Intranasal Steroid as Medical Therapy For Sleep-Disordered Breathing in Children

The proportion of participants with resolution of significant Sleep Disordered Breathing (SDB) symptoms as defined by the parent completed Brouillette questionnaire < -1 at 12 weeks

The Brouillette questionnaire is a validated symptom questionnaire that investigates the presence of respiratory sleep disorders and the frequency of apnoea and pathological snoring. Each item is scored from 0 to 3 (0 = absence of symptoms, 1 = occasional symptoms, 2 = frequent symptoms, and 3 = constant symptoms), and the overall score is directly proportional to disease severity. The proportion of participants in each treatment arm with resolution of symptoms at 12 weeks will be calculated with 95% confidence intervals (CIs). The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 12 weeks

An improvement of score in parent completed Pediatric Sleep Questionnaire-sleep disordered breathing subscale (PSQ-SDB subscale) at week 6 when compared with baseline measured at the start of the intervention period (week 0)

The Pediatric Sleep Questionnaire - sleep disordered breathing subscale is a validated questionnaire which contains 22 symptom items that ask about snoring frequency, loud snoring, observed apneas, difficulty breathing during sleep, daytime sleepiness, inattentive or hyperactive behaviour, and other paediatric Obstructive Sleep Apnoea (OSA) features. Responses are "yes" = 1, "no" = 0, and "don't know"=missing. The mean scores and 95% confidence intervals (CIs) in the two treatment arms will be calculated and the treatment arms will be compared using a linear regression adjusted for centre.

Time frame: 6 weeks

An improvement of score in parent completed Obstructive Sleep Apnoea-18 (OSA-18) questionnaire at week 6 when compared with baseline measured at the start of intervention period (week 0).

The Obstructive Sleep Apnoea-18 (OSA-18) questionnaire is a validated questionnaire and consists of 18 questions concerning sleep disturbances, physical symptoms, emotional distress, daytime function, and caregiver concerns. The mean scores and 95% confidence intervals (CIs) in the two treatment arms will be calculated and the treatment arms will be compared using a linear regression adjusted for centre.

Time frame: 6 weeks

An improvement of score in parent completed Pediatric Quality of Life Inventory (PedsQL) at week 6 when compared with baseline measured at the start of the intervention period (week 0).

The Pediatric Quality of Life Inventory (PedsQL) is a validated, standardised, generic assessment instrument that provides a modular approach to measure health related quality of life in healthy children and adolescents and those with acute and chronic disorders. This questionnaire consists of 23 items evaluating physical, emotional, social and scholastic functioning, and it integrates both generic core scales and disease-specific modules. The mean scores and 95% confidence intervals (CIs) in the two treatment arms will be calculated and the treatment arms will be compared using a linear regression adjusted for centre.

Time frame: 6 weeks

An improvement of score in parent completed Strengths and Difficulties Questionnaire (SDQ) at week 6 when compared with baseline measured at the start of the intervention period (week 0).

The Strengths and Difficulties Questionnaire (SDQ) is a validated brief behavioural screening questionnaire about 3-16 year olds. The mean scores and 95% confidence intervals (CIs) in the two treatment arms will be calculated and the treatment arms will be compared using a linear regression adjusted for centre.

Time frame: 6 weeks

An improvement of score in parent completed Glasgow Children's Benefit Inventory (GCBI) at week 6 when compared with baseline measured at the start of the intervention period (week 0).

The Glasgow Children's Benefit Inventory (GCBI) consists of 24 questions on the consequences of a specified intervention on various aspects of the day-to-day child life, without reference to any specific symptoms, and it can be apply to children of any age. The mean scores and 95% confidence intervals (CIs) in the two treatment arms will be calculated and the treatment arms will be compared using a linear regression adjusted for centre.

Time frame: 6 weeks

Proportion of parent responders who think their child needs surgery to remove their tonsils or adenoids (T&A) at 6 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study. "Do you think your child needs surgery to remove their tonsils or adenoids (T\&A)?"

Time frame: 6 weeks

Proportion of parent responders who think their child needs surgery to remove their tonsils or adenoids (T&A) at 12 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study. "Do you think your child needs surgery to remove their tonsils or adenoids (T\&A)?"

Time frame: 12 weeks

Proportion of parent responders who think their child needs surgery to remove their tonsils or adenoids (T&A) at 6 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study. "Do you think your child needs surgery to remove their tonsils or adenoids (T\&A)?"

Time frame: 6 months

Proportion of parent responders who would be happy to proceed with tonsils and adenoids surgery (T&A) if recommended to them at 6 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study. "If T\&A surgery were recommended to you now, would you be happy to proceed?"

