Journal of Voice

Efficacy of Speech-language Pathology therapy in Chronic Cough: Systematic Review

with Meta-analysis
--Manuscript Draft--

Manuscript Number:

Article Type: Review article

Keywords: chronic cough; speech-language pathology therapy; systematic review

Corresponding Author: Vanessa Veis Ribeiro, PhD

Universidade Federal da Paraiba
Lagarto, Sergipe BRAZIL

First Author: Vanessa Veis Ribeiro, PhD

Order of Authors: Vanessa Veis Ribeiro, PhD

Maria Christina Bussamara Casmerides

Zélia Maria Conceição da Silva Reis

Ícaro Vinícius de Santana

Rodrigo Dornelas do Carmo

Mara Behlau

Abstract: Objectives: To analyze the efficacy of speech-language pathology therapy in adults

with chronic cough. Data Synthesis: This is a systematic review with meta-analysis that
answered the clinical question: "In adults with chronic cough, what is the effect of the
speech-language pathology therapy in the cough frequency and cough threshold, in
the self-assessment and the vocal quality, compared to another intervention?"
(PROSPERO 2021/CRD42021226729). An electronic search (MEDLINE, Web of
Science, EMBASE, SCOPUS, Cochrane Library, and Lilacs), and a manual search
(Journal of Voice, Brazilian Library of Theses and Dissertations, Open Grey and
Clinical Trials) with specific search strategies was performed. The risk of bias was
assessed using the Cochrane Collaboration's tool for assessing the risk of bias in
randomized trials. Meta-analysis (standardized difference of means, Inverse Variance,
and random effects model) and heterogeneity analysis (Tau², and I²) were performed.
We found 610 studies and selected five. There was a risk of selection, performance,
and detection bias. The data were heterogeneous, and there was no difference
between interventions in self-perception of cough impact (z=0.2195, p=0.8262;
tau²=0.702, I²=86.11%) and the frequency and severity of cough (z=-0.2020, p=0.839;
tau²=0.865, I²=88.77%). Conclusion: There was no difference in the efficacy of speech-
language pathology management and other interventions in the self-perception of
patients with chronic cough.

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Manuscript File

Centro de Estudos da Voz

To Prof. Robert T. Sataloff,

Editor-in-Chief, Journal of Voice

Dear Prof. Sataloff,

I wish to submit an original article for publication in the Journal of Voice, titled

“Efficacy of Speech-language Pathology therapy in Chronic Cough: Systematic

Review with Meta-analysis” The paper was coauthored by Vanessa Veis Ribeiro,

Maria Christina Bussamara Casmeride, Zélia Maria Conceição da Silva Reis, Ícaro

Vinícius de Santana, Rodrigo Dornelas do Carmo, and Mara Behlau. I attest to the

fact that all authors listed on the title page have read the manuscript, legitimacy of the

data and its interpretation, and agree to its submission to the Journal of Voice.

This paper consists of a study that was conducted in order to analyze the efficacy

of speech-language pathology therapy in adults with chronic cough. This manuscript has

not been published elsewhere in part or in entirety and is not under consideration by

another journal. We have read and understood your journal’s policies, and we believe

that neither the manuscript nor the study violates any of these. There are no conflicts of

interest to declare.

Thank you for the opportunity to submit this research paper for the Journal of Voice.

August 23th, 2021.

Sincerely,

Vanessa Veis Ribeiro, Maria Christina Bussamara Casmeride, Zélia Maria Conceição da

Silva Reis, Ícaro Vinícius de Santana, Rodrigo Dornelas do Carmo, and Mara Behlau

Centro de Estudos da Voz – CEV

Postal address: Machado Bitencourt Street, n. 361, Vila Clementino, São Paulo - SP,

Brazil. ZIP CODE: 04044-001

E-mail: fgavanessavr@gmail.com
Manuscript File Click here to view linked References

