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UNIVERSITY OF WISCONSIN-LA CROSSE Graduate Studies ACOUSTIC ANALYSIS AS A SURROGATE FOR GAS EXCHANGE A Manuscript Style Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science, Clinical Exercise Physiology Amanda J. Peterson College of Science and Health Clinical Exercise Physiology May, 2013

UNIVERSITY OF WISCONSIN-LA CROSSE Graduate Studies ACOUSTIC

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UNIVERSITY OF WISCONSIN-LA CROSSE

Graduate Studies

ACOUSTIC ANALYSIS AS A SURROGATE FOR GAS EXCHANGE

A Manuscript Style Thesis Submitted in Partial Fulfillment of the Requirements for the

Degree of Master of Science, Clinical Exercise Physiology

Amanda J. Peterson

College of Science and Health

Clinical Exercise Physiology

May, 2013

iii

ABSTRACT

Peterson, A.J. Acoustic analysis as a surrogate for gas exchange. MS in Clinical Exercise

Physiology, May 2013, 37pp. (C. Foster)

Measurement of ventilatory (VT) and respiratory compensation (RCT) threshold is a

standard practice during exercise testing with measurement of respiratory gas exchange

(RGE). Previous work suggested the feasibility that a conceptually simple breath sound

analysis (BSA) technique might be an alternative to direct RGE. This study extends

observations of the relationship between VT and RCT detection using RGE and BSA.

Healthy subjects (n=20) performed two incremental, maximal cycle ergometer exercise

tests (25W + 25W per 2 min). Heart rate (HR) and Rate of Perceived Exertion (RPE)

were recorded during the last thirty seconds of each stage using radiotelemetry and the

Category Ratio RPE scale. RGE was performed using open circuit spirometery with VT

and RCT determined from v-slope and ventilatory equivalents. BSA was performed

using proprietary software from a microphone in the breathing valve, and included

measurements of respiratory rate and sound intensity (the product of tidal

volume/inspiratory and expiratory time). There was a significant relationship between the

HR at VT and RCT combined (R2=0.72) and power output (PO) at VT and RCT

combined (R2=0.78) between the RGE and BSA, with the best fit line basically

equivalent to the line of identity. The conceptually simple BSA appears to be a viable

surrogate for direct measurement of VT and RCT using RGE.

iv

ACKNOWLEDGEMENT

I would like to thank Carl Foster, Scott Doberstein, and Glenn Wright for

advising me throughout this research and for being on my thesis committee. I would like

to express my deepest appreciation to Carl Foster for always promoting a stimulating

learning environment where I was able to grow as a young professional, as well as an

individual – the lessons I have learned mean so much more than what can be found on the

pages of a book. Finally, I would like to thank my family and my new ‘LEHP Family’

for all of the support and encouragement throughout this year. “Read It and Weep”.

v

TABLE OF CONTENTS

PAGE

LIST OF FIGURES………………………………………………………………………vi

INTRODUCTION…………..……………….………….…………………………..........1

Current Technology…………………………………………………………….2

Purpose…………………………………………………………………………4

METHODS……………………………………………………………...………………...6

Subjects…………………………………………………………………………6

Table 1. Descriptive characteristics of the subject population………….6

Procedures………………………………………………………………………6

STATATISTICAL ANALYSIS.…………………………………………….……………8

RESULTS……………….……….……………………………………….……….………9

DISCUSSION……………………………………………………………………………15

REFERENCES……………….………………………………………………………….18

APPENDICES…………………………………………………………………………...21

Appendix A. Informed Consent…………….………………………...……….21

Appendix B. Review of Literature…………………..…….……........………..24

vi

LIST OF FIGURES

FIGURE PAGE

1. Comparison of PO at VT between GE and BRI…………………………….….....9

2. Comparison of PO at RCT between GE and BRI………………………………..10

3. Comparison of HR at VT between GE and BRI…………………………………11

4. Comparison of HR at RCT between GE and BRI……………………………….12

5. GE PO values at VT and RCT combined………………………………………..13

6. BRI PO values at VT and RCT combined……………………………………….13

7. GE HR values at VT and RCT combined………………………………………..14

8. BRI HR values at VT and RCT combined……………………………………….14

1

INTRODUCTION

The ability to make metabolic threshold measurements has long been a reference

standard for measuring sustainable exercise capacity (McLellan & Skinner, 1981).

