Pilot observational cohort study to determine whether waveform and flow traces from mechanical insufflation–exsufflation (MI-E) can be used to identify laryngeal responses to MI-E and thus optimise treatment algorithms in neuromuscular patients in a tertiary centre: a protocol description

Abstract

Introduction

Patients with neuromuscular disease often have a weak and ineffective cough due to respiratory muscle weakness. One treatment option is mechanical insufflation–exsufflation (MI-E), also known as cough assist, which is known to increase cough strength. However, some patients have a laryngeal response to MI-E, which can make the treatment ineffective. Currently, the only method for assessing this is via nasal endoscopy while using MI-E. Some MI-E devices have onboard secure data (SD) cards, which allow the visualisation of waveforms. We hypothesise that the waveforms can be used to identify laryngeal responses to the MI-E.

Methods and analysis

Participants will complete baseline assessments of spirometry, peak cough flow and sniff nasal inspiratory pressure. A nasal endoscope will be used to visualise the larynx during simultaneous MI-E via a mask with a drilled hole. MI-E will be delivered by an experienced physiotherapist. Four cycles of MI-E at a range of prescriptions will be delivered. MI-E waveforms will be downloaded into Care Orchestrator Essence software (Philips, Murraysville). Data will be collected prospectively and reviewed in a descriptive context, providing trends and potential rationales describing the waveforms in comparison to the nasal endoscope videos.

Ethics and dissemination

This protocol has been reviewed by the East of England-Cambridge Central Research Ethics Committee, who have granted a favourable ethical opinion. The study opened to recruitment in January 2022 and aims to publish trial results in June 2024.

Trial registration number

NCT05189600.

Correspondence to Stephanie K Mansell; [email protected]

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Patients with neuromuscular disease have impaired cough strength, which mechanical insufflation–exsufflation (MI-E) can be used to treat. MI-E can induce a laryngeal response, reducing effectiveness of treatment.

WHAT THIS STUDY ADDS

• Laryngeal response can only be detected using laryngoscope; we aim to evaluate whether waveforms from MI-E devices can identify laryngeal responses.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Waveforms from MI-E devices could be used to identify laryngeal responses and to optimise prescriptions.

Background

People with neuromuscular disease (NMD) can develop weak respiratory muscles and subsequently can suffer with impaired cough strength.¹ Having an impaired cough strength reduces the ability of the individual to clear their pulmonary secretions via the normal mucocilliary escalator. This impaired cough can lead to: recurrent respiratory infections, potential hospitalisations, increased symptom burden, reduced quality of life and potentially subsequent increased mortality.^{2 3}

One treatment option for managing respiratory secretions and a weak cough is mechanical insufflation–exsufflation (MI-E), also known as cough assist.⁴ MI-E involves a positive insufflation pressure applied to aid people to reach a maximum insufflation capacity (MIC), followed by a negative exsufflation pressure which aids expiratory flow bias, enhancing the mucociliary escalator and aiding expulsion of pulmonary secretions.⁵ This treatment technique is known to increase the peak cough flow (PCF) to an effective level, at which patients are able to clear pulmonary secretions.⁶ This treatment can be applied as a prophylactic measure to prevent the buildup of retained secretions, or during a period of a respiratory infection to assist admission avoidance.^7–9 It has been demonstrated to be a more time efficient treatment option when patients are unwell compared with chest physiotherapy without the use of MI-E.¹⁰

It is known that patients, especially those with bulbar dysfunction, can have an abnormal laryngeal response to MI-E, which can make the treatment technique difficult to apply and potentially ineffective.^11–14 In these patients, the larynx can close and narrow during the insufflation phase of the MI-E, resulting in MIC not being met. Without adequate insufflation, a sufficient expiratory flow bias cannot be achieved, and cough remains ineffective. The pharynx can also become constricted and narrowed during exsufflation, additionally causing reduction in expiratory flow, meaning cough effectiveness can be reduced, and pulmonary secretions cannot be expelled. Within a research environment and at specialist centres, nasal endoscopy has been used to visualise the larynx and quantify the laryngeal response to MI-E.^{11–13 15 16}

The next step of establishing how treatment prescriptions might be amended to avoid laryngeal responses or minimise their impact has yet to be taken. Furthermore, anecdotally in clinical practice, the use of nasal endoscopy to assess laryngeal responses to MI-E is not routine due to procedural practicalities, lack of resources, lack of trained staff and acceptance by patients.

