Obstructive Sleep Apnea, Obstructive Sleep Disordered Breathing, Sleep Disordered Breathing, Snoring
Conditions
Keywords
Apnea, Sleep Apnea Syndromes, Snoring, Sleep Apnea, Obstructive, Respiration Disorders, Respiratory Tract Diseases, Signs and Symptoms, Respiratory Signs and Symptoms, Sleep Disorders, Intrinsic, Dyssomnias, Sleep Disorders, Respiratory Sounds
Brief summary
Obstructive sleep-disordered breathing (SDB) in childhood is a disorder of breathing during sleep characterized by intermittent upper airway obstruction. Snoring, labored breathing and apneas reported by the parents are the most frequent symptoms.Obstructive SDB can result from many different abnormalities including large adenoids and tonsils or obesity. Intermittent upper airway obstruction during sleep is accompanied by low oxygen or high carbon dioxide in the blood and arousals from sleep. If obstructive SDB is not treated, complications may develop such as: i) enuresis; ii) delay in somatic growth rate; iii) central nervous system morbidity (e.g. hyperactivity and learning difficulties); and iv) elevated blood pressure. Overnight polysomnography (PSG) is considered the gold-standard method for defining severity of obstructive SDB and subgroups of children with snoring who should be treated. However, PSG is a labor-intensive, time-consuming and expensive diagnostic method, which is not available in many community settings. Thus, there is an urgent need for developing easy-to-use and low-cost diagnostic methods which can be used to determine severity of obstructive SDB and define subgroups of children with snoring and large adenoids and tonsils who will benefit from adenotonsillectomy (AT). Pulse oximetry is a widely available, non-invasive method which allows continuous monitoring of oxygen transport by hemoglobin. Episodes of upper airway obstruction are frequently accompanied by reductions in the hemoglobin oxygen transport (oxygen desaturation of hemoglobin).The hypothesis of this research project is that subgroups of children with snoring and adenotonsillar hypertrophy and certain abnormalities in oxygenation detected by nocturnal pulse oximetry will benefit from AT in a community setting.
Detailed description
Time in the waiting list for undergoing AT at the Department of Otorhinolaryngology, Chania General Hospital St. George is approximately 3 months. In the present study, children will be recruited and randomized in the Active Comparator (AT group) or in the Control Group (No AT group) at the time of the initial clinic visit, if they fulfill the Inclusion Criteria and their parents consent to participation in the study. Children in the AT group will undergo the baseline study evaluation at the end of the 3-month waiting time and thus immediately prior to AT. They will also undergo the follow-up study evaluation at 3 months postoperatively. Children in the Control group will undergo their baseline study evaluation at the time of entering the surgical waiting list. They will undergo the follow-up study evaluation 3 months later, immediately prior to AT.
Interventions
PROCEDUREAdenotonsillectomy (AT)
Standard surgical intervention for treatment of obstructive sleep-disordered (SDB).
Sponsors
Aghia Sophia Children's Hospital of Athens
Chania General Hospital St. George
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with obstructive SDB (snoring \>3 nights/week over the last 6 months) * Tonsillar size \>2 \[Brodsky 1989\] * Considered as an AT candidate during the clinic visit by ear, nose and throat (ENT) surgeon
Exclusion criteria
* Recurrent tonsillitis defined as at least 3 episodes in each of the last 3 years or at least 5 episodes in each of the last 2 years or at least 7 episodes in the past year. * Apparent craniofacial anomalies (e.g. Crouzon syndrome or Pierre-Robin sequence) * Obstructive breathing while awake or any other clinical signs that merit prompt AT as recommended by the treating ENT physician. * History of clinically important cardiovascular disease or cardiac arrhythmia. * History of: sickle cell disease; symptomatic asthma; epilepsy; use of sedative medication * History of: genetic disorders; neurological or neuromuscular disorders * Use of: systemic or intranasal corticosteroids; montelukast Footnote Brodsky score Upon inspection of the oropharynx * grade 1 indicates that the tonsils are hidden in the pillars * grade 2 indicates that the tonsils are beyond the anterior pillar and occupy between 25 and 50% of the pharyngeal space * grade 3 indicates that the tonsils are beyond the pillars but not to the middle and occupy \>50% and up to 75% of the pharyngeal space * grade 4 indicates that the tonsils occupy \>75% of the pharyngeal space