1 Efficacy of Speech-language Pathology therapy in Chronic Cough: Systematic

2
3 Review with Meta-analysis
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8 Author names and affiliations:
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10 Vanessa Veis Ribeiro, PhD. Speech-Language Pathology Department,
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12 Universidade Federal da Paraíba - UFPB. Cidade Universitária, Conjunto Presidente
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15 Castelo Branco III, João Pessoa - PB, Brazil. ZIP CODE: 58051-900. E-mail:
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17 fgavanessavr@gmail.com
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19 Maria Christina Bussamara Casmerides, Speech-Language Pathology. Doctoral
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21 Student ORL/CCP - Laringe e Voz, Universidade Federal de São Paulo - UNIFESP.
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24 R. Botucatu, 740 - Vila Clementino, São Paulo - SP, Brazil. ZIP CODE: 04023-062.
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26 E-mail: mcbcasmerides@unifesp.br
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28 Zélia Maria Conceição da Silva Reis, Student Speech-Language Pathology
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30 Department, Universidade Federal de Sergipe - UFS. Governador Marcelo Dedá
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Avenue, 13, Centro, Lagarto, Sergipe, Brazil. ZIP CODE: 49400-000. E-mail:
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35 zelhinhasr@gmail.com
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37 Ícaro Vinícius de Santana, Student Speech-Language Pathology Department,
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39 Universidade Federal de Sergipe - UFS. Governador Marcelo Dedá Avenue, 13,
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Centro, Lagarto, Sergipe, Brazil. ZIP CODE: 49400-000. E-mail:
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44 santana.v.icaro@gmail.com
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46 Rodrigo Dornelas do Carmo, PhD. Speech-Language Pathology Department,
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48 Universidade Federal do Rio de Janeiro – UFRJ. Prof. Rodolpho Paulo Rocco Street,
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50 Cidade Universitária, Rio de Janeiro - RJ, Brazil. ZIP CODE: 21910-590. E-mail:
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53 rodrigodornelas@medicina.ufrj.br
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55 Mara Behlau, PhD. Speech-Language Pathology Department, Universidade Federal
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57 de São Paulo - UNIFESP. Botucatu Street, 802, Vila Clementino, São Paulo, São
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59 Paulo, Brazil. ZIP CODE: 04023-062. Centro de Estudos da Voz – CEV. Machado
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 Bitencourt Street, n. 361, Vila Clementino, São Paulo - SP, Brazil. ZIP CODE: 04044-
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2 001. E-mail: mbehlau@uol.com.br
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5
6
7 Corresponding author:
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9 Vanessa Veis Ribeiro
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11 Centro de Estudos da Voz – CEV
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13 Postal address: Machado Bitencourt Street, n. 361, Vila Clementino, São Paulo - SP,
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16 Brazil. ZIP CODE: 04044-001
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18 E-mail: fgavanessavr@gmail.com
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22 Declaration of interest:
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There are no conflicts of interest to declare.
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29 Funding: None.
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Manuscript File Click here to view linked References

Efficacy of Speech-language Pathology therapy in Chronic Cough: Systematic Review