Measured thresholds derived from either blood lactate analysis (Karlsson & Jacobs, 1982;

Kindermann, Simon, & Keul, 1979) or respiratory gas exchange (Wasserman, Hansen,

Sue, Whipp & Casaburi, 1994; Wasserman & McIlroy, 1964) have a long history of

proven usefulness when evaluating functional capacity and developing exercise

prescriptions. Recent professional society guidelines (Mezzani, Hamm, Jones, McBride,

Moholdt, Stone, Urhausen, & Williams, 2012) suggest that threshold measurement may

be superior to the relative percent of oxygen consumption (VO2) or heart rate reserve

(HRR) that have been the gold standard for exercise prescription for a generation

(ACSM, 2010). Though a variety of methods exist to make such measurements, current

methodology requires a high level of precision and attention to detail and generally

requires equipment that is quite expensive, thus out of the range of the vast majority of

the health-fitness community, and outside the skill set of much of the clinical exercise

physiology community. A conceptually simple process, such as measuring respiratory gas

exchange, is sophisticated, as well as, time consuming.

Alternatively, the air moving into and out of the respiratory system during exercise

creates sound. Since conventional respiratory gas analysis is at least partially based on

breathing frequency and volume, it seems reasonable to suspect that analysis of breath

sounds might provide an alternative approach to direct threshold determination. Acoustic

2

analysis of breath sounds is a new, yet relatively simple technology. It has shown promise

in terms of evaluating clinical disorders such as sleep apnea. Recent studies from our

laboratory have demonstrated the promise of acoustic analysis as a surrogate to obtain

such measurements, specifically ventilatory threshold (VT) and respiratory compensation

threshold (RCT) (Foster, Yee, Stamopolous, & Nacy, 2012).

Current Technology

A plethora of data exist regarding measurement of metabolic thresholds. Methods

range in complexity, from the more simplistic, such as the Rating of Perceived Exertion

(RPE) (Eston, Davies, & Williams, 1987; Noble, & Robertson, 1996) and the Talk Test

(TT) (Foster, Porcari, Anderson, Paulson, Smaczny, Webber, Doberstein, & Udermann,

2008; Jeans, Foster, Porcari, Gibson, & Doberstein, 2011), to the technically complex,

such as measuring respiratory gas exchange using open circuit spirometry. Blood lactate

threshold (LT) and the “onset of blood lactate accumulation” (OBLA) have also been

utilized as a marker for exercise capacity (Bang, 1936; Christansen, Douglas, & Haldand,

1914; Hill, Long, & Lupton, 1924; Owles, 1930) which is more or less equivalent to

thresholds measure using respiratory gas exchange. Heart rate (HR) and the HR

performance curve have also been useful when determining threshold based functional

capacity (Pokan, Hofman, Preidler, Leitner, Dusleag, & Eber, 1993). Percent of peak

power output (PO), expressed in watts (W), also give an indication of exercise capacity

(DeKoning, Foster, Bakkum, Kloppenburg, Thiel, Joseph, Cohen, & Porcari, 2011;

Condello, Reynolds, Schnieder, Wheery, Knutson, Casolino, Doberstein, Gibson, de

Koning, & Foster, 2012).

3

Exercise tests which obtain large amounts of metabolic, ventilatory, and

circulatory data are the most widely accepted determinant of aerobic fitness (Wasserman

et al., 1994). Tests utilizing open circuit spiometry produce measurements for VT, RCT,

and max VO2 have been a long standing ‘tradition’ as the gold standard in the exercise

discipline. Despite the well-accepted role of metabolic measures, on a basis of cost, time,

and availability to the ‘normal’ population, alternative methods need be investigated,

analyzed, reproduced, and introduced into the spectrum of deriving metabolic threshold

measurements.

Respiratory gas exchange (GE), and measurements for VT and RCT, are

determined from a relatively simple analysis of pulmonary ventilation, VO2 and carbon-

dioxide production (VCO2). During exercise, an increase in the need for oxygen (O2) is

required as well as increased removal of carbon dioxide (CO2) (Wasserman et al., 1994).

Simultaneously, an increase in lung function, pulmonary circulation, cardiovascular

function, and peripheral circulation is necessary. In conjunction, total ventilation

increases, using both tidal volume and respiratory rate (West, 1990). Minute ventilation

(VE) increases at a rate appropriate to cover CO2 produced during exercise (Wasserman et

al., 1994), at least up to RCT.

Air movement during inspiration and expiration (basic breathing mechanics)

produces breath sounds, which are a conceptually simple diagnostic tool that has been

used in the field of medicine for many years (Reichert, Gass, Brandt & Andres, 2008).