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Subjects Without Oxygenation Abnormalities | 3 months (follow-up), 0 months (baseline) | Change in number of participants with a McGill oximetry score =1 (usual oxygen saturation of hemoglobin-SpO2\>95%; fewer than 3 drops below 90%; and fewer than 3 clusters of desaturation events) between 3 months and 0 months. McGill oximetry score=1: normal or inconclusive nocturnal oximetry; McGill oximetry score=2: mild hypoxemia; McGill oximetry score=3: moderate hypoxemia; McGill oximetry score=4: severe hypoxemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (OSA-18 Score) | 3 months (follow-up), 0 months (baseline) | Change in obstructive sleep apnea (OSA)-18 total score between follow-up and baseline. OSA-18 is a quality of life survey including 18 questions on sleep disturbance, physical symptoms, emotional symptoms, daytime function and caregiver concerns. It is used to assess the impact of obstructive sleep apnea on child's life. Scores less than 60 suggest a small impact, between 60 and 80 moderate impact and above 80 a large impact. OSA-18 score ranges between 18 and 126. |
| Sleepiness | 3 months (follow-up), 0 months (baseline) | Change in Modified Epworth Sleepiness Scale between follow-up and baseline Modified Epworth Sleepiness Scale ranges from 0 to 24; higher score indicates more daytime sleepiness. |
| Somatic Growth-1 | 0 months (baseline), 3 months (follow-up) | Percent of subjects achieving an increase in weight z-score of at least 0.5. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population. |
| Somatic Growth-2 | 0 months (baseline), 3 months (follow-up) | Percent of subjects achieving an increase in body mass index z-score of at least 0.5. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population, |
| Enuresis | 3 months (follow-up), 0 months (baseline) | Percent of subjects who achieved frequency of nocturnal enuresis \< 1 night per week at follow-up (3 months), if they had incontinence at least 1 night per week at baseline (0 months). |
| Cardiovascular Effects-1 | 3 months (follow-up), 0 months (baseline) | Change in mean pulse rate between follow-up and baseline. |
| Cardiovascular Effects-2 | 3 months (follow-up), 0 months (baseline) | Change in mean frequency of pulse rate rises (at least 6 beats per min) between follow-up and baseline. |
| Symptoms Predicting Obstructive Sleep Apnea (OSA) | 3 months (follow-up), 0 months (baseline) | Change in Pediatric Sleep Questionnaire sleep-related breathing disorder (PSQ-SRBD) scale, between follow-up and baseline. PSQ-SRBD scale ranges between 0 and 1. PSQ-SRBD score \<0.33 is associated with low risk of apnea-hypopnea index \>5 episodes/h; PSQ-SRBD score \>=0.33 is associated with high risk of apnea-hypopnea index \>5 episodes/h. |
| Cardiovascular Effects-4 | 3 months (follow-up), 0 months (baseline) | Change in morning diastolic blood pressure z-score between follow-up and baseline. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population, |
| Systemic Inflammation | 3 months (follow-up), 0 months (baseline) | Change in morning serum C-reactive protein concentration between follow-up and baseline. |
| Improvement in Baseline SpO2 | 3 months (follow-up), 0 months (baseline) | Proportion of subjects who had an increase from baseline in SpO2 of \>1.6% |
| Behavioral Abnormalities-1 | 3 months (follow-up), 0 months (baseline) | Change in the DuPaul Questionnaire for Parents score between follow-up and baseline. |
| Behavioral Abnormalities-2 | 3 months (follow-up), 0 months (baseline) | Change in the Achenbach Questionnaire for Parents score between follow-up and baseline. |
| Effects on Sympathetic Nervous System Activation | 3 months (follow-up), 0 months (baseline) | Change in ratio of morning urine norepinephrine concentration to urine creatinine concentration between follow-up and baseline. |
| Cardiovascular Effects-3 | 3 months (follow-up), 0 months (baseline) | Change in morning systolic blood pressure z-score between follow-up and baseline. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population, |
Countries
Greece
Participant flow
Recruitment details
Recruitment between June 2013 and April 2016; ENT Clinic of a Regional Hospital in Greece (Chania, Crete).
