10.14639/0392-100X-N2742
Objective. The aim of this study was to compare the efficacy of voice therapy combined with standard anti-reflux therapy in reducing symptoms and signs of laryngopharyngeal reflux (LPR). Methods. A randomised clinical trial was conducted. Fifty-two patients with LPR diagnosed by 24 h multichannel intraluminal impedance-pH monitoring were randomly allocated in two groups: medical treatment (MT) and medical plus voice therapy (VT). Clinical symptoms and laryngeal signs were assessed at baseline and after 3 months of treatment with the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Voice Handicap Index (VHI) and GRBAS scales. Results. Groups had similar scores at baseline. At 3-month follow-up, a significant decrease in RSI and RFS total scores were found in both groups although it appeared to be more robust in the VT group. G and R scores of the GRBAS scale significantly improved after treatment in both groups, with better results in the VT group. The VHI total score at 3 months improved more in the VT group (VHI delta 9.54) than in the MT group (VHI delta 5.38) (p &lt; 0.001). Conclusions. The addition of voice therapy to medications and diet appears to be more effective in improving treatment outcomes in subjects with LPR. Voice therapy warrants consideration in addition to medication and diet when treating patients with LPR.
text/xml
1827-675X
2742
en
Thomas L. Carroll
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
multichannel intraluminal impedance-pH monitoring
Is there a role for voice therapy in the treatment of laryngopharyngeal reflux? A pilot study
Text.Serial.Journal
https://www.actaitalica.it/
44
Laryngology
2024-02-27
2023-09-04
2024-02-28
2024-02-28
27-35
1
Thomas L. Carroll
2024/02/27
10.14639/0392-100X-N2742
27
Department of Otolaryngology-Head and Neck Surgery, BWH Voice Program, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
1827-675X
multichannel intraluminal impedance-pH monitoring
en
35
Is there a role for voice therapy in the treatment of laryngopharyngeal reflux? A pilot study
https://www.actaitalica.it/article/download/2742/1071
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2024;44:27-35; doi: 10.14639/0392-100X-N2742




Laryngology


Is there a role for voice therapy in the treatment
of laryngopharyngeal reflux? A pilot study
Maria Rosaria Barillari1,2, Andrea Nacci3, Luca Bastiani4, Giuseppina Mirra1, Giuseppe Costa1, Antonino Maniaci 2,5,
Ludovico Docimo6, Salvatore Tolone6, Federica Giumello1, Fabrizio Minichilli4, Carlos M. Chiesa Estomba2,7,
Jerome R. Lechien2,8,9, Thomas L. Carroll10
1
  Division of Phoniatrics and Audiology, Department of Mental and Physical Health and Preventive Medicine, “L. Vanvitelli” University,
Naples, Italy; 2 Laryngology Study Group of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological
Societies (YO-IFOS); 3 ENT Audiology and Phoniatric Unit, University of Pisa, Pisa, Italy; 4 Clinical Physiology Institute, Consiglio
Nazionale delle Ricerche Area della Ricerca di Pisa (CNR), Pisa, Italy; 5 Department of Medical, Surgical and Advanced Technologies
G.F. Ingrassia, ENT Section, University of Catania, Italy; 6 Division of General, Mininvasive and Bariatric Surgery, “L. Vanvitelli” University,
Naples, Italy; 7 Department of Otorhinolaryngology-Head and Neck Surgery, Hospital Universitario Donostia-Biodonostia Health
Research Institute, Donostia-San Sebastian, Spain; 8 Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, Paris
Saclay University, Paris, France; 9 Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research
Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium; 10 Department of Otolaryngology-Head and
Neck Surgery, BWH Voice Program, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA


