Is a change in mouth opening associated with improvements in quality of life in children with type 1 obstructive sleep apnoea after adenotonsillectomy? Protocol for the JawChild prospective cohort study

Abstract

Introduction

Adenotonsillectomy is the primary treatment for type 1 obstructive sleep apnoea (OSA1). Although polysomnography (PSG) remains the gold standard for measuring Apnoea-Hypopnoea Index, it is a labour-intensive procedure and does not correlate with improvements in quality of life postadenotonsillectomy. Mouth breathing is associated with poorer quality of life in children. Mandibular movement (MM), which measures mouth opening, is a validated measure of respiratory effort that can be easily and safely assessed in children using the JAWAC technology. This study aims to evaluate the relationship between changes in quality of life and changes in mouth opening in children with OSA1 after undergoing adenotonsillectomy. Secondary objectives include evaluating changes in quality of life, clinical symptoms and other MM and PSG metrics in the same population.

Methods and analysis

This exploratory, non-randomised, monocentric, prospective cohort study with a non-blinded single arm will include 50 children aged 3–7 years, undergoing adenotonsillectomy at the Clinique Saint Jean, Montpellier, France. Quality of life will be measured using the parent version of the Paediatric Quality of Life Inventory and MM metrics will be measured during PSG using the JAWAC system during the inclusion visit and 3 months after adenotonsillectomy. The primary outcome will be the correlation between the changes in quality of life and mouth opening (1/10 mm) postadenotonsillectomy. Secondary analyses will evaluate changes in clinical symptoms, PSG measures and other MM metrics including respiratory effort, as well as the associations between these measures.

Ethics and dissemination

This study was approved by an independent ethics committee (Comité de Protection des Personnes Est) on 24 March 2025 (2024-A02761-46) and will be conducted in accordance with French law, good clinical practice and the guidelines of the Declaration of Helsinki. Study findings will be disseminated through international peer-reviewed journal articles as well as public, academic presentations at national and international conferences.

Trial registration number

NCT06973928.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The JAWAC is a simple, non-invasive measure of respiratory effort and mouth opening that offers a possible alternative to polysomnography, a labour-intensive measure.

• The study will take place at a French hospital that, due to the single-payer insurance system in France, should include patients from a range of socioeconomic categories and geographical (urban vs rural) locations.

• This exploratory study will be non-randomised and monocentric with a non-blinded single arm.

Introduction

Obstructive sleep-disordered breathing (oSDB) encompasses a range of abnormal breathing patterns during sleep, from snoring to complete airway obstruction, caused by increased upper airway resistance and pharyngeal collapsibility.¹ Although often considered an adult disease, oSDB also occurs in children and has been linked to metabolic, cardiovascular and neurocognitive morbidity, and lower quality of life in paediatric patients.² In children, OSDB is also associated with reduced cognitive performance,³ impaired memory consolidation⁴ and greater sleepiness.⁵ The most common form of paediatric oSDB is type 1 obstructive sleep apnoea (OSA1), which typically occurs in young, non-obese children without craniofacial or neurological comorbidities.⁶ This condition is characterised by nasal and/or throat blockages due to lymphoid tissue hypertrophy. Adenotonsillectomy to remove enlarged tonsils and/or adenoids is generally the first-line treatment for OSA1.⁷

Currently, OSA1 is diagnosed based on a combination of clinical characteristics and the measurement of the Apnoea-Hypopnoea Index (AHI), which is considered an indicator of OSA severity. However, two notable paradoxes exist. First, polysomnography (PSG), the gold standard for measuring AHI, is labour-intensive, costly and impractical for follow-up in a paediatric population. Second, while AHI reportedly describes the severity of OSA, no correlation has been established between AHI and quality of life in children.⁸

Mandibular movement (MM) is a valid measure of respiratory effort that overcomes the limitations of AHI. MM can be easily assessed in children using the JAWAC system. In a preliminary study of 25 patients, Martinot et al reported that postadenotonsillectomy changes in respiratory effort-related arousal, measured using PSG, correlated with changes in MM (duration and index).⁹ A recent review underlines that MM is an emerging biomarker in paediatric sleep-disordered breathing for both the diagnosis and monitoring of paediatric OSA.¹⁰ However, changes in symptoms and quality of life were not evaluated. Additionally, mouth opening, evaluated using the MM signal, was considered a surrogate measure of respiratory effort, rather than a variable of interest.

