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Volume 11 No. 10
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Accepted Papers





Scientific Investigations

Long-Term Improvements in Sleep and Respiratory Parameters in Preschool Children Following Treatment of Sleep Disordered Breathing

Lisa M. Walter, PhD1,3; Sarah N. Biggs, PhD1,3; Lauren C. Nisbet, PhD1; Aidan J. Weichard, BSc(Hons)1; Samantha L. Hollis, BA(Hons)1; Margot J. Davey, MBBS1,2,3; Vicki Anderson, PhD4; Gillian M. Nixon, MD1,2,3; Rosemary S.C. Horne, PhD1,3
1The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia; 2Melbourne Children's Sleep Centre, Monash Children's, Monash Medical Centre, Melbourne, Australia; 3Department of Paediatrics, Monash University, Melbourne, Australia; 4Clinical Sciences Research, Murdoch Childrens Research Institute, Melbourne, Australia

ABSTRACT

Study Objectives:

Sleep disordered breathing (SDB) in preschool-aged children is common, but long-term outcomes have not been investigated. We aimed to compare sleep and respiratory parameters in preschool children to examine the effects of treatment or non-treatment after 3 years.

Methods:

Children (3–5 years) diagnosed with SDB (n = 45) and non-snoring controls (n = 30) returned for repeat overnight polysomnography (39% of original cohort), 3 years following baseline polysomnography. Children with SDB were grouped according to whether they had received treatment or not. SDB resolution was defined as an obstructive apnea hypopnea index (OAHI) ≤ 1 event/h, no snoring detected on polysomnography and habitual snoring not indicated by parents on questionnaire.

Results:

Fifty-one percent (n = 23) of the children with SDB were treated. Overall, SDB resolved in 49% (n = 22), either spontaneously (n = 8) or with treatment (n = 14). SDB remained unresolved in 39% (n = 9) of those treated and 64% (n = 14) of the children who were untreated. Two of the non-snoring controls developed SDB at follow-up. The treated group had significantly lower OAHI (p < 0.01), respiratory disturbance index (p < 0.001), total arousal and respiratory arousal indices (p < 0.01 for both) at follow-up compared with baseline. There were no differences between studies for the untreated group.

Conclusion:

Although treatment resulted in an improvement in indices related to SDB severity, 39% had SDB 3 years following diagnosis. These findings highlight that parents should be made aware of the possibility that SDB may persist or recur several years after treatment. This is relevant regardless of the severity of SDB at baseline and the treatment given.

Citation:

Walter LM, Biggs SN, Nisbet LC, Weichard AJ, Hollis SL, Davey MJ, Anderson V, Nixon GM, Horne RS. Long-term improvements in sleep and respiratory parameters in preschool children following treatment of sleep disordered breathing. J Clin Sleep Med 2015;11(10):1143–1151.


Obstructive sleep disordered breathing (SDB) in children is most prevalent during the preschool years.1 In otherwise healthy children, SDB is predominantly due to enlargement of the adenoids and tonsils within a comparatively small pharynx, leading to obstruction of the upper airway during sleep.2,3 SDB is a continuum of disease severity from primary snoring (PS) through to obstructive sleep apnea (OSA). We have previously reported that OSA is associated with adverse cardiovascular sequelae, including elevated blood pressure during REM sleep and altered autonomic function in preschool-aged children.4,5 Furthermore, both PS and OSA have been associated with behavioral deficits in these young children.6 The cardiovascular and neurocognitive sequelae of SDB are not as severe in this age group as those reported in school-aged children.47 However, the fact that such young children are already experiencing impairments of autonomic control of their cardiovascular system is of concern, and highlights the need for efficacious treatment of OSA at an early age.

BRIEF SUMMARY

Current Knowledge/Study Rationale: Treatment of sleep disordered breathing in children has been shown to result in initial improvements in sleep disordered breathing severity; however, in a substantial number of school-age children, these benefits are no longer apparent in the long term. It remains unknown if similar to older children, the immediate benefits of treatment are the same for preschool-aged children and, if so, whether the benefits are still present in the longer term.