Anderson et al. (2001) suggested that the human ear is able to detect such breath sounds,

both normal and abnormal. Furthermore, these breath sounds from a recording are

potentially able to distinguish potential pathological conditions. Moreover, mathematical

4

analysis of breath sounds has been shown to be clinically useful. (Anderson, Qiu,

Whittaker & Lucas, 2001).

BreathResearch Incorporated (BRI) (California, USA) is a well-established,

research based company. They have developed a strategy for acoustic analysis of breath

recordings, generated from a proprietary algorithm, which is designed to provide

information about health, fitness, and overall wellness. Seven metrics of the breath

recording are taken into account, including: rate, depth, tension, flow, variability, apnea,

and respiratory cycle. Subsequent to recording breath sounds, a “BRI” score is produced

based on these seven metrics. Breath sounds which are captured and analyzed provide

useful information about health and wellness; a conceptually simple method of analyzing

acoustics is utilized to produce such information.

Published data including the correlation of such acoustic analysis and markers of

metabolic thresholds is limited, but promising (Foster et al., 2012). Preliminary data

correlating markers of VT and RCT derived through gas exchange, have been shown to

be similar to those derived utilizing this form of acoustic analysis (Foster et al., 2012).

Increases in HR, as well as, PO were also comparable without significant differences.

However, this preliminary data was based on a study where acoustic analysis and

respiratory gas exchange measurements were derived from two separate exercise tests,

which presents an inherent limitation based on assuming that responses during different

exercise tests are the same.

Purpose

The purpose of the current study was to determine which variables derived from

acoustic analysis of breathing are related to VT and RCT thresholds as defined by

5

respiratory gas analysis. We hypothesized a combination of variables from acoustic

analysis will define VT and RCT better than any single variable. Finally, for reliability

purposes, to determine if derived variables of acoustic analysis compare to normal GE

variables, acoustic and gas analysis tests were conducted in duplicate using simultaneous

measurements.

6

METHODS

Subjects

The University of Wisconsin – La Crosse Institutional Review Board for the Protection

of Human Subjects approved this study and all subjects provided written informed

consent prior to participation. Twenty (n=20), healthy young adults; males (n=9) and

females (n=11) were recruited and preliminary measurements, such as height and weight,

were obtained. Descriptive characteristics of the subject population, subdivided by

gender, are presented in Table 1.

Table 1. Descriptive characteristics of the subject population (n=20).

Males

(n=9)

Females

(n=11)

Age (years)

21.7 ± 1.00

20.5 ± 1.43

Height (cm)

183.8 ± 7.81 166.0 ± 6.79

Weight (kg)

106.6 ± 10.67 59.6 ± 5.43

VO2 Max (ml/kg/min) 39.5 ± 7.45 39.4 ± 5.37

Values represent mean ± standard deviation.

Procedures

The subjects performed two incremental cycle ergometer exercise tests until

maximal exertion, with at least 24 hours rest between tests. Power output began at 25W

and was increased in increments of 25 W, every two minutes. Heart Rate and RPE were

recorded during the last 30 seconds of each stage using radiotelemetry and the Category

7

Ratio RPE scale (Borg, 1973; Borg, 1980), respectively. Breath recordings were captured

using a small microphone developed by BreathResearch Incorporated, inserted in a Hans

Rudolph breathing valve, allowing both GE and acoustic analysis data to be collected

simultaneously.

The acoustic analysis was digitally analyzed for breathing frequency and a

variable referred to as ‘intensity’ (obtained from the expiratory phase of the acoustic

signature, which is conceptually similar to the tidal volume divided by the expiratory

time). Independent of information about respiratory gas analysis, the acoustic signature

was analyzed based on the first derivative of change in breathing frequency and

‘intensity’ and candidates for the VT and RCT were identified.

The VT and RCT from the respiratory GE data were analyzed using conventional

markers including the v-slope and ventilator equivalents (Beaver, Wasserman, & Whipp,

1986). When the exercise time at the VT and RCT did not agree between the v-slope and

GE equivalent data, information of respiratory rate, total pulmonary ventilation and the

HR performance curve were used to rectify the data.

8

STATISICAL ANALYSIS

Comparisons of VT and RCT estimated by the acoustic analysis versus the

directly measured values based on GE were made using paired t-tests and linear

regression, with the GE value assumed to be the ‘true’ value. Comparisons of the

reproducibility of VT and RCT, based on GE and on acoustic analysis, were made using

paired t-tests and intraclass correlations (ICC). Statistical significance was accepted when

p<0.025, with Bonferroni correction for multiple t-tests. All analyses were conducted

using the Statistical Package for the Social Sciences (SPSS, Version 19; SPSS Inc.,

Chicago, IL.)