1
2 with Meta-analysis
3
4
5
6
Abstract
7
8
9 Objectives: To analyze the efficacy of speech-language pathology therapy in adults with
10
11 chronic cough. Data Synthesis: This is a systematic review with meta-analysis that answered
12
13 the clinical question: "In adults with chronic cough, what is the effect of the speech-language
14
15
pathology therapy in the cough frequency and cough threshold, in the self-assessment and
16
17
18 the vocal quality, compared to another intervention?" (PROSPERO
19
20 2021/CRD42021226729). An electronic search (MEDLINE, Web of Science, EMBASE,
21
22 SCOPUS, Cochrane Library, and Lilacs), and a manual search (Journal of Voice, Brazilian
23
24 Library of Theses and Dissertations, Open Grey and Clinical Trials) with specific search
25
26
27 strategies was performed. The risk of bias was assessed using the Cochrane Collaboration's
28
29 tool for assessing the risk of bias in randomized trials. Meta-analysis (standardized difference
30
31 of means, Inverse Variance, and random effects model) and heterogeneity analysis (Tau²,
32
33 and I²) were performed. We found 610 studies and selected five. There was a risk of
34
35
36 selection, performance, and detection bias. The data were heterogeneous, and there was no
37
38 difference between interventions in self-perception of cough impact (z=0.2195, p=0.8262;
39
40 tau²=0.702, I²=86.11%) and the frequency and severity of cough (z=-0.2020, p=0.839;
41
42 tau²=0.865, I²=88.77%). Conclusion: There was no difference in the efficacy of speech-
43
44
language pathology management and other interventions in the self-perception of patients
45
46
47 with chronic cough.
48
49 Keywords: chronic cough; speech-language pathology therapy; systematic review
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 Introduction
1
2 Cough is a physiologic reflex defense mechanism to clean the lower airways (1). It
3
4 can be classified according to its duration, i.e., acute cough (lasting less than three weeks),
5
6
7
subacute cough (lasting from three to eight weeks), or chronic cough (lasting more than eight
8
9 weeks) (2). In cases (7,13,14) that the chronic cough is resistant to medical treatment, it is
10
11 called refractory chronic cough.
12
13 The chronic cough’s main symptoms are a sensation of tickling, discomfort, laryngeal
14
15
irritation, or sensitivity which will stimulate the cough reflex (1). Chronic cough may
16
17
18 negatively impact the quality of life regarding social, physiological, and physical aspects with
19
20 uncomfortable days or asymptomatic days (5). Coughing can also result in phono-traumatic
21
22 behaviors (4).
23
24 The treatment of cough includes pharmaceutical treatment with antitussive (15,16),
25
26
27 and recently cough suppression therapy. This cognitive-behavioral approach aims the
28
29 refractory chronic cough suppression by breaking the cycle of reciprocal irritation of cough
30
31 receptors and it is used especially when medical intervention has failed (17). The reduction
32
33 of exposure to laryngeal irritants, such as oral breathing, gastro-esophageal reflux, alcohol
34
35
36 intake, among others, will reduce phono-traumatic behaviors due to constant coughing.
37
38 The speech-language pathology therapy for chronic cough aims to suppress cough,
39
40 reduce cough reflex sensitivity or increase cough reflex threshold and, reduce laryngeal
41
42 irritation. Thus, the therapy includes counseling on cough and laryngeal well-being; cough
43
44
suppression, control, or replacement; and improving the respiratory and laryngeal control
45
46
47 (4,17).
48
49 The speech-language pathology intervention for chronic cough is recent; nonetheless,
50
51 they present positive outcomes regarding self-perception, cough frequency, and cough
52
53 threshold. In addition, there is improvement in the vocal quality of patients who had
54
55
56 presented vocal deviations due to phono trauma related to coughing (7). However, the
57
58 speech-language pathology intervention still lacks consensus regarding the procedures and
59
60 outcomes. The comparison between speech-language pathology rehabilitation and other
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 intervention, such as indirect therapy and pharmaceutical treatment, may contribute to the
1
2 speech-language pathology management of chronic cough.
3
4 This study aimed to analyze the efficacy of speech-language pathology therapy in the
5
6
7
frequency and cough reflex threshold, in the self-assessment, and the vocal quality of adults
8
9 with chronic cough.
10
11
12
13 Methods
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15
This study is a systematic review with meta-analysis (SRM) of effectiveness. The
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18 protocol was registered at PROSPERO (2021/CRD42021226729). The study followed the
19
20 PRISMA-ScR guideline (18).
21
22 The study design followed the PICO strategy where:
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24 P (patient): over 18 years old, with the diagnosis of chronic cough
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26
27 I (intervention): speech-language pathology therapy with direct and indirect interventions
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29 C (comparison): another intervention of direct or indirect therapy, pharmaceutical treatment,
30
31 or placebo
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33 O (outcomes): cough frequency and cough threshold, self-perception, vocal quality.
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35
36 The research question was: In individuals with chronic cough, what is the effect of the
37
38 speech-language pathology therapy in the cough frequency and cough threshold, in the self-
39
40 assessment, and the vocal quality when compared to another intervention?
41
42 Electronic and manual searches were performed. The electronic searches included
43
44
MEDLINE, Cochrane Library, EMBASE, Web of Science, SCOPUS, and LILACS database.
45
46
47 The specific search strategies are described in Figure 1. The manual search was performed
48
49 directly in the Journal of Voice, in the Brazilian Digital Library of Theses and Dissertations
50
51 (BDTD), in the Open Grey, and in Clinical Trials. In addition to scanning the references of the
52
53 included articles.
54
55
56 <Insert Figure 1>
57
58 Two independent authors performed the search, selection, data extraction, and the
59
60 risk of bias analysis.
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 Eligibility criteria were established to perform the selection. The inclusion criteria
1
2 were: participants over 18 years old; the presence of a medical diagnosis of chronic cough;
3
4 speech-language pathology therapy with direct and indirect interventions; placebo control
5
6
7
intervention, pharmaceutical treatment, indirect intervention, or other direct intervention;
8
9 evaluation before and after the intervention including cough frequency and cough threshold,
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11 self-assessment of the cough frequency and cough severity symptoms, self-assessment