SUMMARY
Objective. The aim of this study was to compare the efficacy of voice therapy combined
with standard anti-reflux therapy in reducing symptoms and signs of laryngopharyngeal
reflux (LPR).
Methods. A randomised clinical trial was conducted. Fifty-two patients with LPR diagnosed
by 24 h multichannel intraluminal impedance-pH monitoring were randomly allocated in two
groups: medical treatment (MT) and medical plus voice therapy (VT). Clinical symptoms and
laryngeal signs were assessed at baseline and after 3 months of treatment with the Reflux Symp-
tom Index (RSI), Reflux Finding Score (RFS), Voice Handicap Index (VHI) and GRBAS scales.
Results. Groups had similar scores at baseline. At 3-month follow-up, a significant de-
crease in RSI and RFS total scores were found in both groups although it appeared to be
more robust in the VT group. G and R scores of the GRBAS scale significantly improved
after treatment in both groups, with better results in the VT group. The VHI total score at 3
months improved more in the VT group (VHI delta 9.54) than in the MT group (VHI delta             Received: September 4, 2023
                                                                                                  Accepted: November 13, 2023
5.38) (p < 0.001).
Conclusions. The addition of voice therapy to medications and diet appears to be more
                                                                                                  Correspondence
effective in improving treatment outcomes in subjects with LPR. Voice therapy warrants
                                                                                                  Maria Rosaria Barillari
consideration in addition to medication and diet when treating patients with LPR.                 E-mail: mariarosaria.barillari@unicampania.it
KEY WORDS: voice therapy, laryngopharyngeal reflux, treatment, multichannel
intraluminal impedance-pH monitoring                                                                How to cite this article: Barillari MR, Nacci
                                                                                                    A, Bastiani L, et al. Is there a role for voice
                                                                                                    therapy in the treatment of laryngopharyn-
                                                                                                    geal reflux? A pilot study. Acta Otorhi-
Introduction                                                                                        nolaryngol Ital 2024;44:27-35. https://doi.
                                                                                                    org/10.14639/0392-100X-N2742
Laryngopharyngeal reflux (LPR) is an inflammatory condition where stom-
                                                                                                  © Società Italiana di Otorinolaringoiatria
ach contents move in a retrograde fashion, enter and affect the upper aero-                       e Chirurgia Cervico-Facciale
digestive tract 1 causing a variable presentation of symptoms that can include
dysphonia (chronic or intermittent), excessive throat clearing, globus sensa-                                    OPEN ACCESS
tion, chronic cough, vocal fatigue or vocal effort, sore throat and dysphagia                     This is an open access article distributed in accordance with
among others 2,3. The prevalence of LPR-related symptoms ranges from 10%                          the CC-BY-NC-ND (Creative Commons Attribution-Non-
                                                                                                  Commercial-NoDerivatives 4.0 International) license. The
to 30% in otolaryngology department consultations, reaching up to 50% in                          article can be used by giving appropriate credit and mentio-
                                                                                                  ning the license, but only for non-commercial purposes and
clinical laryngology practices 4. The prevalence may be increasing given the                      only in the original version. For further information: https://
ever-worsening lifestyle and dietary habits of most Western cultures 4. Treat-                    creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                            27
M.R. Barillari et al.




ment options for LPR include diet and lifestyle modifica-         ity was calculated. The above-described evaluation protocol
tions, proton pump inhibitors (PPIs), H2 blockers and/or          was performed at baseline (T0) and at the end of 12 consecu-
alginate or magaldrate 3.                                         tive weeks of treatment (T1) in all patients enrolled.
Preliminary data suggests a potential role for voice therapy
                                                                  Endoscopic evaluation and Reflux Finding Score
in improving both symptoms and signs of LPR, especially
                                                                  (RFS)
in the setting of patients with dysphonic complaints. A com-
                                                                  Laryngoscopic examination was performed using a Storz
bination of voice therapy, medications and dietary changes
                                                                  70° rigid optic (KARL STORZ GmbH & Co. KG, Tuttin-
may be more effective in improving LPR patient outcomes
                                                                  gen, Germany; diameter: 5.6 mm; equipped with an ATMOS
compared to medical management alone 5-7. To the best of
                                                                  Endo-Stroboscope L - ATMOS Medizin Technik GmbH &
the authors’ knowledge, these prior studies selected patients
                                                                  Co KG, Lenzkirch, Germany) and operated through the en-
with LPR using subjective measures alone with or without
                                                                  doscopic software Daisy (2014; ver. 3.6.15, Amplifon SPA,
oesophagoscopy findings of oesophagitis; no objective re-
                                                                  Milan, Italy) with a videoendoscopy module (OMVISIA,
flux tests that can diagnose LPR were included. Therefore,
                                                                  2014, ver. 2.0.8 - Amplifon SPA Milan, Italy). A flexible en-
the aim of the current study was to compare the efficacy of       doscopic examination (Xion EF-N 3.4 nasopharyngoscope
voice therapy in combination with standard anti-reflux ther-      - XION GmbH, Berlin, Germany) was performed in patients
apy to standard anti-reflux therapy alone in reducing laryn-      unable to undergo rigid videoendoscopy. All videoendoscop-
geal signs and symptoms (beyond dysphonia alone) after 3          ic examinations were performed by the same trained laryn-
consecutive months of treatment in patients with multichan-       gologist (M.R.B.) and images were shared and anonymously
nel intraluminal impedance-pH (MII-pH) diagnosed LPR.             evaluated by two other laryngologists (G.C., A.N.) and one
                                                                  voice therapist (G.M.), all experienced in the field of voice
Materials and methods                                             disorders and LPR management. The RFS was rated by two
Patients                                                          independent physicians (G.C., A.N.) blinded to the patients’
Subjects with a diagnosis of LPR were prospectively en-           treatment group and the stage of the study and, given the
rolled from the Division of Phoniatrics and Audiology of          subjective interpretation of the scale, inter-rater agreement
the “Luigi Vanvitelli” University Hospital, Naples (Italy),       for the RFS score was calculated.
from December 2021 to March 2023.                                 Multichannel intraluminal impedance-pH moni-
Patients met the following inclusion criteria: (1) age range      toring (MII-pH)
18-65 years; (2) clinical suspicion of LPR based on a Re-         MII-pH was performed by a trained physician (S.T.) before
flux Symptom Index (RSI) > 13 8,9, Reflux Finding Score           starting a therapeutic protocol in order to confirm reflux epi-
(RFS) > 7 10 and positive 24h MII-pH monitoring 11.               sodes. In brief, a catheter with impedance electrode pairs
Exclusion criteria consisted of: (1) presence of any other or-    located at 3-5, 7-9 and 15-17 cm above the low oesopha-
ganic laryngeal disorders needing medical, rehabilitative or      geal sphincter (LES) and 2 pH sensors at 5 and 15 cm above
surgical treatment (e.g., tumours or vocal fold paralysis); (2)   the LES was used (Sandhill Diversatek, Highlands Ranch,
history of previous medical/surgical treatments, radiotherapy     Colorado-United States). Traces were analysed with Bio-
or voice therapy for head and neck diseases; (3) presence of      view software and reviewed manually by a single expert in-
confirmed neurological and psychiatric illness or treatment;      vestigator (S.T.). The occurrence of reflux at most proximal
(4) alcohol abuse; (5) current smokers; (6) history of upper      channel was recorded and the test was considered positive
respiratory tract infection or treatment within the last month;   in presence of more than 14 reflux episodes recorded at the
(7) active seasonal allergies or asthma; (8) pregnancy; (9)       most proximal site 11.
previous anti-reflux surgery/oesophageal surgical procedure;
(10) other concurrent major medical condition.                    Therapeutic procedures
                                                                  All consecutive patients included in the study were ran-
Clinical and instrumental evaluation                              domly allocated to either the medical treatment group (MT
LPR was initially suspected through the administration of         group) – e.g., diet, lifestyle changes and medications- or
the RSI 8,9 and videolaryngoscopic examination plus RFS 10        the voice therapy group (VT group) – e.g., voice therapy
and confirmed by MII-pH 11. Voice-related symptoms were           plus diet, lifestyle changes and medications.
further assessed with the GRBAS scale 12,13 and the Italian       Patients were randomly allocated into group A (MT group)
Voice Handicap Index (VHI)- original 30 question version 14.      or group B (VT group) using block randomisation. A block
The GRBAS scale was administered by two trained physi-            size of 4 was used, from which 6 blocks with 6 different se-
cians (G.C. and M.R.B.) and the overall interrater reliabil-      quences (AABB, ABBA, ABAB, BBAA, BAAB, BABA)