9

RESULTS

The comparison of PO at VT between GE and BRI is presented in Figure 1. The

PO achieved at VT was not significantly different (p=0.077) between GE (105±37) and

BRI (111±30). The effect size (0.28) suggests very small differences between GE and

BRI. The correlation between PO at VT between GE and BRI was (r=0.849). The results

suggest no meaningful difference for PO at VT between GE and BRI.

y = 0.6484x + 43.419R² = 0.639

0

50

100

150

200

250

300

0 50 100 150 200 250 300

PO

Bre

ath

Re

sear

ch In

c.

PO Gas Exchange

Power Output - VT

Figure 1. Comparison of PO at VT between GE and BRI.

The comparison of PO at RCT between GE and BRI is presented in Figure 2. The

PO at RCT was significantly different (p=0.004) between GE (174±40) and BRI

(162±34). The effect size (0.50) suggests only moderate differences between GE and

BRI. The correlation between PO at RCT between GE and BRI was (r=0.796). Despite

10

the statistical differences in the mean values, the results suggest no meaningful difference

for PO at RCT between GE and BRI.

y = 0.6868x + 42.598R² = 0.6343

0

50

100

150

200

250

300

0 50 100 150 200 250 300

PO

Bre

ath

Re

sear

ch In

c.

PO Gas Exchange

Power Output - RCT

Figure 2. Comparison of PO at RCT between GE and BRI.

The comparison of HR at VT between GE and BRI is presented in Figure 3. The

HR at VT was significantly different (p=0.006) between GE (114±14) and BRI (119±11).

The effect size (0.56) suggests moderate differences between GE and BRI. The

correlation between HR at VT between GE and BRI was (r=0.745). Despite significantly

different mean values, the results suggest no meaningful difference for HR at VT

between GE and BRI.

11

y = 0.6131x + 48.575R² = 0.5554

50

75

100

125

150

175

200

50 75 100 125 150 175 200

HR

Bre

ath

Res

earc

h In

c.

HR Gas Exchange

Heart Rate - VT

Figure 3. Comparison of HR at VT between GE and BRI.

The comparison of HR at RCT between GE and BRI is presented in Figure 4. The

HR at RCT was significantly different (p=0.005) between GE (148±16) and BRI

(142±14). The effect size (0.33) suggest small differences between GE and BRI. Despite

significant differences in the mean values, the correlation between HR at RCT between

GE and BRI was (r=0.664). The results suggest no meaningful difference for HR at RCT

between GE and BRI.

12

y = 0.5645x + 58.386R² = 0.4408

50

75

100

125

150

175

200

50 75 100 125 150 175 200

HR

Bre

ath

Re

sear

ch In

c.

HR Gas Exchange

Heart Rate - RCT

Figure 4. Comparison of HR at RCT between GE and BRI.

Estimates of the reliability of HR and PO for GE and BRI are presented in Figures

5-8. The ICC based on Cronbach’s Alpha (VT and RCT combined) was (0.811)

(p=0.626) for HR and (0.906) (p=0.861) for PO combined for GE and (0.755) (p=0.948)

for HR and (0.920) (p=0.640) for PO combined for BRI.

13

y = 0.7474x + 36.043R² = 0.6951

0

50

100

150

200

250

300

0 50 100 150 200 250 300

Test

2

Test 1

Gas Exchange - Power OutputVT & RCT

Figure 5. GE PO values at VT and RCT combined, Test 1 vs Test 2.

y = 0.7339x + 38.001R² = 0.7456

0

50

100

150

200

250

300

0 50 100 150 200 250 300

Test

2

Test 1

BreathResearch Inc. - Power OutputVT & RCT

Figure 6. BRI PO values at VT and RCT combined, Test 1 vs Test 2.

14

y = 0.7471x + 31.844R² = 0.469

80

100

120

140

160

180

200

80 100 120 140 160 180 200

Test

2

Test 1

Gas Exchange - Heart RateVT & RCT

Figure 7. GE HR values at VT and RCT combined, Test 1 vs Test 2.

y = 0.6545x + 45.153R² = 0.37

80

100

120

140

160

180

200

80 100 120 140 160 180 200

Test

2

Test 1

BreathResearch Inc. - Heart RateVT & RCT

Figure 8. BRI PO values at VT and RCT combined, Test 1 vs Test 2.