12
13 using the Leicester Cough Questionnaire (30,31) or perceptual-judgment of the vocal degree
14
15
of deviation.
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17
18 The exclusion criteria were: children or patients without chronic cough diagnosis; not
19
20 undergo speech-language pathology therapy; no control group; no assessment of cough
21
22 frequency and cough threshold, no self-assessment of the cough frequency and cough
23
24 severity symptoms, and no self-assessment using the Leicester Cough Questionnaire or
25
26
27 perceptual-judgment of the vocal degree of deviation before and after the intervention. The
28
29 selection procedures of the articles were: 1) reading the title and abstract to verify the
30
31 inclusion criteria; and 2) reading the full article to verify the exclusion criteria.
32
33 The risk of bias was assessed independently by two authors using the Cochrane
34
35
36 Collaboration's tool for assessing risk of bias in randomized trials. Disagreements were
37
38 analyzed by a third author.
39
40 The qualitative data were extracted according to the publication (authors, year,
41
42 country, and design), the sample (gender, age, and diagnosis), and the experimental and
43
44
control interventions (group size, number of sessions, intervention, and session time). The
45
46
47 quantitative data were also extracted for the meta-analysis: analysis of self-assessment
48
49 using the Leicester Cough Questionnaire (LCQ) and cough frequency and cough severity
50
51 symptoms; analysis of cough frequency and cough threshold using the Leicester Cough
52
53 Monitor (LCM); analysis of the overall degree of vocal deviation using the Consensus
54
55
56 Auditory-Perceptual Evaluation of Voice (CAPE-V).
57
58 The qualitative data were individually described. The meta-analysis of continuous
59
60 quantitative variables was performed considering the standardized difference of means, the
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63
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 Inverse Variance statistical test, and the random-effects model. The heterogeneity analysis
1
2 used the Tau² test and the maximum likelihood estimator, the Cochran Q test, and the I²
3
4 statistic. In cases of heterogeneity, a confidence interval prediction for true results was
5
6
7
performed. Studentized residuals and Cook's distances were used to examine whether
8
9 studies might be outliers and/or influential in the context of the model. The rank correlation
10
11 was used to verify the asymmetry of the funnel plot, considering the standard error of the
12
13 results as a predictor.
14
15
16
17
18 RESULTS
19
20 Figure 2 presents the flow diagram for searching and selecting articles. The electronic
21
22 searches found 289 studies (MEDLINE = 24; EMBASE = 17; WEB OF SCIENCE = 198;
23
24 COCHRANE LIBRARY= 10; SCOPUS = 40; LILACS = 0) and the manual search found 321
25
26
27 studies (Citation searching = 2; Journal of Voice = 312; BDTD = 0; OpenGrey = 0; Clinical
28
29 Trials = 3). A total of 45 studies were excluded from the electronic search due to duplicity;
30
31 hence, 244 studies were initially considered. By reading the title and abstract, 35 articles
32
33 were included; next, 32 articles were excluded according to the exclusion criteria. Three
34
35
36 articles were selected from the manual search. After reading the full articles, one was
37
38 excluded according to the inclusion and exclusion criteria. Therefore, five articles were
39
40 selected for further analysis.
41
42 <Insert Figure 2>
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44
One study (10) presented a high risk of selection and performance bias and, unclear
45
46
47 risk of other bias. Four studies (11,8,12) had unclear detection bias (Figure 3).
48
49 <Insert Figure 3>
50
51 Overall, the present Systematic Review with Meta-analysis (SRM) presented a 20%
52
53 of high risk of selection and performance bias, and an 80% risk of unclear detection bias
54
55
56 (Figure 4).
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58 <Insert Figure 4>
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 Chart 1 shows that the studies were performed between 2006 and 2020; most studies
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2 are from Australia and published in the last five years. All articles were experimental studies.
3
4 Frequently, the sample characterization were patients of both genders, aged between 54 and
5
6
7
64 years old and diagnosed with chronic cough. The number of participants ranged from 9 to
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9 44. Most interventions consisted of four sessions. The sessions lasted from 30 to 60 minutes;
10
11 however, 30 minutes was more frequent. Regarding the intervention groups, the
12
13 Experimental Group was submitted to the SPEICH-C program, and the Control Group was
14
15
submitted to the Healthy Life Style Education Intervention Program.
16
17
18
19
20
21
22 Three studies included the analysis of self-assessment using the LCQ. The
23
24 mean difference ranged from -0.91 to 0.82; most estimates were positive (67%). The
25
26
27 estimated mean difference based on the random-effects model was 0.115 (95% CI: -
28
29 0.916 to 1.147) (Figure 5). Therefore, the mean result did not differ significantly from
30
31 zero (z = 0.2195, p = 0.8262), as shown in Figure 6. According to the Cochran Q test,
32
33 the true results are heterogeneous (Q (2) = 14.164, p = 0.001, tau² = 0.702, I² =
34
35
36 86.11%). A 95% prediction range for true results is given by -1.8237 to 2.0548. Thus,
37
38 although the average result is estimated as positive, in some studies the true result
39
40 may be negative. The studentized residuals revealed that one study (7) might be an
41
42 outlier in this model. However, according to Cook's distances, no study can be
43
44
considered excessively influential. Due to the number of studies that presented this
45
46
47 outcome, it was impossible to redo the meta-analysis without the outlier.
48
49 <Insert Figures 5 and 6>
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51 The rank correlation did not indicate funnel plot asymmetry (p = 1.000), as
52
53 shown in Figure 7.
54
55
56 <Insert Figure 7>
57
58 Three studies included the analysis of self-assessment using cough frequency
59
60 and cough severity symptoms (Figure 8). The estimated mean difference based on the
61
62
63
64
65
 random-effects model was -0.116 (CI 95%: -1.241 to 1.009). Thus, the mean result did
1
2 not differ significantly from zero (z = -0.2020, p = 0.839) (Figure 9). According to the
3
4 Cochran Q test, the true results are heterogeneous (Q (2) = 22.504, p <0.001, tau² =
5
6
7
0.865, I² = 88.77%). A 95% prediction range for true results is given by -2.2585 to
8
9 2.0265. Hence, although the average result is estimated as negative, in some studies
10
11 the true result may be positive. The studentized residuals revealed that no study was
12
13 considered an outlier. According to Cook's distances, no study can be considered
