www.sciencedirect.com Open in urlscan Pro
162.159.137.70 Public Scan

Back to summary

Submitted URL:
http://url8687.acrm.org/ls/click?upn=1mOBFXAw-2B0gmPzgMHcdk0ZhnR6aFvbFCqFleqe-2FWngybb71NXJ6w5ga7M7d4wA4Qvqd2Cxg4v9os3Dw...
Effective URL:
https://www.sciencedirect.com/science/article/pii/S2590109522000209
Submission: On June 13 via api (June 13th 2023, 3:22:47 pm UTC) from US — Scanned from DE

Form analysis
1 forms found in the DOM

GET /search#submit

<form class="QuickSearch" action="/search#submit" method="get" aria-label="form">
  <div class="search-input">
    <div class="search-input-container search-input-container-no-label"><label class="search-input-label u-hide-visually">Search ScienceDirect</label><input type="search" id="article-quick-search" name="qs" value="" class="search-input-field"
        aria-label="Search ScienceDirect" aria-describedby="article-quick-search-description-message" placeholder="Search ScienceDirect"></div>
    <div class="search-input-message-container">
      <div aria-live="polite" class="search-input-validation-error"></div>
      <div id="article-quick-search-description-message"></div>
    </div>
  </div><button class="button small u-margin-xs-left button-primary" role="button" aria-disabled="false" type="submit" aria-label="Submit search"><span class="button-text"><svg role="img" focusable="false" viewBox="0 0 100 128" height="20"
        width="18.75" class="icon icon-search" aria-label="Search">
        <path
          d="m19.22 76.91c-5.84-5.84-9.05-13.6-9.05-21.85s3.21-16.01 9.05-21.85c5.84-5.83 13.59-9.05 21.85-9.05 8.25 0 16.01 3.22 21.84 9.05 5.84 5.84 9.05 13.6 9.05 21.85s-3.21 16.01-9.05 21.85c-5.83 5.83-13.59 9.05-21.84 9.05-8.26 0-16.01-3.22-21.85-9.05zm80.33 29.6l-26.32-26.32c5.61-7.15 8.68-15.9 8.68-25.13 0-10.91-4.25-21.17-11.96-28.88-7.72-7.71-17.97-11.96-28.88-11.96s-21.17 4.25-28.88 11.96c-7.72 7.71-11.97 17.97-11.97 28.88s4.25 21.17 11.97 28.88c7.71 7.71 17.97 11.96 28.88 11.96 9.23 0 17.98-3.07 25.13-8.68l26.32 26.32 7.03-7.03">
        </path>
      </svg></span></button><input type="hidden" name="origin" value="article"><input type="hidden" name="zone" value="qSearch">
</form>

Text Content

JavaScript is disabled on your browser. Please enable JavaScript to use all the
features on this page. Skip to main contentSkip to article
ScienceDirect
* Journals & Books

*
* Search

RegisterSign in

* View PDF
* Download full issue

Search ScienceDirect

OUTLINE

1. Abstract
2. KEYWORDS
3. List of abbreviations
4. Methods
5. Results
6. Discussion
7. Conclusions
8. Suppliers
9. Acknowledgments
10. Appendix. Supplementary materials
11. References

Show full outline

FIGURES (4)

1.
2.
3.
4.

TABLES (2)

1. Table 1
2. Table 2

EXTRAS (1)

1. Document

ARCHIVES OF REHABILITATION RESEARCH AND CLINICAL TRANSLATION

Volume 4, Issue 2, June 2022, 100196

ORIGINAL RESEARCH
ADJUNCTIVE INSPIRATORY MUSCLE TRAINING DURING A REHABILITATION PROGRAM IN
PATIENTS WITH BREAST CANCER: AN EXPLORATORY DOUBLE-BLIND, RANDOMIZED, CONTROLLED
PILOT STUDY

Author links open overlay panelAmine Dahhak MSc, Nele Devoogdt PhD, Daniel
Langer PhD
Show more
Outline
Add to Mendeley
Share
Cite
https://doi.org/10.1016/j.arrct.2022.100196Get rights and content
Under a Creative Commons license
open access

ABSTRACT

OBJECTIVE

To investigate whether inspiratory muscle training (IMT) offered adjunctively to
an exercise training program reduces symptoms of dyspnea in survivors of breast
cancer.

