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RESEARCH ARTICLE
Effects of music therapy as an adjunct to chest
physiotherapy in children with cystic fibrosis:
A randomized controlled trial
Alberto Montero-Ruiz
1,2
, Laura A. Fuentes
1
, Estela Pe
´rez Ruiz
1,3
, Nuria Garcı
´a-Agua
Soler
1
, Francisca Rius-Diaz
4
, Pilar Caro Aguilera
1,3
, Javier Pe
´rez Frı
´as
1,3
*, Elisa Martı
´n-
MontañezID
1
*
1Departamento de Farmacologı
´a y Pediatrı
´a, Universidad de Ma
´laga, Instituto de Investigacio
´n Biome
´dica
de Ma
´laga, Facultad de Medicina, Ma
´laga, Spain, 2Consejerı
´a de Educacio
´n, Junta de Andalucı
´a,
Delegacio
´n Territorial de Ma
´laga, Ma
´laga, Spain, 3Hospital Regional Universitario de Ma
´laga, Seccio
´n de
Neumologı
´a Pedia
´trica, Ma
´laga, Spain, 4Departamento de Medicina Preventiva y Salud Pu
´blica,
Universidad de Ma
´laga, Facultad de Medicina, Ma
´laga, Spain
*emartinm@uma.es (EM-M); jpf@uma.es (JPF)
Abstract
Airway clearance therapy (ACT) is considered an important approach to improve airway
clearance in children with cystic fibrosis (CF). Daily ACT administration requires substantial
commitments of time and energy that complicate ACT and reduce its benefits. It is crucial to
establish ACT as a positive routine. Music therapy (MT) is an aspect of integrative strategies
to ameliorate the psycho-emotional consequences of chronic diseases, and a MT interven-
tion could help children with CF between the ages of 2 and 17 develop a positive response.
The aim of this randomized controlled trial was to evaluate the effects of specifically com-
posed and recorded instrumental music as an adjunct to ACT. We compared the use of spe-
cifically composed music (Treated Group, TG), music that the patient liked (Placebo Group,
PG), and no music (Control Group, CG) during the usual ACT routine in children with CF
aged from 2 to 17. The primary outcomes, i.e., enjoyment and perception of time, were eval-
uated via validated questionnaires. The secondary outcome, i.e., efficiency, was evaluated
in terms of avoided healthcare resources. Enjoyment increased after the use of the specifi-
cally composed music (children +0.9 units/parents +1.7 units; p<0.05) compared to enjoy-
ment with no music (0 units) and familiar music (+0.5 units). Perception of time was 11.1 min
(±3.9) less than the actual time in the TG (p<0.05), 3.9 min (±4.2) more than the actual time
in the PG and unchanged in the CG. The potential cost saving related to respiratory exacer-
bations was €6,704.87, while the cost increased to €33,524.35 in the CG and to €13,409.74
in the PG. In conclusion, the specifically composed, played and compiled instrumental
recorded music is an effective adjunct to ACT to establish a positive response and is an effi-
cient option in terms of avoided costs.
Trial registered as ISRCTN11161411. ISRCTN registry (www.isrctn.com).
PLOS ONE
PLOS ONE | https://doi.org/10.1371/journal.pone.0241334 October 30, 2020 1 / 15
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OPEN ACCESS
Citation: Montero-Ruiz A, Fuentes LA, Pe
´rez Ruiz
E, Garcı
´a-Agua Soler N, Rius-Diaz F, Caro Aguilera
P, et al. (2020) Effects of music therapy as an
adjunct to chest physiotherapy in children with
cystic fibrosis: A randomized controlled trial. PLoS
ONE 15(10): e0241334. https://doi.org/10.1371/
journal.pone.0241334
Editor: Nancy Beam, PLOS ONE, UNITED STATES
Received: June 15, 2019
Accepted: October 12, 2020
Published: October 30, 2020
Copyright: ©2020 Montero-Ruiz et al. This is an
open access article distributed under the terms of
the Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
files.
Funding: This research was supported by the
project PIN-0342-2016 from Consejerı
´a de Salud
de la Junta de Andalucı
´a and Plan Propio de
Investigacio
´n de la Universidad de Ma
´laga. The
funders had no role in study design, data collection
and analysis, decision to publish, or preparation of
the manuscript.
