use

Specifically indicated for adjunctive treatment of hypertension & reduction of stress

Can be safely used with pharmacological and/or non-pharmacological interventions

Does not require a prescription Any changes in medication should be discussed with the doctor who

prescribed them

RESPeRATE Indications for use (FDA k# 020399 OTC)The RESPeRATE is intended for use as a relaxation treatment for the reduction of stress by leading the user through interactively guided and monitored breathing exercises. The device is indicated for use only as

an adjunctive treatment for high blood pressure, together with other pharmacological and/or non-pharmacological interventions.

RESPeRATE Indications for use (FDA k# 020399 OTC)The RESPeRATE is intended for use as a relaxation treatment for the reduction of stress by leading the user through interactively guided and monitored breathing exercises. The device is indicated for use only as

an adjunctive treatment for high blood pressure, together with other pharmacological and/or non-pharmacological interventions.

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World-Renowned Scientific Advisory Board

Henry R. Black, M.D. – Executive Committee, American Heart Association Council on High Blood Pressure Research

Jay N. Cohn, M.D. – Founder Heart Failure Society of America; Past President, American & International Societies of Hypertension

Joseph L. Izzo, MD. - Vice Chair Research, Department of Medicine, University of Buffalo; Editorial Board, American Journal of  Hypertension (AJH) & Journal of Clinical Hypertension (JCH).

Ehud Grossman, M.D. – President, Israeli Society of Hypertension; Editorial board, Journal of Human Hypertension .

Giuseppe Mancia, M.D. - Past President, International & European Society of Hypertension

Thomas Pickering, M.D. – Past President, Society of Behavioral Medicine; Past Secretary, American Society of Hypertension; Author of Joint National Committee on Hypertension (JNC VI).

Michael Weber, M.D. – Immediate Past President, American Society of Hypertension; Past editor of the American Journal of Hypertension.

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RESPeRATE: Featured By Leading Medical & General Publications

Respiratory Pacing & the Physiological Mechanism of Action

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Slow & deepbreathing

Relaxationresponse

HealthbenefitsYoga, TM…

Evidence shows a direct effect

Its health benefits are taken for granted to be associated with eliciting the “relaxation response”

Paced Breathing is Traditionally Used For Meditation and Healing

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CNSCardioVascular

Heart Failure

Hypertension

Sleep Apnea

Asthma

Migraine

Insomnia

Panic Disorders

Stress

COPD

Pulmonary

THERAPEUTIC INTERACTIONS

CNS

Cardiovascular Pulmonary

Paced breathing modifies multi-system disorders

mainly via neural pathways

Paced Breathing

DISEASE AND AFFECTED SYSTEMS

Therapeutic Possibilities (from literature)

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Therapeutic Breathing Pattern Beneficial for Hypertension

Slow & deep breathing (<10 breaths/min)

Long exhalation

Without effort

• Sympathetic Outflow • Vagal Outflow • Baroreflex sensitivity • Chemoreflex sensitivity

On exhaling

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Breathing

INhale EXhale

IN & EXPacing tones

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1

3

Breathing pattern modification

Computerized unit – detects inspiration & expiration times and generates guiding tones with slightly longer duration

Headphones – hear tones with which user SYNCHRONIZES breathing

Respiration sensor – detects breathing pattern via changes in belt tension

Principle of Interactively Guided Breathing by the RESPeRATE (RR) Device

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0 5 10 15

Minutes of exercise

0

5

15

Respiration rate (breaths/min)

Expiration time (sec)

Inspiration time (sec)

Longer exhalation

Effortless breathing

Compliance & performance automatically stored

“Slow breathing” (< 10 /min)

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13 “slow breathing minutes”

Compliance = Total min. spent in slow breathing

Performance = Measures for quality of use

Typical RESPeRATE Session (from logged data)

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Interactive Respiratory-Pacing Technology

Headphones

Respiration Sensor

RESPeRATEanalyzed your breathing and

composes prolonged inhale

& exhale tones

You synchronize your breathing to RESPeRATEguiding tones

RESPeRATEcomputerized unit

15 minutesFew times a week

* Lowers BP up to 36/20 mmHg (top 10% reductions) Average reductions for high BP 14/8 mmHg

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1. Breathing rate

2. Pulmonary stretch receptors activation

3. Sympathetic outflow

4. Microvascular tone

5. Total peripheral resistance

6. Blood Pressure

Accumulated Effects of Paced Breathingon the Cardiovascular System

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Increased Capillary

Flow

Increased Heart Rate Variability

GUIDED 5-6 /min

HR(bpm)

PP(mmHg)

Respiration signal

CapillaryBlood Flow

Time (sec)Time (sec)