DESIGN

Double-blind, parallel-group, randomized controlled trial.

SETTING

Outpatient rehabilitation program in a university hospital.

PARTICIPANTS

Ninety-eight female patients with breast cancer who completed adjuvant treatment
and subsequently entered cancer rehabilitation were screened for participation.
Inclusion criteria were reduced inspiratory muscle strength and/or symptoms of
dyspnea. Twenty patients (N=20) were randomly assigned to an intervention group
(n=10) or a control group (n=10).

INTERVENTION

Both groups received a 3-month exercise training program in combination with
either IMT (intervention) or sham-IMT (control).

MAIN OUTCOME MEASURES

Changes in dyspnea intensity perception (10-point Borg Scale) at comparable time
points (isotime) during constant work rate cycling was the primary outcome.
Secondary outcomes included changes in respiratory muscle function, exercise
capacity, and changes in symptoms of dyspnea during daily life (Transitional
Dyspnea Index [TDI]).

RESULTS

The intervention group achieved a larger reduction in exertional dyspnea at
isotime compared with the control group (−1.8 points; 95% CI, −3.7 to 0.13;
P=.066). The intervention group also exhibited larger improvements in dyspnea
during daily life (TDI score, +2.9 points; 95% CI, 0.5-5.3; P=.022) and improved
both respiratory muscle endurance (+472 seconds; 95% CI, 217-728; P=.001) and
cycling endurance (+428 seconds; 95% CI, 223-633; P=.001) more than the control
group.

CONCLUSIONS

Because of the limited sample size all obtained findings need to be interpreted
with caution. The study offers initial insights into the potential of adjunctive
IMT in selected survivors of breast cancer. Larger multicenter studies should be
performed to further explore the potential role and general acceptance of this
intervention as a rehabilitation tool in selected patients after breast cancer
treatment.

* Previous article in issue
* Next article in issue

KEYWORDS

Breast neoplasms
Breathing exercises
Dyspnea
Exercise
Muscle strength
Physical therapy modalities
Randomized controlled trial
Rehabilitation

LIST OF ABBREVIATIONS

BDI
Baseline Dyspnea Index
IMT
inspiratory muscle training
PImax
maximal inspiratory pressure
MID
minimal important difference
TDI
Transitional Dyspnea Index

Breast cancer is the most prevalent type of cancer in women worldwide.1 As a
result of early diagnosis and advanced treatments, the number of survivors of
breast cancer increases.2 However, up to 90% of survivors of breast cancer
experience long-term impairments after treatment.3 These may include decreased
strength, decreased aerobic capacity, and fatigue.3, 4, 5

Additionally, dyspnea, marked by a sensation of breathing discomfort (especially
on physical exertion) is a frequently reported symptom in survivors of (breast)
cancer.6, 7, 8, 9 Potential causes of exertional dyspnea could be impairments in
pulmonary function and respiratory muscle function.6 Kluthcovsky et al studied
cancer-related fatigue in survivors of breast cancer and observed an association
between fatigue and dyspnea.5 These authors noticed that patients often used the
terms fatigue or exhaustion when referring to dyspnea. As a result, symptoms of
dyspnea remain often undiagnosed and frequently untreated.5 Furthermore,
respiratory muscle function is often not assessed, leaving the association
between respiratory muscle function and dyspnea underexplored. Both limb and
respiratory muscle strength is often decreased in these patients.6,7,9 Moreover,
chest wall compliance is frequently reduced after cancer treatments, which
increases the load on the respiratory muscles, especially during exercise.6,10
Impairments in pulmonary function are also common and will further increase
respiratory muscle work during exercise.11

Exercise training programs are effective in improving physical fitness and
reducing fatigue after breast cancer treatment.4,12,13 These programs typically
consist of a combination of aerobic and resistance exercises.12,13 Implementing
specific inspiratory muscle training (IMT) adjunctively to exercise training
programs has previously resulted in larger improvements in respiratory muscle
function and dyspnea in patients with chronic respiratory disease.14,15

There is currently, however, no evidence for the effects of adjunctive
inspiratory muscle training added to an exercise training program in survivors
of breast cancer. Therefore, this study aimed to evaluate the effectiveness of
adjunctive IMT in symptomatic survivors of breast cancer with impaired
respiratory muscle function. We hypothesized that adjunctive IMT would result in
larger improvements in symptoms of dyspnea compared with an exercise training
program offered without adjunctive IMT.