Introduction
Cystic fibrosis (CF) is an inherited autosomal recessive multisystemic disease characterized
mainly by respiratory and digestive disorders [1,2]. Due to a defect in the CF transmembrane
conductance regulator gene, excess dehydrated and thick secretions are produced in the lungs,
liver, pancreas, intestine, sweat and salivary glands and reproductive organs [3]. The cause of
morbi-mortality is linked to respiratory manifestations due to the accumulation of mucus in the
airways, which ultimately leads to secondary infections, bronchiectasis, and respiratory failure
[2]. Routine airway clearance therapy (ACT) is one of the main approaches used to improve air-
way clearance [4,5]. These airway clearance techniques are prescribed daily and, in the case of
children, are to be given by their parents until children and adolescents are old enough to be
actively involved in their own ACT. Therefore, ACT is well established as an integral part of the
management of CF and is aimed at minimizing symptoms, reducing the frequency of exacerba-
tions and improving lung function [5]. However, ACT requires substantial commitments of
time and energy, leading to low levels of ACT adherence [6] and decreases in its benefits [7].
Individuals with CF and their parents report elevated symptoms of psychological burden
[8]. To avoid these negative effects related to this daily routine, it is important to establish ACT
as an enjoyable task, and a music therapy (MT) strategy could help people with CF develop a
positive response. In pulmonary diseases, MT interventions are components of integrative
strategies adopted to ameliorate physical or psycho-emotional consequences [9,10]; however,
MT interventions in CF are infrequent, and in any case very few. To our knowledge, only five
studies have evaluated the effects of music-based strategies, based on playing instruments [11],
singing [12,13] or listening to music [14,15], as adjunct therapy in children with CF. In this
sense, it has been shown that listening to carefully selected motivational music while walking,
which was chosen by physiotherapists, can lead to a positive affective response during exercise,
increasing the enjoyment of exercise in CF patients between the ages of 8 and 18 [15]. Further-
more, a study carried out in children with CF who were less than 24 months old indicated that
listening to specifically composed and recorded music as an adjunct to ACT increased chil-
dren’s and parents’ enjoyment of ACT and assisted in the establishment of a positive routine
[14]. Although Calik-Kutukcu and colleagues [15] showed that listening to selected motiva-
tional music can have a positive effect on exercise, Grasso and colleagues [14] revealed that lis-
tening to recorded music specifically composed, is an effective mean to increase the positive
effects found during ACT routine with toddler, being more effective than familiar music. We
planned this clinical trial considering the importance of these specific characteristics to
enhance the positive effect of music [14] and also, the lack of literature on the use of music
during ACT with CF children older than 24 months old. Thus, the purpose of the current
study was to evaluate the effects of listening to specifically composed, played and recorded
music as an adjunct to ACT in children with CF older than 2 years old. We hypothesized that
the use of the specifically composed music may provide benefits compare to patients-preferred
music or the use of no music. The primary aims were to examine (1) a possible increase in
patients’ and parents’ enjoyment of the ACT routine and (2) a possible decrease in perception
of time taken to complete the routine. As a secondary aim, we wanted to analyze the efficiency
of the music therapy intervention in terms of avoided healthcare resources.
Materials and methods
Study participants
Individuals with CF between the ages of 2 and 17 were recruited from the Pediatric Pulmonol-
ogy Unit at Malaga Regional Hospital, which was providing care to 80 people with CF at the
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Competing interests: The authors have declared
that no competing interests exist.
time of study. Participants who met all of the inclusion criteria, none of the exclusion criteria
(Table 1) and provided written informed consent were included in the trial. Due to all the par-
ticipants were minors, written informed consent was obtained from their parents, which was
also signed by children aged >12.
The study was conducted according to the Declaration of Helsinki and was approved by the
Ethics in Human Research Committee of Malaga Regional Hospital on October 27, 2016. The
authors confirm that all ongoing and related trials for this intervention are registered. We reg-
istered the trial on the ISRCTN registry (ISRCTN11161411: www.isrctn.com.) on June 15,
2019. Patient recruitment and follow-up were conducted from February 1, 2018 to July 31,
2018. The delay in registering this study in a publicly accessible register was because the trial
was previously registered in the Andalusian Ethics Biomedical Research Registry (PEIBA) in
October 2016. Thus, the trial was registered before recruiting the first participant in the study.
We thought the PEIBA register was included in the WHO list of approved registries, but in
June 2019, we realized that the PEIBA registry was not a publicly accessible registry; therefore,
we decided to register the trial in the ISRCTN registry immediately.