One of the newer models of MI-E (E70, Philips Respironics, Murraysville, USA) has an on-board secure data (SD) card which records by breath-by-breath waveform data (figure 1.) showing changes in pressure and flow, which can be viewed in the Care Orchestrator Essence software (Philips Respironics). The research team have already used this successfully to assess how well physiotherapists use MI-E.¹⁷ If physiotherapists were able to use the waveforms in Care Orchestrator Essence to identify laryngeal responses to MI-E, it would mean that in clinical practice, physiotherapists would more readily be able to identify laryngeal response as a potential problem, as well as identifying potential strategies in treatment prescription to limit laryngeal response, thus optimising treatment in these often difficult and complex patients.

Figure 1. Mechanical insufflation--exsufflation waveform example.

Primary research objective

The primary objective of this research is to collect and review MI-E waveforms and nasal endoscopy video recordings to identify whether MI-E waveforms can be used to identify laryngeal responses to MI-E. The impact of different MI-E settings on laryngeal response will also be evaluated.

Methods and analysis

Patient and public involvement (PPI)

Service users were actively involved in the design of the research, specifically, they provided feedback on how many sessions they felt would be needed for the data collection. Patients were actively engaged in developing the participant-facing documentation, including the participant information sheet and the consent form. PPI will be sought to aid dissemination of the study results.

Study design

This is a prospective open-label pilot observational cohort study of 20 participants.

Patient entry

Twenty patients with NMD will be recruited from patients via a number of routes. Primarily, patients will be under the care of the Royal Free London NHS Foundation Trust; potential participants will be identified by the research team through ward rounds, screening of outpatient clinic lists and raising awareness of the study to colleagues. Patients will also be recruited through promoting the study via NMD charities, appropriate patient and public events, the National Institute of Health Research ‘be part of research’ website and networks with other clinicians.

Inclusion criteria

• Patients with NMD.

• Age≥18.

Exclusion criteria

• Unable to comply with protocol.

• Unable to give informed consent.

• Evidence of obstructive airways disease FEV1:FVC<0.7.

• Patients with a history of^18–20:

  • Un-drained pneumothorax.

  • Severe bronchospasm.

  • Head injury with Intercranial pressure (ICP) >25 mm Hg.

  • Severe arterial hypotension (mean arterial pressure <65 mm Hg).

  • Tracheoesophageal fistula.

  • Significant haemoptysis.

  • Facial fractures.

  • Vomiting.

  • Flail segment.

  • Epistaxis within 2 weeks.

Withdrawal and stopping criteria

Participants have the right to withdraw from the study at any time without providing a reason. Any data already collected will remain in the study.

Data management

Sample size

The sample size of this study is 20. Previous studies in a similar patient population investigating the effects of MI-E have found useful and meaningful results with similar sample sizes.^11–13

Analysis

Data will be collected based on demographic information such as age, sex, ethnicity and neuromuscular condition. Given the sample size of 20, non-parametric descriptive statistic will be used to report the demographics. Continuous data will be reported using median and IQR, and categorical data will be reported using percentages. Data will be collected prospectively and reviewed in a descriptive context, providing trends and potential rationales describing the waveforms in comparison to the videos. Published examples will be used to guide interpretation while taking into consideration the fact that published examples have not simultaneously observed waveforms and the larynx.^21–25 Specifically, waveforms will be scrutinised for:

• Laryngeal response during insufflation, as indicated by

  • inspiratory flow limitation.

  • spikes in flow at the beginning of insufflation with subsequent flattening of the flow curve until the end of insufflation.

  • spikes (‘bunny ears’) during insufflation on the pressure curve.

  • oscillations on the flow-time curve during insufflation.

• Laryngeal response during exsufflation as indicated by

  • expiratory flow limitation as indicated by flattening of the exsufflation curve.

  • oscillations on the flow-time curve during insufflation.

