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Volume 14 No. 04
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Accepted Papers





Scientific Investigations

The Role of Functional Respiratory Imaging in Treatment Selection of Children With Obstructive Sleep Apnea and Down Syndrome

Monique A.L.J. Slaats, MD1; Dieter Loterman, MSc2; Cedric van Holsbeke, MSc, PhD2; Wim Vos, MSc, PhD2; Kim Van Hoorenbeeck, MD, PhD1; Jan de Backer, MSc, PhD2; Wilfried de Backer, MD, PhD3; Marek Wojciechowski, MD1; An Boudewyns, MD, PhD1; Stijn Verhulst, MD, PhD4
1Department of Pediatrics, University Hospital Antwerp, Antwerp, Belgium; 2Technology, Biomedical Physics, FluidDA, Kontich, Belgium; 3Department of Pulmonology, University Hospital Antwerp, Antwerp, Belgium; 4Department of Pediatrics, Pediatric Sleep Lab at Antwerp University Hospital, Antwerp, Belgium

ABSTRACT

Study Objectives:

The complexity of the pathogenesis of obstructive sleep apnea (OSA) in children with Down syndrome (DS) is illustrated by a prevalence of residual OSA after adenotonsillectomy. The aim of this study was to investigate whether upper airway imaging combined with computation fluid dynamics could characterize treatment outcome after adenotonsillectomy in these children.

Methods:

Children with DS and OSA were prospectively included. All children underwent an evaluation of the upper airway and an ultra-low dose computed tomography scan of the upper airway before adenotonsillectomy. The upper airway tract was extracted from the scan and combined with computational fluid dynamics. Results were evaluated using control polysomnography after adenotonsillectomy.

Results:

Thirty-three children were included: 18 boys, age 4.3 ± 2.3 years, median body mass index z-score 0.6 (−2.9 to 3.0), and median obstructive apnea-hypopnea index was 15.7 (3–70) events/h. The minimal upper airway cross-sectional area was significantly smaller in children with more severe OSA (P = .03). Nineteen children underwent a second polysomnography after adenotonsillectomy. Seventy-nine percent had persistent OSA (obstructive apneahypopnea index > 2 events/h). A greater than 50% decrease in obstructive apnea-hypopnea index was observed in 79% and these children had a significantly higher volume of the regions below the tonsils.

Conclusions:

This is the first study to characterize treatment outcome in children with DS and OSA using computed tomography upper airway imaging. At baseline, children with more severe OSA had a smaller upper airway. Children with a less favorable response to adenotonsillectomy had a smaller volume of regions below the tonsils, which could be due to enlargement of the lingual tonsils, glossoptosis, or macroglossia.

Commentary:

A commentary on this article appears in this issue on page 501.

Citation:

Slaats MA, Loterman D, van Holsbeke C, Vos W, Van Hoorenbeeck K, de Backer J, de Backer W, Wojciechowski M, Boudewyns A, Verhulst S. The role of functional respiratory imaging in treatment selection of children with obstructive sleep apnea and Down syndrome. J Clin Sleep Med. 2018;14(4):651–659.


BRIEF SUMMARY

Current Knowledge/Study Rationale: The complexity of the pathogenesis of obstructive sleep apnea (OSA) in children with Down syndrome (DS) is illustrated by a prevalence of residual OSA after adenotonsillectomy. The most common causes of persistent OSA in DS include macroglossia, glossoptosis, recurrent enlargement of the adenoid, tonsils, and enlarged lingual tonsils; however, there are still children who have these risk factors and benefit from adenotonsillectomy (decrease of greater than 50% in obstructive apnea-hypopnea index).

Study Impact: This is the first study that investigated whether upper airway imaging combined with computational fluid dynamics could influence treatment selection after adenotonsillectomy in these children. This study suggests that upper airway imaging could probably provide objective values for treatment selection by creating cutoff values of volumes below the tonsils.