Study design
The MT intervention evaluated consisted of the use of instrumental music that was specifically
composed, played and compiled for children with CF and that was used as an adjunct to each
part of the ACT routine without modifying the usual treatment regimens or programmed clinic
visits; therefore, there was no risk of harm. We compared the use of this specifically composed
music with (1) the use of music the patients liked, also called familiar music, and (2) the use of
no music during ACT management. The participants were randomly allocated using the ‘Sub-
jects assignment to treatment’ module of the software for the epidemiologic analysis of tabulated
data Epidat (version 3.1) [18]. A design for equal-sized groups was chosen. After we set the num-
ber of groups (n = 3) and the total sample size (n = 54), Epidat made a random assignment
according to the participant order number, with each participant assigned to one of the 3 follow-
ing conditions: (1) Treated Group (TG)–use of the specifically composed music as an adjunct to
the ACT routine; (2) Placebo Group (PG)–use of music the patients liked as an adjunct to the
ACT routine; and (3) Control Group (CG)–the standard practice of the ACT routine.
Table 1. Clinical trial inclusion and exclusion criteria.
Inclusion
criteria
Participants diagnosed with CF based on international criteria [16]: a positive sweat test (chloride
value 60 mmol/L); 2 CF-causing CFTR mutations; and clinical features compatible with CF
Participants undergoing periodic clinic visits in the CF unit
Participants in the target age range
Participants with an understanding of the purpose of the study
Exclusion
criteria
Participants without ACT prescription
Participants with severe hearing loss
Participants with clinical complications such that the ACT may have to be adapted or may be
contraindicated: radiologic or clinical risk of pneumothorax or pneumomediastinum;
barotrauma in the month prior to entry in the study; or past history of massive or life-threatening
hemoptysis [17]
Transplant recipients or patients awaiting a lung transplant
Abbreviations: CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; ACT, airway
clearance therapy.
Information about the clinical variables (age of diagnosis, body mass index, Bhalla score and respiratory infection
exacerbations) was obtained from the clinical center.
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In our Pediatric Pulmonology Unit, ACT is divided into 3 sections: nebulizer inhalation
treatment, airway clearance techniques and relaxation/antibiotic nebulizer treatment, if neces-
sary. Participants in the TG were given a music CD with music that was composed, played and
compiled specifically for children with CF by a professional musician and music teacher under
the recommendations of the CF specialists at the Pediatric Pulmonology Unit. The recommen-
dations provided for developing the music were (1) to encourage enjoyment; (2) to elicit relax-
ation, maintaining children’s interest to facilitate deep inhalation during the inhaled treatment
sections; (3) to provide appropriate rhythmic support for the management of airway clearance
techniques to improve mucus clearance; and (4) to promote distraction from the time spent
on the routine. The CD consisted of instrumental composed music played on percussion
instruments to use as an adjunct to ACT during the 3-month trial period. The music CD had 3
sections related to the ACT routine: section A for the nebulizer treatment, section B for ACT
work and bronchial clearance and section C for relaxation and nebulization. The CD was 40
min long, corresponding to the average length of the ACT routine. Section A contained 4 slow
songs (65 bpm) with a total of 13 min of relaxing music for the duration of the nebulizer
inhalation treatment. Section B consisted of 5 moderate rhythmical songs (mean = 112.4 bpm)
and was a total of 23 min long; it provided a rhythmic structure to support the management of
airway clearance techniques such as huffing, coughing, percussions or vibrations. Section C
was a 4-min-long relaxing song that was a variation of a section A song. The music was per-
formed with pitched percussion instruments (marimba, vibes, glockenspiel and xylophone)
and unpitched percussion instruments (drums, congas, bongos, multipercussion set and small
percussion instruments) that are widely used in MT interventions [19,20]. MuseScore software
was used to write the scores, and the software Audacity was used to record and edit the audio.
The music was compiled on a CD. Participants in the PG were given recommendations for the
use of familiar music as an adjunct to ACT during the 3-month trial period. The recommenda-
tions encouraged the patients to listen to slow, relaxing music that they liked during the first
and last ACT sections, and moderate rhythmical songs in the middle section. The CG was
composed of participants who were asked to continue with their usual ACT routine during the
3-month trial period. Participants in these 2 groups (PG and CG) were given the music CD to
keep at the end of the study.
Questionnaires designed and validated by Grasso and colleagues were employed in the cur-
rent study [14]. We evaluated the internal consistency by calculating Cronbach’s alpha coeffi-
cient among the items referring to the ‘enjoyment’ construct in an independent sample of
people with CF over 18 and their parents [14] (Cronbach’s alpha = 0.856).