28
                                                                                           Voice therapy and laryngopharyngeal reflux




were further created. These blocks were repeated until a         cifically, a good hydration programme may be favoured by
total of 13 blocks with a size of 4 each was generated, giv-     nasal breathing through a damp gauze to be performed for
ing a list of 52 in total.                                       10 consecutive minutes up to three times a day and before
Therapeutic protocol included an anti-reflux diet, lifestyle     starting every voice therapy session. Patients were instruct-
modifications and a combination of proton pump inhibitors        ed to breathe through the nose with the nostrils wrapped in
(PPIs, pantoprazole 20 mg twice daily, fasting) and post-        the damp gauze both normally and while performing vocal
meal magnesium alginate three times per day for 12 con-          warm-up exercises (to further facilitate direct hydration of
secutive weeks. The recommended anti-reflux diet regimen         the vocal fold cover) 16.
consisted of predominantly Mediterranean diet. Patients
                                                                 Diaphragmatic breathing
were also provided with a detailed list of potentially reflux-
                                                                 A conscious use of the diaphragm in terms of deep, but not
ogenic foods and beverages 15. Lifestyle changes empha-
                                                                 forced, inspirations and prolonged exhalations, is essential
sised included moderate and daily physical activity, weight
                                                                 both for the functionality of the LES and for adequate pho-
loss/reduction of body mass index (BMI), improved sleep
                                                                 nation. Diaphragmatic breathing exercises were instructed
quality and control of psychosocial stress.
                                                                 to be performed every day, in sessions of 60 respirations,
Voice therapy training                                           2 to 3 times every day. The patient is instructed to inhale a
The intentions of the voice therapy training were twofold:       deep breath through the nose and then exhale through the
first, teaching different exercises in order to reduce the       mouth and repeat. The patient may perform these exercises
amount of refluxate that reaches the pharyngo-laryngeal          both in the upright and supine positions and, during breath-
tract; second, using traditional voice therapy techniques to     ing and phonation, the patient is asked to put one hand on
act on LPR-related hoarseness with the intention of reduc-       the abdomen to increase awareness of movements related
ing vocal effort and vocal trauma.                               to their diaphragmatic excursion.
All subjects in the VT Group underwent in-person voice           After the first 3-4 sessions which were primarily aimed
therapy sessions of about 45 minutes each, twice a week,         at vocal hygiene, adequate hydration, breathing support
for 12 consecutive weeks. They were also instructed to per-      and relaxation training, the voice therapist and physician
form further vocal exercises at home (e.g., sessions of 15       introduced the rehabilitative protocol to the patient. This
minutes each, three times a day) for the entire period. All      included basic vocal exercises such as humming and vocal
sessions were performed by the same speech-language pa-          fry, and specific vocal exercises.
thologist (G.M.) specialised in assessment and rehabilita-       Vocal fry should be used to test the ‘viscosity’ of the vocal
tion of patients with voice disorders and LPR. The voice         fold cover and it is suggested as a manoeuver to ‘clean’ the
therapy training included a general approach to voice coun-      vocal folds, especially in the case of endolaryngeal sticky
seling, posture control and relaxation training, vocal hy-       mucus. It is also useful to verify the freedom and the ampli-
giene management, hydration, breathing support, and gen-         tude of the vibrating wave.
eral and specific vocal exercises. The entire rehabilitation     Humming, on the other hand, is an excellent exercise to
protocol had previously been established by the LPR Study        warm up the voice and to activate the vocal cords in a gen-
Group of the YO-IFOS under the supervision of an expert          tle but firm way. Through this exercise the air -and conse-
voice therapist and senior laryngologists.                       quently the sound- will be projected forward, and this will
Posture control and relaxation training                          allow the larynx to be well relaxed and agile.
To reduce muscle tension and any kind of vocal effort the        Vocal exercises
relaxation training was implemented. It is mainly based on       An adequate excursion and mobilisation of the larynx
isotonic exercises to relax the cervical muscles and was re-     would be able to improve the management of the vocal
peated up to 3 times including resting between one exercise      tract and vocal dynamics reducing vocal effort and voice
and the next. In this context, patients are invited to stretch   hyperfunctional behaviours. Therefore, direct exercises
their head, arms and shoulders while yawning deeply and          may involve:
subsequently shaking arms and legs to release them from          • active mobilisation of the larynx by means of loud yawn
tension.                                                            technique, B technique, ascending/descending glissandi
Vocal hygiene programme                                             (from a low note to a high note and vice versa) and vow-
The vocal hygiene programme includes avoiding exposure              els emission in lingual retroposition;
to laryngeal irritants, periods of voice rest, reduction or      • passive mobilisation of the larynx through laryngeal
avoidance of vocal abuse/misuse and hard glottal attack and         manipulation both in static (during quiet breathing) and
adequate and daily hydration of the glottal plane. More spe-        dynamic (during phonation and swallowing).