Participants by arm
| Arm | Count |
|---|---|
| AT (Adenotonsillectomy) Group Group underwent AT (adenotonsillectomy) immediately after the baseline nocturnal oximetry evaluation
Adenotonsillectomy (AT): Standard surgical intervention for treatment of Obstructive SDB. | 68 |
| Control Group No AT (adenotonsillectomy) for 3 months after the baseline nocturnal oximetry evaluation. | 72 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Baseline oximetry not acceptable | 11 | 7 |
| Overall Study | Follow-up oximetry not acceptable | 10 | 7 |
| Overall Study | Lost to Follow-up | 4 | 7 |
Baseline characteristics
| Characteristic | AT (Adenotonsillectomy) Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 5.9 years STANDARD_DEVIATION 1.6 | 6 years STANDARD_DEVIATION 1.6 | 6 years STANDARD_DEVIATION 1.6 |
| Body mass index z-score | 0.3 units on a scale STANDARD_DEVIATION 1.4 | 0.2 units on a scale STANDARD_DEVIATION 1.6 | 0.2 units on a scale STANDARD_DEVIATION 1.5 |
| Failure to thrive | 6 Participants | 12 Participants | 18 Participants |
| Obese | 12 Participants | 14 Participants | 26 Participants |
| OSA-18 total score | 59.4 units on a scale STANDARD_DEVIATION 16.3 | 58.3 units on a scale STANDARD_DEVIATION 15.7 | 58.8 units on a scale STANDARD_DEVIATION 15.9 |
| Overweight or obese | 25 Participants | 28 Participants | 53 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Greece | 68 participants | 72 participants | 140 participants |
| Sex: Female, Male Female | 33 Participants | 34 Participants | 67 Participants |
| Sex: Female, Male Male | 35 Participants | 38 Participants | 73 Participants |
| Tonsillar size 3+ | 61 Participants | 65 Participants | 126 Participants |
| Tonsillar size 4+ | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 68 | 0 / 72 |
| other Total, other adverse events | 0 / 68 | 0 / 72 |
| serious Total, serious adverse events | 0 / 68 | 0 / 72 |
Outcome results
Primary
Change in Number of Subjects Without Oxygenation Abnormalities
Change in number of participants with a McGill oximetry score =1 (usual oxygen saturation of hemoglobin-SpO2\>95%; fewer than 3 drops below 90%; and fewer than 3 clusters of desaturation events) between 3 months and 0 months. McGill oximetry score=1: normal or inconclusive nocturnal oximetry; McGill oximetry score=2: mild hypoxemia; McGill oximetry score=3: moderate hypoxemia; McGill oximetry score=4: severe hypoxemia.
Time frame: 3 months (follow-up), 0 months (baseline)
Population: Subjects with a McGill oximetry score =1 or with a McGill oximetry score \>1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Change in Number of Subjects Without Oxygenation Abnormalities | 12 Participants |
| Control Group | Change in Number of Subjects Without Oxygenation Abnormalities | 10 Participants |
p-value: 0.5495% CI: [0.5, 3.3]Chi-squared
Primary
Change in Number of Subjects Without Oxygenation Abnormalities
Number of subjects who achieved a desaturation index (≥3% drop) of \<2 episodes/h at 3 months (follow-up), if they had a desaturation index of ≥ 3.5 episodes/h at 0 months (baseline)
Time frame: 3 months (follow-up), 0 months (baseline)
Population: Subjects with a desaturation index of ≥ 3.5 episodes/h at 0 months (baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Change in Number of Subjects Without Oxygenation Abnormalities | 14 Participants |
| Control Group | Change in Number of Subjects Without Oxygenation Abnormalities | 2 Participants |
p-value: <0.00195% CI: [2.9, 68.4]Chi-squared
Secondary
Behavioral Abnormalities-1
Change in the DuPaul Questionnaire for Parents score between follow-up and baseline.
Time frame: 3 months (follow-up), 0 months (baseline)
Secondary
Behavioral Abnormalities-2
Change in the Achenbach Questionnaire for Parents score between follow-up and baseline.
Time frame: 3 months (follow-up), 0 months (baseline)
Secondary
Cardiovascular Effects-1
Change in mean pulse rate between follow-up and baseline.
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Cardiovascular Effects-1 | -0.1 beats per minute |
| Control Group | Cardiovascular Effects-1 | -0.9 beats per minute |
p-value: 0.547Wilcoxon (Mann-Whitney)
Secondary
Cardiovascular Effects-2
Change in mean frequency of pulse rate rises (at least 6 beats per min) between follow-up and baseline.
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Cardiovascular Effects-2 | -1.2 pulse rate rises per hour |
| Control Group | Cardiovascular Effects-2 | -0.1 pulse rate rises per hour |
p-value: 0.062Wilcoxon (Mann-Whitney)
Secondary
Cardiovascular Effects-3
Change in morning systolic blood pressure z-score between follow-up and baseline. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population,
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Cardiovascular Effects-3 | 0.5 z score |
| Control Group | Cardiovascular Effects-3 | -2 z score |
p-value: 0.208Wilcoxon (Mann-Whitney)
Secondary
Cardiovascular Effects-4
Change in morning diastolic blood pressure z-score between follow-up and baseline. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population,
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Cardiovascular Effects-4 | -1 z score |
| Control Group | Cardiovascular Effects-4 | -6 z score |
p-value: 0.585Wilcoxon (Mann-Whitney)
Secondary
Effects on Sympathetic Nervous System Activation
Change in ratio of morning urine norepinephrine concentration to urine creatinine concentration between follow-up and baseline.