Study Impact: Although our results are limited by a small sample size, our results suggest that the long-term effectiveness of treatment of sleep disordered breathing differs across the severity spectrum, which was most evident with regard to respiratory outcomes, indicating that treatment is more efficacious in the long-term in children with moderate to severe SDB, whereas treatment is not as effective in resolving less severe SDB. We propose that pediatricians should make parents cognizant of the possibility that in the years following treatment, their child's SDB may not be completely ameliorated or may return, and should present for further investigations if there are ongoing concerns.

The most common treatment for OSA in this age group is adenotonsillectomy8; however, to date, no studies have investigated the effects of treatment on outcomes such as OSA symptoms, sleep and respiratory indices and cardiovascular parameters, exclusively in preschool-aged children. The studies that have assessed the efficacy of treatment for children with OSA have included a wide age range,911 older children,1214 or short follow-up periods of less than one year.11,12,14,15 Similarly, the studies that have investigated the converse, i.e. the effect of no treatment, have also included a wide age range,14,1618 were only conducted in older children,12,17,1921 had short or variable follow-up periods,19 or did not use the gold standard of overnight polysomnography but relied on parental questionnaires to assess SDB severity.19,22 Of importance, the majority of these latter studies only studied habitual snoring, and could not distinguish between children with mild or more severe OSA.

The most recent study to assess the efficacy of treatment, the Childhood Adenotonsillectomy Trial (CHAT), studied a large cohort of 464 children aged 5 to 9 years and compared the effects of immediate adenotonsillectomy to watchful waiting for a period of 7 months in children with mild OSA.12 This study demonstrated that children in the early-adenotonsillectomy group had significant improvements in behavior, quality-of-life, and polysomnographic findings, and a significantly greater reduction in symptoms than the watchful-waiting group. However, in another study Huang et al.13 demonstrated that any initial improvements in OSA severity observed six months following adenotonsillectomy, were no longer present after 3 years in 67% of school-aged children. It remains unknown if similar to older children, the immediate benefits of adenotonsillectomy are the same for preschool-aged children and, if so, whether the benefits are still present in the longer term. It has been shown using lateral cephalometric radiographs of healthy non-snoring children that the soft tissue of the nasopharynx grows more rapidly from 3 to 5 years of age compared with the bony structures, resulting in a decrease in the size of the nasopharyngeal airway at this age.3 From 6 to 13 years of age, the bony structures continue to grow while the soft tissues remain stable or decline in size, leading to a larger nasopharyngeal airway in older children.3 This may have significant effects on the outcomes of either treatment or non-treatment of SDB in children during the preschool years compared to older children.

In this study, we aimed to compare sleep and respiratory parameters in healthy weight, preschool-aged children to examine the effects of treatment or non-treatment after 3 years. We hypothesized that preschool-aged children who received treatment would have improved sleep and respiratory parameters 3 y after diagnosis.

METHODS

Ethics approval for this project was granted by the Monash Health and Monash University Human Research Ethics Committees. Written informed consent was obtained from parents after a full explanation of the procedure. There was no monetary incentive for participation.

Subjects

At baseline, 151 children (3–5 years) referred clinically to the Melbourne Children's Sleep Centre for assessment of SDB and 41 age-matched, non-snoring controls recruited from the community, underwent overnight polysomnography from 2008 to 2011. Children with conditions or taking medications known to affect sleep, breathing, blood pressure, or neurocognitive function were not recruited. Neurocognitive, behavioral, and cardiovascular data from the baseline study have been previously published.46,23 Three years following the baseline study, subjects were invited to return for follow-up polysomnography. Parents of children who did not participate in the follow-up study were asked what treatment, if any, their child had following the baseline study.

Protocol

At the time of the baseline and follow-up polysomnography studies, children were otherwise healthy and not undergoing treatment with nasal steroids, leukotriene receptor antagonists, or antibiotics. Prior to both polysomnography studies, height and weight were measured and converted to a body mass index (BMI) z-score to adjust for gender and age.24 Questionnaires relating to demographics and general health and the OSA-18, were completed on the night of the polysomnography by the parents.

Polysomnography

Electrophysiological signals were recorded using standard pediatric recording techniques25 as previously published.46 In summary electroencephalogram (EEG), left and right electrooculogram (EOG), submental electromyogram (EMG), left and right anterior tibialis muscle EMG and electrocardiogram (ECG) were attached. Thoracic and abdominal breathing movements, transcutaneous carbon dioxide (TcCO2), nasal pressure, oronasal airflow, oxygen saturation (SpO2), and a photoplethysmographic pulse oximeter (PPG) was used to record the pulse waveform necessary for pulse transit time analysis.