The development of new technologies has created opportunities for enhancing precision medicine approaches that are uniquely adapted to the paediatric population.¹¹ However, no previous studies have identified a simple, objective biomarker that is associated with quality of life and surgical effectiveness in children who undergo adenotonsillectomy. Given the observed associations between mouth opening, respiratory effort and quality of life in paediatric patients, the primary aim of this exploratory, prospective, non-blinded, single arm study is to evaluate the relationship between changes in quality of life and changes in mouth opening, evaluated using the JAWAC, in children with OSA1 who undergo adenotonsillectomy. The secondary aims will include studying the relationships between change in quality of life and changes in common MM and PSG metrics as well as evaluating variations in quality of life, changes in clinical symptoms and the relationship between MM and PSG metrics in the same population of children who undergo adenotonsillectomy.

Methods and analysis

Study design and objectives

This study will evaluate changes in quality of life, MM metrics and PSG metrics in paediatric patients who undergo adenotonsillectomy to treat OSA1, and investigate the relationships between these variables. The study will take place at the Clinique Saint Jean located in Montpellier, France. Due to its explorative and descriptive nature, the study is a non-randomised, monocentric, prospective cohort study with a non-blinded single arm. During the preinclusion visit, surgeons will screen patients consulting for potential adenotonsillectomy for eligibility to participate in the study (V0). During the inclusion visit (V1), one of the two parents or legal representatives of each participant will give informed consent and then answer quality of life and sleep-related symptoms questionnaires. Patients will undergo PSG coupled with JAWAC measurements. During the surgical visit (V2), patients will undergo adenotonsillectomy. 3 months later, during the follow-up visit (V3), patients will undergo PSG coupled with JAWAC measures again, and the same legal guardian will answer the same quality of life and sleep-related symptoms questionnaires. 4 months after surgery, patients will attend a surgeon follow-up consultation (V4). Overall, the study protocol follows the national recommendations for standard OSA management,⁶ with the addition of questionnaires at V1 and V3, and a systematic PSG coupled with a MM measure at V3. Only one consultation (V3) will occur in addition to the standard patient pathway. Therefore, we expect rates of study discontinuation to be low. Data from any patients who do discontinue or deviate from the intervention will be excluded. Undesirable events will be recorded throughout the study at V1, V2, V3 and V4. The study flow is shown in figure 1.

Figure 1. Study flow. *Standard care.

Population and eligibility criteria

The study population will include paediatric patients between the ages of three and 7 years old, who consulted with a surgeon at the study centre for potential adenotonsillectomy. To be eligible to participate, patients must be beneficiaries of the French single payer national medical insurance system, be able to attend all scheduled visits and comply with trial procedures, and legal guardians must give informed consent. Full inclusion and exclusion criteria are listed in table 1. The study centre is a private French hospital that, due to the single-payer insurance system in France, should include patients from a range of socioeconomic categories and geographical (urban vs rural) locations.

Table 1. Inclusion and non-inclusion criteria.

Inclusion criteria

Non-inclusion criteria

Age: 3–7 years old Received a surgical indication for AT Beneficiary of the French single-payer national medical insurance system Informed consent given Able to attend all scheduled visits and comply with all trial procedures

Previous AT Subject has already participated in the current study Craniofacial malformation syndrome BMI according to age >97th percentile Previous or current stimulant medication (methylphenidate) Current orthodontic treatment Asymmetric score of the tonsil with a tonsil Brodsky score of ≤2 Subjects who are in a dependency or employment with the sponsor or the investigator Participation in another clinical trial or administration of an unapproved drug within the last 4 weeks before the screening date

AT, adenotonsillectomy; BMI, body mass index.