METHODS

TRIAL DESIGN

The design of the study is a double-blind, parallel-group, randomized controlled
trial. Patients who agreed to participate were randomized into an intervention
group or a control group at a 1:1 ratio. Both groups participated in an exercise
training program, but only the intervention group received additional
respiratory muscle training. The control group received a sham treatment. This
study was approved by the local ethics committee (reference no. MP003175).

PARTICIPANTS

Participants were recruited in the local university hospitals, Department of
Physical Medicine and Rehabilitation, between May 2018 and January 2019. Stable
patients with breast cancer who completed adjuvant treatment were allowed to
undergo the offered rehabilitation program and were therefore eligible to
participate in the study. Additionally, patients had to exhibit reduced maximal
inspiratory pressure ([PImax] below predicted normal value), indicative of
impaired respiratory muscle function or symptoms of dyspnea in daily life (score
≤9/12 on Baseline Dyspnea Index [BDI]) to remain eligible.16 Exclusion criteria
were the presence of underlying chronic cardiac or respiratory disease that
might have contributed to symptoms of dyspnea. Participants had to provide
written informed consent before participation in accordance with the Declaration
of Helsinki.

Group allocation was conducted using sealed opaque envelopes in random block
sizes of 4 and 6 (order unknown to investigators) according to an established
method.17 Participants and outcome assessors were blinded to group allocation.
Therapists offering the exercise training program or the adjunctive intervention
were not blinded to group allocation.

INTERVENTION

After baseline measurements, a 3-month intervention program was started. Both
groups followed the identical exercise training program. Additionally, the
intervention group performed 2 IMT sessions per day, consisting of 30 breaths
against a resistance of 50% of their PImax, 4-5 minutes per session, for 7 d/wk,
for 12 weeks, using an electronic tapered flow resistive loading device
(POWERbreathe KHP2).a This device enables constant monitoring of training data
and ensures higher performed total work during training sessions than other
methods.18 Patients were instructed to fill their diaries by copying stored data
from the device. Total work and training load during the training program were
subsequently extracted from the diaries. Supervised training sessions, including
measurements of PImax, were planned to be performed on-site every 2 weeks after
the exercise training sessions of the rehabilitation program. Furthermore,
training loads were increased at these visits to maintain the external load at
∼50% of PImax at respective measurements throughout the study period. Ratings of
perceived inspiratory effort on a modified Borg scale (10-point Borg Scale of
4-5 of 10) were used to support decisions on increasing training load. The
control group completed the same amount of IMT sessions but trained at ∼10% of
their initial PImax. This training load remained unchanged to avoid training
stimuli. To increase adherence, both treatments were presented as active
interventions. The training was presented as strength training in the
intervention group and as endurance training in the control group. Participants
in the control group were able to follow the active treatment after the
completion of the study. All assessments except for the maximal cardiopulmonary
exercise test and the lung diffusion capacity were repeated after the
intervention period.

ASSESSMENTS

Supplemental table S1 presents an overview of all outcome measurements. An
overview of the study design is depicted in supplemental table S2.

PULMONARY FUNCTION

Full pulmonary function testing including spirometry, lung volumes, and
diffusion capacity was performed at the department of pneumology according to
current European Respiratory Society guidelines.19, 20, 21 Reference values from
the Global Lung Function Initiative were used to interpret the outcomes.22,23

RESPIRATORY MUSCLE FUNCTION

Respiratory muscle function was evaluated by measuring the PImax and maximal
expiratory pressure using a microRPM Pressure Meterb and respiratory muscle
endurance (POWERbreatheKH2)a in accordance with international guidelines.24
During assessments of maximal mouth pressures, patients had to perform maximal
quasi-static inspiratory and expiratory efforts starting from either residual
volume or total lung capacity for the measurements of PImax and maximal
expiratory pressure, respectively. The maximum 1-second plateau pressure of the
3 best maneuvers that differed by <10% was retained and compared with reference
values.19 The endurance breathing test was conducted with an established
protocol.24 After standardized instructions, patients were instructed to breathe
against a constant submaximal external resistance until task failure.24 Patients
were encouraged to perform as many forceful and deep inhalations and complete
exhalations in the device as possible. Breathing duration, number of breaths,
and total external work performed during the protocol were registered.