14
15
excessively influential.
16
17
18
19
20 <Insert Figures 8 and 9>
21
22 The Rank correlation did not indicate funnel plot asymmetry (p = 1.000).
23
24 <Insert Figure 10>
25
26
27 It was impossible to perform the meta-analysis with the overall degree of vocal
28
29 deviation and the cough frequency and cough threshold once only two studies
30
31 presented outcomes for each one. Table 1 shows that the individual results differed
32
33 regarding the most effective intervention for both studies.
34
35
36
<Insert Table 1>
37
38
39
40 Discussion
41
42 Chronic cough is an important topic that has been gaining ground in speech-
43
44
language pathology in the last two decades, with the pioneering work of an Australian
45
46
47 group in recent years (7,11,12). However, speech-language pathology intervention still
48
49 lacks consensus regarding the procedures to obtain effective results. Thus, this study
50
51 aimed to analyze the efficacy of speech-language pathology therapy in adults with
52
53 chronic cough.
54
55
56 All articles were experimental studies with sample randomization and
57
58 intervention control, hence, randomized clinical trials. Despite this, the risk of bias
59
60 showed no important information regarding the blinding of evaluators, therefore
61
62
63
64
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 presenting a high uncertain risk of detection bias; in addition to a high risk of selection
1
2 and performance bias in one study (20). The detection bias is related to the blinding
3
4 method of the evaluators regarding which intervention the patient performed; this is
5
6
7
necessary to ensure that the patient group does not affect the outcomes. Despite
8
9 presenting the requirements for an experimental study, one article (10) did not define
10
11 the same number of sessions for the participants in the intervention groups. This can
12
13 compromise results reliability.
14
15
Australia has attracted attention for the high quality of studies related to chronic
16
17
18 cough in the speech-language pathology field. They counted with four (7,10,11,12) of
19
20 the five selected studies in this review, which were all coordinated by the same
21
22 researcher. Most of the studies included men and women (10,11,12), one study
23
24 included only women (7) and, the other only men (8). There is no consensus on the
25
26
27 prevalence of chronic cough in men or women; there are reports of higher prevalence
28
29 in men (21) while there are reports of high prevalence in women (23). According to the
30
31 literature, the chronic cough onset is more frequent in middle age (23), which is in
32
33 accordance with the present study whose participants had between 54 and 64 years
34
35
36
old. There was high variability in the number of participants per study, from nine
37
38 (Kapela et al 2020) to 44 participants (Vertigan et al 2006). The sample size is
39
40 important to reduce the risk of type II error (25). It is noteworthy to highlight the
41
42 absence of sample calculation; thus, it was impossible to verify if the number of
43
44
patients was enough to analyze the effectiveness of an intervention method. This
45
46
47 weakness can be easily adjusted in future studies.
48
49 Three studies had four interventions sessions (8,11,12), one study had five (7)
50
51 and another study had a mean value of 1.9 sessions for the EG and 2.8 sessions for
52
53 the CG.
54
55
56 A systematic review regarding nonpharmacological interventions for refractory
57
58 chronic cough (23) showed that two to four sessions of education, cough suppression
59
60 techniques, breathing exercises, and counseling are enough to achieve positive
61
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63
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 results. The session time in four studies (8,10,11,12) ranged between 30 and 60
1
2 minutes, and one study (7) did not specify the session time. The literature brings no
3
4 consensus regarding the optimal time per session, however, the values are similar to
5
6
7
another systematic review (20) with a maximum session time of 60 minutes. Session
8
9 time is an important parameter, and no data on this aspect makes it impossible to
10
11 replicate the intervention.
12
13 Among the interventions, the SPEICH-C program was more commonly used in
14
15
the Experimental Group; used in two (11,12) out of the six interventions. This was the
16
17
18 first speech-language pathology intervention for chronic cough. The SPEICH-C
19
20 program involves four components: education about the nature of cough, strategies to
21
22 control the cough, vocal hygiene education to reduce laryngeal irritation and,
23
24 psychoeducational counseling (12). Regarding the control group, the Healthy Life Style
25
26
27 Education Intervention Program (HLE) was more common. It consists of four
28
29 components: relaxation, stress management, exercise, and diet (12). Two studies used
30
31 Speech Pathology Intervention considering diverse techniques and approaches
32
33 commonly used for voice therapy (7,10).
34
35
36
The meta-analysis was performed for the self-assessment of the cough impact
37
38 on the patient’s quality of life or the self-assessment of cough severity symptoms. Self-
39
40 assessment questionnaires are used to assess data regarding the patient’s perception
41
42 of cough symptoms (9). The questionnaires that assess the impact of a given problem
43
44
or symptom explore the influence that the person’s perception has on his daily life,
45
46
47 culture and, values regarding his aims, expectations, standards and, worries (34). In
48
49 addition to health, physical, emotional, mental, and functional factors, they also include
50
51 factors related to daily life, work, family and, friends (27,28). The patient's perspective
52
53 regarding their disorder and their improvements are important for the monitoring
54
55
56 process during the treatment. It is a simple, fast and, low-cost analysis, easier than
57
58 other assessments used in speech-language pathology practice. Although the
59
60 importance of this dimension, which reflects the unique experience of patients who
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 suffer from chronic cough, objective measures are also necessary. These objective
1
2 measures will provide information regarding cough frequency and cough threshold and,
3
4 additional measures such as the overall degree of vocal deviation, especially for cases
5
6
7
with dysphonia.
8
9 Regarding the analysis of the cough frequency and cough threshold, for one
10
11 study (8), the speech-language pathology intervention presented better outcomes; for
12
13 another study (7), better outcomes were observed for the speech-language pathology
14
15
intervention and pharmaceutical treatment. The LCM is a validated instrument to
16
17
18 assess the cough frequency. Currently, it is the best tool to objectively assess chronic
19
20 cough in research and clinical practice (32). It is a recent measure, which may justify its
21
22 absence in past studies.
23
