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Physiotherapy 93 (2007) 30–36

Preliminary investigations into the effects of breathing retrainingtechniques on end-tidal carbon dioxide measures in patients

with asthma and healthy volunteers during a singletreatment session

Anne Bruton a,∗, Mary Armstrong a, Claire Chadwick a,Denise Gibson a,b, Kate Gahr a

a School of Health Professions and Rehabilitation Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UKb Physiotherapy Department, Southampton University Hospital Trust, Tremona Road, Southampton SO16 6YD, UK

bstract

bjectives Preliminary investigations into the physiological effects of breathing retraining techniques in order to establish the feasibility ofhe proposed methodology, produce data for power calculations and determine the potential for future research in this area.esign Two preliminary, exploratory studies with an experimental design.etting Research laboratories.articipants Study 1: 15 patients with mild to moderate asthma and nine healthy volunteers. Study 2: 15 healthy volunteers.nterventions Physiological data from asthma patients and healthy volunteers were recorded before, during and after a single session oflow breathing and breath holds. A separate group of healthy participants carried out the slow breathing technique with and without visualiofeedback.utcome measures The primary outcome was end-tidal carbon dioxide (ETCO2), and the secondary outcomes were respiratory rate, pulse

ate, oxygen saturation and lung function.esults All groups showed an increase in ETCO2 from baseline during slow breathing. Study 1 found a mean rise in ETCO2 of 0.48 kPa

95% confidence interval (CI) 0.28–0.68] for healthy participants and 0.46 kPa (95% CI 0.29–0.63) for asthma patients. In healthy volunteers,TCO2 stayed above baseline for 5 minutes after the intervention. ETCO2 rose minimally (mean 0.06 kPa) in both groups after breath holds.tudy 2 found a mean rise in ETCO2 of 0.35 kPa (95% CI 0.09–0.60) during slow breathing with visual feedback, and 0.36 kPa (95% CI.13–0.60) during slow breathing without visual feedback.onclusions The results of these preliminary studies provide data to power larger studies. They suggest that ETCO rises during slow

2

reathing in both asthma patients and healthy volunteers, and that this effect may persist beyond the intervention itself in healthy volunteers.he use of visual biofeedback had no effect on ETCO2 in healthy volunteers.2006 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

eywords: Carbon dioxide; Asthma; Breathing retraining; Biofeedback

ta

ntroduction

Patients with hyperventilation symptoms are frequentlyeferred to physiotherapists for breathing retraining. One ofhe physiological hypotheses underpinning this practice is

∗ Corresponding author. Tel.: +44 23 8059 5283; fax: +44 23 8059 5303.E-mail address: ab7@soton.ac.uk (A. Bruton).

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031-9406/$ – see front matter © 2006 Chartered Society of Physiotherapy. Publisoi:10.1016/j.physio.2006.07.006

hat such patients either have lower levels of carbon dioxide orre more sensitive to carbon dioxide than healthy individuals1]. Although this theory has been accepted by many clini-ians, there is very little evidence to support it at the present

ime. Equally, there is little evidence that raising carbon diox-de has any beneficial effect on people with hyperventilationymptoms. However, it is often claimed that altering thereathing pattern will raise an individual’s carbon dioxide

hed by Elsevier Ltd. All rights reserved.

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evels, and that this somehow leads to ‘de-sensitisation’ toarbon dioxide and hence reduces the sensation of breath-essness [2]. The evidence for change in carbon dioxides a potential mechanism for breathing retraining has beeneviewed recently by one of the authors [3].

Biofeedback has been defined as any technique that,ia the provision of information, can increase the abilityf an individual to control or voluntarily alter physiologi-al activity [4]. Biofeedback has been used to treat asthmand some psychological disorders that can affect respiration5,6]. It is not known if the use of visual biofeedback hasny effect on an individual’s ability to alter carbon dioxideevels.