Time frame: 3 months (follow-up), 0 months (baseline)
Secondary
Enuresis
Percent of subjects who achieved frequency of nocturnal enuresis \< 1 night per week at follow-up (3 months), if they had incontinence at least 1 night per week at baseline (0 months).
Time frame: 3 months (follow-up), 0 months (baseline)
Population: 24 of 68 participants in the AT group and 22 of 72 participants in the control group had nocturnal enuresis at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Enuresis | 10 Participants |
| Control Group | Enuresis | 4 Participants |
p-value: 0.08495% CI: [0.84, 6.25]Chi-squared
Secondary
Improvement in Baseline SpO2
Proportion of subjects who had an increase from baseline in SpO2 of \>1.6%
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Improvement in Baseline SpO2 | 6 Participants |
| Control Group | Improvement in Baseline SpO2 | 7 Participants |
Secondary
Quality of Life (OSA-18 Score)
Change in obstructive sleep apnea (OSA)-18 total score between follow-up and baseline. OSA-18 is a quality of life survey including 18 questions on sleep disturbance, physical symptoms, emotional symptoms, daytime function and caregiver concerns. It is used to assess the impact of obstructive sleep apnea on child's life. Scores less than 60 suggest a small impact, between 60 and 80 moderate impact and above 80 a large impact. OSA-18 score ranges between 18 and 126.
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT (Adenotonsillectomy) Group | Quality of Life (OSA-18 Score) | -32.4 score on a scale | Standard Deviation 16.9 |
| Control Group | Quality of Life (OSA-18 Score) | -0.8 score on a scale | Standard Deviation 9.1 |
p-value: <0.001t-test, 2 sided
Secondary
Sleepiness
Change in Modified Epworth Sleepiness Scale between follow-up and baseline Modified Epworth Sleepiness Scale ranges from 0 to 24; higher score indicates more daytime sleepiness.
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT (Adenotonsillectomy) Group | Sleepiness | -2.75 score on a scale | Standard Deviation 3.07 |
| Control Group | Sleepiness | 0.01 score on a scale | Standard Deviation 2.04 |
p-value: <0.00195% CI: [-3.63, -1.9]t-test, 2 sided
Secondary
Somatic Growth-1
Percent of subjects achieving an increase in weight z-score of at least 0.5. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population.
Time frame: 0 months (baseline), 3 months (follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Somatic Growth-1 | 23 Participants |
| Control Group | Somatic Growth-1 | 21 Participants |
p-value: 0.55395% CI: [0.71, 1.89]Chi-squared
Secondary
Somatic Growth-2
Percent of subjects achieving an increase in body mass index z-score of at least 0.5. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched). Negative numbers indicate values lower than the reference population and positive numbers indicate values higher than the reference population,
Time frame: 0 months (baseline), 3 months (follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Somatic Growth-2 | 22 Participants |
| Control Group | Somatic Growth-2 | 13 Participants |
p-value: 0.05795% CI: [0.98, 3.27]Chi-squared
Secondary
Symptoms Predicting Obstructive Sleep Apnea (OSA)
Change in Pediatric Sleep Questionnaire sleep-related breathing disorder (PSQ-SRBD) scale, between follow-up and baseline. PSQ-SRBD scale ranges between 0 and 1. PSQ-SRBD score \<0.33 is associated with low risk of apnea-hypopnea index \>5 episodes/h; PSQ-SRBD score \>=0.33 is associated with high risk of apnea-hypopnea index \>5 episodes/h.
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AT (Adenotonsillectomy) Group | Symptoms Predicting Obstructive Sleep Apnea (OSA) | -0.32 score on a scale | Standard Deviation 0.15 |
| Control Group | Symptoms Predicting Obstructive Sleep Apnea (OSA) | -0.01 score on a scale | Standard Deviation 0.09 |
p-value: <0.00195% CI: [-0.35, -0.27]t-test, 2 sided
Secondary
Systemic Inflammation
Change in morning serum C-reactive protein concentration between follow-up and baseline.
Time frame: 3 months (follow-up), 0 months (baseline)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AT (Adenotonsillectomy) Group | Systemic Inflammation | 0 mg/dL |
| Control Group | Systemic Inflammation | 0 mg/dL |
p-value: 0.074Wilcoxon (Mann-Whitney)