Participants completed a baseline questionnaire, a follow-up questionnaire and an evalua-
tion questionnaire during the 3-month trial period. The baseline questionnaire was completed
in a face-to-face interview immediately following recruitment during a routine clinic visit. The
follow-up and the evaluation questionnaires were completed via telephone interviews 6 and 12
weeks after the first interview, respectively. We used the middle questionnaire collecting infor-
mation about experience with physiotherapy routine as a follow-up strategy, instead of evaluat-
ing the intervention. Nonclinical research staff performed the interviews and was trained
previously. Adolescent participants completed questionnaires independently and were given
the option to have their parents join them for the interviews. In all cases, the parents of adoles-
cents joined. After the baseline questionnaire, participants received a reference sheet contain-
ing the Likert-type response scales and a list of descriptive words for reference during the
telephone interviews. This reference sheet was also posted on the MT intervention website (an
additional support for participants, which included a summary of the intervention, the refer-
ence sheet and contact information).
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Outcome measures
The primary outcomes, i.e., enjoyment and perception of time, were evaluated via the validated
questionnaires specified above [14]. Enjoyment was assessed on 7-point Likert-type scales
completed by participants, where +3 was the most enjoyment, 0 was neutral and −3 was the
least enjoyment. Participants also chose 3 descriptive words from a list of 12 words that best
described their own experiences of ACT. Parents ranked their own enjoyment and their chil-
dren’s enjoyment on these scales when the children were under 8 years old. Parents also chose
the 3 descriptive words in these cases.
Perception of time was assessed as the difference between the actual time taken to complete
ACT (measured using a stopwatch) and the apparent time to complete ACT (subjective per-
ception) [14]. The actual time was evaluated as the response (given in minutes) to the question
‘How long does the ACT routine take?’ The apparent time was evaluated as the response
(given in minutes) to the question ‘How long does it feel like it takes to complete ACT?’.
The secondary outcome, i.e., efficiency of the intervention, was evaluated in terms of
avoided healthcare resources to treat respiratory infection exacerbations that required hospi-
talization. The number of exacerbations and the number of days hospitalized during the previ-
ous 3 months and during the 3-month trial period were obtained from the clinic history.
Hospitalization cost (expressed in Euros) was estimated based on the associated diagnosis-
related group (DRG) (DRG 131: CF-Pulmonary disease, average hospitalization: 11.14 days)
[21]. The DGR is a unit for classifying patients by diagnosis, average length of hospital stay
and therapy received.
Statistical analysis
To calculate the sample size, the perception of time taken to complete ACT was used as the
main variable. In the study by Grasso [14], the control group values for this variable were 0.2
min ±10.2 (mean ±SD); based on an assumption of these values as a baseline, a power of 80%,
a confidence level of 95%, and a similar variability at the end of the study, a difference of 8 min
would be considered statistically significant with a sample size of 13 participants. A total of 39
participants are necessary to enable a valid answer to the research question. The variables are
expressed as the mean (±SD) or n (%). To compare quantitative measures, ANOVA/Kruskal-
Wallis tests were used, while chi-square test was used for the qualitative demographic variable
‘gender’. To compare the differences in the change in the variables between the different
groups, from a global point of view, a repeated measures multivariate analysis of variance
(MANOVA) test was applied with a between-participants factor (different groups) and a
within-participants factor (different time points of data collection). Depending on compliance
with the assumption of sphericity, Greenhouse-Geisser correction was used. Box test and
Levene test were used to ensure homogeneity of covariance matrices and error variances,
respectively. To more specifically compare the differences between the baseline and final mea-
sures in each group, the Wilcoxon test was applied. To compare the response to the use of
music after the intervention in the TG and PG, the Mann–Whitney U test was used. Statistical
significance was declared at the 0.05 level. Statistical analysis was performed using SPSS soft-
ware (version 24.0; IBM SPSS Statistics, Chicago, IL).
Results
A total of 54 patients met all the inclusion criteria and agreed to participate in the intervention.
As we explain in the study design, the participants were randomly allocated into the TG
(n = 18), PG (n = 18) and CG (n = 18). Eleven patients were withdrawn when they could not
be contacted by telephone to be interviewed (n = 3), rejected their consent (n = 2) or used the
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music CD (n = 2) or familiar music (n = 4) as an adjunct the ACT less than 50% of the time,
leaving a total of 15 patients in the TG, 15 patients in the CG, and 13 patients in the PG (Fig 1).
The percentage of participants who withdrew from the study (20.4%) was lower than the
potential withdrawal estimated for the study (27.8%, 15 participants). The groups had similar
withdrawal distribution.
The demographic and clinical data and ACT variables are shown in Table 2; the data reflect
standard characteristics of the population of children with CF and show no statistically signifi-
cant differences between groups in the baseline measures.
