Speech and language therapy for management of chronic cough

  • New
  • Protocol
  • Intervention

Authors


Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To evaluate the effectiveness of speech and language therapy for treatment of patients with unexplained chronic cough.

Background

Description of the condition

Cough is defined as an airway defensive reflex comprising an inspiratory phase, followed by a forced expiratory effort initially against a closed glottis (Fontana 2008). The duration of cough can be acute (less than three weeks), subacute (between three and eight weeks), or chronic (longer than eight weeks) (Irwin 2006). Details regarding the theory and treatment of cough can be found in several different clinical fields, including otolaryngology, respiratory medicine, speech and language therapy, respiratory physiology, and physiotherapy (Vertigan 2016a).

Unexplained (idiopathic/refractory) chronic cough (UCC) is a cough that persists after common causes have been evaluated and ruled out and medical management options have not offered any convincing relief from symptoms. This condition is a diagnosis of exclusion following a careful diagnostic workup to exclude other causes of cough such as underlying lung/airways disease, gastro-oesophageal reflux, drugs (such as angiotensin-converting enzyme inhibitors (ACEis)), and rhinosinusitis (Gibson 2016a; Morice 2006; Morice 2007; Morice 2007a; Vertigan 2016a).

Evidence suggests that UCC may be caused by neural hyper-responsiveness. Patients with this condition describe an 'irritation' or 'tickle' within the throat and a heightened urge or need to cough (Hilton 2015). In addition, lower concentrations of tussive agents are required to induce cough in patients with UCC compared with healthy controls (Prudon 2005). It is known that vagal afferent bronchopulmonary C-fibres are important in cough regulation (Canning 2014). Novel drugs targeting C-fibre receptors have been recently trialed in humans. An oral transient receptor potential vanilloid subtype 1 (TRPV1) antagonist had no effect on cough frequency in patients with UCC (Belvisi 2016). However, another trial demonstrated a 75% reduction in cough reflex sensitivity in patients with UCC using a novel P2X3 antagonist (Abdulqawi 2015), supporting the hypothesis of neural hyper-responsiveness and hypersensitive central cough reflex in UCC.

Furthermore, an overlap has been postulated between chronic cough and other upper airway dysfunction presentations, such as inducible laryngeal obstruction (ILO), globus pharyngeus, hyperfunctional muscle tension, voice disorders, and dysphagia symptoms (Ryan 2009; Vertigan 2006; Vertigan 2016a). It has been suggested that these entities may represent different manifestations of an underlying hypersensitive and hyper-responsive upper airway (Vertigan 2007; Vertigan 2010; Vertigan 2016a).

Description of the intervention

Speech and language therapy (SLT) offers a non-pharmacological intervention for people with UCC who may have exhausted medical treatment for their condition, or who wish to pursue a non-pharmacological treatment option (Ryan 2010; Ryan 2014; Vertigan 2006; Vertigan 2016a). SLT has been incorporated into the Treatment of Unexplained Chronic Cough: CHEST guideline and expert panel report (Gibson 2016a), a report detailing treatment of UCC, and the Australian cough guidelines summary statement (Gibson 2010). The aim of SLT intervention is to improve an individual's control over cough, as well as to address symptoms associated with dysphonia and ILO (Vertigan 2016a).

Stemple 2009 states that speech and language therapists possess the correct skill set to treat chronic cough via a combination of detailed knowledge of anatomy and physiology of the upper airway, experience in education and training on respiratory physiology and clinical voice disorders, and proven ability to modify laryngeal behaviour (Altman 2000; Stemple 2009). As there is a hypothesised and clinically recognised overlap between cough and other upper airway and laryngeal disorders, such as ILO, globus pharyngeus, muscle tension dysphonia, and dysphagic symptoms, SLT professionals have the skills required to identify, assess, and manage these overlapping conditions effectively by applying techniques traditionally used to treat muscle tension voice disorders (Blager 1998; Blager 2000; Carney 1997; Chhetri 2014; Dunn 2015; Estill 2009; Estill 2009a; Ryan 2010; TitzeI 2006; Vertigan 2007). SLT assessment can also investigate patient-reported symptoms of dysphagia to identify clinical signs of aspiration that may warrant further investigation.

Furthermore, the trained SLT professional can provide biovisual feedback with videolaryngoscopy, which has been found to be useful for assisting patients in applying techniques and in helping to monitor response to SLT (Balkissoon 2012; Belafsky 2001; Christopher 2010; Hull 2016; Olin 2017).