This paper presents the results of two related preliminarytudies. Study 1 investigated the effects of a single sessionf breathing retraining on end-tidal carbon dioxide (ETCO2)n patients with asthma and healthy volunteers, and Study

explored the effect of using visual feedback to encourageaising ETCO2 during a session of slow breathing in healthyolunteers.

esearch governance

Ethical approval for Study 1 was gained from theouthampton and South West Hants Local Research Ethicsommittee, and the Internal Ethics Committee of the Schoolf Health Professions and Rehabilitation Sciences grantedthical approval for Study 2. The studies were also regis-ered with the Research and Development Departments atouthampton University Hospitals National Health Servicerust and the University of Southampton.

ethods

esign

The studies were designed to test the feasibility of theethodology, produce some data for future power calcula-

ions, and establish the potential for further research in thisrea. They were therefore uncontrolled exploratory studiesith an experimental design.

etting

Study 1 was performed in the Wellcome Trust Clinicalesearch Facility at Southampton General Hospital. Studywas undertaken in the Human Performance Laboratory,

chool of Health Professions and Rehabilitation Sciences,niversity of Southampton.

ample size

As these were preliminary studies, formal power calcula-ions were not appropriate. A convenience sample of 10–20

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py 93 (2007) 30–36 31

articipants per group was therefore deemed appropriate.uring the period of data collection, 15 asthma partici-ants and nine healthy volunteers completed Study 1, and5 healthy volunteers completed Study 2.

articipants

Eligible asthma participants were those aged 18–65 yearsith a clinical diagnosis of mild to moderate asthma for at

east 1 year (based on Global Initiative for Asthma guide-ines [7]). Participants were recruited via asthma chari-ies, research volunteer databases, newspaper advertisementsnd posters. Exclusion criteria for the asthma group weres follows: exacerbation of asthma symptoms, respiratoryract infection and/or change in medication within 4 weeksf data collection; an uncontrolled or current exacerba-ion of allergic rhinitis as evidenced by current medica-ion and/or history of an exacerbation within 4 weeks ofata collection; previous instruction in breathing retrain-ng; other significant uncontrolled medical condition; andn inability to breathe comfortably through the nose withhe mouth closed. Eligible healthy participants were aged8–65 years and were recruited via posters and adver-isements. Exclusion criteria for healthy volunteers weres follows: known respiratory or cardiac disorder; previ-us instruction in breathing retraining; and an inabilityo breathe comfortably through the nose with the mouthlosed.

quipment and outcome measures

The primary outcome measure was ETCO2. Although its recognised that arterial blood gas analysis is the gold stan-ard for measurement of gas composition in arterial blood, itas felt too invasive for this study and could itself cause anx-

ety and hyperventilation. ETCO2 is regarded as equivalento arterial carbon dioxide in normal resting subjects with noentilation/perfusion mismatch and in mild to moderate asth-atics [8]. During the interventions, ETCO2 was recorded

sing continuously sampled expired air (4 second epoch) byBCI Sleep Capnocheck® (Smiths Medical, London, UK).his is a portable capnograph capable of recording physiolog-

cal data continuously for several hours; the data can then beransferred to a computer for further analysis. The companypecifications state the response time to be 375 millisecondsto 90% of value) and the accuracy to be ±0.3 kPa in a rangerom 0 to 13.3 kPa. Expired air was sampled via oronasalannulae. Peripheral haemoglobin oxygen saturation (SpO2),espiratory rate and heart rate were also recorded by theapnograph.

Other outcome measures were spirometric lung functionests, i.e. forced expiratory volume in one second (FEV1),orced vital capacity (FVC) and peak expiratory flow (PEF),easured using a Vitalograph portable spirometer (Alpha III,italograph Ltd., Buckingham, UK).