SYMPTOMS OF DYSPNEA

A modified Borg Scale (0-10) was used during the endurance breathing test,
constant work rate cycling test (primary outcome), and 6-minute walk test to
assess the intensity of dyspnea throughout the tests. The Multidimensional
Dyspnea Profile scale was used to assess dyspnea by evaluating overall breathing
discomfort at the end of the constant work rate cycling test.25 To measure the
change in the severity of dyspnea during daily life we used the BDI and the
corresponding Transitional Dyspnea Index (TDI). The BDI/TDI consist of 3
different categories, namely functional impairment, magnitude of task, and
magnitude of effort.26 All categories were rated in 5 grades, from 0 (severe) to
4 (unimpaired).26 Scores were added up to obtain a general score, ranging from
0-12 representing the severity of dyspnea at baseline. Therefore, the lower the
score, the worse the severity of dyspnea.26 The TDI was subsequently used to
quantify the change in dyspnea from baseline. Changes in dyspnea were rated by 7
grades, ranging from −3 (major deterioration) to +3 (major improvement) for each
category.26 The change scores on all categories were added up to give a general
image of the change in dyspnea during daily life, ranging between −9 and +9. The
modified Medical Research Council dyspnea scale rates dyspnea intensity on a
score between 0 (unimpaired) and 4 (severe) in terms of breathing possibility
during daily activities.27 This dyspnea scale and the BDI/TDI explore dyspnea
intensity differently; hence, they complement each other perfectly.28

EXERCISE CAPACITY

Assessment of maximal exercise capacity was performed during the initial
screening procedure through a cardiopulmonary exercise test, which was performed
on an electronically-braked cycle ergometer (Ergoline 800s)c with detailed
metabolic and cardiopulmonary measurements (Vs229d).c Endurance exercise
capacity was assessed using constant work rate cycling against a workload (W) of
80% of the peak work rate achieved during the cardiopulmonary exercise test.
Before the constant work rate cycling test, forced vital capacity and maximal
voluntary ventilation were assessed by spirometry. Throughout the test, heart
rate, oxygen saturation, minute ventilation, and other breathing and exercise
parameters were recorded. Secondary parameters were extracted as 30-second
averages that were subsequently used to determine values at a standardized time
point (isotime) and peak exercise. In addition, minute-by-minute intensity of
dyspnea and leg discomfort was evaluated using a modified Borg Scale (0-10).29
Blood pressure and inspiratory capacity were measured every 2 minutes. In
addition, functional exercise capacity was evaluated using a 6-minute walk
test.30 Before and after the test, patients were asked to rate leg discomfort
and symptoms of dyspnea on a modified Borg Scale (0-10).29 Additionally, the
walking distance was measured as well as oxygen saturation and heart rate
throughout the test.

PERIPHERAL MUSCLE STRENGTH

Handgrip strength was measured using handheld dynamometry. Patients had to keep
the elbow of the tested side in 90 degrees of flexion and a neutral position of
pro- and supination while performing the test. Both sides were tested 3 times,
and the maximal value was retained.31,32

STATISTICAL ANALYSES

A sample size of 10 patients in the intervention group and 10 patients in the
control group was required to detect a between-group difference of 1.3±1 units
for the change in dyspnea intensity rating on a modified Borg Dyspnea Scale
(0-10) between pre-and postintervention assessments at isotime during the
constant work rate cycling test with a statistical power (ß) of 80% and a risk
for a type I error (α) <5%. All data were analyzed following the
intention-to-treat principle. Statistical procedures were performed using SPSS
version 27.0.d Postintervention between-group differences were compared
adjusting for baseline differences in an analysis of covariance, and adjusted
mean differences between groups are reported alongside their 95% CI.33 In
addition, paired samples t tests or Wilcoxon tests were applied to examine
within-group differences before and after treatment. To further investigate
within-group changes from pre- to post intervention at different time points
during the constant work rate cycling test, 2-way repeated-measures analyses of
variance were conducted. Alongside these results, partial η2 values are reported
as a measure of effect size. Furthermore, exploratory correlates of training
outcomes with changes in respiratory muscle function and symptoms of dyspnea
were investigated using linear bivariate correlation tests.