Concerning the baseline use of adjuncts to ACT prior to the intervention, the most com-
mon adjuncts to ACT were the use of television or other audiovisual devices by 28 (66.7%) par-
ticipants, while music was used by 10 (23.8%) participants. There were no statistically
significant differences in the ACT baseline adjunct measures between the 3 groups. During the
intervention, audiovisual devices were frequently used as adjuncts to ACT in the CG (12,
80%), while 12 (80%) and 11 (73.3%) patients in the TG used the music CD frequently after 6
Fig 1. Flow diagram of the clinical trial.
https://doi.org/10.1371/journal.pone.0241334.g001
Table 2. Demographic and clinical data and baseline ACT variables.
Parameters Control Group (n = 15) Placebo Group (n = 13) Treated Group (n = 15)
Age, years
1
7.2 ±4.3 (2–16) 8.1 ±5.6 (2–17) 7.9 ±4.7 (2–17)
Age of diagnosis, months
1
6.8 ±8.4 (0.5–24) 6.8 ±6.8 (1–24) 6.4 ±7 (0.5–24)
Male
2
8 (53.3) 9 (69.2) 10 (66.7)
BMI
3
16.6 ±1.7 (13.7–19.4) 16.3 ±2.2 (12.1–19.1) 16.9 ±2.2 (12.8–19.6)
Bhalla score
1
19.4 ±3.8 (13–25) 18 ±5 (10–25) 18.9 ±4.7 (9–24)
ACT frequency per day
1
1.3 ±0.5 (1–2) 1.4 ±0.5 (1–2) 1.4 ±0.5 (1–2)
Time to take an ACT session, minutes
3
26 ±3.4 (10–60) 22.4 ±3.7 (10–45) 27.3 ±3.4 (10–60)
Continuous variables are expressed as the mean ±SD (range). Categorical data are expressed as n (%).
1
Median ±SD (range): Kruskal-Wallis test was performed to compare groups.
2
N (%): Chi square test was performed to compare groups for the variable ’gender’.
3
Median ±SD (range): ANOVA test was performed to compare groups. No statistically significant differences were identified.
Abbreviations: BMI, body mass index; ACT, airway clearance therapy. Bhalla score: a lung damage severity rating system for high-resolution computed tomography in
cystic fibrosis. The lower the Bhalla score is, the more severe the condition [22].
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or 12 weeks, respectively. The frequent use of familiar music decreased during the interven-
tion, being used by 10 (76.9%) participants after 6 weeks and 6 (46.2%) participants after 12
weeks. Throughout, participants in the TG and PG used music more than 50% of the time.
The results on children’s enjoyment are shown in Fig 2A. The differences between the 3
groups did not reach statistical significance (group, p = 0.197). However, the change over time
in children’s enjoyment between the groups was statistically significant (interaction,
p = 0.042), and a statistically significant change in children’s enjoyment before and after the
intervention (time points, p = 0.006) was observed. The use of the specifically composed music
or the familiar music was associated with a positive change in children’s perceived enjoyment
of ACT after 12 weeks compared to the use of no music. Thus, the change in enjoyment from
baseline was +0.9 units for the TG (p = 0.004) and +0.56 units (p = 0.035) for the PG compared
with no change in the CG (-0.06 units). A similar response was observed for parents’ enjoy-
ment (Fig 2B); the use of the music CD (+1.7 units, p = 0.009) and familiar music (+0.5 units)
was associated with a positive change in parents’ perceived enjoyment of ACT after 12 weeks
compared with no music (+0.14 units). Again, the differences between the 3 groups did not
reach statistical significance (group, p = 0.493). However, the change over time in parents’
enjoyment between the groups was statistically significant (interaction, p = 0.011), and a statis-
tically significant change in parents’ enjoyment before and after the intervention (time points,
p = 0.001) was observed.
Moreover, the evaluation of the descriptive words chosen to describe the response to ACT
showed that, after use of the music CD, no negative responses were expressed by the children
and parents, while prior to the use of the specific music, 6 (40%) children and 4 (30.8%)
parents expressed negative perceptions. No changes in negative response were observed in the
CG or PG patients or parents. In addition, no adverse effects from the experimental conditions
were observed.
Concerning the analysis of the outcome ’perception of time’, based on Grasso and col-
leagues study [14], the perception of time taken to complete the ACT routine changed posi-
tively after the intervention. Thus, the use of music CD as an adjunct to ACT routine not only
eliminated the feeling of spending much more time taking the ACT routine, but also led par-
ticipants to feel the length of the ACT 11.1 min (±3.9) shorter than the actual time they spent
to carry it out. However, PG and CG continued feeling the length of ACT routine longer than
the actual time they spent taking it. Thus, PG felt the length of routine 3.9 min (±4.2) longer
than actual time, and no changes were observed in the CG, feeling the length of the routine 9.0
min (±3.9) longer than actual time (Fig 3). A statistically significant change in the perception
of time before and after the intervention (time points, p = 0.001), a statistically significant
interaction of time and group (interaction, p = 0.004), and statistically significant differences
in the perception of time between the 3 groups (group, p = 0.038) were observed (Fig 3).