Polysomnographic Analysis

A minimum of 4 h of sleep was required for children to be included in the study. Polysomnographic studies were manually sleep staged in 30-s epochs and respiratory events scored by experienced pediatric sleep technologists according to slightly modified AASM 2007 rules that were used clinically at the time of the follow-up studies and which equate to the AASM 2012 updated rules.25,26 Modification consisted of the inclusion of respiratory event related arousals (RERA) associated with arousal or desaturation into the obstructive apnea hypopnea index (OAHI). Counting RERAs defined as a discernible decrease in airflow, is consistent with AASM 2012 scoring guidelines where the scoring of hypopneas requires > 30% decrease in airflow.27 Baseline studies which were conducted prior to the laboratory updating these scoring criteria were re-scored by 2 trained technicians who maintained a concordance rate > 85% for both sleep and respiratory events. Obstructive apneas were defined as > 90% fall in airflow for ≥ 90% of event duration, with continued or increased respiratory effort. Mixed apneas consisted of a central component followed by an obstructive component. An obstructive hypopnea was associated with ≥ 50% fall in airflow signal for ≥ 90% of the event, associated with an arousal, awakening or ≥ 3% desaturation. RERAs were scored where there was a discernible decrease in amplitude and flattening of the nasal pressure trace, associated with snoring, noisy breathing, elevation of the end-tidal or transcutaneous pCO2 and/or visual evidence of increased work of breathing, leading to an arousal from sleep or ≥ 3% desaturation.

Wake after sleep onset (WASO) was calculated as the percentage of time awake during the sleep period time (SPT), with SPT defined as the amount of time in minutes from sleep onset until lights on at the end of the study. Total sleep time (TST) was defined as SPT excluding all periods of wake. The OAHI was defined as the total number of obstructive apneas, mixed apneas, obstructive hypopneas and RERAs per hour of TST. Criteria for the categorization of SDB severity mirrored current clinical practice, based on OAHI: children were classified as having primary snoring (PS, OAHI ≤ 1 event/h); mild OSA (Mild OSA, OAHI between > 1–5 events/h); or moderate/severe OSA (MS, OAHI > 5 events/h). Other variables were calculated as previously detailed46 and included the respiratory disturbance index (RDI), REM RDI, central apnea hypopnea index (CnAHI), sleep latency, REM latency, sleep efficiency, total arousal index (Total AI), total spontaneous arousal index (Total SAI), total respiratory arousal index (Total RAI), SpO2 nadir, the number of times the SpO2 dropped by ≥ 4% per hour of TST (ODI4), the number of times SpO2 dropped to below 90% per hour of TST, the average TcCO2 per hour of TST (Av TcCO2). AI, SAI, and RAI were also calculated separately for REM and NREM.

Data Analysis

At follow-up, the children were initially divided into 3 groups according to whether they had received treatment (Controls, Treated, Untreated). The decision to refer children to an otolaryngologist for surgical treatment following the baseline study was made by the children's treating pediatric sleep physician in consultation with parents following assessment of the polysomnography report, and was made independently of the researchers. It must also be noted that following review of the baseline polysomnography reports, the final decision to perform either adenoidectomy or adenotonsillectomy on the children with PS in our study was made by an otolaryngologist. As not all children who were treated had resolution of their SDB at follow-up, and the SDB in a number of children who were not treated resolved spontaneously, further analyses were performed with the children with SDB being regrouped according to whether their SDB had resolved (Controls, Resolved, Unresolved). SDB was considered resolved at follow-up when the OAHI was ≤ 1, there was no snoring reported on the polysomnography night, and the parents documented that they had not observed their child snoring loudly, holding their breath, making choking or gasping sounds during sleep, or being restless with frequent awakenings on the OSA-18 questionnaire (i.e., answered “none of the time” to the 4 Sleep Disturbance subscale questions).28 In contrast, if the child did not snore on the night of the PSG, had an OAHI ≤ 1, but the parents documented that they had observed their child snoring loudly, holding their breath, making choking or gasping sounds during sleep, or being restless with frequent awakenings on the OSA-18 questionnaire, then the child was classed as having primary snoring. We decided to use this combination of criteria to classify resolution of SDB as a single night PSG study may miss a diagnosis of primary snoring, which studies have identified has similar effects on BP, neurocognition, and behavior in school-aged children (our cohort were school-aged at follow-up) as children with OSA.7,29,30