RESULTS

STUDY POPULATION

Figure 1 displays the flow of participants throughout the different phases of
the study. Twenty stable patients with breast cancer were enrolled. One patient
in the control group was not willing to complete the exercise training program
nor the sham intervention and was subsequently dropped out of the study.
Additionally, another patient from the control group did not follow the sham
intervention but did perform pre and post measurements and was subsequently
conserved in the analyses. Finally, the exercise and breathing pattern data of a
patient in the intervention group was missing during the postintervention
constant work rate cycling test because of calibration issues.

1. Download : Download high-res image (477KB)
2. Download : Download full-size image

Fig 1. Consolidated Standards of Reporting Trials flow diagram displaying the
progress of participants through the phases of the study.

BASELINE CHARACTERISTICS

Table 1 presents an overview of the baseline characteristics. All participants
were female and aged between 36 and 69 years, and except for PImax (mean
difference, −17cmH2O; 95% CI, −30 to −4; P=.015), no relevant baseline
differences were observed between groups. This was also true for the different
adjuvant treatments that patients received. These data are presented in fig 2.

Table 1. Baseline characteristics

CharacteristicIntervention (n=10)Control (n=10) Age (y)51±555±9 Height
(cm)165±6168±5 Weight (kg)71±1475±15Medical treatmentsType of breast
surgery Mastectomy (% received)9070 Tumorectomy (% received)1030Type of axillary
surgery Axillary lymph node dissection (% received)4020 Sentinel node biopsy (%
received)5080 Unknown (% received)100Type of adjuvant treatment Radiotherapy (%
received)7070 Chemotherapy (% received)4060 Immunotherapy (%
received)3030 Hormone therapy (% received)10060Pulmonary function FVC, L (%
predicted)3.7±0.5 (105±12)3.5±0.6 (101±14) FEV1, L (% predicted)2.9±0.4
(103±12)2.8±0.7 (100±18) FEV1/FVC (%)78.8±6.778.7±6.6 RV, L (% predicted)1.9±0.2
(107±12)2.3±0.3 (121±20) FRC, L (% predicted)3.1±0.4 (112±15)3.2±0.5
(114±15) TLC, L (% predicted)5.7±0.6 (111±10)5.9±0.7 (112±13) TLco, mmol/min/kPa
(% predicted)6.3±0.9 (82±11)6.4±0.8 (86±11)Respiratory muscle function PImax,
cmH2O (% predicted)−74±11 (69±10)−91±15 (91±15) PEmax, cmH2O (% predicted)139±27
(77±15)145±26 (85±14) Endurance breathing time (s)209±79266±126 External
resistance (% PImax)62±1061±7Symptoms of dyspnea BDI, 0-128.4±2.48.6±1.9 MDP,
0-106.7±1.86.4±2.9 mMRC, 0-40.8±0.41.0±0.7Exercise capacityMaximal exercise
capacity V̇o2max, L/min (% predicted)2.0±0.4 (91±19)2.0±0.4 (97±27) Load
(W)123±28118±30 Maximal heart rate, 1/min (% predicted)158±13 (93±6)151±17
(94±11) Constant work rate cycling Duration, min7.0±3.36.2±4.5 Load, W (% peak
work rate)98±20 (80±4)94±22 (80±2)Functional capacity 6MWD, m (%
predicted)557±92 (84±14)553±105 (86±18)Peripheral muscle strength Handgrip
strength, N (% predicted)255±53 (94±19)248±29 (102±21)

NOTE. Data are presented as mean ± SD unless otherwise indicated.

Abbreviations: FEV1, forced expiratory volume in 1 second; FRC, functional
residual capacity; FVC, forced vital capacity; MDP, multidimensional dyspnea
profile; mMRC Modified Medical Research Council Scale; PEmax, maximal expiratory
pressure; % PImax, percentage of the mean inspiratory load relative to the
PImax; % predicted, percentage of the predicted normal value; RV, residual
volume; 6MWD, 6-minute walking distance; TLC, total lung capacity; TLco,
diffusing capacity of the lungs for carbon monoxide; VC, vital capacity;
V̇o2max, maximal oxygen uptake.

1. Download : Download high-res image (141KB)
2. Download : Download full-size image

Fig 2. Adjuvant treatments received by study participants.