During assessment, the SLT professional evaluates cough characteristics, the urge to cough, and indicators suggestive of ILO (Ryan 2014; Traister 2014). Phonation is often cited as a trigger for coughing episodes, and, given the overlap with dysphonia, a clinical voice assessment can use recognised descriptive rating scales of perceptual voice characteristics, such as rough, breathy, and strained vocal qualities. Hyperfunction in the larynx during phonation can signify laryngeal dysfunction and can serve as a contributory factor to cough reflex sensitivity (Hirano 1981; Omori 2011; Ryan 2014; Vertigan 2007).

When available, the SLT professional can assess instrumental voice (Ryan 2010; Zelcer 2002), for example, by using the multi-dimensional voice analysis programme (Computerised Speech Lab; Pentax Medical, Montvale, NJ, USA) or visualising the larynx via videolaryngoscopy during voice use according to a recognised protocol (RCSLT 2008). Manual assessment of tension in the extrinsic laryngeal musculature is a useful tool for assessing hyperfunction, which can be detected in muscle tension voice disorders (Rubin 2000; Vertigan 2016a).

Vertigan 2012 and Vertigan 2016 outlined a multi-dimensional SLT intervention for chronic cough management consisting of the following elements.

Education

Education is identified as a crucial element of the SLT approach with focus on encouraging adherence, with the aim of acceptance that patients can control their cough and take ownership of implementing strategies to ignore the urge to cough and stop themselves from coughing. Educators provide information on the importance of sustained application of cough suppression techniques (Vertigan 2012).

Education on the perpetuating nature of the cough is provided, potentially leading to increased sensitivity, laryngeal trauma, and tension. Specific goals for therapy are planned with the patient. The ultimate goal of SLT is for the patient to control the cough, even in the presence of the sensation/urge to cough.

Symptom control techniques

The aim of these strategies is to ask the patient to prevent, stop, or interrupt the cough despite having the triggering sensation. The patient is then asked to substitute the cough with a competing response (e.g. distraction, cough suppression swallow, relaxed throat breathing, a sip of fluids, laryngeal deconstriction) (Estill 2009; Vertigan 2007). Laryngeal control techniques for any coexisting inducible laryngeal obstruction are also included in the SLT therapy intervention (Blager 2000; Boone 1993; Chhetri 2014; Kotby 1993).

A hierarchy for applying control techniques is devised with the patient; this can include graded exposure to desensitise the patient to particular triggers (Gibson 2015)

Reducing laryngeal irritation via vocal hygiene

Vocal hygiene advice is commonly used in the SLT approach to clinical voice disorders (Blager 1988), and it may be beneficial in the treatment of UCC (Vertigan 2012). Vocal hygiene consists of advice on effects of smoking, mouth breathing (up to 50% of people with UCC habitually mouth-breathe), caffeine, and alcohol on laryngeal mucosa. Easy voicing and adequate hydration are emphasised and demonstrated to reduce the risk of phonotrauma (Boone 1993; Kotby 1993; Murry 2004; Solomon 2014; Vertigan 2007). Information on diet and behavioural management of gastroesophageal and laryngopharyngeal reflux is provided (Koufman 2011).

Psychoeducational counselling

The therapist assesses readiness to engage in SLT, as this may impact the efficacy of therapy (Prochaska 1982). Acceptance that the patient can control the cough (internal locus of control), self-efficacy (Bandura 1986), and the effort required of the patient are made explicit, with emphasis on treatment being "hard work". Realistic, targeted goal setting helps the therapist to direct interventions and monitor progress (Murry 2004; Ryan 2010; Vertigan 2012).

Overall goals of speech and language therapy interventions can be summarised as follows (Gibson 2015).

  1. Reduce the sensitivity of the cough reflex.

  2. Encourage improvement in voluntary control of cough.

  3. Reduce irritation of the larynx.

Whilst previous studies assessing the effectiveness of interventions for UCC have involved input from other allied health professionals (e.g. Chamberlain Mitchell 2017), it has been noted that the added benefit of contributions of other professionals, in addition to SLTs, is unclear (e.g. Smith 2017).

How the intervention might work

SLT interventions aim to improve individuals' control over cough and symptoms associated with any overlapping dysphonia and ILO (Vertigan 2016a), but the mechanism by which the above-detailed, multi-modal SLT intervention may reduce cough severity and frequency, leading to improvement in health-related quality of life, is poorly understood.