Statistical Analyses

Statistical analyses were performed using SPSS (IBM Statistics version 20). Data were first tested for normality and equal variance. The difference between the children who participated in the follow-up study and those who did not, in (1) the proportion of children who were treated, and (2) the proportion who had improved since the baseline study indicated by parental report, were performed using Fisher exact tests. Demographic data were compared between the controls, treated and untreated groups, using one-way ANOVA with Bonferroni post hoc tests. For both treated vs untreated and resolved vs unresolved analyses, sleep and respiratory data were compared between baseline and follow-up studies using linear mixed model analyses to allow for intra-individual variation across repeated observations and to independently determine the fixed effects of group, time (baseline vs follow-up studies) age, BMI z-score, neck, waist and hip circumference, and the waist-to-hip ratio. Subject code was used as the random factor in this analysis. When there was a significant interaction between group and time in the mixed model analyses, Kruskal-Wallis (H) and Mann-Whitney U tests, and one-way ANOVA (F) with Bonferroni adjustment were used post hoc to determine where the significant differences were between groups at both the baseline study and the follow-up study, for nonparametric and parametric data, respectively. For both grouping methods, the differences between the baseline and follow-up studies within each group were compared using the Wilcoxon signed rank test and the paired Student t-test, for nonparametric and parametric data, respectively. The effect size of the Wilcoxon signed rank tests (r) and the paired student t-tests (d) were also calculated when there was a significant interaction between group and time.

RESULTS

Of 191 children who participated in the baseline study, 36 could not be contacted, 76 declined further participation, 2 controls were ineligible as they had developed medical conditions that excluded them from participation, and a further 2 controls were unable to undertake sleep studies in the available time period. Thirty percent (n = 45) of the clinically referred group and 75% (n = 30) of controls agreed to participate in the follow-up study, and all underwent a repeat overnight polysomnography. Two children from the control group were subsequently excluded from analysis as they had developed SDB. There was no significant difference in the proportion of participants and non-participants who received treatment (Table 1). Parents of both participants and non-participants were asked whether they considered that their children's sleep and breathing had improved since the baseline study. As non-participants would not return for a PSG study, the only way to obtain an estimate of their SDB status was from parental report. We included their responses only to provide an indication of whether they felt that treatment had helped their child, or whether their child had improved or gotten worse without treatment. There was no significant difference in the proportion of children who were considered improved between the participants (76%, n = 34) and the non-participants (63%, n = 48).

Treatment received by the participants of the follow-up study and the children who declined to participate in the follow-up study.

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Table 1

Treatment received by the participants of the follow-up study and the children who declined to participate in the follow-up study.

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Group age, gender, and anthropomorphic data for participants for the baseline and follow-up studies in the control, treated and untreated groups are presented in Table 2. There were no significant group differences at baseline or follow-up for any of the demographic measures, apart from there being more males than females in the treated group.

Group age, gender and anthropomorphic data for baseline and follow-up studies in the control, treated and untreated groups.

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Table 2

Group age, gender and anthropomorphic data for baseline and follow-up studies in the control, treated and untreated groups.

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Change in Sleep Disordered Breathing Severity and Treatment from Baseline to Follow-up

The changes in SDB severity and treatment received between the baseline and follow-up studies are presented in Figure 1. Of the 30 controls studied at baseline, 1 had developed Mild OSA and 1 MS OSA at follow-up. There were 23 children with PS at baseline. At follow-up, 43% of the children with PS at baseline no longer snored, 26% continued to have PS, 22% worsened to Mild OSA and 9% to MS OSA. There were 12 children with Mild OSA at baseline. At follow-up, 42% children no longer snored, and 25% children improved to PS. A further 25% of children still had Mild OSA at follow-up and 8% worsened to MS OSA. There were 10 children diagnosed with MS OSA group at baseline. Of these, 70% no longer snored at follow-up, 20% improved to Mild OSA and 10% continued to have MS OSA. Overall at follow-up, SDB had resolved in 49% of the whole cohort, in 57% of the children who were treated, and in 35% of children who were untreated. Treatment was more likely to bring about complete resolution of SDB in children with MS-OSA (70%, 7/10) compared to those with Mild OSA (50%, 3/6) or PS (57%, 4/7).