RESPIRATORY MUSCLE TRAINING

Supplemental table S3 presents an overview of the mean training data for each
group. Adherence with prescribed training sessions was 63%±18% and 41%±28% in
the intervention and control group, respectively (total sessions performed,
105±49 vs 68±37). Total work performed throughout the training intervention was
higher in the intervention group than the control group (21670J±12266J vs
2813J±1781J; 95% CI, −27615 to −10099; P=.002). In the intervention group,
training resistance started at 47%±9% of their baseline PImax in the first week
of training and ended at 59%±16% in the last week of training. Weekly mean
inspiratory resistance (%PImax baseline) is shown in fig 3.

1. Download : Download high-res image (135KB)
2. Download : Download full-size image

Fig 3. Mean inspiratory resistance during weekly inspiratory muscle training
sessions throughout the intervention period. Training resistance is expressed as
percentage baseline maximal inspiratory pressure measured from residual volume.
Percentage adherence to prescribed training sessions is displayed under weekly
averages of training resistance. Values are mean ± SE.

MAIN OUTCOMES

After the intervention period, exertional dyspnea scores at isotime were
significantly lower only in the intervention group, while between-group
differences were not statistically significant (P=.066) in analogy with
between-group differences in multidimensional dyspnea profile scores of dyspnea
unpleasantness recorded at peak exercise (P=.091) (table 2). The intervention
group exhibited a significantly larger increase in constant work rate endurance
cycling time than the control group (see table 2 and fig 4). Reductions in
sensations of leg fatigue and minute ventilation during exercise were comparable
between groups (see table 2 and fig 3). Changes in breathing pattern were also
comparably small in both groups (see table 2 and supplemental fig S1). The
scores on the TDI questionnaire increased significantly in the intervention
group compared with the control group (P=.022) (see table 2). As displayed in
table 2, PImax increased from −74±11 cmH2O to −93±19 cmH2O in the intervention
group and from −91±16 cmH2O to −98±13 cmH2O in the control group (unadjusted
mean difference, 12cmH2O; 95% CI, −5 to 30; P=.164; d=0.668). Furthermore, there
was a significant and very large (d=1.962) increase in respiratory muscle
endurance time in favor of the intervention group (see table 2). Improvements in
functional exercise capacity as assessed by the 6-minute walk distance and
changes in handgrip strength were comparable between groups (see table 2).