Patient and public involvement

Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

Outcomes and interventions

Questionnaires

Several self-report questionnaires that have been validated in French will be used to assess the participants’ quality of life as well as their clinical symptoms during the inclusion visit (V1) and 3 months after adenotonsillectomy (V3). Quality of life will be evaluated using two versions of the parent version of the Paediatric Quality of Life Inventory (PedsQL),¹² according to the participants’ ages. The PedsQL PPR 2–4 will be used for participants between 3 and 4 years old, and the PedsQL PPR 5–7 will be used for participants from 5 to 7 years old.

The Sleep-related Breathing Disorder scale of the Paediatric Sleep Questionnaire (PSQ)13,15 total and subscale scores will be used to evaluate subjects’ sleep-related symptoms. The Severity Hierarchy Score (SHS) will be used to evaluate the participants’ respiratory symptoms. Two versions of the Sleep Disturbance Scale for Children (separate versions for 3–4 and for 5–7 year olds) will be used to evaluate the subjects’ behaviour, according to their age.¹⁶ Two versions of the Strengths and Difficulties Questionnaire (separate versions for 3–4 and for 5–7 year olds) will be used to assess participants’ emotional and behavioural symptoms.¹⁷

Overnight PSG

Each child will undergo laboratory-based PSG recorded by certified technicians at V1 and V3. All PSG will be conducted during a supervised overnight hospitalisation at the Pediatric Sleep Center of Clinique Saint-Jean (Montpellier, France). The child will sleep in a dedicated room with one parent. Electrode placement and equipment setup will be performed according to the standards of the American Academy of Sleep Medicine by a trained sleep technician from the unit. The examination will be continuously monitored in real-time from the control room, allowing for live polysomnographic parameter tracking. If necessary, electrodes and sensors will be repositioned to correct any signal deterioration. In the event of a technical or medical issue, the standard procedures of the unit will be applied, including notifying the lead physician, intervention by an on-call doctor if needed, and involvement of the biomedical and/or technical department in case of technical problems.

The following general sleep-related measures will be collected: time in bed (TIB), total sleep time (TST), sleep efficiency, sleep-onset latency, rapid eye movement (REM) stage latency, duration of wake after sleep onset, time and percentage of TST spent in sleep stage (N1, N2, N3 and REM sleep), micro-arousal index, photoplethysmography arousal index, micro-arousal index associated with respiratory events and periodic limb movement (PLM) index, PLM-related arousal index.

Respiratory-related measures will be collected, including: AHI, apnoea index, hypopnoea index, AHI during REM sleep, obstructive AHI, central AHI, respiratory-related arousal index, respiratory disturbance index, percentage of TST spent in dorsal position, dorsal and non-dorsal AHI, mean SpO2, time below 90% peripheral oxygen saturation (SpO2), % of TST below 90% of SpO2, oxygen desaturation ≥3% index, time spent snoring, and thoraco-abdominal asynchrony.

Validity and quality of the JAWAC/PSG signals will be collected for TST and TIB, including: JAWAC, respiratory flow, SpO2, respiratory belt, electroencephalography, electromyography and electrooculography signals.

Mandibular movements

MM will be measured using the JAWAC magnetic sensor, a midsagittal MM magnetic sensor (Brizzy, Nomics, Liege, Belgium) that measures the distance between two resonant circuits placed on the forehead and on the chin. The transmitter generates a pulsed magnetic wave of low energy. The change in the magnetic field recorded at the receiver is inversely related to the cube of the distance between the chin and forehead probes. The distance between two probes is measured in mm with a resolution of 0.1 mm. This signal provides the instantaneous position of the mandible and its change concurrently to an arousal.

The JAWAC will be used to measure common MM metrics, listed and defined in table 2, in patients. Polysomnographic resolution will be defined as an AHI <2 and OAI <1.¹⁸ Symptomatic resolution will be defined as an OSA symptom score, measured using the PSQ <0.33 with a >25% improvement from baseline.

Table 2. Mandibular movement (MM) variables.