INTRODUCTION

Down syndrome (DS) is associated with a high prevalence of sleep disturbances including sleep-disordered breathing.1,2 Sleep-disordered breathing consists of a spectrum of breathing abnormalities during sleep ranging from primary snoring to obstructive sleep apnea (OSA). OSA is more prevalent in children with Down syndrome (DS) compared to healthy children (prevalence 24% to 79% versus up to 4%, respectively).1,35 Hill et al. recruited a large cohort of young children with DS to determine the prevalence and predictors of OSA. Children with DS (n = 188) aged from 6 months to 6 years were included. Eighty-two children (44%) received a diagnosis of OSA by cardiorespiratory polygraphy or full overnight laboratory polysomnography (PSG) and 42 of them (51%) had moderate to severe OSA.5

Children with DS have certain anatomical factors that predispose for this higher risk of OSA: underdeveloped midface and mandibular hypoplasia, macroglossia, posterior-placed tongue, hypotonia, smaller upper airway, lymphoid hyperplasia, and obesity.610 OSA is associated with a range of complications including hyperactivity with behavioral problems and cardiovascular sequelae such as pulmonary hypertension. Children with DS have preexisting medical, cognitive, and behavioral deficits and may therefore suffer more from sleep disturbances and the complications. For instance, Breslin et al. concluded that OSA was associated with a reduced cognitive flexibility and lower verbal IQ in 38 children with DS.11 Furthermore, children with DS have a reduced cardiovascular response with delayed reoxygenation after obstructive respiratory events and reduced sympathetic drive, which is a potential explanation for their increased risk of pulmonary hypertension.1113 Therefore, OSA should be correctly treated. Adenotonsillectomy (AT) is the first-line surgical treatment in children with DS and OSA. However, persistent OSA (obstructive apnea-hypopnea index [oAHI] > 2 events/h) is seen in up to 87% of children with DS after AT.1417 A thorough preoperative evaluation of the upper airway is therefore needed to identify the level and degree of upper airway obstruction to select the most appropriate treatment. Several methods are available to evaluate the upper airway such as (cine)-magnetic resonance imaging (MRI), computed tomography (CT), drug-induced sleep endoscopy (DISE), and functional respiratory imaging (FRI).18 Donnelly et al. evaluated the causes of persistent OSA in children with DS after adenoidectomy or tonsillectomy by cine-MRI and concluded that the most common causes of persistent OSA in DS include macroglossia, glossoptosis, and recurrent enlargement of the adenoid, tonsils, and enlarged lingual tonsils.19 Maris et al. described the pattern of upper airway obstruction in children with DS by DISE. Surgical treatment (adenoidectomy, tonsillectomy, or AT) resulted in significant improvement; however, 52% had oAHI > 5 events/h, probably due to this multilevel collapse.20 FRI is a technique to calculate flow patterns, upper airway volumes, and resistance/ conductance. To our knowledge, no studies have used FRI or upper airway volumes of CT to characterize the upper airway in children with DS and OSA. Several studies evaluated the value of FRI in healthy or obese children with OSA.2123 Slaats et al. investigated whether FRI or clinical examination could predict treatment outcome for OSA in normal-weight, nonsyndromic children and concluded that a less constricted airway, as characterized by both FRI and a lower tonsil score, was associated with a less favorable response to AT or tonsillectomy.24 The aim of this study was to investigate whether upper airway imaging combined with computational fluid dynamics for FRI could characterize treatment outcome in children with DS and OSA. Our hypothesis is that upper airway imaging has an extra value in treatment selection of children with DS and OSA.

METHODS

This study was approved by the ethics committee at the Antwerp University Hospital. Informed consent was obtained from each subject and/or parent.