Time frame: 6 weeks

Proportion of parent responders who would be happy to proceed with tonsils and adenoids (T&A) surgery if recommended to them at 12 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "If T\&A surgery were recommended to you now, would you be happy to proceed?"

Time frame: 12 weeks

Proportion of parent responders who would be happy to proceed with tonsils and adenoids (T&A) surgery if recommended to them at 6 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "If T\&A surgery were recommended to you now, would you be happy to proceed?"

Time frame: 6 months

Proportion of parent responders who would be happy to proceed with tonsils and adenoids (T&A) surgery if recommended to them at 12 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "If T\&A surgery were recommended to you now, would you be happy to proceed?"

Time frame: 12 months

Proportion of parents who think their child still needs a review by a hospital specialist at 6 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Do you think your child's symptoms need review by a hospital specialist?"

Time frame: 6 weeks

Proportion of parents who think their child still needs a review by a hospital specialist at 12 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Do you think your child's symptoms need review by a hospital specialist?"

Time frame: 12 weeks

Proportion of parents who think their child still needs a review by a hospital specialist at 6 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Do you think your child's symptoms need review by a hospital specialist?"

Time frame: 6 months

Proportion of parents who think their child still needs a review by a hospital specialist at 12 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Do you think your child's symptoms need review by a hospital specialist?"

Time frame: 12 months

Proportion of parents who would be happy to have their child taken off the hospital clinic waiting list at 6 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Would you be happy to have your child taken off the hospital clinic waiting list?"

Time frame: 6 weeks

Proportion of parents who would be happy to have their child taken off the hospital clinic waiting list at 12 weeks

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Would you be happy to have your child taken off the hospital clinic waiting list?"

Time frame: 12 weeks

Proportion of parents who would be happy to have their child taken off the hospital clinic waiting list at 6 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Would you be happy to have your child taken off the hospital clinic waiting list?"

Time frame: 6 months

Proportion of parents who would be happy to have their child taken off the hospital clinic waiting list at 12 months

This will be measured by asking parents the following question on a parent assessment questionnaire developed for the study: "Would you be happy to have your child taken off the hospital clinic waiting list?"

Time frame: 12 months

Parent satisfaction with run-in phase and treatment phase therapy as an alternative to tonsillectomy and/or adenoidectomy at 6 weeks (Likert Scale)

A study specific questionnaire using a 5 point Likert Scale will be used to evaluate parent satisfaction of ease of administration of drug, effectiveness of treatment, side effects. A higher score will indicate higher satisfaction. The mean scores and 95% confidence intervals in the two arms will be calculated and the treatment arms will compared using a linear regression adjusted for center.

Time frame: 6 weeks

Parent satisfaction with run-in phase and treatment phase therapy as an alternative to tonsillectomy and/or adenoidectomy at 12 weeks (Likert Scale)

A study specific questionnaire using a 5 point Likert Scale will be used to evaluate parent satisfaction of ease of administration of drug, effectiveness of treatment, side effects. A higher score will indicate higher satisfaction. The mean scores and 95% confidence intervals in the two arms will be calculated and the treatment arms will compared using a linear regression adjusted for center.

Time frame: 12 weeks

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) defined by Ear Nose Throat (ENT) surgery at 6 months

Parents will be contacted by email with a short survey to record whether their child is either on a waitlist for ENT surgery or has undergone ENT surgery. The proportion of participants in each treatment arm who have progressed to Tonsillectomy and/or Adenoidectomy for SDB will be calculated with 95% confidence intervals. The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 6 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing defined by ENT surgery at 12 months

Parents will be contacted by email with a short survey to record whether their child is either on a waitlist for ENT surgery or has undergone ENT surgery. The proportion of participants in each treatment arm who have progressed to Tonsillectomy and/or Adenoidectomy for SDB will be calculated with 95% confidence intervals. The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 12 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) based on symptoms of SDB reported in parent-completed Brouillette questionnaire at 6 months

The Brouillette questionnaire is a validated symptom questionnaire that investigates the presence of respiratory sleep disorders and the frequency of apnoea and pathological snoring. Each item is scored from 0 to 3 (0 = absence of symptoms, 1 = occasional symptoms, 2 = frequent symptoms, and 3 = constant symptoms), and the overall score is directly proportional to disease severity. The proportion of participants in each treatment arm with resolution of symptoms at 6 months will be calculated with 95% confidence intervals (CIs). The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 6 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) based on symptoms of SDB reported in parent-completed Brouillette questionnaire at 12 months.