Variable	Abbreviation	Definition	Unit
Large MM	MML	When mandibular movement amplitudes are larger than normal (≥0.3 mm from peak to peak) during two or more respiratory cycles. This movement is synonymous with ventilatory effort.	Number
Sharp MM	MMS	A single sudden large mandibular movement occurring during a respiratory cycle, with an amplitude >1 mm and/or an amplitude ≥200% of the previous and/or the ensuing MM’s amplitude. This type of movement is symptomatic of a cortical micro-arousal or a Respiratory Effort-Related Arousal, with a sudden closure of the mandible.	Number
MM opening	MMO	The degree of mouth opening (how wide the mouth opens) during mandibular movement.	mm
Fixed thresholds	tMM0.4 tMM0.3 tMM0.2	Durations during non-rapid eye movement sleep when mandibular movement was higher than 0.4 mm (tMM0.4), 0.3 mm (tMM0.3) and 0.2 mm (tMM0.2).	Second

Tonsillectomy and adenoidectomy

The surgical approach will be standardised for all patients. Tonsillotomy will be performed using the Coblation technique. This intracapsular procedure involves reducing the tonsil tissue to the level of, or slightly below, the tonsillar pillars. When deemed appropriate by the surgeon, adenoidectomy will be performed concurrently with tonsillotomy. Adenoidectomy will be carried out using a cold steel technique with a curette.

Demographic data

Data related to sex, age, body mass index, tonsil Brodsky grade, Friedman palate position, asthma (yes/no), attention-deficit/hyperactivity disorder diagnosis, attention-deficit/hyperactivity disorder medication, prematurity (yes/no), orthodontic care (yes/no), myofunctional therapy (yes/no) and dental class will be collected from patient records.

Sample size

We used a two-sided Fisher’s z test at a 0.05 significance level to calculate that a sample size of 38 is needed to achieve 90% power in detecting a Pearson correlation coefficient (ρ) of 0.75 (between changes in quality of life and mouth opening after adenotonsillectomy). To account for potential loss to follow-up, we plan to recruit 50 patients.

Recruitment

Trained study investigators will undertake recruitment at the study centre during patients’ regularly scheduled consultations for potential adenotonsillectomy (V0). All children who participate in this study will benefit from earlier management, as follow-up polysomnographic evaluations generally occur 9 months after surgery (compared with 3 months in the current study) due to wait times. Patients will be compensated for expenses related to this follow-up PSG, up to a limit of €50.

Study discontinuation

Participation of subjects to the study is voluntary. The subjects’ legal guardians have the right to withdraw their consent from the study at any time for any reason and without jeopardising their medical care. The investigator also has the right to withdraw patients in agreement with the sponsor or his delegate.

Subjects must be withdrawn from the study under the following circumstances:

• The subject’s legal guardian withdraws consent.

• Development of an intercurrent illness or condition which would interfere with the subject’s continued participation.

• In the case of violation of the protocol or occurrence of a significant protocol violation during the clinical trial, assessment of the impact on the study results by the coordinating investigator and the methodologist.

• Any situation that, in the opinion of the investigator, would pose unacceptable risks to the subject if trial participation is continued.

For any discontinuation, the investigator should obtain all required details and should document the date and reason of the premature termination in the electronic case-report form (eCRF). If the reason for withdrawal is an adverse event, the specific event will be recorded in the eCRF. The investigator will make thorough efforts to document the outcome. Patients prematurely withdrawn or lost to follow-up will be analysed at least in the safety set and in the conditions of confidentiality.

When possible, in case of withdrawal, the investigator will perform all examinations scheduled for the final study visit, which includes recording of adverse events. In any case, the patient will be treated in accordance with standard care in the centre. Children who participate in this study should not participate in any other interventional studies until completion of the final study visit.

Data management

Each patient will be identified by an anonymous identifier. All clinical and paraclinical data as well as data from questionnaires will be entered into e-CRF by investigators or research assistants under the responsibility of the investigators. The e-CRF will be developed using Redcap (Research Electronic Data Capture) to capture all relevant medical information from patients included in the project and ensure data quality at entry. Each user (investigators or research assistants) will have a unique username and password, providing access only to their centre’s data. An audit trail function will be included to supervise and trace all users’ actions. The encrypted data will be transmitted to the data-management centre via a secure internet connection.