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rotocol for Study 1 (single breathing retrainingession)

Prior to data collection, participants were given the oppor-unity to ask questions before signing a consent form.aseline data were collected, consisting of demographic andnthropometric data, i.e. age, gender, height, weight; medicalistory; current medication; the Nijmegen hyperventilationuestionnaire, which scores from 0 to 64 and a score of ≤23s deemed positive [9]; the Hospital Anxiety and Depressionuestionnaire, which scales anxiety and depression from 0

o 21, a score of ≤8 is deemed significant and a score of11 is deemed highly significant [10]; and baseline spiro-etric lung function tests, i.e. FEV1, FVC and PEF. Asthma

articipants also completed the Mini Asthma Quality of Lifeuestionnaire which scores from 1 to 7 (1 indicating gooduality of life) [11], and the Asthma Control Questionnairehich scores from 0 to 6 (0 being maximum control) [12].Participants were then seated in a comfortable chair in

quiet room and instrumented with an infrared absorptionaturation probe on the index finger of the non-dominantand and nasal cannulae. After resting quietly for 10 minutes,aseline measures of respiratory rate, pulse rate, SpO2 andTCO2 were recorded over a period of 5 minutes. Participantsere then taught one of the breathing techniques (see Inter-entions section) by a clinical specialist physiotherapist, therder being determined by the selection of a sealed envelope.nce the physiotherapist felt that this technique had beenastered, participants rested for a further 5 minutes before

hysiological recordings were repeated to ensure return toaseline measures. The participant was then asked to performhe breathing technique, and physiological recordings were

ade continuously during the intervention and for 5 minutesfterwards. The physiotherapist gave additional instructionss required during the intervention. Lung function tests werehen repeated. Participants rested for another 10 minutes orntil physiological readings had returned to baseline. Thehole process was then repeated for the second breathing

echnique.

rotocol for Study 2

Healthy volunteers attended the Human Performance Lab-ratory at the School of Health Professions and Rehabilitationciences, University of Southampton. After signing a consentorm, baseline demographic, anthropometric and lung func-ion data were collected. Participants were taught the slowreathing technique. They were assigned to one of two groupslternately. In one group, each participant carried out the slowreathing intervention initially without visual feedback, thenith feedback. In the other group, the order was reversed.

articipants remained seated and were instrumented with thexygen finger probe and ETCO2 sensor whilst baseline dataalues were collected. The two conditions, i.e. with feedbacknd without feedback, were then described and demonstrated.

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py 93 (2007) 30–36

articipants were instructed to slow breathe for 3–5 minutesnder the first condition assigned whilst physiological dataere recorded. They then rested until values returned to base-

ine before slow breathing under the other condition.

nterventions

The two breathing retraining techniques used in Study 1ere controlled breath holds and slow breathing. Both tech-iques were carried out in a relaxed sitting position. Theontrolled breath holds required the breath hold to be car-ied out at the end of a tidal breath (at end expiratory lungolume) and maintained until the first sensation of breathingiscomfort, or desire to breathe, was felt. The interventiononsisted of three controlled breath holds with a 1-minuteest period between breath holds. Slow breathing was used inoth studies and required the participant to reduce breathingrequency as much as possible for a period of 3–5 minutes (asolerated). In Study 1 alone, participants were instructed toim to take less than 8 breaths/minute. No attempt was madeo control volume in either study. The ‘with feedback’ condi-ion in Study 2 required participants to look at the capnographcreen and to try to get the ETCO2 displayed number to gos high as possible by slowing their breathing. The ‘withouteedback’ condition required the participants to face awayrom the capnograph, so that none of the screen display wasisible.

ata analysis

All data were entered into SPSS for Windows (Version 12)or analysis. Inferential statistics were not appropriate as thetudies were preliminary and no a priori power calculationsad been performed.

Descriptive statistics have been used to describe partic-pants’ data before, during and after the interventions. Barraphs and box and whisker plots have been used to illustratehe primary outcome data.

esults

tudy 1

Table 1 shows the summarised anthropometric and ques-ionnaire data for the participants. On average, the asthmaatients were 10 years older than the healthy participants andad higher scores for anxiety and hyperventilation, but theseid not reach the threshold of clinical significance. Table 2hows the summarised baseline lung function and physiologi-

al data. Lung function and physiological data were similar inhe asthma and healthy groups. Table 3 shows the summarisedhysiological data during and after breathing interventions.igs. 1 and 2 visually depict the summarised ETCO2 data.