24 The overall degree of vocal deviation using the CAPE-V (29) was used in two
25
26
27 studies. Another study (12) perceptually judged the voice quality with the A Sound
28
29 Judgment, an educational tool; which was proposed by Australian authors and is
30
31 designed to help students develop skills in perceptual voice analysis (33). No
32
33 consensus was observed in this aspect: one study (7) had a better outcome with the
34
35
36
speech-language pathology intervention and another (10) presented better outcomes in
37
38 the control group that underwent speech-language pathology intervention and watched
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40 supplemental pre-recorded videos of speech pathology exercises for chronic refractory
41
42 cough. Patients frequently report talking as a trigger for coughing (35). Different
43
44
mechanisms are proposed to link vocal deviation and chronic cough. When talking and
45
46
47 laughing the reduction in the lower esophageal sphincter tonus can lead to cough or
48
49 the vocal fold adduction during phonation may stimulate the laryngeal pressure
50
51 receptors and lead to cough (22). The vocal quality due to cough is hoarseness,
52
53 breathiness, and strain. There are different degrees of laryngeal hyperresponsiveness,
54
55
56 altered glottic closure, irregularities in vocal fold vibration and, paradoxical movements
57
58 of the vocal folds.
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 In this review, the experimental groups that underwent speech-language
1
2 pathology therapy alone did not have a larger effect size when compared to the control
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4 group, in any of the self-assessment outcomes.
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6
7
One of the meta-analyses used the LCQ, an instrument that assesses the self-
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9 reported quality of life measure of chronic cough considering different aspects of the
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11 patient's life (9). In this analysis, there was no difference in effect size, the true results
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13 were heterogeneous and one study (7) might be an outlier. This was observed once
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15
the effect size was favorable for the speech-language pathology intervention in two
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18 studies (8,10). These studies compared the isolated speech-language pathology
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20 intervention, with a control group that underwent speech-language pathology
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22 intervention and watched supplemental pre-recorded videos of speech pathology
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24 exercises and indirect interventions. However, one study (7) compared speech
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27 pathology therapy intervention with a control group that underwent speech pathology
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29 therapy associated with pharmacological treatment using Pregabalin; the control group
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31 presented better outcomes. Pregabalin is an anti-cough drug that acts directly on the
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33 symptoms reducing laryngeal sensations, possible cough triggers. It is a psychoactive
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36
drug that may alter the individual’s behavior, conscience, and perception of cough
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38 severity (7). Thus, the drug might have reduced the intensity of the coughing without
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40 actually changing the cough frequency, hence, providing a better quality of life for the
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42 patient. However, it is noteworthy that pregabalin is a neuromodulator with a fast and
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44
short duration action mechanism, its withdrawn will not maintain the treatment effect.
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47 Probably, the effect was sustained after treatment due to the speech-language
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49 pathology therapy effect on behavioral changes and cough mechanisms (7). Despite
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51 the positive effect obtained with this drug, pregabalin is known to be associated with
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53 dizziness and falls, which was observed in one of the studies (7). Considering the side
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56 effects, the drug use with speech-language pathology therapy must be analyzed
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58 individually by a physician. Furthermore, this data was observed in only one publication
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60 (7), more studies are needed to confirm this outcome.
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 The speech-language pathology intervention varied, however, the programs
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2 had common aspects such as counseling on hygiene and psychological aspects,
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4 strategies for cough suppression and, respiratory and laryngeal control exercises. The
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6
7
counseling provides information regarding the nature of cough, laryngeal hygiene,
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9 reduction of laryngeal irritation, and psychological aspects (1,2,17). Cough suppression
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11 helps patients to control their cough with strategies that identify, prevent, suppress or
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13 replace the cough (1,17). Finally, respiratory and laryngeal control trains breathing,
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15
voice production, and provides better breathing and speaking coordination using
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18 exercises and guidance (17).
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20 No statistical difference was observed in the second meta-analysis with the self-
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22 assessment of the cough frequency and cough severity symptoms, also, the results
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24 were heterogeneous. There was variability in the comparison group; a study associated
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27 speech-language pathology therapy with pharmacological treatment (7), another study
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29 associated speech-language pathology intervention and watching supplemental pre-