                                                                                                                                 29
M.R. Barillari et al.




Statistical analysis                                                                           The overall inter-rater reliability of the GRBAS scale, meas-
All statistical analyses were completed using SPSS Version 24                                  ured as Cohen kappa, was found to be good (kappa G Score
(IBM Corp, Armonk, US) and significance was set at p < 0.05.                                   = 0.84; kappa R Score = 0.88; kappa B Score = 0.86) as
Categorical variables were expressed as percentages while                                      well as the inter-rater reliability of the RFS (kappa = 0.81).
continuous variables were expressed as mean ± standard de-                                     As shown in Figure 1, the VT and MT groups were statisti-
viation (SD) or interquartile range (IQR). Cohen’s kappa was                                   cally similar regarding VHI, RFS, RSI and GRBAS scale.
performed to measure the reliability of the GRBAS score and                                    The mean RSI total score was > 13 (MT-T0: mean = 17.8;
of the RFS. For comparison between categorical and nominal                                     SD = 2.9; median = 17.5; IQR = 15-20.2. VT-T0: mean = 18.0,
variables, the Pearson Chi-Square and the Fisher’s Exact Test                                  SD = 3.0; median = 18.0; IQR = 15-21) and the mean RFS
were used. For all the variables the Kolmogorov-Smirnov nor-                                   total score was > 7 (MT-T0; mean 9.2, SD = 1.5; median = 9;
mality test was used. Non-parametric tests (Mann Whitney U                                     IQR = 8-10; VT-T0 = mean 9.7, SD = 1.6, median = 9,
test, Wilcoxon test) were used to evaluate non-normally dis-                                   IQR = 8-11) in both groups, thus suggestive for LPR. The
tributed variables. To evaluate the degree of improvement in                                   mean VHI total score was ≤ 30 in all enrolled patients and
clinical scores between the 2 groups, the deltas of each meas-                                 therefore suggestive of a mild degree of perceived dysphonia
ure were calculated (Δ VHI score = VHI score T1-VHI score                                      (MT-T0: mean = 22.1; SD = 6.6; median = 20; IQR = 16-30.
baseline; Δ RFS score = RFS score T1-RFS score baseline; Δ                                     VT-T0: mean = 22.8; SD = 6.8; median = 22; IQR: 16-30).
RSI score = RSI score T1- RSI score baseline).                                                 Compared to the GRBAS scale, no subject showed any
                                                                                               grade of Asthenia (A score) and/or Strain (S score) at base-
                                                                                               line, while a slight, insignificant difference of global grade
Results
                                                                                               of dysphonia- G score (MT group 1.31; VT group 1.42; p-
Although 78 patients with suspected LPR had originally                                         value: ns), Roughness-R score (MT group 0.96; VT group
been assessed for eligibility, 7 patients declined the MII-                                    0.96; p-value: ns) and Breathiness-B score (MT group
pH test. Of the remaining 71 patients with positive MII-pH,                                    0.31; VT group 0.31; p value: not significant) was observed
12 did not conform to the inclusion/exclusion criteria, 5                                      (Fig. 1).
did not complete the follow-up evaluation and were thus                                        Statistical evaluation of voice characteristics in patients
excluded from final analyses, and the remaining 2 patients                                     from both groups before therapy (T0) and 3 months after
failed to complete the VT intervention.                                                        therapeutic intervention (T1) is summarised in Table II.
Therefore, the final sample consisted of 52 patients (32                                       Overall, an amelioration of vocal parameters after 3 months
females and 20 males), equally distributed in each group                                       of treatment was observed. This was statistically significant
(N = 26). The sociodemographic and basic clinical char-                                        in both groups with the exception of the B- score that im-
acteristics of the two groups at baseline are reported in Ta-                                  proved significantly in the VT group at T1, but not in the
ble I. None of the characteristics analysed in terms of sex,                                   MT group. In brief, patients who underwent VT training
professional voice use and age showed any statistically sig-                                   had a significant improvement of G- score and R-score
nificant differences between the MT and VT groups.                                             which was significant compared with the MT group (G