It has been postulated that SLT interventions may reduce cough sensitivity in patients with UCC (Smith 2005; Vertigan 2006). However, a multi-centre randomised controlled study demonstrated no differences between intervention and control groups with capsaicin cough challenge (Chamberlain Mitchell 2017). The psychoeducational and control strategies component may support subjective improvement in chronic cough management techniques and may reduce upper airway muscle tension (Canning 2006; Gibson 2009). Improved laryngeal hygiene attained via hydration and education on reduction of laryngeal injury may support lower phonation threshold pressure, thereby reducing stimulation of cough receptors (Casper 2003; Solomon 2014).

Why it is important to do this review

Chronic cough is a significant unmet need. Cough is the most common reason why patients seek medical advice (Morice 2006), and for chronic cough, most patients seek advice three or more times (Chamberlain Mitchell 2017). The prevalence of UCC in the population varies in the most recent studies from 4% (Colak 2017) to 9.6% (Song 2015). Cough presents a considerable financial burden, with acute cough costing approximately £979 million in the UK, including £875 million in loss of productivity and £104 million in healthcare costs (Morice 2006). The cost of chronic cough to the economy remains unclear.

The negative impact of chronic cough on quality of life is far reaching and has been well described (Decalmer 2007; French 1998). Urinary incontinence associated with chronic cough is a particularly distressing symptom (Hrisanfow 2013).

Few effective medical treatments for individuals with UCC are known. For this group, current guidelines advocate the use of gabapentin (Gibson 2016a; Vertigan 2016a). One study demonstrated a reduction in subjective cough scores in response to slow-release morphine sulphate (Morice 2007; Morice 2007a). Another study examined amitriptyline in patients with postviral vagal neuropathy and cough, but guidelines do not currently recommend this treatment (Jeyakumar 2006). SLT has been advocated as an attractive non-pharmacological option for managing UCC without the risks and side effects associated with pharmacological agents; SLT is the focus of this review (Krakowiak 2017).

Objectives

To evaluate the effectiveness of speech and language therapy for treatment of patients with unexplained chronic cough.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs). We will include studies reported in full text, those published as an abstract only, and unpublished data. We will include cluster trials and first period data from cross-over trials, if available.

Types of participants

We will include participants with a diagnosis of chronic unexplained (idiopathic/refractory) cough who have undergone a full diagnostic workup to exclude an underlying cause, as per published guidelines or local protocols. If we identify eligible studies in children (17 years of age and younger), we will analyse them separately from adult studies.

Types of interventions

We will include studies that use recognised speech and language therapy techniques for UCC, such as the multi-dimensional SLT intervention described in the Background section (education, symptom control or vocal hygiene, psychoeducational counselling), and/or other recognised SLT laryngeal control techniques as defined by trialists.

We will include other co-interventions, provided they are not part of the randomised treatment.

We will include studies comparing speech and language therapy and usual care versus usual care, such as reassurance, lifestyle advice, and background medications. We will also include studies that have compared SLT versus an 'active' control such as non-prescribed/over-the-counter cough products (e.g. lozenges). We will exclude from this review studies in which participants received angiotensin-converting enzyme inhibitors (ACEis). We will include trials that deliver any number of sessions but will investigate in subgroup analyses the number of sessions provided (Ryan 2010).

Types of outcome measures

Primary outcomes
  1. Health-related quality of life (assessed via a validated measure)

  2. Serious adverse events.

Secondary outcomes
  1. Objective cough counts (e.g. using the Leicester cough monitor)

  2. Symptoms (preferentially assessed on validated symptom scales)

  3. Clinical improvement (as defined by trialists)

  4. Subjective measures of cough (e.g. visual analogue scale (VAS)/numerical cough scale score)

  5. Cough reflex sensitivity (as measured by cough challenge)

  6. Adverse events/side effects

Reporting in the study one or more of the outcomes listed is not an inclusion criterion for this review.

Search methods for identification of studies

Electronic searches

We will identify studies from the following sources.

  1. Cochrane Airways Trials Register.

  2. Cochrane Central Register of Controlled Trials (CENTRAL), via the Cochrane Register of Studies (CRS-Web).

  3. MEDLINE Ovid SP 1946 to date.

  4. Embase Ovid SP 1974 to date.

We have presented the search strategy for MEDLINE in Appendix 1. We will adapt this for use in other databases.

In addition, we will search the following trials registries.

  1. US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov).

  2. World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch).

We will search all sources from inception to the present, with no restriction on language of publication.

Searching other resources

We will check the reference lists of all primary studies and review articles for additional references. We will search for errata or retractions from included studies published in full text on PubMed and will report within the review the date this was done.