SPONTANEOUS16-17 /min Respiration rate

Respiratory Pacing Increases Capillary Blood Flow (Reduces Vasoconstriction) & HRV

Parati G, Gavish B, Izzo JL, Hypertension Primer (2003)

Clinical Studies Highlights

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Clinical Trials Highlights

7 separate published clinical trials1-6 (over 280 patients), of which 4 were randomized, controlled 1,2,5

Significant & sustained 14/8 mmHg average reduction for high blood pressure, independent of both gender and medication status

Greater reductions for older patients (18/8 mmHg for age>65)

Found effective for Refractory Hypertension6 and Isolated Systolic Hypertension5

Significant and consistent results measured at the clinic1-6, at home2-6 and with a 24-hour ambulatory blood pressure monitor3

No observed side effects

[1] Schein M et al, J Human Hyperten 2001; 15(4): 271 – 278 (Data pooled from first two studies) [2] Grossman E et al, J Human Hyperten 2001; 15(4): 263 - 269. [3] Rosenthal T et al, Am J Hyperten 2001; 14(1): 74 - 76. [4] Meles E et al, Am J Hyperten 2004; 17:370-74. [5] Elliott et al J clinical Hypertension 2004; 6(10): 553-559.[6] Reuven Viskoper et al, Am J 2003; Vol 16:484-487[7] Parati et al, Hypertension Primer, 3rd edition, pp 118

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Number of patients 286

% Males 55%

Age (average) 5811

Age in Years (%)

<40 3%

40-60 57%

>60 40%

% Medicated 78%

# of meds

1 med 34%

2 med 36%

>3 meds 30%

Systolic BP (mmHg) 15013

Diastolic BP (mmHg) 909

Patient PopulationTested in Medicated, Elderly & Difficult-to-Control Populations

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Double blind and randomized

Study Treatment Control Comments

1 RR Walkman +6 m no treat

2 RR Walkman +6 m no treat

3 RR +BPM Walkman +BPM  

4 RR + BPM - 24ABPM

5 RR + BPM BPM +6 m with treat

6 RR +BPM BPM  

7 RR +BPM -  

9 RR +usual care ** Usual care**  Hyp. Diabetics

8 RR -  Korean study

POOLED DATA

Study Designs All included the same 8-week daily treatment with RESPeRATE

20Uncontrolled: Sys >140, n=129; Dia >90, n=83

Pooled from 7 studies Significant BP reduction vs. control.

Independent of gender or medication

Greater response in patients age >65 y -18/-8 vs -8/-3 mmHg

No side effectsElliott et al ESH 2004

BPchange(mmHg)

Sys Dia Sys Dia

-16

-12

-8

-4

0

P=0.008

- 13.7 -8.4 - 8.9 - 4.1

P=0.002

Control Treatment

Significant Blood Pressure Reductions

21Each point represents an individual RR patient (n= 211)

50 60 70 80 90 100 110

Diastolic BP (mmHg)

100

120

140

160

180

Normal

Pre-HTN

Stage 1

Stage 2

50 60 70 80 90 100 110100

120

140

160

180

Normal

Pre-HTN

Stage 1

Stage 2

Before After 8 weeks

Diastolic BP (mmHg)

Sys

tolic

BP

(m

mH

g)

Sys

tolic

BP

(m

mH

g)

Compared to Control: 4% of Stage 2 (p<0.005) and 34% of Stage 1 (p<0.05)

BP Controlled in 46% Patients of Stage 1 & 28% of Stage 2 Who Used RR

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120

130

140

150SBP

80

85

90

95

64 # months

Benefit Maintained (Month 2 to Month 6) in Compliant Patients

2Treatment month

0 62 40

40

60

80

20

Requested45 or more

DBP

Slow breathing minutes per weekOffice BP in mmHg

N=13, mean SEMeles E et al. Data on file

23 Elliott et al. Am J Hyperten, 2005, 18(5): 211A. Baseline & end home BP are averaged over 10 days.

0

10

20

30Control Treatmen

t

Base End

Base End

For office SBP>140 mmHg and home SBP<135 mmHgFor office DBP> 90 mmHg and home DBP< 85 mmHg

P=0.002

Control Treatment

Base End

Base End

5

10

15

20

P=0.02

0

81% 20% 75% 40%

S

ysto

lic B

P

(mm

Hg)

D

iast

olic

BP

(m

mH

g)

RR Eliminated Most of the “White Coat Effect”

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110115120125130135140145150

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Hour

Systolic BP

(mmHg)

After 8 wks 15 min daily treatment

Before treatment

All-Day Sustained High BP Reductions24h ABPM Monitoring

* Am J Hyperten 2001; 14(1): 74 – 76

N=14; p<0.001

Significant 24-hour reduction within 8 weeks of 15 min. RESPeRATE daily treatment

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Bulk of Reduction Within 3-4 Weeks

N=66; p<0.001 Treatment week

Home Systolic BP change(% of 8 wk reduction)

0 1 2 3 4 5 6 7 8

Control0%

25%

50%

75%

100%

* Meles E et al, Am J Hyperten 2004; 17:370-74.