• Evidence of good mask fit as indicated by a return to baseline flow prior to exsufflation.

• Gas decompression spikes as indicated by a sharp spike at the start of exsufflation.

• The visualisation of the larynx will enable differentiation between a laryngeal response and the gas decompression spike.

• Examine the nasal endoscopy videos for laryngealresponse with no changes in the waveforms.

• Examine the waveforms and the laryngeal response videos for new waveform patterns not yet identified by other authors.

Trial design

Screening

Patients will be screened based on:

• neuromuscular condition.

• ability to consent.

• over the age of 18.

• no history of any contraindication specified in the exclusion criteria.

Baseline assessments

The baseline assessments that will be undertaken are:

• spirometry.

• PCF.

• sniff nasal inspiratory pressure.

Devices

The two devices used within the trial are

• Endoscope: Olympus CV-170, Germany. A device that allows for nasal endoscopy with video recordings of the upper airway.

• Phillips Respironics, MI-E device E70, which provides positive and negative pressure to elicit a cough.

Intervention

The participant will undergo MI-E optimisation by an experienced clinician, taking into account published research^{13 18 22–24 26–29} to establish their ideal prescription; this will be based on each individual, including: PCF, chest wall movement, comfort and secretions. The optimal settings will be reviewed with the nasal endoscope. The participant will undergo four sessions of MI-E cycles (table 1). There will be a 20% adjustment to calculate the pressures required, as illustrated in table 1. These prescriptions have been chosen as, based on current literature, these are most likely to elicit a laryngeal response, therefore providing the necessary data for the waveforms.^{11–13 28} The MI-E device uses a face mask, which will be adapted by drilling a hole in the mask to accommodate the nasal endoscope. We will do this in a clean environment, and masks will be decontaminated in line with manufacturers recommendations prior to use with participants. While the MI-E is being performed, the nasal endoscope will be visualising and recording any laryngeal response (figure 2A). Risks of both MI-E and nasal endoscopy have been identified and will be appropriately managed (online supplemental appendix 1). Lubricant gel will be used to improve comfort and tolerability of the nasal endoscope for participants. Local anaesthetic will not be used as it will affect the observed laryngeal response. Xylometazoline hydrochloride 0.1% will be used to dilate the nasal passage if required.

Table 1

Example of mechanical insufflation–exsufflation pressures with optimal settings +50/–55 with 20% variation

	Insufflation pressure	Exsufflation pressure
Optimal setting	+50	−55
Setting 1	+60 (+20%)	−66 (+20%)
Setting 2	+40 (-20%)	−44 (−20%)
Setting 3	+60 (+20%)	−44 (−20%)
Setting 4	+40 (-20%)	−66 (+20%)

Figure 2. (A) Application of the mechanical insufflation-exsufflation device and nasal endoscopy (with consent). (B) Example of images from nasal endoscope (with consent).

Device application

The MI-E device will be used with an adapted face mask. During the procedure, the facemask will cover the participant’s nose and mouth for the duration of the MI-E cycle. This is held in place by the respiratory physiotherapist.

The MI-E device will provide positive pressure (insufflation) and negative pressure (exsufflation) with the respiratory physiotherapists prompting the patient to actively cough during exsufflation.

The device will use the cough trak mode that will recognise when the participant is breathing in to initiate the MI-E cycle; this will be repeated three times to complete one cycle. This will be repeated with predefined setting changesable (example in 1) to illicit a laryngeal response.

During each MI-E cycle, the vocal cords will be visualised during the nasal endoscope, as shown in figure 2B and online supplemental video 1.

Ethics and dissemination

Ethics

This protocol has been reviewed by the East of England-Cambridge Central Research Ethics Committee (REC reference: 21/EE/0233), who have granted a favourable ethical opinion.

Consent

Participants who are unable to provide informed consent are excluded from the study. The research team will take consent prior to the study baseline measurements and following the participant’s review of the participant information sheet, which clearly sates the risks of participating in the research study. Potential participants will be given a minimum of 24 hours to consider if they wish to participate in the study. Consent for participants who are non-English speaking will be obtained using a translator. Those who are unable to physically sign the consent form will provide verbal consent with the research team signing on their behalf; this is in recognition of the physical disability experienced by the patient population.