Table 2. Changes in primary and secondary outcome measurements

OutcomeInterventionControlEmpty CellEmpty CellPretrainingPost
TrainingPretrainingPost TrainingAdjusted Difference (95% CI) at Post
TrainingRespiratory muscle strength PImax (cmH2O)−74±11−93±19⁎−91±16−98±13−1
(−19 to 18) PEmax (cmH2O)139±25144±28143±26141±276 (-14 to 25)Respiratory muscle
endurance test Endurance breathing time (s)209±79741±282⁎269±133321±236472 (217
to 728)† Total work (J)103±61560±403⁎206±131326±157⁎336 (24 to 648)† Average
power (W)2.0±1.25.9±2.5⁎4.5±2.26.9±1.9⁎1.4 (−1.2 to 4.0) Average volume
(L)1.8±0.72.6±0.7⁎2.1±0.62.5±0.4⁎0.3 (−0.3 to 0.8)CWR cycle ergometer exercise
test Work rate (W)99±2398±2394±2494±24 Reason stopping (%
dyspnea)57±1753±1941±2648±15−10 (−32 to 12)Isotime Exercise capacity
(s)400±218367±272 Dyspnea isotime (Borg units)5.8±2.13.3±1.9⁎6.0±3.35.2±2.8−1.8
(−3.7 to 0.13) Leg discomfort (Borg units)5.4±1.74.0±1.9⁎7.6±2.67.6±1.8−1.3
(−3.2 to 0.6) Heart rate (beats/min)150±21139±22⁎127±28134±26−15 (−27 to −3)† VE
(L/min)57.2±23.247.7±19.0⁎55.7±16.051.7±13.6−5.1 (−12.7 to 2.5) VT
(L)1.86±0.521.73±0.521.69±0.221.65±0.24−0.05 (−0.30 to 0.19) RR
(breaths/min)31±628±634±1032±10−2 (−7 to 2) V̇o2
(L/min)1.71±0.461.48±0.44⁎1.56±0.381.49±0.30−0.1 (−0.3 to 0.0) VCo2
(L/min)1.95±0.621.55±0.51⁎1.68±0.411.64±0.34−0.27 (−0.55 to
0.00)† RQ1.13±0.161.03±0.151.08±0.081.11±0.10−0.11 (−0.21 to −0.00)† IC
(L)2.43±0.352.57±0.472.47±0.292.49±0.360.12 (−0.18 to 0.42)Peak
exercise Exercise time (s)467±218933±267⁎460±272500±294428 (223 to 633)† Dyspnea
(Borg units)6.9±2.36.0±2.27.6±3.26.9±2.6−0.5 (−2.6 to 1.5) Leg discomfort (Borg
units)6.4±2.46.2±2.78.8±1.67.6±1.8−1.1 (−3.8 to 1.7) Heart rate
(beats/min)155±16145±29134±26139±24−16 (−31 to 0) VE
(L/min)58.4±22.257.0±17.359.0±12.657.6±10.2−0.2 (−10.6 to 10.1) V̇o2
(L/min)1.76±0.441.64±0.321.64±0.331.59±0.26−0.00 (−0.25 to 0.24)Symptoms of
dyspnea TDI total score (−9 to +9)7.0±1.24.1±3.02.9 (0.5 to 5.3)† MDP (A1, 0 to
10)6.7±1.94.8±3.5⁎6.4±3.16.6±2.6−2.0 (−4.3 to 0.4) mMRC (0 to
4)0.8±0.40.2±0.4⁎1.0±0.70.7±0.7−0.4 (−0.8 to 0.1)Functional exercise
capacity 6MWD (m), dyspnea post
6MWD, leg discomfort post
6MWD (N), handgrip strength557±87
2.9±1.4
2.7±1.7
255±53584±71⁎
2.4±1.6545±101
3.3±2.4580±85
2.2±0.9−5 (−45 to 35)
0.2 (−1.2 to 1.6)
1.1 (−1.1 to 3.5)
4 (−15 to 23)2.6±1.6
255±504.8±2.9
248±293.6±2.2
256±34

NOTE. Data are presented as mean ± SD.

Abbreviations: CWR, constant work rate; IC, inspiratory capacity; isotime, the
time of the post measurement equal to the end of time of the premeasurement;
MDP, multidimensional dyspnea profile; mMRC, modified medical research council
scale; peak exercise, averaged last 30 s of loaded cycling; PEmax, maximal
expiratory pressure; RQ, respiratory quotient; RR, respiratory rate; 6MWD,
6-minute walking distance; 10-point Borg, modified Borg Dyspnea Scale (0-10);
VCo2, carbon dioxide production; VE, ventilation; V̇o2, oxygen consumption; VT,
tidal volume.

⁎

P<.05, within-group differences pre- vs post intervention by paired t test or
Wilcoxon test.

†

P<.05, between-group differences intervention vs control by analysis of
covariance.

1. Download : Download high-res image (471KB)
2. Download : Download full-size image

Fig 4. Dyspnea intensity, sensation of leg discomfort, and VE assessed during
constant work rate cycling tests. Pre- and-postactive intervention measures of
(A) dyspnea intensity, (C) leg discomfort, and (E) VE. Pre- and postcontrol
intervention measures of (B) dyspnea intensity, (C) leg discomfort, and (E) VE.
Values are mean ± SE. Abbreviation: VE, ventilation. *Paired-samples t test:
P<.05, post vs preintervention. †Two-way repeated measures analysis of variance:
P=.01 for pre- to postassessment effect.

External work performed during the respiratory muscle training intervention
correlated significantly with changes in exercise time during the constant work
rate cycling test (r=0.785, P<.001), changes in respiratory muscle endurance
time (r=0.544, P=.020), and TDI scores (r=0.697, P=.001). Furthermore, changes
in training load significantly correlated with changes in PImax (r=−0.558,
P=.020).

DISCUSSION

This study investigated the effects of adjunctive IMT on respiratory muscle
function, symptoms of dyspnea, and exercise capacity in selected survivors of
breast cancer. We observed relevant additional improvements in respiratory
muscle function, endurance cycling time, and symptoms of dyspnea during daily
activities after adjunctive IMT. Moreover, this study implemented a sham
treatment, effectively blinding the control group and accounting for placebo
treatment effects in the process.