Table I. Sociodemographic and basic clinical characteristics of the two groups at baseline.
                                                                            MT group                                 VT group
                                                                     N                    %                    N                  %                            p value
 Gender                                          Female              16                 61.5                  16                61.5                        1.000 * (ns)
                                                  Male               10                 38.5                  10                38.5
 Professional voice use                            No                8                  30.8                   7                26.9                        0.760 * (ns)
                                                   Yes               18                 69.2                  19                73.1
 Active smoker                                     No                26                  100                  26                 100                        1.000 ** (ns)
                                                   Yes               0                    0                    0                  0
 Ex smoker                                         Yes               11                 42.3                   8                30.8                        0.565 * (ns)
                                                   No                15                 57.7                  18                69.2
                                                                                     Mean (sd)                               Mean (sd)
 Age                                                                 26             42.0 (11.9)               26             43.0 (12.9)                    0.774 ° (ns)
* Significance (2-sided) Pearson Chi-Square; ** Significance Fisher’s Exact Test; ° Significance Independent Samples Test; ns: not significant; MT: medical treatment; VT: voice therapy.




30
                                                                                                                                     Voice therapy and laryngopharyngeal reflux




                                                                                                      score at T0 = 1.42 ± 0.50; T1 = 0.5 ± 0.51; p value: <
                                                                                                      0.0001; R score at T0 = 0.96 ± 0.77; T1 = 0.46 ± 0.50; p
                                                                                                      value: 0.001). Similarly, the improvement in the VHI total
                                                                                                      score at T1 was significant in both groups, but in the VT
                                                                                                      group it was almost double (MT-VHI score at T0 = 22.07;
                                                                                                      T1 = 16.69; p value: < 0.001. VT-VHI score at T0 = 22.81;
                                                                                                      T1 = 13.27; p value: < 0.001).
                                                                                                      In terms of LPR-related symptoms and signs, RSI and RFS
                                                                                                      scores and their sub-items are compared between T0 and T1
                                                                                                      in Figures 2 and 3. Figure 2 depicts the significant decrease
                                                                                                      in the RSI total score at T1 in both groups (RSI total score in
                                                                                                      MT group at T0 = 17.77 ± 2.9; RSI total score in MT group
                                                                                                      at T1 = 12.31 ± 3.3; p value < 0.001; RSI total score in VT
                                                                                                      group at T0 = 17.96 ± 3.1; RSI total score in VT group at
                                                                                                      T1 = 10.81 ± 3.5; p value < 0.001). Interestingly, the mean RSI
 VHI: Voice Handicap Index; RFS: Reflux Finding Score; RSI: Reflux Symptom Index; G: Global           total score at T1 falls below 13 in both groups, e.g., below the
 Grade of dysphonia; R: Roughness; B: Breathiness.
                                                                                                      significance value for symptoms attributable to LPR 8.
Figure 1. Clinical data at baseline (T0) in all enrolled patients in the MT and                       Similarly, the RFS total score (Fig. 3) significantly im-
VT groups. No significant differences were found between groups. Compari-                             proved in both groups at T1 compared to the baseline
sons were performed by Mann-Whitney U test.                                                           (RFS in MT group at T0 = 9.19 ± 1.5; RFS in MT group


Table II. Voice characteristics of patients from both groups at baseline (T0) and post-treatment (T1). VHI: Voice Handicap Index.
                                            MT Group                                                                          VT Group
                            Baseline                               T1                                       Baseline                       T1
                     N            Mean (sd)              N            Mean (sd)               p value          N        Mean (sd)          N        Mean (sd)       p value
 VHI score          26           22.07 (6.6)             26          16.69 (6.7)               .000           26       22.81 (6.8)         26       13.27 (5.3)       .000
 G score            26           1.31 (0.47)             26          0.96 (0.72)               .003           26       1.42 (0.50)         26       0.5 (0.51)        .000
 R score            26           0.96 (0.72)             26          0.73 (0.60)               .034           26       0.96 (0.77)         26       0.46 (0.50)       .001
 B score            26           0.31 (0.47)             26          0.19 (0.40)              .564(ns)        26       0.31 (0.47)         26       0.12 (0.32)       .025
G: Global Grade of dysphonia; R: Roughness; B: Breathiness. All comparison were performed by Wilcoxon test.




Figure 2. Comparison between RSI total score and RSI sub-items at baseline and T1 (after 3 months) in the VT and MT groups (the red circles in the figure in-
dicate statistical significance; comparison by Wilcoxon test).