15

DISCUSSION

The primary purpose of this study was to determine whether variables derived

from acoustic analysis of breath sounds could be used as surrogates of VT and RCT,

defined by respiratory gas analysis. An additional purpose of this study was to determine

if acoustic analysis was a reliable method of obtaining metabolic threshold

measurements. This was done by comparing a newly developed, proprietary acoustic

analysis of breathing sounds with the gold standard technique of respiratory GE using

open circuit spirometry. There was a tendency for the acoustic analysis to slightly

overestimate both HR and PO at VT, and slightly underestimate both HR and PO at RCT.

However, despite statistically significant differences, the small magnitude of the

differences in mean values and strong correlations between acoustic analysis and

respiratory gas analysis suggests no meaningful difference between VT and RCT

determined via acoustic analysis and respiratory gas exchange.

Comparable data to this study are limited. The results agree generally with

preliminary data which correlated to markers of VT and RCT derived through gas

exchange to those derived utilizing an earlier version of the acoustic analysis algorithm

(Foster et al., 2012). In the previous study, measurements were derived from two separate

exercise tests, which represent an inherent limitation, requiring the assumption that

responses during different exercise tests are the same. In that earlier study, exercise was

performed on fitness industry ergometers, which are inherently less accurate and reliable

than the laboratory ergometer used in this study.

16

The conceptual basis of BRI is sound intensity, which effectively represents the

Tidal Volume/expiratory time. Since the Tidal Volume increases rapidly at the beginning

of exercise, and then slowly throughout the remainder of incremental exercise bouts

(Davis, Whipp, & Wasserman, 1980), and expiratory time is probably getting smaller

over a bout of incremental exercise, the logic of the BRI approach is reasonable. The

current acoustic analysis technique did not allow for acceptable direct measurement of

expiratory time in simultaneous measurements. Some ‘extraneous sounds’, caused by the

microphone being inside the breathing valve, made interpretation of the breath recordings

more difficult. Follow up experiments, which are currently underway, may give better

estimates of the magnitude of decrease in expiratory time. Perhaps simultaneous

collection of measurements may not have been the best method. This caused difficulty

with the BRI approach which was developed using an independent microphone. Further

studies may yield advances in the BRI algorithm.

It is suggested that further research using acoustic analysis be conducted, with

special attention to reproducibility and reliability and to making measurements of

changes in inspiratory and expiratory time, data which is not in the literature. Tests

utilizing the methods, during independent, well controlled exercise tests may provide

easier analysis of acoustic recordings. Further, other elements of the acoustic analysis that

BRI routinely uses with analysis of resting breathing recordings may prove of interest.

Experimentation with stage length should also be investigated. Shorter exercise stages

may yield a clearer demarcation of the phases of the respiratory cycle. Conventionally, it

is believed that VT is better detected utilizing a shorter protocols (Wasserman, Hansen,

Sue, & Whipp, 1987). We chose to use longer stages, on the premise that more nearly

17

steady state conditions would be achieved. However, a more ramp like procedure might

yield better results.

The data support the concept that a simple analysis of breath sounds during

exercise can provide a reasonable surrogate of physiologic threshold events measured

using state of the art GE technology. As such, the acoustic analysis may provide a

simpler method for making threshold measurements, which may be useful both

diagnostically and for exercise prescription.

18

REFERENCES

American College of Sports Medicine. (2010). Guidelines for exercise testing and

prescriptions. 8th ed. Philadelphia. (PA): Lippincott Williams and Wilkins.

Anderson, K., Qiu, Y., Whittaker, A. R., & Lucas, M. (2001). Breath sounds, asthma, and

the mobile phone.The Lancet, 358 (9290), 1343-1344.

Bang, O. (1936). The lactate content of the blood during and after muscular exercise in

men. Skandivica Archives of Physiology Supplement. 10: 51-82.

Beaver, W.L., Wasserman, K., & Whipp, B.J. (1986). A new method for detecting the

anaerobic threshold by gas exchange. Journal of Applied Physiology. 60: 2020-

2027.

Borg, G. (1980). A category scale with ratio properties for intermodal and interindividual

comparisons. Proceedings of the 22nd

International Congress of Psychology.

Leipzig; VEB Deutscher Verlag.

Borg, G.A.V. (1973). Perceived exertion: a note on `history’ and methods. Medicine and

Science in Sports. 5: 90-93.

Christansen, J., Douglas, C.G., & Haldand, J.S. (1914). The absorption and dissociation

of carbon dioxide of human blood. Journal of Physiology (London). 48: 244-271.

Condello, G., Reynolds, E., Schnieder, A., Wheery, E., Knutson, M., Casolino, E.,

Doberstein, S., Gibson, M., de Koning, J.J., & Foster, C. (2012). A simplified

approach for estimateing VT and RCT. Medicine & Science in Sports &

Exercise. 44: 2416.