A. Bruton et al. / Physiotherapy 93 (2007) 30–36 33

Table 1Anthropometric and questionnaire data from Study 1: mean (standarddeviation)

Healthy (n = 9) Asthma (n = 15)

Age (years) 32 (11.3) 42 (13.3)Gender (M/F) 3/6 7/8Height (m) 1.68 (0.08) 1.70 (0.08)Weight (kg) 69.1 (11.1) 75.9 (10.4)Body mass index 25 (2.7) 26 (3.1)HAD anxiety score 6 (2.7) 7 (4.7)HAD depression score 0.9 (0.6) 1.6 (1.4)Nijmegen score 7 (4.9) 15 (6.9)Mini AQLQ NA 6.2 (0.5)ACQ NA 0.5 (0.5)

HAD: Hospital Anxiety and Depression; Mini AQLQ: Mini Asthma Qual-ity of Life Questionnaire; AQG: Asthma Control Questionnaire; NA: notapplicable.

Table 2Baseline lung function and physiology data from Study 1: mean (standarddeviation)

Healthy (n = 9) Asthma (n = 15)

FEV1 (l) 3.22 (0.46) 3.28 (0.79)FEV1% predicted 99.40 (14.43) 97.27 (15.79)FVC (l) 4.03 (0.58) 4.28 (0.79)FVC % predicted 106.80 (16.18) 106.67 (13.41)FEV1%FVC 81 (5.41) 77 (6.61)PEF (l/minute) 484 (64.22) 509 (95.21)PEF % predicted 110 (11.42) 105 (16.90)Baseline maximal breath

hold time (seconds)28 (14.01) 30 (7.37)

Baseline end-tidal CO2

(kPa)5.21 (0.88) 5.48 (0.50)

Baseline respiratory rate(breaths/minute)

14 (4.04) 13 (3.52)

Baseline SpO2 (%) 96.30 (1.02) 95.84 (1.59)Baseline pulse rate

(beats/minute)71 (11.69) 69 (11.26)

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Fig. 1. End-tidal CO2 before, during and after the slow breathing interven-tion in Study 1.

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pf

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EV1: forced expiratory volume in 1 second; FVC: forced vital capacity;EF: peak expiratory flow; SpO2: peripheral haemoglobin oxygen satura-

ion.

TCO2 rose in both groups during the slow breathing inter-

ention, and remained slightly elevated during the 5 minutesf normal breathing after the intervention in healthy volun-eers. ETCO2 was negatively correlated with respiratory ratehroughout the study (Pearson’s r = 0.63 in asthma partici-

hi

able 3hysiological data during and after breathing interventions from Study 1: mean (sta

Healthy (n = 9)

During slowbreathing

After slowbreathing

Afho

nd-tidal CO2 (kPa) 5.70 (0.94) 5.36 (0.83)espiratory rate (breaths/minute) 7 (1.4) 14 (4.9) 1pO2 (%) 96.3 (1.4) 96.4 (0.8) 9ulse rate (beats/minute) 69 (11.3) 72 (12.1) 7EV1 N/A 3.23 (0.45)EF N/A 490 (79.21) 49

EV1: forced expiratory volume in 1 second; PEF: peak expiratory flow; SpO2: per

ig. 2. End-tidal CO2 before and after the controlled breath hold interventionn Study 1.

ants, 0.47 in healthy participants). ETCO2 rose minimallyollowing breath holds in both groups.

tudy 2

Table 4 shows the summarised baseline data for the 15ealthy volunteers in Study 2. Table 5 summarises the phys-ological data during slow breathing, with and without the

ndard deviation)

Asthma (n = 15)

ter breathlds

During slowbreathing

After slowbreathing

After breathholds

5.27 (0.63) 5.94 (0.57) 5.45 (0.54) 5.55 (0.50)5 (4.7) 6 (1.6) 13 (2.9) 13 (2.6)4.6 (5.9) 96.0 (1.5) 95.9 (1.5) 95.4 (1.0)3 (11.9) 70 (12.1) 69 (10.8) 70 (9.7)3.21 (0.40) N/A 3.29 (0.77) 3.30 (0.76)2 (92.70) N/A 507 (88.60) 509 (85.43)

ipheral haemoglobin oxygen saturation.