The analysis of the use of the specifically composed, played and compiled music as an
adjunct to ACT compared to the use of familiar music chosen based on the recommendations
given in the study showed a clear positive response in children and parents (2.0±1.4 units, in
both cases) to the use of the music CD and a positive response to the use of familiar music (1.0
±1.4 units, children; 0.9±1.4 units, parents), with statistically significant differences (p = 0.029,
children; p = 0.026, parents). In addition, the music CD was considered useful by 14 (93.3%)
participants (p = 0.023), while the familiar music was useful only to 7 (53.8%). All participants
except one (93.3%) in the TG reported that they would consider using this music or new
recorded music in the future (p = 0.03), but only 5 (38.5%) participants in the PG said they
would consider the use of familiar music. Anecdotal reports indicated that the music CD facili-
tated the relaxation of children and increased enjoyment of ACT (12, 85.7%), helping divert
children’s and parents’ attention away from the time spent on ACT. An enhancement of ACT
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Fig 2. Change in children’s and parents’ enjoyment. (A) Children’s and (B) parents’ enjoyment. Enjoyment was assessed on 7-point Likert-type
scales, where—3 was the least enjoyment, + 3 was the most enjoyment, and 0 was neutral. Values were measured at baseline and in the final
interviews. The data are presented as the mean (±SD). Wilcoxon test was performed to compare the differences between the baseline and final
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management was also reported. However, only 2 (28.6%) participants in the PG reported these
facts. Concerning the time to take an ACT session, the TG tended to spend more time per ses-
sion than the PG (37.1±18.9 min vs. 27.2±12.1 min, p = 0.09).
The number of respiratory infection exacerbations that required hospitalization in each
group and their related cost are shown in Table 3. The average length of hospital stay was
13.66 days. According to the official DRG prices published in Spain, a hospitalization for CF
costs a total of €6,704.87. As we can observe, only one child suffered an exacerbation during
the intervention in the TG, while 3 and 6 exacerbations were reported in the PG and CG,
respectively. Conversely, during the preintervention period, 2 exacerbation episodes were suf-
fered in the TG group, and one each was reported in the PG and CG groups. Based on these
data, the use of the music CD as an adjunct in the ACT yielded a potential cost saving of
€6,704.87. However, in the CG, the cost increased to €33,524.35, and in the PG, the cost
increased to €13,409.74.
Discussion
The results of this study indicate that the specifically composed, played and compiled instru-
mental recorded music is an effective adjunct to ACT. Overall, its use demonstrates effective-
ness in improving children’s and parents’ enjoyment of ACT, reducing the perception of time
taken to complete ACT. Furthermore, the use of the music CD can be considered an efficient
option in terms of the avoided costs related to respiratory infection exacerbations.
Although patients and parents consider ACT to be an integral part of CF management, they
report serious difficulties in carrying it out [23,24]. Chest physiotherapy requires significant
measures in each group. Changes in children’s enjoyment: p = 0.004 (Treated Group);
&
p = 0.035 (Placebo Group); p = 0.89 (Control Group).
Changes in parents’ enjoyment: p = 0.009 (Treated Group); p = 0.096 (Placebo Group); p = 0.492 (Control Group).
https://doi.org/10.1371/journal.pone.0241334.g002
Fig 3. Change in perception of time. To analyze the perception of time, the apparent time value reported on the questionnaire was subtracted from the
actual time value given (actual time—apparent time = perception of time). Positive value: perception of ACT shorter. Negative value: perception of ACT
longer. Values above 0: participants felt they spent less time taking the ACT routine than the actual time they spent to taking it. Values below 0:
participants felt they spent more time taking the ACT routine than the actual time they spent taking it. Differences were calculated at baseline and the final
interviews. The data are presented as the mean (±SD). Wilcoxon test was performed to compare the differences between the baseline and final measures in
each group. Changes: p = 0.003 (Treated Group); p = 0.076 (Placebo Group); p = 0.857 (Control Group).
https://doi.org/10.1371/journal.pone.0241334.g003
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commitments of time and energy, being crucial to establish ACT as a well-structured positive
routine [7,23–25]. Providing enjoyable and stimulating strategies can be an effective tool for
increasing the participation of the population in health-oriented activities [26]. In rehabilita-
tion programs for chronic obstructive pulmonary disease, patient enjoyment is a factor
enabling patients to engage in these programs [27,28]. These enjoyable innovative strategies
also include MT interventions that are carried out in the home or community groups [29–31].