Confidentiality

All data will be handled in accordance with the General Data Protection Regulation 2018. Case report forms will not bear the participant’s name or other directly identifiable data. Data collected will be anonymised, password protected and only accessible by the research team. SD cards will provide a backup of the MI-E waveform data, which will be stored securely.

Sponsor

The Royal Free London NHS Foundation Trust will act as the sponsor.

Audits and inspection

Trial related monitoring, audits, research ethics committee review and regulatory inspections will be conducted in line with UK policy framework for health and social care research.³⁰

Trial closure

The end of the trial will be on completion of 20 patients through the trial.

Trial management

A trial management group (TMG) will monitor all aspects of the conduct and progress of the trial, ensure the protocol is adhered to and take appropriate action to safeguard participants in the quality of the trial. The TMG will meet monthly during the data collection period and will consist of the chief investigator (Stephanie Mansell), named researchers (Dr Amar Shah, Rhiannon Parry and Charlotte Greenfield) and the clinical trials coordinator (Francesca Gowing). The trial steering committee (TSC) will provide overall supervision of the trial and ensure it is conducted in accordance with the principles of good clinical practice and the relevant regulations. The TSC will meet 6 monthly during the time of the trial. Members of the TSC will include the chief investigator (Stephanie Mansell) and named researchers (Dr Swapna Mandal, Dr Richard Orrell and Mr Yogesh Batt).

Publication policy

All publications and presentations relating to the study will be authorised by the TSC. The first publication of the trial results will include the TMG and the TSC as authors.

Timelines

The trial start date was January 2022, with an end date of January 2024 and anticipated publication date of June 2024.

Discussion

The outcome and potential benefit of this trial will provide an initial indication of whether the waveforms from the MI-E device can be used to identify laryngeal responses to MI-E, thus providing better and more effective guidance of treatment prescription. Use of the waveforms would remove the need for invasive procedures and be more cost effective. The feasibility data could be used to inform further future trials. The data from this trial could be used to guide the development of MI-E devices, for example, on-screen waveforms, which would guide healthcare professionals in setting the MI-E prescriptions. Furthermore, the data from this trial could inform the development of algorithms to automate the prescription of MI-E.

As in all clinical trials, there are limitations to this protocol. Feedback from funders and patient groups has meant that it is outside of the scope of this protocol to include healthy subjects. It will, therefore, not be possible to determine typical MI-E waveform patterns. Given this work is pilot work, we cannot validate potential findings; further research will be required to validate any conclusions from this trial. Given the pilot nature of this work and the small sample size, statistical analysis will not be appropriate. However, this pilot will inform future trials. Additionally, the results of this trial will not inform clinicians whether the use of waveforms to identify laryngeal response is safe, only if it is a feasible technique.

The authors would like to acknowledge the support of Robert Chase, Philips Respironics.

The authors would also like to acknowedge the contribution of those who have worked on the trial via the National Institute for Health Research (NIHR) Associate Principle Investigator Scheme: Louise Coase and Sarah Pierce

Data availability statement

No data are available.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

This study involves human participants and was approved by East of England-Cambridge Central Research Ethics Committee (REC reference: 21/EE/0233). Participants gave informed consent to participate in the study before taking part.

Footnote

Twitter @skmansell

Contributors Conceptualisation: SKM. Methodology: SKM, AS, RP, CG, SM and YB. Resources: SKM, RP and AS. Data curation, writing - original draft: SKM, RP, AS. Writing - review and editing: all authors. Supervision: SKM, SM and YB. Project administration: FG and SKM. Funding acquisition: SKM, CG, SM and YB.

Funding This work was supported by the Private Practice Physiotherapy Fund (grant number 350). The funder (Private Physiotherapy Education Fund) has not made any contribution to this protocol.

Competing interests SKM: consultancy for Philips Respironics, educational grants from Philips Respironics and Dolby Vivisol, Research grants from Philips Respironics. SM: consultancy for Philips Respironics, educational grants from Dolby Vivisol. AS: educational grants from Dolby Vivisol.

Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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