Individual clinical and paraclinical data needed for the study analyses must be entered into the eCRF as they are obtained, anonymised by the investigator, authenticated by an electronic signature of the investigator. All entered and missing data must be justified.

Statistical methods

Study outcomes are summarised in table 3. All statistical analyses will be conducted by the Institut Desbrest d’Épidémiologie et de Santé Publique (IDESP) at the University of Montpellier. A comprehensive statistical analysis plan, maintained by IDESP, will outline the analyses prior to data extraction. Any deviations from this plan, along with their justifications and any additional or alternative analyses, will be documented in the final report.

Table 3. Study outcomes.

	Outcome measure	Metrics
Primary outcome	Quality of life	The change in total score and subscales from V1 to V3, measured using the parent version of the Paediatric Quality of Life inventory Parent Proxy Report ages 2–4 or Parent Proxy Report ages 5–7
	Mouth opening	The change in mouth opening (1/10 of millimetres) from V1 to V3, measured using JAWAC analysis
Secondary outcomes	Other measures from the JAWAC	The change in mandibular movements (MM) from V1 to V3, including MML, MMO, MMS, tMM0.4, tMM0.3 and 0.2 tMM0.2
	Polysomnography	The change in polysomnography respiratory disturbance index, as defined by the American Academy of Sleep Medicine 2018, from V1 and V3
	Sleep symptoms	The change in Sleep-related Breathing Disorder scale of the Paediatric Sleep Questionnaire from V1 to V3
	Respiratory symptoms	The change in Severity Hierarchy Score from V1 to V3
	Behaviour	Changes in the Sleep Disturbance Scale for Children, with two versions adapted for age (2–4 and 5–7 years), from V1 to V3
	Emotional symptoms	Changes in the Strengths and Difficulties Questionnaire, with two versions adapted for age (2–4 and 5–7 years), from V1 to V3

Inclusion visit (V1); Follow-up visit 3 months after adenotonsillectomy (V3); MML; MMO; MMS, MMS; total durations with MM greater than 0.4 mm (tMM0.4), 0.3 mm (tMM0.3) and 0.2 mm (tMM0.2).

MM, mandibular movement; MML, large MM; MMO, MM opening; MMS, sharp MM.

All analyses will be conducted using statistical software (SAS, V.9.4; SAS Institute and R V.4.3.0). A two-sided p value of less than 0.05 will be considered statistically significant.

The baseline features of the overall population and of each group will be described. Categorical variables will be reported as frequencies and percentages and continuous variables as either means with SD or medians with first and third quartiles.

The primary outcome analysis (correlation between change in quality of life and change in mouth opening after AT) will be done using the estimation of the correlation coefficient. A linear regression will be used for the analysis of the main criteria before and after adjustment on confounding variables. Due to the exploratory nature of the study, we cannot define an exhaustive list of confounding variables a priori; however, we intend to include age, gender and type of surgery (tonsillectomy with or without removal of adenoids). Variables included in the final model will be chosen using a backward selection procedure. Variables with p<0.15 in the univariable analysis will be tested for inclusion in the final model. Results will be presented as adjusted regression coefficients with 95% CIs.

No missing data are expected for the main criteria of judgement. Due to the expected low rate of predicted missing values, we will not use any imputation method for the main outcome. Analyses will be performed on the complete cases. We will indicate the number of observed data in each table.

We have prespecified a single primary analysis of a single primary outcome. For the secondary and exploratory outcomes, a false discovery rate method will be used.

Data monitoring and quality control

To ensure accurate, complete and reliable data, the sponsor or its representatives will do the following:

• Provide instructional material to the study sites, as appropriate.

• Provide a start-up training session to instruct the investigator(s) and study coordinator(s) on the protocol, the correct completion of the eCRF, study procedures, and the transmission of data in a timely manner to the clinical database for statistical analyses.