Davis, J.A., Whipp, B.J., & Wasserman, K. (1980). The relation of ventilation to

metabolic rate during moderate exercise in man. Journal of Applied Physiology.

44: 97-108.

DeKoning, J. J., Foster C., Bakkum A., Kloppenburg S., Thiel C., Joseph T., Cohen J., &

Porcari J. P., (2011). Regulation of pacing strategy during athletic

competition. PLoS ONE, 6(1), 1-5. doi: 10.1371/journal.pone.0015863

Eston, R.G., Davies, B.L., & Williams, J.G. (1987). Use of perceived effort ratings to

control exercise intensity in young healthy adults. European Journal of Applied

Physiology and Occupational Physiology. 56 (2): 222-224.

19

Foster C, Yee NB, Stamopoulos C, Nacy G., (2012). Breath sound analysis as a surrogate

for gas exchange measurement of ventilatory and respiratory compensation

thresholds. Proceedings European College of Sports Science 17: 58.

Foster, C., Porcari, J.P., Anderson, J., Paulson, M., Smaczny, D., Webber, H., Doberstein,

S., & Udermann, B. (2008). The talk test as a marker of exercise training

intensity. Journal of Cardiopulmonary Rehabilitation & Prevention. 28 (1): 24-

30.

Jeans, EA, Foster, C, Porcari, JP, Gibson, M, and Doberstein, S. (2011). Translation of

exercise testing to exercise prescription using the talk test. Journal of Strength

and Conditioning Research. 25(3): 590-596.

Hill, A.V., Long, C.N.H., & Lupton, H. (1924). Muscular exercise, lactic acid and the

supply and utilization of oxygen: Part VI. The oxygen debt at the end of exercise.

Proceedings of the Royal Society of London. 97: 127-137.

Karlsson, J., & Jacobs, I. (1982). Onset of blood lactate accumulation during muscular

exercise as a threshold concept: Theoretical considerations. International Journal

of Sports Medicine. 3: 190-201.

Kindermann, W., Simon, G., & Keul, J. (1979). The significance of the aerobic-anaerobic

transition for the determination of work load intensities during endurance training.

Europoean Journal of Applied Physiology. 42: 25-34.

McLellan, T.M., & Skinner, J.S. (1981). The use of the aerobic threshold as a basis for

training. Canadian Journal of Applied Sport Sciences. 6: 197-201.

Mezzani, A., Hamm, L.F., Jones, A.M., McBride, P.E., Moholdt, T., Stone, J.A.,

Urhausen, A., & Williams, M.A. (2012). Aerobic exercise intensity assessment

and prescription in cardiac rehabilitation. Journal of Cardiopulmonary

Rehabilitation and Prevention. 32: 327-350.

Noble, B.J., & Robertson. (1996). Perceived Exertion. Champaign, IL; Human Kinetics.

pp. 4-5, 61-77.

Owles, W.H. (1930). Alterations in the lactic acid content of the blood as a result of light

exercise and associated changes in the CO2 combining power of the blood and in

the alveolar CO2 pressure. Journal of Physiology. 69: 214-237.

Pokan, R., Hofman, P., Preidler, K., Leitner, H., Dusleag, J., Eber, et al. (1993).

Correlation between inflection of heart rate/work performance curve and

myocardial function in exhausting cycle ergometer exercise. European Journal of

Applied Physiology. 67: 385-388.

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Reichert, S., Gass, R., Brandt, C., & Andres, E. (2008). Analysis of respiratory sounds:

State of the art.Clin Med: Circ Respirat Pulm Med. 2: 45-58.

Wasserman, K., Hansen, J. E., Sue, D. Y., Whipp, B. J., & Casaburi, R.

(1994). Principles of exercise testing and interpretation. 2: 2, 36, 96.

Wasserman, K., Hansen, J.E., Sue, D.Y., & Whipp, B.J. (1987). Principles of exercise

testing and interpretation. Philadelphia: Lea & Febiger.

Wasserman, K., & McIlroy, M.B. (1964). Detecting the threshold of anaerobic

metabolism. American Journal of Cardiology. 14: 844-852.

West, J. B. (1990). Ventilation. Respiratory Physiology. 4: 11-20.