                                                                                                                                                                             31
M.R. Barillari et al.




Figure 3. Comparison between RFS total score and RFS sub-items at baseline and T1 (after 3 months) in the VT and MT groups (the red circles in the figure
indicate statistical significance; comparison by Wilcoxon test).


at T1 = 7.35 ± 2.3; p value < 0.001. RFS in VT group at                        ment improved significantly: the MT group showed a mean
T0=9.69 ± 1.6; RFS in VT group at T1=6.08 ± 2.3; p value                       delta VHI of 5.38 points (median, 5; IQR, 6.2/3.7), while the
< 0.001). Unlike RSI values, the average RFS values did                        VT group demonstrated a higher delta VHI of 9.54 (median,
not return below the normal threshold of < 7.                                  9; IQR, 12.2/-7) (p value < 0.001; U di Mann-Whitney test).
Upon analysing the change in the individual sub-items of
RSI and RFS, an improvement was seen in all the param-                         Discussion
eters evaluated at T1 in both groups as reported in Figure 2.
More specifically, we observed the following:                                  This study intended to evaluate whether adding voice ther-
1) Improvement of all the evaluated parameters of the RSI                      apy to medical and diet/lifestyle treatment would be more
    - which was statistically significant for the items globus                 effective in managing LPR-related symptoms and signs
    sensation, chronic cough and excess throat mucus - in                      compared to medical treatment and diet/ lifestyle modifica-
    the MT group at T1 compared to baseline (Fig. 2);                          tions alone. This topic has already been considered in the
2) Improvement of all parameters evaluated of the RSI in                       literature with encouraging data for voice and LPR specific
    the VT group, which was statistically significant for the                  outcomes, although this study is the first to select LPR pa-
    majority of the items at T1 compared to the baseline,                      tients using MII-pH technology and treat patients medi-
    in particular globus sensation, chronic cough, choking,                    cally with more than acid-suppression medications, such
    excess throat mucus, throat clearing and hoarseness                        as PPIs, alone.
    (Fig. 2);                                                                  How subjects are selected for inclusion in studies evaluating
3) A statistically significant improvement in the MT group                     the medical management of LPR is important. The prior stud-
    at T1 compared to baseline was seen for the following                      ies that evaluated adding voice therapy to more traditional LPR
    RFS items: endolaryngeal mucus, diffuse laryngeal                          management require scrutiny in this area. There is significant
    oedema and erythema/hyperaemia (Fig. 3).                                   controversy regarding the ability of RSI and RFS to diagnose
A significant improvement in the VT group compared to                          LPR and prior work on this subject has employed these criteria
the baseline of the RFS items endolaryngeal mucus, diffuse                     without objective reflux testing. The current study team admit-
laryngeal oedema, vocal fold oedema and erythema/hyper-                        tedly did not have access to the newest “LPR” pH-impedance
aemia with improvement, although not significant, of the                       catheters during the period of data collection for this study.
item posterior commissure hypertrophy (Fig. 3).                                The “LPR” catheters have distal impedance electrode pairs but
Although the improvement of the VHI, RFS and RSI total                         also pharyngeal impedance electrode pairs that cross the up-
score was evident in both groups, it was observed that, for all                per oesophageal sphincter (UES) and place the proximal pH
the scores evaluated, the delta scores was greater for the VT                  sensor at or above the UES. The catheter configuration used
group (Fig. 4). The VHI total score after 3 months of treat-                   in the current study has its most proximal impedance electrode



32
                                                                                                                                       Voice therapy and laryngopharyngeal reflux




 VHI: Voice Handicap Index; RFS: Reflux Finding Score; RSI: Reflux Symptom Index. Comparisons were performed by Mann-Whitney U test.


Figure 4. The delta (change in score: positive delta means improvement, negative delta means worsening sign or symptom) of measures (T1-Baseline): VHI,
RFS and RSI.