• Make periodic visits to the study site.

• Be available for consultation and stay in contact with the study site personnel by mail, telephone and/or fax.

• Review and evaluate eCRF data and use.

• Conduct quality review of the database.

The sponsor will designate data monitors who will make routine monitoring to check compliance with the protocol, the completeness, accuracy and consistency of the data, and adherence to good clinical practice (GCP). The data monitors will present the protocol, all procedures related to the study, and guidelines for completing the eCRF to the investigator during an initiation visit performed before the first patient is included. The data monitor will be allowed to have access to all source documents needed to verify the eCRF entries and other protocol-related documents.

The principal investigator must ensure that eCRFs are completed in a timely manner and must allow periodical access to eCRFs, patient records, drug logs and all other study-related documents and materials. The investigator will agree to provide the monitor direct access to the subjects’ source data, which may exist in the form of hospital records, patient files and notes, and laboratory assessment reports and results.

Audits and inspections

The purpose of an audit is to confirm that the study is conducted as per protocol, International Council for Harmonisation (ICH)-GCP and applicable regulatory requirements, that the well-being and the rights of the subjects enrolled have been protected, and that the data relevant for the evaluation of the investigational product have been recorded, processed and reported in compliance with the planned arrangements. The investigators will permit direct access to all study documents, drug accountability records, medical records and source data. The process will be independent of the investigators and the sponsor.

Ethics and dissemination

Research ethics approval

This study (NCT06973928) will be carried out in accordance with French law, GCP guidelines and the Declaration of Helsinki. This study was approved on 24 March 2025 (2024-A02761-46) by an independent ethics committee (Comité de protection des personnes (CPP) Est II).

Protocol amendments

The study shall be conducted as described in this approved protocol. Any future revisions/amendments to the protocol will not be permitted without prior approval by the study steering committee. Any amendments to the protocol will require Independent Ethics Committee/Institutional Review Board (Comité de Protection de Personnes) approval prior to implementation of any changes made to the study design.

Consent and assent

Investigators will seek consent to enter the study from one of the two parents or the legal representative of each participant only after full explanation has been given, an information sheet offered, and time given for patients to consider the options. An information sheet will also be given to each patient. Signed consent must be obtained from one of the two parents or legal representative of participants. In addition, each participant has the opportunity to be assisted by a person of trust, in order to support their decisions. The consent form should also be signed by the person carrying out the consent procedure. An original completed consent form must be retained at each site and all patients must be given an original of the patient information sheet and the signed consent form.

Confidentiality

Investigators and research assistants (under the responsibility of the investigators) will add all required data to the e-CRF. Redcap (Research Electronic Data Capture) will be used to control the quality of the data added to the e-CRF at entry. A unique username and password give specific users access to the centre’s data on Redcap. An audit trail function is included allowing supervision and traceability of all actions from all users. The encrypted data is transmitted to the data-management centre via a secure internet connection. The patients will be identified using anonymous study-specific numbers.

Availability of data and dissemination

The study dataset is the property of the sponsor (Groupe Adène, Montpellier, France) and will be made available to the steering committee and participating investigators. Aggregated study results will be published in a peer-reviewed journal. Authorship will be attributed according to the criteria stipulated by the International Committee of Medical Journal Editors. In agreement with French Law, study participants will be provided with results on request. Members of the public may request the data set from the study director following publication of the results.

Discussion

AHI, measured using PSG, is used to describe OSA severity, but does not reflect quality of life in patients with OSA. Furthermore, a follow-up PSG after adenotonsillectomy is rarely conducted because PSG is a labour-intensive procedure.

We will assess MM using the JAWAC device, which is non-invasive, safe and easy to use in children.⁹ The study results will indicate whether this measure could be implemented as a useful biomarker of adenotonsillectomy efficacy in children with OSA.

A limitation of this protocol is that the study is monocentric and prospective with a non-blinded single arm. However, we believe this design is appropriate considering the explorative and descriptive nature of the study. Future randomised, multicentre trials will be needed to confirm evidence from the present study.