Changes in sleep disordered breathing severity groups from baseline to follow-up.

This figure displays the number of children from each group who had either resolved or unresolved SDB at follow-up, and the number of children who had received treatment including the percentage of those treated from each group whose SDB resolved or remained unresolved. SDB, sleep disordered breathing; PS, primary snoring; OSA, obstructive sleep apnea; MS, moderate-severe; A, adenoidectomy; AT, adenotonsillectomy; nasal surgery, correction of deviated septum.

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Figure 1

Changes in sleep disordered breathing severity groups from baseline to follow-up. This figure displays the number of children from each group who had either resolved or unresolved SDB at follow-up, and the number of children who had received treatment including the percentage of those treated from each group whose SDB resolved...

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All 16 children who had OSA at follow-up were referred for clinical assessment; 5 were subsequently prescribed nasal steroids and 1 had an adenotonsillectomy. No further medical intervention was decided on for 8 children in consultation with parents, and 2 families could not be contacted.

Baseline and follow-up data of individual children and group means for OAHI are presented for controls, treated and resolved, untreated and resolved, treated and unresolved, and untreated and unresolved groups in Figure 2. Two of the control children had developed SDB by the follow-up study and their changes in OAHI are indicated in Figure 2A by the open circles. These children have not been included in following analyses of sleep and respiratory parameters. The mean OAHI in the treated children whose SDB had resolved was reduced at follow-up compared to baseline for all children (Figure 2B). The untreated children whose SDB had resolved all had either PS or very mild OSA at baseline (Figure 2C). Fifty-two percent (12/23) of children with unresolved SDB, whether treated or not, had more severe SDB at follow-up (Figure 2D and 2E). Of the 9 children who had received treatment but still had residual SDB at follow-up, 3 had PS at baseline (1 had adenoidectomy only and remained with PS, 2 had adenotonsillectomy and worsened to Mild OSA); 3 had Mild OSA at baseline (1 had adenotonsillectomy and 1 had nasal steroids and remained with Mild OSA, 1 had adenotonsillectomy and worsened to MS OSA at follow-up); 3 had MS OSA at baseline (all 3 had adenotonsillectomy, 2 improved to Mild OSA and 1 remained with MS OSA). This 5-way grouping was not used for further analyses as separating the children with SDB into four groups did not have adequate power for statistical testing.

Individual subject obstructive apnea hypopnea index at the baseline and follow-up studies.

(A) Controls, n = 28 (open circles represent children who were controls at baseline who developed SDB); (B) Treated and Resolved, n = 14; (C) Untreated and Resolved, n = 8; (D) Treated and Unresolved, n = 9; (E) Untreated and Unresolved groups, n = 14. Graphs also indicate group means ± SEM.

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Figure 2

Individual subject obstructive apnea hypopnea index at the baseline and follow-up studies. (A) Controls, n = 28 (open circles represent children who were controls at baseline who developed SDB); (B) Treated and Resolved, n = 14; (C) Untreated and Resolved, n = 8; (D) Treated and Unresolved, n = 9; (E)...

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Respiratory Parameters Following Treatment or Non-Treatment

Data for the respiratory parameters for the control, treated and untreated groups at baseline and follow-up are presented in Table 3. There was a significant effect of treatment on OAHI, which was statistically different between groups at both baseline (H = 31.9, p < 0.001) and follow-up (H = 9.2, p < 0.05). OAHI was significantly higher in the treated group compared with the untreated group at baseline (p < 0.01); however, there was no longer any difference between these 2 groups at follow-up, as the OAHI of the treated group significantly decreased at follow-up compared with baseline (p < 0.01). RDI and REM RDI followed an identical pattern of significance as OAHI. Age, BMI z-score, neck, waist and hip circumference, and the waist-to-hip ratio did not predict improvement in any of the respiratory parameters.

Respiratory parameters of participants at baseline and follow-up study with children divided into control, treated, and untreated groups.