Regarding children with CF, the use of the music CD as an adjunct to ACT elicited a positive
affective response in patients and parents, in line with the findings reported in infants for the
use of specific music during ACT [14] or the use of motivational music while walking by chil-
dren with CF [15]. Concerning the utilization of familiar music based on recommendations,
enjoyment was also increased, and similar results were also found in infants [14]. However,
the characteristics of the music compiled on the CD duplicated the positive effect of familiar
music, with the music CD being the best option. In addition, no negative descriptive words
about ACT were chosen by children or parents after using the music CD. It is evident that cer-
tain musical elements that were taken into account at the time of the composition and playing
of this therapeutic music had an important influence on the positive attitudes that were
observed. Therefore, the results of the current work together with the previous infant study
[14] indicate that music could be used to assist in the establishment of ACT as a positive rou-
tine and that the use of particular music that is composed, played and compiled specifically for
children with CF enhances this positive effect.
The music CD used in the current study incorporated elements to encourage positive
responses, ACT rhythmical interaction and distraction. Thus, the music included fluid
rhythms [32], varied and bright timbres [32–34], intensity changes that were not excessively
marked [32,33], variable sound frequencies [32] and mainly major tonalities [35]. Moreover,
the music CD incorporated slow rhythms [15,36], intervals and consonant chords [34,37] and
sounds without excessively rapid vibrations [33] to elicit relaxation.
Music therapy studies in the pediatric context have demonstrated that the selection of
appropriate music and its elements can positively alter children’s experiences of medical inter-
ventions through distraction and/or relaxation [38–45]. Therefore, it is known that induced
relaxation during appropriate music listening is one of the novel MT strategies implemented
in the management of pulmonary diseases [46]. Relaxation is essential in the course of drug
inhalation to achieve an optimal drug concentration in the lungs. In this study, the music CD
could facilitate distraction and relaxation during ACT, improving the management of the own
ACT. Thus, reports about the use of the music CD suggest that the music itself provided dis-
traction, relaxation and rhythmic support for the management of nebulizer inhalation treat-
ment and airway clearance techniques. In addition, because the music CD was structured in 3
sections with similar lengths to each ACT section, children and/or parents were not required
to time the sections of ACT, and the music reportedly distracted them from the time spent on
the routine.
Table 3. Healthcare resources in children with cystic fibrosis according to the different groups.
Groups Preintervention During the intervention Change
Exacerbations (n) Related cost (€) Exacerbations (n) Related cost (€) Exacerbations (n) Related cost (€)
Treated (n = 15) 2 13,409.74 1 6,704.87 -1 -6,704.87
Placebo (n = 13) 1 6,704.87 3 20,114.61 +2 +13,409.74
Control (n = 15) 1 6,704.87 6 40,229.22 +5 +33,524.35
Preintervention: 3-month period before the intervention; intervention: 3-month trial period; exacerbation: number of respiratory infection exacerbations that required
hospitalization. Hospitalization cost (€) was estimated based on the associated diagnosis-related groups.
https://doi.org/10.1371/journal.pone.0241334.t003
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Regarding the clear change in perception of time observed after using the music CD, it is
evident that certain music elements have an important influence on this variable. Certainly,
the use of the music CD decreased the perception of ACT as a long activity, while this effect
was not found in the PG or CG. Although no significant change in perception of time was
observed in the infant study [14], the anecdotal responses indicated that the time spent doing
ACT with specific recorded music seemed to pass more quickly than during their usual
routine.
Music can be effective as a distracting stimulus when used in pulmonary rehabilitation
training for chronic obstructive pulmonary disease. Among the benefits of music is an increase
in the total time spent on therapy sessions [47,48]. In this sense, the music CD also had an
effect on the time to take an ACT session in our study. During the intervention, the use of the
CD increased the time spent per session, making the time spent close to the required session
time [5,49]. Furthermore, 2 patients in the TG increased the ACT frequency per day from one
to 2 times.
Regarding the evaluation of its efficiency, although our MT strategy was longer than many
MT interventions that have been carried out for pulmonary diseases (2 to 10 week time span)
[10,12,13,30,50], the measure of rate of lung function decline (as FEV1% predicted/year), may
not be appropriate [51,52]. Therefore, we had to use a clinical outcome that could be measured
during this follow-up, i.e., respiratory infection exacerbations. Thus, the efficiency of the inter-
vention was evaluated in terms of avoided healthcare resources to treat respiratory infection
exacerbations that required hospitalization, and the use of the music CD as an adjunct to ACT
could represent a potential cost saving.