Data collection and analysis

Selection of studies

Two review authors (CS and PM) will independently screen the titles and abstracts of the search results and will code them as 'retrieve' (eligible or potentially eligible/unclear) or 'do not retrieve'. We will retrieve the full-text study reports of all potentially eligible studies, and two review authors (CS and PM) will independently screen them for inclusion, while recording reasons for exclusion of ineligible studies. We will resolve any disagreements through discussion; if required, we will consult a third person/review author (AV). We will identify and exclude duplicates and will collate multiple reports of the same study, so that each study, rather than each report, is the unit of interest in the review. We will record the selection process in sufficient detail to complete a PRISMA flow diagram and 'Characteristics of excluded studies' tables (Moher 2009).

Data extraction and management

We will use a data collection form that has been piloted on at least one study in the review to record study characteristics and outcome data. Two review authors (SM and JB) will extract the following study characteristics from included studies.

  1. Methods: study design, total duration of study, details of any 'run-in' period, number of study centres and locations, study setting, withdrawals, and dates of study.

  2. Participants: N, mean age, age range, gender, severity of condition, diagnostic criteria, baseline lung function, smoking history, inclusion criteria, and exclusion criteria.

  3. Interventions: intervention, comparison, concomitant medications, and excluded medications.

  4. Outcomes: primary and secondary outcomes specified and collected, and time points reported.

  5. Notes: funding for studies and notable conflicts of interest of trial authors.

Two review authors (SM and JB) will independently extract outcome data from included studies. We will note in the 'Characteristics of included studies' table if outcome data were not reported in a usable way. We will resolve disagreements by consensus or by involving a third person/review author (PM). One review author (SM) will transfer data into the Review Manager file (RevMan 2014). A second review author (CS) will double-check that study characteristics and data are entered correctly by comparing data presented in the systematic review against the study reports.

Assessment of risk of bias in included studies

Two review authors (SM and JB) will assess risk of bias independently for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve any disagreements by discussion or by consultation with another review author (PM). We will assess risk of bias according to the following domains.

  1. Random sequence generation.

  2. Allocation concealment.

  3. Blinding of participants and personnel.

  4. Blinding of outcome assessment.

  5. Incomplete outcome data.

  6. Selective outcome reporting.

  7. Other bias.

We will judge each potential source of bias as high, low, or unclear and will provide a quote from the study report together with a justification for our judgement in the 'Risk of bias' table. We will summarise risk of bias judgements across different studies for each of the domains listed. We will consider blinding separately for different key outcomes when necessary (e.g. for unblinded outcome assessment, risk of bias for all-cause mortality may be very different than for use of a patient-reported pain scale). When information on risk of bias relates to unpublished data or correspondence with a trialist, we will note this in the 'Risk of bias' table.

When considering treatment effects, we will take into account risk of bias for studies that contribute to that outcome.

Assessment of bias in conducting the systematic review

We will conduct the review according to this published protocol and will justify any deviations from it in the 'Differences between protocol and review' section of the systematic review.

Measures of treatment effect

We will analyse dichotomous data as odds ratios (OR) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). If data from rating scales are combined in a meta-analysis, we will ensure that they are entered with a consistent direction of effect (e.g. lower scores always indicate improvement).

We will undertake meta-analyses only when this is meaningful, that is, when treatments, participants, and the underlying clinical question are similar enough for pooling to make sense.

We will describe skewed data narratively (e.g. as medians and interquartile ranges for each group).

When multiple trial arms are reported in a single study, we will include only the relevant arms. If two comparisons (e.g. intervention A vs usual care and intervention B vs usual care) are combined in the same meta-analysis, we will either combine the active arms or halve the control group to avoid double-counting.

If adjusted analyses are available (ANOVA or ANCOVA), we will use these as a preference in our meta-analyses. If both change from baseline and endpoint scores are available for continuous data, we will use change from baseline unless there is low correlation between measurements in individuals. If a study reports outcomes at multiple time points, we will use change in baseline and endpoint scores.

When both per-protocol/completer and intention-to-treat (ITT) analyses are provided in a single report, we will use the latter.

Unit of analysis issues

For dichotomous outcomes, we will use participants, rather than events, as the unit of analysis (i.e. number of people admitted to hospital, rather than number of admissions per person). However, if rate ratios are reported in a study, we will analyse them on this basis. We will meta-analyse data from cluster-RCTs only if available data have been adjusted (or can be adjusted) to account for the clustering.

Dealing with missing data

We will contact investigators or study sponsors to verify key study characteristics and to obtain missing numerical outcome data when possible (e.g. when a study is identified as an abstract only). When this is not possible, and the missing data are thought to introduce serious bias, we will take this into consideration when determining the GRADE rating for affected outcomes.