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Table 3

Respiratory parameters of participants at baseline and follow-up study with children divided into control, treated, and untreated groups.

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Sleep Characteristics in the Treated and Untreated Groups

Data for sleep characteristics following treatment or non-treatment of SDB are presented in Table 4. The only difference found was a reduction in arousal indices at follow-up in the treated group. Age, BMI z-score, neck, waist and hip circumference, and the waist-to-hip ratio did not predict any of the sleep parameters.

Sleep characteristics of participants for baseline and follow-up study with the children divided into control, treated, and untreated groups.

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Table 4

Sleep characteristics of participants for baseline and follow-up study with the children divided into control, treated, and untreated groups.

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Analyses of Only Children Treated with Adenotonsillectomy

The data were reanalyzed with the treatment group consisting of only children who had adenotonsillectomy (n = 17). There were no differences in the pattern of significance from the original analyses for demographic, respiratory, or sleep parameters (data not shown).

Analyses by Resolution of Sleep Disordered Breathing

To determine whether there was any effect of resolution of SDB (as distinct from treatment) on sleep, we regrouped the data according to whether the SDB was resolved or unresolved. The resolved group was not different to the unresolved group at baseline for either OAHI or RDI. Consistent with group definition, OAHI and RDI were significantly lower in the resolved group at follow-up compared with baseline (p < 0.001 for both); however, there was no difference between studies for the unresolved group indicating lack of improvement in this group (data not shown). Age, BMI z-score, neck, waist and hip circumference, and the waist-tohip ratio did not predict any improvement in the respiratory parameters. Apart from improvements in the RAI (Controls: baseline, 0.6 ± 0.1 events/h TST vs follow-up, 0.7 ± 0.1 NS; Resolved: 5.3 ± 1.2 vs 0.7 ± 0.1 p < 0.01, d = 0.8; Unresolved: 3.6 ± 0.8 vs 3.2 ± 0.6 NS), as might be expected parallel to the improvement in OAHI, no other differences were seen in sleep parameters according to whether or not the SDB had resolved.

DISCUSSION

A number of studies have reported on the efficacy of treatment for SDB in children in the short term. Although the participants of this study did not undergo a PSG immediately following treatment to determine the immediate effect of treatment, nonetheless, this is the first study to investigate SDB in preschool-aged children in the long term. Irrespective of whether the children with SDB at 3 years posttreatment have residual SDB that never completely resolved following treatment, or whether their SDB resolved in the short term and recurred, we have identified that the long-term effectiveness of treatment of SDB, differs across the severity spectrum. This was most evident with regard to respiratory outcomes. Treatment was more likely to bring about complete resolution of respiratory symptoms in children with MS-OSA (70%, 7/10) compared to those with Mild OSA (50%, 3/6) or PS (57%, 4/7). We speculate that children with underlying allergic rhinitis, which is more likely to persist long term despite treatment, may be over-represented in the PS and Mild OSA groups. SDB resolved in 57% of the children who received treatment overall, with the remaining 43% having some degree of residual sleep disordered breathing, 11% (1/9) of whom had PS at follow-up. Although the number of children who participated in this study was comparatively small, and caution needs to be taken when extrapolating the findings to a larger population, we propose that pediatricians should make parents cognizant of the possibility that in the years following treatment, their child's SDB may not be completely ameliorated and that they should present for further investigations if there are ongoing concerns.

Our findings are consistent with previous studies, including a wide age range and/or short follow-up periods, which reported that improvements in respiratory indices following adenotonsillectomy in children leads to improvements in sleep and arousal indices.9,11,12 Sleep is a dynamic process that undergoes significant changes from infancy through to adolescence.31 During childhood, the cardiorespiratory system and the anatomical structure of the nasopharynx and surrounding lymphoid tissue also mature and develop.3,32,33 Therefore, studies that include wide age ranges must account for the age of the subjects during analysis and when interpreting the data. A significant confounder of previous studies was the inclusion of obese children in the cohorts, whereas in our study all of the children were of normal weight. As obesity is associated with SDB, with or without adenotonsillar hypertrophy,34 determining the efficacy of a treatment targeting adenotonsillar hypertrophy alone is confounded by the inclusion of obese subjects.