APPENDIX A

INFORMED CONSENT

22

INFORMED CONSENT FOR “Acoustic Analysis as a Surrogate for Gas

Exchange”

1. I, ______________________, give my informed consent to participate in this

study designed to evaluate the validity of acoustic analysis as a

reliable/reproducible surrogate for gas exchange when determining metabolic

thresholds of exercise, and in turn verify its reliability as a test for prescribing

exercise. As a participant in this study, I understand that I will be in the Human

Performance Lab on two separate occasions for approximately 45 minutes each

session to complete the two separate exercise tests. I have been informed that the

study is under the direction of Carl Foster, Ph.D. who is a Professor in the

Department of Exercise and Sport Science at the University of Wisconsin-La

Crosse. I consent to the presentation, publication and other release of summary

data from the study, which is not identifiable with myself.

2. I have been informed that there are two phases of the overall study. In both

phases, I will be required to perform a maximal incremental exercise test on a

cycle ergometer, while my breathing will be monitored from a scuba-like

mouthpiece, and my heart rate is monitored from a chest strap. Every two

minutes, the principle investigator will increase the resistance on the bicycle, and

I will be asked how hard I am working using a rating of perceived exertion scale

(RPE). This will continue until I have reached my maximum exercise potential. I

also understand that during these tests a recording of my breathing will be taken

for analysis.

3. I have been informed that during these two exercise tests, there are no risks to me

as a participant other than the fatigue normally associated with high intensity

exercise. I may also find the scuba-like mouthpiece used to monitor my breathing

to be an inconvenience, however it will not cause me any harm.

4. The primary benefit of this study is to determine if variables derived from my

breath sounds can be correlated to different threshold measurements taken

through respiratory gas exchange conventionally. RPE and heart rate will be

recorded as a basis, as they are shown to be reproducible among individuals from

one test to the next; as well as correlate with VO2 Max test measurements (RPE,

heart rate, and metabolic respiratory responses). If this can be shown, a new –

simplistic - method of potentially determining metabolic thresholds may be

studied further.

5. I have been informed that the investigators will answer questions regarding the

procedures throughout the course of the study.

23

6. I have been informed that I am free to decline participation, or to withdraw from

the study at any time without penalty.

7. Concerns about any aspects of this study may be referred to Dr Carl Foster (608

785 8687). Questions about the protection of human subjects may be addressed to

Dr Bart Vanvoorhis (608 785 6892), Chair of the UW-L Institutional Review

Board for the protection of human subjects.

Investigator: _______________________

Subject (Print Name): _______________________ Subject Signature:

_____________________________

Date: _________________

I have observed the informed consent process for this subject and am writing my name

below to signify that I believe that the subject understands the nature of the study and the

risks that they are being asked to assume.

Witness: __________________________

APPENDIX B

REVIEW OF LITERATURE

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REVIEW OF LITERATURE

The purpose of this document is to review the literature concerning an innovative

proposed method to determine metabolic threshold measurements, such as ventilatory

threshold (VT) and respiratory compensation threshold (RCT), by using acoustic analysis

of breath sounds as a surrogate.

Current Methodology

A plethora of data exists regarding measurement of metabolic thresholds.

Methods range in complexity, from the more simplistic, self-reported, and subjective,

such as the Rate of Perceived Exertion (RPE) scale and the Talk Test (TT). To the

technically complex, objective, such as heart rate (HR), maximal oxygen consumption

(VO2max), heart rate reserve (HRR), and respiratory gas exchange. Blood lactate threshold

(LT) and the “onset of blood lactate accumulation” (OBLA) have been utilized as a

marker for exercise capacity (Bang, 1936; Christansen, Douglas, & Haldand, 1914; Hill,

Long, & Lupton, 1924; Owles, 1930). HR and HRR, as it relates to oxygen (O2) uptake

kinetics, have also been useful when determining functional capacity in exercise. Power

output (PO) and percent peak power output, which is expressed in watts (W), also give

one an indication of exercise capacity (DeKoning, 2012).

Exercise tests which obtain large amounts of metabolic, ventilatory, and

circulatory data are the most widely accepted determinant of aerobic fitness (Wasserman,

26

Hansen, Sue, Whipp & Casaburi, 1994). Tests utilizing open circuit spiometry produce

measurements for VT, RCT, and VO2max have been a long standing ‘tradition’ in

the exercise discipline. Respiratory gas exchange, and measurements for VT and RCT, is

determined from a relatively simple analysis of VO2 and carbon-dioxide production.

Analyzers measuring O2 and CO2 can be calibrated to produce a highly accurate

measurements, which also yields accurate measures for VO2/VCO2 (Meckel, 2002).

Mechanics of Breathing

The process of breathing is self-sustaining, involuntary and voluntary, and can be

influenced by many factors. Behavior factors influencing breathing include: crying,

laughing, coughing, whistling, singing, and talking (Meckel, 2002; Shea, 1996).