pair at 17 cm above the LES. Traditional gastro-esophageal                                          (RFS) of LPR after 12 weeks of treatment with acid sup-
reflux disease (GERD) criteria (32 or more impedance events                                         pression, alginate therapy and a recommendation for a
at 17 cm above LES and expecting symptom correlation with                                           Mediterranean diet in addition to emphasising moderate
events) used to designate a positive test using traditional MII-                                    and daily physical activity, weight loss/reduction of BMI,
pH catheters has been shown to miss LPR positive episodes                                           improved sleep quality and control of psychosocial stress.
in the pharynx (as would be detected on “LPR” type MII-pH                                           Additionally, sub-items of the RSI and RFS were evaluated
catheters) 18. However, more recently published data and ongo-                                      to determine if individual items were more susceptible to
ing work by one of the senior authors (T.C.) has demonstrated                                       the improvement with the addition of voice therapy. When
that 2 or more pharyngeal events are likely to be present if there                                  evaluating the sub-items of the RSI, globus sensation, ex-
are 14 or more impedance events at 17 cm or more above the                                          cess throat mucus and chronic cough improved in both MT
LES using the older pH-impedance catheter configuration, as                                         and VT groups after 3 months of treatment. Interestingly, in
was used in the current study 11. For these reasons, 14 or more                                     the VT group there was also a significant improvement of
impedance events at 17 cm above the LES was used to include                                         throat clearing, hoarseness and choking episodes.
a subject as one who has signs and symptoms due to LPR.                                             Although the RFS improved in both groups in a significant
Using criteria of RSI and RFS without MII-pH reflux testing                                         way after 3 months of treatment, it maintained a score of
to include their subjects, Vashani et al. 5 and Beech et al. 7                                      > 7. Therefore, the score still indicated the presence of ob-
reported that treatment of LPR with medication and voice                                            jective signs of LPR, suggesting a slower amelioration of
therapy resulted in improved subjective measurements in                                             laryngeal signs compared with the symptom scores. It may
their patients. Vashani et al. did include oesophagitis on                                          also suggest that the remaining signs were multifactorial in
oesophagoscopy to include subjects, although this is not a                                          the first place and the signs evaluated by the RFS may not
proven diagnostic finding in those with LPR, akin to many                                           be specific to LPR. These results were consistent with those
with LPR having normal oesophagoscopy. A few years lat-                                             of other previous reports in which physical findings tend to
er, Park et al. 6 reported, on a sample of 100 LPR patients,                                        improve slower than clinical symptoms 20. Analysing the
that the symptom-associated scores (RSI, VHI) improved                                              sub-items, we found that laryngeal hyperaemia and endola-
in a clinically significant manner regardless of adding voice                                       ryngeal mucus significantly improved in both groups but,
therapy. However, voice therapy shortened the time of re-                                           interestingly, vocal fold oedema significantly improved in
covery by 2 months and the improvement in the RSI or VHI                                            the VT group and not in the MT group.
remained more improved in the voice therapy plus medical                                            This study emphasises the important role that voice therapy
management group at the final 3-month follow-up evalu-                                              can play in support to anti-reflux medical, diet and lifestyle
ation compared to the medical management group alone.                                               treatments alone: 1) to reduce the mucosal damage induced
Moreover, a recent systematic review 19, asserted that for                                          by acid, pepsin and bile salts, by means of exercises that
patients with LPR and predominant vocal symptoms there                                              tone and strengthen the LES (breathing support); 2) to
is evidence that supports voice therapy.                                                            avoid damaging, compensatory phonatory behaviours that
Our study demonstrates that voice therapy significantly im-                                         patients may develop in response to chronic reflux and the
proved clinical symptoms (RSI, VHI, GRBAS) and signs                                                subsequent true vocal fold inflammatory changes, thus im-



                                                                                                                                                                             33
M.R. Barillari et al.




proving the quality of the voice with little perceived vocal       pandemic that limited access to the outpatient facilities for
effort; 3) to redirect patients with chronic, irritative laryn-    several months. Second, the diagnosis of LPR was made us-
geal symptoms to use alternative behaviours to throat clear-       ing event-number criteria based on prior research compar-
ing, coughing etc., thus promoting the recovery of the neg-        ing the more traditional configuration of MII-pH catheters
ative mucosal changes by alleviating the ongoing causes of         to the newest “LPR” type MII-pH catheter configuration
repetitive, mechanical irritation and injury.                      (also called hypopharyngeal-oesophageal multichannel in-
As reported in some pathophysiologic models 21, LPR pa-            traluminal impedance with dual pH testing, or HEMII-pH).
tients demonstrated a chronic downregulation of mucin              While admittedly not as clean as using the newer HEMII-
genes with chronic dehydration of their mucous (“sticky            pH catheters themselves, understanding that the number
mucus”) which led to increased viscosity with negative             of pharyngeal events can be extrapolated from the current
consequences on true vocal fold vibration. Dryness of              MII-pH catheter data was more attractive than using acid-
Reinke’s space has been also recently suggested as an addi-        only/GERD criteria that would have missed patients with
tional microscopic change related to reflux 21. Furthermore,       true LPR. Third, an intermediate follow-up (after 1 and 2
chronic cough and throat clearing secondary to the dehy-           months of treatment) was not performed in our patients for
dration and accumulation of endolaryngeal sticky mucus             similar reasons, and it is felt that interval follow-up visits
may be responsible for an exacerbation of the pressure ap-         between T0 and T1 would have been very useful in assess-
plied to the mucosa during these behaviours and phonation,         ing whether patients undergoing VT improved their clinical
increasing vocal microtraumas, altering the resistance of          and endoscopic parameters more rapidly than the MT group.
the epithelium and worsening the overall clinical picture          Similarly, the current study lacks further 6-month follow-up
in a vicious cycle. Adequate hydration of the true vocal           to assess whether voice therapy training is able to provide
folds may be useful in counteracting the chronic dehydra-          patients longer term results compared to medical treatment
tion of mucous, simultaneously reducing throat clearing,           alone. Fourth, the evaluation of the voice quality with objec-
hoarseness and globus sensation 22. Hydration may also             tive assessment including acoustic measurements or blinded
facilitate normal phonation by helping to prevent negative         perceptual voice ratings was also not performed. Finally, it
consequences on the vibration process, especially on the           would have been useful to evaluate the pressure level of the
free-edge of the vocal fold, which may reduce the ampli-           LES before and after voice therapy training in the VT group
tude of the mucosal wave and may shorten the closed phase          by means of esophageal manometry.
during phonation 22. Relaxation training, breathing support
and vocal exercises should also be useful to prevent the hy-
                                                                   Conclusions
perfunctional behaviours of the thyroarytenoid muscle and
the secondary muscle tension dysphonia.                            Voice therapy appears to be associated with better subjective
As demonstrated in recent literature, daily and correctly          improvement of signs and symptoms in patients with MII-
applied diaphragmatic training exerts a compression ac-            pH-diagnosed LPR after 3 months of treatment compared to
tion on the LES, counteracting sudden variations in intra-         those receiving medical, diet and lifestyle treatment alone.
abdominal pressure. Prior studies have shown that breath-          Voice therapy should be taken into consideration as part of
ing exercises may improve LES fibre tension, reducing the          an integrated treatment protocol for patients with LPR. Fur-
frequency of one-time oesophageal relaxation and increas-          ther studies with larger sample sizes and both shorter and
ing the rate of gastric emptying 23. Moreover, as shown by         longer follow-ups are warranted to confirm the present re-
Amhadi et al, standardised diaphragmatic breathing signifi-        sults and to determine if voice therapy may more efficiently
cantly improved quality of life and was able to induce sig-        improve signs and symptoms of LPR and/or maintain these
nificant change in LES pressure when evaluated by oesoph-          results longer than traditional medical reflux treatments.
ageal manometry 24. Preliminary data published by Moffa
et al. 25 emphasised how a specific inspiratory muscle train-      Conflict of interest statement
ing technique could be useful, alone or in association with        The authors declare no conflict of interest.
diet/PPI, in significantly improving GERD symptoms, RSI
and laryngeal endoscopy score after 4 weeks of treatment.          Funding
This study includes some important limitations. First, the         This research did not receive any specific grant from funding
number of enrolled patients is relatively small, and the re-       agencies in the public, commercial, or not-for-profit sectors.
sults should be consequently considered as preliminary. The
relatively small sample size is due, in part, to the purposeful-   Author contributions
ly restrictive inclusion criteria as well as to the SARS-COV-2     MRB: designed and coordinated the study, participated in