Reports of the effect of treatment on resolution of SDB vary greatly between studies, ranging from 25% reported by Tauman et al.11 to 79% in the CHAT study.12 In this study, we found resolution of SDB in 61% of the children who were treated. These differences between studies may be due to a combination of the different follow-up periods, the different ages studied, the inclusion of obese children, and the different definitions used to define normalization and resolution of SDB. Our definition of resolution (or normalization), identified a group of children with absolutely complete resolution of their SDB. They had an OAHI ≤ 1, there was no snoring reported on the polysomnography, and the parents documented that they never observed their child snoring loudly, holding their breath, making choking or gasping sounds during sleep, or being restless with frequent awakenings on the OSA-18 questionnaire. In contrast, previous studies have defined resolution of OSA as an OAHI < 1 event/h TST,9,11,13 or a reduction in both the OAHI score to < 2 events/h and the OAI score to < 1 event/h.12 Our criteria for resolution of SDB allowed us to differentiate between the children whose SDB had completely resolved and those children who had residual PS. This is an important distinction as there is mounting evidence that PS is not a benign condition, but is associated with elevated blood pressure29,30 and deficits in neurocognition7 and behavior,6,35 similar to those found in children with OSA. Furthermore, by including a non-snoring control group, we were able to determine that resolution of SDB returned indices of sleep and respiration that were abnormal at baseline to comparable levels to controls following treatment.

In addition, the current study did not focus on adenotonsillectomy alone, but included children who had adenoidectomy only, nasal steroids, and in one case, nasal surgery. Removing only the adenoids has been associated with an increased risk of persistent OSA when compared to adenotonsillectomy in children.36 Repeat adenoidectomy is sometimes required for persistent or recurrent symptoms, with the likelihood of repeat adenoidectomy being 2.5 times higher in children under 5 years of age at the time of the first surgery and also higher in those whose first surgery was adenoidectomy alone.37 Adenoidectomy was the treatment option for 17% (4/23; 3 with PS and 1 MS OSA) of the children who were treated in our study; however, SDB remained unresolved in only one of those children (one with PS). As many children in our cohort had PS or Mild OSA, we chose to include nasal steroids in the treatment group as this is a recognized treatment for mild OSA,38 rather than omitting these children.

Previous studies that have investigated SDB in children in the long term, have been in older children.13,39 Huang et al.13 demonstrated that at three years following treatment, 68% of the cohort had an abnormal apnea-hypopnea index (AHI), including those children who had an AHI < 1 event/h at 6 months. In a previous study by our group in school-aged children 54% of children with SDB continued to snore, having either persistent or new OSA after 4 years, irrespective of treatment.39 This is similar to the 49% of children with unresolved SDB that we report herein.

More difficult to assess are the long-term outcomes of untreated SDB, as it would be unethical not to offer treatment to those who may benefit, particularly those with severe OSA. Studies that have previously investigated SDB in children who were untreated have only examined short-term outcomes9 or did not use polysomnography to quantify SDB severity.19 One small (n = 20) study has evaluated the natural history of children with PS,16 with a 3-year follow-up period and outcomes being assessed using polysomnography.16 The authors concluded that PS did not progress to OSA in the majority of children and was only mild in the instances when OSA did occur. Of note, none of the children had resolution of their PS and either remained with the same AHI or worsened. In contrast, our findings indicate that while PS in some children resolves without treatment, in a similar proportion it significantly worsens. We identified that of the 10 children with PS at baseline that was resolved at follow-up, 6 were not treated. However, 10 of the 13 children with PS at baseline whose SDB did not resolve, also did not receive treatment (5 still had PS at follow-up, 3 worsened to Mild OSA, and 2 to MS OSA). It is believed that the etiology of SDB may be multifactorial, with airway narrowing, muscle tone, and genetics contributing to the predisposition for a child to snore and have obstructed breathing during sleep,40 which we postulate resolves naturally in some children and persists in others.

As stated previously, all of the children with MS OSA were treated, so it remains unknown if their OSA might have resolved spontaneously or improved with age if they had not been treated. Given that a number of the children with PS or Mild OSA improved over time, it could be argued that a number of the children with MS OSA might also have improved. However, it must also be noted that even after adenotonsillectomy, one child with MS OSA showed no reduction in OSA severity after three years and two children only improved to Mild OSA. There is no literature available on how long children with SDB need to have the condition before the detrimental effects on the cardiovascular system, neurocognition and behavior may become intractable. Results from both the treated and untreated groups suggest the need for follow-up assessment in children diagnosed with SDB.