The Brouillette questionnaire is a validated symptom questionnaire that investigates the presence of respiratory sleep disorders and the frequency of apnoea and pathological snoring. Each item is scored from 0 to 3 (0 = absence of symptoms, 1 = occasional symptoms, 2 = frequent symptoms, and 3 = constant symptoms), and the overall score is directly proportional to disease severity. The proportion of participants in each treatment arm with resolution of symptoms at 12 months will be calculated with 95% confidence intervals (CIs). The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 12 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) based on symptoms of SDB reported in parent-completed Pediatric Quality of Life Inventory (PedsQL) at 6 months

The Pediatric Quality of Life Inventory (PedsQL) is a validated, standardised, generic assessment instrument that provides a modular approach to measure health related quality of life in healthy children and adolescents and those with acute and chronic disorders. This questionnaire consists of 23 items evaluating physical, emotional, social and scholastic functioning, and it integrates both generic core scales and disease-specific modules. The proportion of participants in each treatment arm with resolution of symptoms at 6 months will be calculated with 95% confidence intervals (CIs). The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 6 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) based on symptoms of SDB reported in parent-completed Pediatric Quality of Life Inventory (PedsQL) at 12 months

The Pediatric Quality of Life Inventory (PedsQL) is a validated, standardised, generic assessment instrument that provides a modular approach to measure health related quality of life in healthy children and adolescents and those with acute and chronic disorders. This questionnaire consists of 23 items evaluating physical, emotional, social and scholastic functioning, and it integrates both generic core scales and disease-specific modules. The proportion of participants in each treatment arm with resolution of symptoms at 12 months will be calculated with 95% confidence intervals (CIs). The treatment arms will be compared using a Mantel Haenszel chi-squared test.

Time frame: 12 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) based on treatment for Sleep Disordered Breathing (SDB) at 6 months

Parents will be emailed a survey with the following questions about any treatment their child may have had for SDB 1. Specialty of Dr seen and number of appointments 2. Medical Treatment used, and duration of treatment The study team will describe additional treatment received by the treatment arm and investigate and describe any imbalance by the treatment arm.

Time frame: 6 months

Progression to Tonsillectomy and/or Adenoidectomy for Sleep Disordered Breathing (SDB) based on treatment for Sleep Disordered Breathing (SDB) at 12 months.

Parents will be asked the following questions about any treatment their child may have had for SDB 1. Specialty of Dr seen and number of appointments 2. Medical Treatment used, and duration he study team will describe additional treatment received by the treatment arm and investigate and describe any imbalance by the treatment arm. of treatment

Time frame: 12 months

Number of adverse events (AEs) throughout the treatment phase

Participants will also be asked questions about hospitalisation, accidents, new or changed medications. In addition AE's will be documented from physical examination findings, clinically significant lab results or other documents (including diaries where solicited AE's are prompted and correspondence from their primary care physician) that are relevant to participant safety. Adverse events and adverse reactions (non-serious or serious will be captured) The number of AEs will be summarised and listed in each of the treatment arms.

Time frame: 6 weeks

Number of adverse events (AEs) within the first week of the treatment

Participants will also be asked questions about hospitalisation, accidents, new or changed medications. In addition AE's will be documented from physical examination findings, clinically significant lab results or other documents (including diaries where solicited AE's are prompted and correspondence from their primary care physician) that are relevant to participant safety. Adverse events and adverse reactions (non-serious or serious will be captured) The number of AEs will be summarised and listed in each of the treatment arms.

Time frame: 1 week

Compliance of medical therapy measured by weight of sent and returned bottles of medication

Bottles will be weighed before they are given to participants and weighed when they are returned. The amount used will be calculated and used to determine if the participant was compliant with dosing. The amount of one spray of medication will be measured to allow for compliance to be calculated. Compliance with treatment will be calculated as the proportion of prescribed doses over 6 weeks that was consumed based on the weight of the bottles. The mean compliance will be summarised for the run-in period and both treatment arms. The proportion of participants with 80% and more compliance will be given for each treatment arm. The amount of one spray of medication will be measured to allow for compliance to be calculated.

Time frame: -6 weeks and 6 weeks (start of run-in phase to end of treatment phase)

Clinical factors at baseline that are associated with response to interventions, based on statistical analysis

Logistical regression models will be fitted to determine whether clinical factors at baseline or severity of SDB symptoms at baseline were associated with response to the intervention. Treatment arm, the symptom or factor of interest, and the interaction between the treatment arm and the symptom or factor will be included in this model. Symptoms or factors of interest include demographic factors, severity of SDB at baseline, history of atopy and history of tonsillitis.

Time frame: 6 weeks