34
                                                                                                              Voice therapy and laryngopharyngeal reflux




data acquisition and analysis, interpreted the data and drafted              10
                                                                                  Belafsky PC, Postma GN, Koufman JA. The validity and reliability of
                                                                                  the Reflux Finding Score (RFS). Laryngoscope 2001;111:1313-1317.
and revised the manuscript; AN, GM, GC: participated in                           https://doi.org/10.1097/00005537-200108000-00001
data acquisition and analysis; drafted the work; revised the                 11
                                                                                  Sikavi D, Cai J, Leung R, et al. Impaired proximal esophageal con-
manuscript; LB, FM: participated in data acquisition and                          tractility predicts pharyngeal reflux in patients with laryngopharynge-
made the statistical analysis; TLC: substantial contributed                       al reflux symptoms. Clin Transl Gastroenterol 2021;12:E00408. doi:
to the conception and design of the study; interpreted the                        10.14309/ctg.0000000000000408
study results; revised the work; made final approval of the
                                                                             12
                                                                                  Dejonckere P, Remacle M, Fresnel-Elbaz E, et al. Differentiated per-
                                                                                  ceptual evaluation of pathological voice quality: reliability and cor-
version to be published; JL, CCE, AM: critically revised the                      relations with acoustic measurements. Rev Laryngol Otol Rhinol
manuscript; LD, ST, FG: participated in data acquisition and                      1996;117:219-224.
analysis. All authors critically reviewed the article for impor-             13
                                                                                  Barillari MR, Volpe U, Mirra G, et al. Surgery or rehabilitation: a
tant intellectual content and approved the final manuscript.                      randomized clinical trial comparing the treatment of vocal fold polyps
                                                                                  via phonosurgery and traditional voice therapy with “Voice Therapy
                                                                                  Expulsion” training. J Voice 2017;31:379.e13-379.e20. https://doi.
Ethical consideration                                                             org/10.1016(j.voice.2016.07.002
The data published in the present work derives from the                      14
                                                                                  Schindler A, Ottaviani F, Mozzanica F, et al. Cross-cultural adapta-
project “LPR and psycological distress” approved by the                           tion and validation of the Voice Handicap Index into Italian. J Voice
                                                                                  2010;24:708-714. https://doi.org/10.1016/j.jvoice.2009.05.006
Institutional Ethical Committee of the “L. Vanvitelli”                       15
                                                                                  Lechien JR, Bobin F, Mouawad F, et al. Development of scores assess-
University Hospital, (Naples, Italy) (Prot. 0035783/i,                            ing the refluxogenic potential of diet of patients with laryngopharyn-
15/12/2021). All procedures were conducted ethically, with                        geal reflux. Eur Arch Otorhinolaryngol 2019;276:3389-3404. https://
all study procedures being performed in accordance with                           doi.org/10.1007/s00405-019-05631-1
the requirements of the World Medical Association’s Dec-
                                                                             16
                                                                                  Borragan M, Mediavilla BG, Legina MA et al. Nasal breathing
                                                                                  through a damp gauze enhances surface hydration of the vocal folds
laration of Helsinki.                                                             and optimizes vocal function. J Voice 2023;37:973.e1-973.e10. htt-
                                                                                  ps://doi.org/10.1016/j.jvoice.2021.06.023
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