Assessment of heterogeneity

We will use the I² statistic to measure heterogeneity among the studies in each analysis. If we identify substantial heterogeneity, we will report this and explore possible causes by performing prespecified subgroup analysis. 

Assessment of reporting biases

If we are able to pool more than 10 studies, we will create and examine a funnel plot to explore possible small-study and publication biases.

Data synthesis

We will use a random-effects model and will perform a sensitivity analysis with a fixed-effect model.

'Summary of findings' table

We will create a 'Summary of findings' table using the following outcomes.

Primary outcomes
  1. Health-related quality of life (assessed with a validated measure)

  2. Serious adverse events

Secondary outcomes
  1. Symptoms

  2. Clinical improvement (as defined by trialists)

  3. Subjective measures of cough (e.g. VAS/numerical cough score)

  4. Cough reflex sensitivity (as measured by cough challenge)

  5. Objective cough counts

  6. Adverse events/side effects

Reporting one or more of the outcomes listed here in the study is not an inclusion criterion for the review.

We will use the five GRADE considerations (risk of bias, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to studies that contribute data for the prespecified outcomes. We will use the methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), using GRADEpro software (GRADEpro GDT). We will justify all decisions to downgrade the quality of studies using footnotes, and we will make comments to aid the reader's understanding of the review when necessary.

Subgroup analysis and investigation of heterogeneity

We plan to carry out the following subgroup analysis on our two primary outcomes (health-related quality of life and serious adverse events).

  1. Number of sessions of SLT (one to three sessions vs four to six sessions vs seven or more sessions).

  2. Speech and language therapist delivered intervention versus intervention delivered by other healthcare professionals.

We will use the formal test for subgroup interactions in Review Manager (RevMan 2014).

Sensitivity analysis

We plan to conduct sensitivity analyses by removing studies when the method of randomisation is judged as unclear or high in the risk of bias assessment. We also plan to conduct sensitivity analyses by removing studies with an active control arm.

We will compare the results from a fixed-effect model with those from the random-effects model.

Acknowledgements

We are especially grateful to Emma Dennett, Liz Stovold, and Emma Jackson of Cochrane Airways, and to Rebecca Normansell and Chris Cates (Cochrane Airways Co-ordinating Editors) for the additional guidance provided.

The Background and Methods sections of this protocol are based on a standard template used by Cochrane Airways.

This project was supported by the National Institute for Health Research via Cochrane Infrastructure funding to Cochrane Airways. The views and opinions expressed therein are those of the review authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS, or the Department of Health.

Appendices

Appendix 1. MEDLINE (Ovid) search strategy

1. Cough/
2. cough$.tw.
3. 1 or 2
4. exp "rehabilitation of speech and language disorders"/
5. ((speech$ or language$) adj5 (therap$ or treatment$ or interven$ or program$ or train$ or exercise$ or rehabilit$)).tw.
6. SLT.ti,ab.
7. or/4-6
8. 3 and 7
9. (controlled clinical trial or randomized controlled trial).pt.
10. (randomized or randomised).ab,ti.
11. placebo.ab,ti.
12. dt.fs.
13. randomly.ab,ti.
14. trial.ab,ti.
15. groups.ab,ti.
16. or/9-15
17. Animals/
18. Humans/
19. 17 not (17 and 18)
20. 16 not 19
21. 8 and 20

Contributions of authors

CS contributed to the Background and Methods sections; will screen the titles and abstracts of the search results and full-text study reports of all potentially eligible studies; and will spot-check study characteristics entered into RevMan for accuracy against the study report.

SBM contributed to the Background section.

SJM contributed to the Background and Methods sections; will extract study characteristics from included studies; will independently extract outcome data from included studies and enter the data into RevMan; and will assess risk of bias independently for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.

SD contributed to the Background and Methods sections.

JB contributed to the Background and Methods sections; will extract study characteristics from included studies; will independently extract outcome data from included studies; and will assess risk of bias independently for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.

AV contributed to the Background and Methods section.

PM contributed to the Background and Methods sections and will screen the titles and abstracts of the search results and full-text study reports of all potentially eligible studies.

Declarations of interest

CS: none known.

SBM: none known.

SJM: none known.

SD: none known.

JB: none known.

AV: none known.

PM: none known.

Sources of support

Internal sources

  • The authors declare that no such funding was received for this systematic review, Other.

External sources

  • The authors declare that no such funding was received for this systematic review, Other.

Ancillary