Respiratory muscle endurance improved considerably more (adjusted mean
difference, +472 seconds; 95% CI, 217-728) after adjunctive IMT in contrast to
the sham control intervention. This constitutes a very large effect size
(d=1.96). Average improvements in PImax in the intervention group of 19 cmH2O
exceeded previously established minimal important differences (MID) of changes
in inspiratory muscle strength in heart failure (MID, 11.4 cmH2O)34 and chronic
obstructive pulmonary disease (MID, 17.2 cmH2O).35 This did, however, not result
in a significant difference between groups, despite an unadjusted difference of
12 cmH2O (95% CI, −5 to 30; P=.164) and a moderate to large effect size
(d=0.668). Improvements in PImax in our control group were larger than studies
in chronic obstructive pulmonary disease lacking a sham control intervention
(7.4±4.9 cmH2O vs 1.3±0.9 cmH2O).36 This together with the relatively small
sample size might have contributed to this observation.

We hypothesized that adjunctive IMT would reduce symptoms of exertional dyspnea
and increase exercise capacity. There was evidence for a reduction of
self-reported dyspnea symptoms during daily life as shown by the significant
improvement on the TDI questionnaire in the intervention group compared with the
control group. Clinical relevance of this finding is illustrated by comparing
the adjusted difference (2.9 points) with the previously established MID of 1
point.37 Although there was no significant between-group difference in change
scores for the perceived intensity of dyspnea at comparable time points during
the constant work rate cycling test, a statistically significant reduction
within the intervention group was observed (see fig 3).

The adjusted difference in dyspnea reduction of −1.8 points on the modified Borg
Scale (0-10) scores at isotime seems clinically relevant compared with the MID
of 1 point established in previous work.38

Improvements in endurance exercise capacity during a constant work rate cycling
test showed a substantial between-group difference (adjusted difference, 428
seconds; 95% CI, 223-633; P=.001). This additional improvement largely exceeds
the MID of 46-105 seconds previously established in patients with chronic lung
disease.15

While both groups showed relevant improvements, no between-group difference was
observed in the 6-minute walk distance (adjusted mean difference, −5 m; 95% CI,
−45 to 35). The lack of between-group differences on this outcome provides
further evidence that constant work rate tests might be more suitable when
investigating the effects of adjunctive interventions.15,39 Regarding handgrip
strength, no changes were observed, indicating the specificity of IMT to affect
respiratory but not peripheral muscles.

STUDY LIMITATIONS

In this study, training adherence was lower (62.7% and 40.7% for intervention
and control groups, respectively) than previous studies using comparable IMT
protocols.15,40 Because of limited staffing and larger physical distance between
the rehabilitation center and the hospital, we offered less regular supervised
sessions than initially planned (every 2 weeks). Nevertheless, the average total
number of training sessions performed (105±49 in the intervention group vs 68±37
in the control group) was considerable and comparable with previous
studies.15,40 However, for future research we recommend implementing regular
supervised sessions to optimize treatment adherence and take full advantage of
IMT programs.

CONCLUSIONS

SUPPLIERS

* a.

POWERbreathe KHP2, HaB International Ltd, Southam, Warwickshire, England, UK.

* b.

microRPM Pressure Meter; BD-CareFusion, San Diego, CA.

* c.

Ergoline 800s; Vs229d; SensorMedics Corporation, Yorba Linda, CA.

* d.

SPSS Version 27.0; IBM, Armonk, NY.

ACKNOWLEDGMENTS

We thank Laura Rommens, MSc, and Jente Geerts, MSc, for their contribution in
the collection and analysis of data as well as for their contribution in
drafting the manuscript. Additionally, we thank Lies Serrien, PT, for her
assistance during patient screening, supervision of training sessions, and
collection of additional data. Lastly, we acknowledge HaB International Ltd
(Southam, UK) for providing training devices on loan for the study duration.

APPENDIX. SUPPLEMENTARY MATERIALS

Download : Download Word document (320KB)

www.sciencedirect.com Open in urlscan Pro 162.159.137.70 Public Scan

Form analysis 1 forms found in the DOM

GET /search#submit

Text Content

www.sciencedirect.com Open in urlscan Pro
162.159.137.70 Public Scan

Form analysis
1 forms found in the DOM