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31 recorded videos of speech pathology exercises (10), and one more performed indirect
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33 therapy (8). Both studies that associated speech-language therapy with another
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intervention in the control group obtained better outcomes when compared to isolated
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38 speech-language therapy. In addition, a study where the control group underwent
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40 Healthy Life Style Education presented the worst outcomes. It is noteworthy that all
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42 study that included speech-language therapy also included healthy lifestyle education,
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44
thus, better outcomes for the intervention is expected (6,11). Overall, the speech-
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47 language pathology therapy was not more efficient than other interventions. However,
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49 when a qualitative interpretation of the results is given, the speech-language pathology
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51 therapy associated with other interventions present optimal outcomes in the patient’s
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53 perception.
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56 Many heterogeneous studies indicate that more primary studies are necessary.
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58 These studies must standardize their outcomes and measures, and their intervention
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60 control. Thus, the synthesized data of the researchers might help the clinician to
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 choose the best intervention for the chronic cough treatment. In addition, further
1
2 studies must include sample calculations.
3
4 This review's limitations are the unclear detection bias and the heterogeneity
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6
7
between studies.
8
9
10
11 Conclusion
12
13 There was no difference in the effect size between the speech-language
14
15
pathology intervention and control intervention in the patient’s self-perception. It was
16
17
18 not possible to perform the analysis of the effectiveness of the speech-language
19
20 therapy intervention in the cough frequency, cough threshold, and overall degree of
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22 vocal deviation due to the small number of studies. The results were heterogeneous.
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24 According to the qualitative analysis, better outcomes are expected when the speech-
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27 language therapy is associated with other rehab procedures such as videos and
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29 pharmacological interventions.
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13 Chronic Refractory Cough. J Allergy ClinImmunolPract. 2019 Jul-Aug;7(6):1756-1761.
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18 Pulm Pharmacol Ther. 2009 Apr;22(2):159-62.
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31 7- Vertigan AE, Kapela SL, Ryan NM, Birring SS, McElduff P, Gibson PG. Pregabalin
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49 20- Desjardins M, Halstead L, Cooke M, Bonilha HS. A Systematic Review of Voice
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56 21- Song WJ, Chang YS, Faruqi S, Kang MK, Kim JY, Kang MG et al. Defining Chronic
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9 refractory chronic cough patients: systematic review. Lung. 2014 Feb;192(1):75-85.
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11 24- Ryan NM, Vertigan AE, Gibson PG. Chronic cough and laryngeal dysfunction
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13 improve with specific treatment of cough and paradoxical vocal fold movement. Cough.
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18 25- Medronho AR, Carvalho DM, Bloch KV, Luiz RR, Werneck GL. Epidemiologia. São
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20 Paulo: Atheneu; 2011
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22 26- Birring SS, Matos S, Patel RB, Prudon B, Evans DH, Pavord ID. Cough frequency,
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24 cough sensitivity and health status in patients with chronic cough. Respir Med. 2006
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27 Jun;100(6):1105-9.
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29 27- Haraldstad K, Wahl A, Andenæs R, Andersen JR, Andersen MH, Beisland E et al.
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31 A systematic review of quality of life research in medicine and health sciences. Qual
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33 Life Res. 2019 Oct;28(10):2641-2650.
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28- Pereira ÉF, Teixeira CS, Santos A. Quality of life: approaches, concepts and
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38 assessment. Rev Bras Educ Fís Esporte. 2012;26(2):241-50.
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40 29- Kempster GB, Gerratt BR, Verdolini Abbott K, Barkmeier-Kraemer J, Hillman RE.
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42 Consensus auditory-perceptual evaluation of voice: development of a standardized
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clinical protocol. Am J Speech Lang Pathol. 2009 May;18(2):124-32.
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47 30- Birring SS, Prudon B, Carr AJ, et al. Desenvolvimento de uma medida de estado
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49 de saúde específica para sintomas para pacientes com tosse crônica: Leicester Cough
50
51 Questionnaire (LCQ). Thorax 2003;58:339-43.
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53 31- Polley L, Yaman N, Heaney L, Cardwell C, Murtagh E, Ramsey J, MacMahon J,
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56 Costello RW, McGarvey L. Impact of cough across different chronic respiratory
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60 Chest. 2008 Aug;134(2):295-302.
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 32- Lee KK, Savani A, Matos S, Evans DH, Pavord ID, Birring SS. Four-hour cough
1
2 frequency monitoring in chronic cough. Chest. 2012 Nov;142(5):1237-43.
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4 33- Oates J, Russell A. Learning voice analysis using an interactive multi-media
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package: development and preliminary evaluation. J Voice. 1998 Dec;12(4):500-12.
8
9 34- Segre M, Ferraz FC. The health's concept. Rev Saúde Pública. 1997;31(5):538-42.
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11 35- Vertigan AE, Haines J, Slovarp L. An update on speech pathology management of