34 A. Bruton et al. / Physiotherapy 93 (2007) 30–36

Table 4Baseline data from Study 2: mean (standard deviation)

Healthy (n = 15)

Age (years) 28 (5.4)Gender (M/F) 1/14Height (m) 1.66 (0.09)FEV1 (l) 3.42 (0.46)FVC (l) 4.00 (0.67)FEV1%FVC 86.00 (7.88)

FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity.

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ig. 3. End-tidal CO2 during slow breathing under each condition intudy 2.

se of visual biofeedback. Figs. 3 and 4 are box and whiskerlots of the ETCO2 data and the respiratory rate data at base-ine and during slow breathing under each condition. The usef visual feedback had no observable effect on ETCO2 (fig-res were slightly lower during the ‘no feedback’ condition)espite participants successfully reducing their respiratoryate further under this condition (mean 5 breaths/minute witheedback compared with 7 breaths/minute without feedback).TCO2 and respiratory rate were again negatively correlatednder both conditions (Pearson’s r = 0.42).

iscussion

As might be expected, respiratory rate was found to benversely correlated with ETCO2. Both of these prelimi-ary studies indicated that ETCO2 can be raised by reducing

bt1s

able 5hysiological data at baseline and during slow breathing, with and without visual f

Baseline During slow brea

nd-tidal CO2 (kPa) 4.75 (0.35) 5.09 (0.47)espiratory rate (breaths/minute) 9 (0.9) 5 (2.0)pO2 (%) 96.60 (1.45) 96.30 (1.50)ulse rate (beats/minute) 70 (11.5) 70 (10.0)

pO2: peripheral haemoglobin oxygen saturation.

ig. 4. Respiratory rate during slow breathing under each condition intudy 2.

reathing rate without instructions about controlling vol-me. Patients with asthma and healthy volunteers respondedimilarly during the intervention, but the effect was moreikely to persist beyond the intervention in healthy volunteers.owever, no formal objective determination of participants’

sthma was made, and classification was dependent on clini-al history, symptoms and medication history. The spirometryata and data from the asthma questionnaires indicate thatatients’ asthma had little or no impact on either lung func-ion or quality of life for these participants.

Reducing respiratory rate should lead to an increase inrterial carbon dioxide, provided that people do not increaseidal volumes to preserve an equivalent minute ventilation.o instructions were given to participants about breathingolume, and as minute ventilation was not recorded duringhis study, no comment can be made on this issue. One of theheories behind the benefits of raising carbon dioxide levelss that it could theoretically reverse any bronchoconstrictiveffects of hypocapnia (if present), and possibly make usef the bronchodilatory effects of hypercapnia [13,14]. It isot known what degree of change in ETCO2 would be suf-cient to alter airway resistance or lung function in healthyolunteers. Van den Elshout et al. [14] studied the effectsf hypercapnia and hypocapnia on respiratory resistance inoth normal and asthmatic subjects. They found that a reduc-

ion in ETCO2 of 1 kPa caused an increase in resistance by3% and a fall in reactance by 45% in asthmatics, while theame reduction in ETCO2 had no effect on healthy subjects.

eedback, from Study 2: mean (standard deviation)

thing (with feedback) During slow breathing (without feedback)

5.11 (0.49)7 (3.0)

96.20 (1.40)70 (11.0)

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onversely, an increase in ETCO2 of 1 kPa resulted in a sig-ificant fall in airway resistance in both asthmatic and normalubjects. In this sample, no change in lung function could beetected, but participants had normal baseline function andorced expiratory tests may not be the most sensitive measuref small changes in airway resistance.