Other factors that could affect the results were not analyzed, for instance, those focused on
enhancing the management of ACT [53,54]. The most appropriate ACT and its management
for each child are assessed in our Pediatric Pulmonology Unit periodically. However, some
home environment factors, such as physical space, are hardly controllable.
The strength of the current intervention is that the study design included an independent
PG. However, participants in the CG in the infant study [14] experienced 2 conditions: a con-
trol and a placebo.
This study has limitations. First, our results were based on data from a single center. How-
ever, this study included half of the children with CF in our region with more than 8 million
inhabitants. Second, due to the nature of intervention, it was only possible to blind outcome
assessors, and there may be potential bias. Third, 11 participants were withdrawn from the
study because they could not be contacted by telephone to be interviewed (n = 3), rejected
their consent as a result of family moved (n = 2) or used the music CD (n = 2) or familiar
music (n = 4) as an adjunct the ACT less than 50% of the time, but the number withdrawn was
still lower than that initially estimated for this study (15 participants). Moreover, the with-
drawn participants were similarly distributed among the 3 groups, with the final sample size
equal to or above the sample size necessary in each group to enable valid answers to the
research question (13 participants).
Further long-term studies are needed to analyze whether this positive experience of ACT
has any sustained effects, patients’ perspectives, as well as the efficiency of the intervention in
terms of lung function.
In summary, we present the first MT intervention for children with CF between the ages of
2 and 17, demonstrating that the specifically composed, played and compiled instrumental
recorded music is an effective adjunct to ACT without adverse reactions and is an efficient
option in terms of avoided costs. The music CD improves children’s and parents’ enjoyment
of ACT, reducing the perception of time taken to complete ACT. Moreover, this music can
provide ACT rhythmic support, distraction and relaxation improving the management of the
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own ACT. Therefore, this MT intervention we can expect better clinical outcomes in CF
patients without changes in treatment regimens or programmed clinic visits in CF units.
Supporting information
S1 File. CONSORT checklist.
(PDF)
S2 File. Trial study protocol—original.
(PDF)
S3 File. Trial study protocol—english version.
(PDF)
S4 File. Music characteristics.
(DOCX)
S5 File. Music scores.
(PDF)
S6 File. Questionnaires. Music CD. Because the recorded music was compiled in a physical
format, i.e., an audio compact disc, the songs used in this study are available from the corre-
sponding authors.
(PDF)
Acknowledgments
The authors wish to thank the children and parents for their participation and the time they
committed to this study and M. Paz Diaz Hue
´lamo for her immediate availability.
Author Contributions
Conceptualization: Alberto Montero-Ruiz, Laura A. Fuentes, Javier Pe
´rez Frı
´as, Elisa Martı
´n-
Montañez.
Data curation: Alberto Montero-Ruiz.
Formal analysis: Nuria Garcı
´a-Agua Soler, Francisca Rius-Diaz, Elisa Martı
´n-Montañez.
Funding acquisition: Alberto Montero-Ruiz, Laura A. Fuentes, Javier Pe
´rez Frı
´as, Elisa Mar-
tı
´n-Montañez.
Investigation: Alberto Montero-Ruiz, Estela Pe
´rez Ruiz, Pilar Caro Aguilera, Elisa Martı
´n-
Montañez.
Methodology: Alberto Montero-Ruiz, Laura A. Fuentes, Nuria Garcı
´a-Agua Soler, Javier
Pe
´rez Frı
´as, Elisa Martı
´n-Montañez.
Project administration: Estela Pe
´rez Ruiz, Javier Pe
´rez Frı
´as, Elisa Martı
´n-Montañez.
Resources: Estela Pe
´rez Ruiz, Pilar Caro Aguilera, Javier Pe
´rez Frı
´as.
Visualization: Nuria Garcı
´a-Agua Soler, Francisca Rius-Diaz, Elisa Martı
´n-Montañez.
Writing – original draft: Alberto Montero-Ruiz, Javier Pe
´rez Frı
´as, Elisa Martı
´n-Montañez.
Writing – review & editing: Alberto Montero-Ruiz, Laura A. Fuentes, Estela Pe
´rez Ruiz,
Nuria Garcı
´a-Agua Soler, Francisca Rius-Diaz, Pilar Caro Aguilera, Javier Pe
´rez Frı
´as, Elisa
Martı
´n-Montañez.
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