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13 chronic refractory cough. J Allergy Clin Immunol Pract 2019;7:1756–61.
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 TABLES
1
2 Table 1 – Individual descriptive analysis of the cough frequency, cough threshold, and
3
4 overall degree of vocal deviation
5
6 Cough frequency and cough threshold Overall degree of vocal deviation
7
8 Mean SD Mean SD Mean SD Mean SD
9
Authors difference difference difference difference difference difference difference difference
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11 pre & post pre & post pre & post pre & post pre & post pre & post pre & post pre & post
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13 EG EG CG CG EG EG CG CG
14
Vertigan et al. 2006
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16 Vertigan et al. 2008
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18 Vertigan et al. 2016 8.9 18.1 11.2 18.3 11.1 15.6 9 18.2
19 Mitchel et al. 2017 8 0.7 1 0.5
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21 Kapela et al. 2020 3.7 6.4 6.4 8.1
22
23 Legend: EG = Experimental Group; CG = Control Group; SD = standard deviation
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 FIGURES
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2 Figure 1 – Electronic search strategies per database
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4 Search Strategies
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7 MEDLINE (("Cough"[Mesh] OR "Chronic Cough"[Title/Abstract]) AND ("Voice
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9 Training"[Mesh] OR "Vocal Therapy"[Title/Abstract] OR "speech
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11 pathology management"[Title/Abstract] OR "behavioral
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13 management"[Title/Abstract] OR "Speech pathology
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treatment"[Title/Abstract]))
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18 Cochrane ("chronic cough" OR "cough") in Title Abstract Keyword AND ("Voice
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20 Library Training" OR "Vocal Therapy" OR "speech pathology management" OR
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22 "Speech pathology treatment") in Title Abstract Keyword - (Word
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24
25
variations have been searched)
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27 EMBASE ('chronic cough':ti,ab,kw OR coughing:ti,ab,kw) AND ('voice
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29 training':ti,ab,kw OR 'vocal therapy':ti,ab,kw OR 'speech pathology
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31 management':ti,ab,kw OR 'speech pathology treatment':ti,ab,kw)
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33
34
Web of All fields: ((cough* OR chronic cough*)) AND All fields: ((Voice Training*
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36 Science OR Vocal Therapy* OR speech pathology management* OR Speech
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38 pathology treatment*))
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40 SCOPUS ( TITLE-ABS-KEY ( "Cough" OR "Chronic Cough" ) AND TITLE-ABS-
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KEY ( "Voice Training" OR "Vocal Therapy" OR "speech pathology
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45 management" OR "behavioral management" OR "Speech pathology
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47 treatment" ) )
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49 LILACS (mh:(("cough"))) AND ((mh:(("voice training"))) OR (tw:("speech
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pathology management")) OR (tw:("vocal therapy")) OR (tw:("speech
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54 pathology treatment")))
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 Figure 2 – Flow diagram for searching and selecting articles
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 1
2 Figure 3 – Individual risk of bias
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 Figure 4 – Individual risk of bias of the systematic review
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 1
2 Figure 5– Forest plot of the analysis of self-assessment using the Leicester Cough
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 Figure 6– Effect size analysis of the self-assessment using the Leicester Cough
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12 Tau²
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14 Estimator: Restricted Maximum-Likelihood
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 Figure 7– Funnel plot for the self-assessment using the Leicester Cough Questionnaire
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27 Rank Correlation Test for Funnel Plot Asymmetry: Kendall’s Tau = -0.333; p = 1.000
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 Figure 8 - Forest plot for the self-assessment using cough frequency and cough
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 Figure 9 – Effect size analysis of the self-assessment using cough frequency and
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12 Tau²
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14 Estimator: Restricted Maximum-Likelihood
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 Figure 10 – Funnel plot for the self-assessment using cough frequency and cough
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30 Rank Correlation Test for Funnel Plot Asymmetry: Kendall’s Tau = -0.333; p = 1.000
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15
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23 CHART
24
25 Chart 1 – Descriptive analysis of the qualitative characteristics of the studies
26
27 EG CG
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29 Age Session Session
Authors Country Design Gender Diagnosis Session Session
30 (mean) n Intervention time n Intervention time
31 number number
32 (minutes) (minutes)
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34 Healthy lifestyle
Vertigan et al 2006 Australia RCT Both 59,4 CC 43 4 SPEICH-C 30 44 4 30
35 education
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37 Healthy lifestyle
38 Vertigan et al 2008 Australia RCT Both 54,5 CC 40 4 SPEICH-C 30 42 4 30
education
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40 Speech pathology Speech pathology
41 EG = 64
42 Vertigan et al 2016 Australia RCT Female RCC 20 5 treatment + - 20 5 treatment + -
CG = 61
43 placebo pregabalin
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45 United EG = 61 Healthy lifestyle
46 Mitchel et al 2017 RCT Male CC 34 4 PSALTI 45 - 60 41 4 45 - 60
47 Kingdom CG = 56 advice
48 Speech pathology
49 EG = 57 Speech pathology
50 Kapela et al 2020 Australia RCT Both RCC 9 Mean 1,9 35 - 45 9 Mean 2,8 Intervention 35 - 45
51 CG = 59 intervention
+ pre-recorded videos
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53
Legend: EG = Experimental Group; CG = Control Group; RCC = Refractory Chronic Cough; CC = Chronic Cough
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