In Study 1, the baseline ETCO2 measures were simi-ar in healthy and asthma participants, being slightly highern the asthma group. This finding contradicts findings pub-ished by previous authors [8,15] who found significantlyower ETCO2 levels in patients with asthma. This findingay reflect the uncertainty over the diagnosis of asthma,

r it may be due to differences in the methodology usedo collect ETCO2 data. Judging by the displayed numbers,he equipment used in these studies seemed to have a sloweresponse time than quoted, and the associated software onlyecorded values every 4 seconds because it was designed forleep studies. One of the problems with measuring ETCO2sing cannulae is that the tube in the airway samples what-ver is going out or coming in. If the expiratory time is short,nd-tidal gas may only be sampled for a fraction of a second,o the sampling tube and analyser cell may not be fully rinsedhrough and the reading never actually gets to true end-tidalevels. Sampling from the exhaled side of a one-way mouth-iece would give better accuracy as all the gas sampled isnd-tidal, except for a small spike of dead-space gas at thetart of each exhalation, but the use of a mouthpiece or face-ask is known to alter breathing patterns significantly [16].The use of visual biofeedback from the capnograph to

ncourage a rise in ETCO2 was not found to be effective in theroup of healthy volunteers, although it did seem to enableslower breathing frequency to be maintained with more

onsistency (Fig. 3). However, in this group of volunteers,espite a low baseline ETCO2, the baseline respiratory rateas already lower than might have been expected, potentiallyaking further reductions more difficult. Biofeedback can

ake many forms. In this study, participants were instructedo look at the capnograph display and to focus on the ETCO2umber, with the objective of increasing ETCO2 by control-ing their breathing. This is something that most people findifficult to relate to or comprehend easily. Therefore, becausef the apparent correlation between breathing frequency andTCO2, in future studies, it would be more appropriate to

ocus on respiratory rate and to instruct participants to keephe displayed rate as low as possible while maintaining con-rol of their breathing. It was also found that it was importanto avoid participants needing to hyperventilate following aession of slow breathing, as this reverses the ETCO2 trendnd thus may cause a ‘rebound’ lower than baseline. Thisan be achieved by not pushing the respiratory rate too lowr persisting for too long. The achievable rate and time arendividual to each participant, so it may be useful to aim

or a percentage reduction from baseline rather than havinghe same specific target for all participants. The relativelylow response time of the capnograph and the complexity ofts display screen also made it less than ideal for providing

py 93 (2007) 30–36 35

iofeedback. For visual biofeedback to be effective, it is prob-bly desirable for individuals to be able to see an immediateesponse to any voluntary changes in breathing parameters,nd to have a single parameter on which to focus.

onclusion

These two preliminary studies provided data to powerarger, controlled trials of the physiological effects of breath-ng techniques. The methodology employed was feasible butxposed some limitations of the equipment used. However,he studies suggest that it is possible to raise ETCO2 in healthyolunteers and people with asthma through instructions toeduce respiratory rate with no attempt to control volume.n healthy volunteers, this rise seems to persist for severalinutes after implementing the breathing technique. The use

f visual biofeedback from the screen of the capnograph hado effect on the ability of healthy volunteers to alter theirTCO2.

cknowledgements

The authors wish to acknowledge the support of the stafff the Wellcome Trust Clinical Research Facility, Mr. Johneath in the pulmonary function department at Southamptonniversity Hospitals Trust, and the participants who kindlyolunteered.

Ethical approval: Southampton and South West Hamp-hire Local Research Ethics Committee for Study 1, Ref.o. 044/04/t, and by the School of Health Professions andehabilitation Sciences, University of Southampton internalthics committee for Study 2, Ref. No. M05/02-01.

Funding: Physiotherapy Research Foundation and HOPEharity. AB was supported by a Postdoctoral Researchellowship from the UK Department of Health at the timef the research.

Conflicts of interest: None.

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