However, the ultimate function of ventilation, both at rest and during exercise, is O2

demand, delivery and utilization, as well as, CO2 removal and disposal (Meckel, 2002).

During exercise, an increase in need for O2 is required (depending on work rate)

as well as increased removal of CO2 (Wasserman et al., 1994). Simultaneously, an

increase in lung function, pulmonary circulation, cardiovascular function, and peripheral

circulation is necessary. In conjunction, total ventilation – which can be measured from

the CO2 present in the expired air – is required to increase accordingly (West, 1990). In

addition, minute ventilation (VE) increases at a rate appropriate to cover CO2 produced

during exercise (Wasserman et al., 1994).

Acoustic Analysis

Air movement, which theoretically is the process of inspiration and expiration,

produces breath sounds, a conceptually simple diagnostic tool that has been used mainly

27

in the field of medicine (Reichert, Gass, Brandt & Andres, 2008). Commonly heard

through the chest wall with the assistance of a stethoscope, different breath sounds can be

heard and distinguished as normal or abnormal, leading to a diagnostic criterion for

pulmonary or respiratory obstructions and diseases.

Anderson et al. (2001) have suggested that the human ear is able to detect such

breath sounds, normal as well as abnormal in a study which concluded the ability to

distinguish asthmatics from non-asthmatics simply based on key sound differences heard

among subjects’ breath recording. The use of a small microphone in a mobile telephone

allowed for recording of breath sounds in a voicemail which were then analyzed and

notably disguisable. Furthermore, a study conducted by Reichert et al. (2008) initiated

that recording and analyzing breath sounds enhanced the understanding of certain

respiratory sounds linked to pathologies.

BreathResearch Incorporated (California, USA) is a well-established, research

based company which utilizes such analyses of breath sounds. Acoustic analysis of breath

recordings, generated from a proprietary algorithm, provides information about health,

fitness, and overall wellness. Seven metrics of the breath recording are taken into

account, including: rate, depth, tension, flow, variability, apnea, and respiratory cycle.

Subsequent to recording breath sounds, a “BRI” score is produced based on these seven

metrics. Breath sounds which are captured and analyzed then provide useful information

about health and wellness; a technically sophisticated, yet conceptually simple, method of

analyzing acoustics is utilized to produce such information.

Published data including the correlation of such acoustic analysis and markers of

metabolic thresholds does not exist, consequently making this study extraordinarily

28

unique. Preliminary results from a pilot study correlated markers of VT and RCT derived

through gas exchange to those found through acoustic analysis and Digital Signal

Processing (DSP) (Foster, Yee, Stamopoulous, Nacy, 2012). An increase in HR and PO

were also comparable, without significant differences, to ensure reproducibility of test

results between the individual subjects. The protocol consisted of subjects performing

two incremental cycle ergometer exercise tests where, during the first, gas exchange

measures were obtained, and, during the second, breath sounds were recorded using a

small microphone with a recording application on an Apple device. On-going data results

correlating Threshold 1 (T1) and Threshold 2 (T2) markers of acoustic analysis are

comparable to those marked during respiratory gas exchange analysis as VT and RCT,

respectively.

The variables contained in the analysis of breath sounds, relevant to produce

comparable data, seem to be duration and intensity of each breath stage at T1 and T2.

Combined variables, such as inhalation/exhalation duration ratio and

inhalation/exhalation intensity ratio, prove useful when analyzing such information and

also allocate a more precise analysis. Generally, it is important to know where the

capacity of the O2 is maximized within a breath cycle (i.e. right after inhalation, right

before exhalation etc).

Validity

Imperative to support this innovative method of acoustic analysis is to test validity

by reproducibility and reliability; similar to testing other simplistic, subjective, self-

reported measurements to guide exercise – such as RPE and the TT. In studies testing the

reliability of such subjective methods, it is best to objectively measure intensity as well

29

(Zanettini et al., 2012). Likewise, and relative to this purposed surrogate, objective

measurements such as HR, RPE, and gas exchange measurements will be taken

simultaneously.

30

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Christansen, J., Douglas, C.G., & Haldand, J.S. (1914). The absorption and dissociation

of carbon dioxide of human blood. Journal of Physiology (London). 48: 244-271.

DeKoning, J. J., Foster C., Bakkum A., Kloppenburg S., Thiel C., Joseph T., Cohen J., &

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Hill, A.V., Long, C.N.H., & Lupton, H. (1924). Muscular exercise, lactic acid and the

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