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Average Slow Breathing time per week (minute)

Ch

ang

e in

Sys

tolic

BP

(m

mH

g)

-16.8mmHg

p<0.001

Extensiveuse

0-20

-15

-10

-5

0

25 50 75 100 125

N=121p<0.01

Nonuse

-3.8mmHg

Dose Response Relationship: Slow Breathing Time vs. SBP Reduction

Minimum requested45 min/wk

* Elliott et al J clinical Hypertension June 2004

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Response to Treatment Increases With Age

35-50 51-65 66-80

AGE (year)

-20

-15

-10

-5

0

BP change (mmHg)

SBP

DBP

P<0.02 for SBP

-2.2

- 8.5

-11.4

-5.0

-6.6

-16.1

Elliott et al ESH 2004

Demonstration

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What RR Can Tell About Its Use?

To user

Displays compliance upon

turning ON

Displays compliance & performance -Press STAT

Goal: at least 45 min.

Feedback on breathing rate and compliance

# slow breathing minutes done in

last 7 days

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Client’s Role in “Treatment with RESPeRATE”?

15-min daily session

Quiet room, no other activities

Record displayed “compliance” in a diary * (optional)

Monitor morning BP and record in a diary (optional)

Follow-up visits with healthcare professional as requested

* The displayed compliance is very important for motivatingthe patient and to give a feeling of control/ self-empowerment.

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RESPeRATE User Survey (2006)Performed in partnership with Ipsos- Vantis

Good compliance: 90% use on regular basis, 73% >2x/week

(8-12 weeks from purchase)

Improved BP: 85% reported RESPeRATE improved their BP

Improved Sense of Well-being: 85% reported RESPeRATE

had a positive impact on their general well being

Easy to Use: 95% reported RESPeRATE was easy to use or

took just a few sessions to learn

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RESPeRATE Professional Programs

Professional Dispensing Program

Value-added service for your clients. Enables you to dispense RR directly from your

clinic. Use RR in your clinic, loan or sell to clients. Fair compensation for your time – fully

controlled by you. Recover initial cost of device within 2-3 clients RR accessories available to facilitate sharing

of device

Professional Coupon Program (NEW!) – pass on a $50 discount to your patients

Take Control Sample Program

Provides you with free* Sample Certificates to enable your patients to experience RESPeRATE first-hand.

8-week trial period for enrolled patient with option to purchase at end of trial

All shipping, billing and handling is looked after directly by InterCure (the developer of RESPeRATE).

* Not including shipping & handling charge of $39.95

3 Programs to Suit Your Practice Needs:

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Questions and Feedback

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“He Who Controls Breathing, Controls Health”

Old Proverb

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Additional Physiological overview

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SensoryInputs

PHASICLUNG

VOLUME

CHANGE

Cardiac Stretch

Receptors

Pulmonary Stretch

Receptors

Brain Stem Signal

Processor

ArterialBaroreflex

CNS

Systemic Vascular

Resistance

Cardiac Output

BLOOD PRESSURE

Sympath. nervous Outflow

Modified from Parati G, Gavish B, Izzo JL, Hypertension Primer (2003)

* Chemoreflex excluded

VOLUME SIGNAL

PRESSURE SIGNAL

Paced Breathing Inhibits Sympathetic Outflow Via Increased Lung Inflation

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50

70

90

110

RESPeRATE vs. Metronome

Baseline Slow Breathing (6bpm) Post Exercise

Exercise Time (min)

2575

125175225

0 0.2 0.4 0.6 0.8 1 6.8 7.3 7.8 8.3 8.8 13 13.5 14 14.5 15

RESPeRATE

MetronomeIncreased

Vasodilatation

HR

(b

pm

)S

kin

Pu

lsat

ile

Blo

od V

olu

me

Ch

ange

)%(

Increased HR modulation

RESPeRATE elicits greater modulation of Heart Rate and pulsatile microvessel blood volume during exercise + vasodilatation effect post exercise

RESPeRATE

Metronome

RESPeRATE

Metronome

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BP Reductions & Vasodilatation via Respiratory-Pacing

Decreases Sympathetic Outflow

Decreased TPR & Improved Baroreceptors Sensitivity

Regular 15 min. Conditioning Leads to Sustained BP Reductions

Respiratory-Pacing; 15 min daily sessions

Spontaneous Respiration Paced Respiration