Although SDB is diagnosed in some children during infancy and the incidence of diagnosis peaks during the preschool age, there is scant evidence relating to the actual age of onset of SDB. For example, have children diagnosed with SDB at 8 years of age been obstructed since infancy? Or did the onset coincide with the rapid growth of the adenotonsillar tissue relative to the small nasopharynx during their preschool years? Parental reports for how long their child has snored prior to diagnosis are often vague and most likely unreliable. Anuntaseree et al.21 surveyed Thai children at 7 and again at 10 years of age by questionnaire, and reported that 31/694 children (4%) who never snored or occasionally snored at 7 years old were habitual snorers 3 years later. In a similar questionnaire based study, Chervin et al.41 reported that 8/191 children (4%) aged 2–13 years who did not snore habitually at baseline, had begun to snore habitually 4 years later. We were in a unique position to objectively evaluate whether non-snoring preschool-aged children might develop SDB when they were older, by using overnight polysomnography. Of the 30 non-snoring controls at baseline, 2 children (7%) were diagnosed with OSA (1 Mild OSA, 1 MS OSA) at the follow-up 3 years later. Our results indicate a slightly higher rate than the previous data obtained by questionnaire, but confirm that development of OSA can occur beyond the preschool period.

A limitation of the study was that only a relatively small number of children (37% of baseline cohort) agreed to participate at follow-up. This creates a potential for bias, in that the parents who consented for their children to undergo a repeat polysomnography may have concerns regarding their children's sleep and/or breathing, whereas those parents who refused participation did not. However, parents of both participants and non-participants were asked if they still had any concerns for their child's sleep or breathing and whether they considered their child's SDB to have improved or not since the diagnostic polysomnography. Analysis of these data indicate that there was no significant difference between the participants and the non-participants in the proportion of children considered to have improved since the baseline study, indicating that there was not a selection bias in our study. Furthermore, a repeat polysomnogram was not conducted immediately following treatment. Therefore, for the children identified with residual SDB at the polysomnography conducted three years following diagnosis, it is not known if their SDB had initially resolved following treatment and returned over the intervening years before the follow-up study, or whether the children had residual SDB from the time of treatment. There were more males than females in the treated group, which reflects not only the male predominance of children with OSA in the whole baseline cohort (66%),4 but also that more parents of males agreed to participate in the follow-up study, which is beyond the control of the researchers.

CONCLUSIONS

This is the first study to analyze the long-term effects of treatment or non-treatment relative to resolution of SDB, in a purely preschool-aged cohort of children. We identified that 3 years after diagnosis, SDB had resolved in 57% of children who received treatment, and in 35% of children who were untreated. However, SDB developed in 7% of previously non-snoring control children. These results highlight that parents should be made aware of the possibility of persisting or recurring SDB several years later, and present for further investigations if there are ongoing concerns. This is relevant regardless of the severity of SDB at baseline and the treatment given, and indicates that an individualized approach to therapy and follow-up may be preferable to a standardized approach.

DISCLOSURE STATEMENT

This was not an industry supported study. This study was supported by a National Health and Medical Research Council of Australia project grant (APP1008919) and the Victorian Government's Operational Infrastructure Support Program. The authors have indicated no financial conflicts of interest.

ABBREVIATIONS

AHI

apnea-hypopnea index

CHAT

Childhood Adenotonsillectomy Trial

EEG

electroencephalogram

EMG

electromyogram

EOG

bilateral electrooculogram

OAHI

obstructive apnea hypopnea index

OSA

obstructive sleep apnea

PPG

pulse oximeter

PS

primary snoring

RDI

respiratory disturbance index

RERA

respiratory event related arousals

SBD

sleep disordered breathing

SpO2

oxygen saturation

SPT

sleep period time

TcCO2

ranscutaneous carbon dioxide

TST

Total sleep time

WASO

wake after sleep onset

ACKNOWLEDGMENTS

The authors thank the children and families who participated in this study and the staff of the Melbourne Children's Sleep Centre for their support.

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