Participants

All children with a confirmed diagnosis of DS, aged from 6 months to 10 years and in whom OSA was diagnosed by PSG at the Pediatric Sleep Center of the Antwerp University Hospital, Belgium were prospectively included for this study between 2012–2015. There was no history of tonsillectomy or AT. Parents completed a standardized questionnaire regarding patient characteristics including ethnicity, sleep, and respiratory comorbidities. All children underwent a thorough evaluation in terms of history and clinical examination. The clinical assessment included height, weight, and grading of tonsillar size by a pediatric otorhinolaryngologist using the Brodsky scale.25 Body mass index (BMI) was calculated as weight in kg divided by height in m2 and BMI z-scores were calculated according to Flemish growth curves for boys and girls (KIGS calculator, Pfizer, New York, New York, United States).

Polysomnography

All children underwent an in-hospital overnight PSG performed by standard pediatric recording and scoring techniques as previously described.24 All tracings were manually scored using the American Academy of Sleep Medicine guidelines.26 OSA was defined if oAHI ≥ 2 events/h. It was classified as mild (2–5 events/h), moderate (5–10 events/h), and severe (≥ 10 events/h) OSA.

Ultra-Low-Dose CT Scan

All children underwent an ultra-low-dose CT scan of the upper airway while awake. Scanning was performed in the supine, neutral position. The scan was performed using a 64-slice CT scanner (LightSpeed, General Electric, Boston, Massachusetts, United States) and contained an average of 350–400 DICOM images. All images have an in-plane spatial resolution of 0.3 mm and are reconstructed with a slice increment of 0.5 mm. All scans were performed by low-dose radiation protocol because the main interest was to obtain images about the air in the upper airway, not the surrounding tissue. This dose was achieved using an 80-kV setting; radiation was between 0.2– 0.4 mSv (depending on the age). All scans were evaluated by a radiologist according to standard protocol and were blinded from the outcomes of PSG tests.

Upper Airway Morphology Extraction From CT Scan

The acquired DICOM images were processed using a software package (Mimics version 17.0, Materialise, Leuven, Belgium). Additionally, segmentation of the upper airway was done using the Hounsfield unit of each voxel in the DICOM images as a discriminatory parameter, making a binary distinction between air and solid structures. The Hounsfield unit is a value for the radiodensity of the tissue and reaches from 1,024 to 3,071. Characteristic values on the Hounsfield scale are 1,000 Hounsfield units and 1,024 Hounsfield units, respectively, corresponding with air and bone. The upper airway from nares to trachea was reconstructed into three-dimensional (3D) models and subdivided into a large number of discrete elements (Figure 1). The model is used for analysis of anatomical parameters, volume meshing (representation of interior volume), and computational fluid dynamics simulation. This way, effective upper airway volume and minimal and mean cross-sectional areas are calculated. Effective upper airway volume is total upper airway volume, excluding low-flow areas around the vocal cords and sinuses. The 3D model of the upper airway was then divided into five zones (Figure 2). Volumes of these segments were calculated in mm3, the smallest cross-sectional area was measured (mm2) and the first zone of minimal area has been calculated. We assume that the adenoids and tonsils are in upper airway volume (zone 3) and tongue base is primarily located in upper airway volume (zone 4) and in some children, partly in zone 3. In some airways, there is a total obstruction of the upper airway.

Reconstructed into 3D model of the upper airway.

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Figure 1

Reconstructed into 3D model of the upper airway.

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3D model of the upper airway divided into 5 zones.

Zone 1 = nostril to bottom of inferior turbinate. Zone 2 = bottom of inferior turbinate to choanae. Zone 3 = choanae to tip of uvula. Zone 4 = uvula to epiglottis. Zone 5 = epiglottis to the first vertebra.

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Figure 2

3D model of the upper airway divided into 5 zones.

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Upper Airway Characteristics Extraction From Computational Fluid Dynamics

The 3D model obtained after segmentation was divided into discrete cells to form a hexahedral dominant computational domain (SnappyHexMesh2.0.1, OpenCFD Ltd/ESI Group, Paris, France). The cell volumes were in the order of 1e14 – 1e8 m3 for computational fluid dynamics analysis. The mesh was not aligned to the axial flow direction and the cells were extra refined near the boundaries, which resulted in a computational grid of the upper airway typically consisting of approximately 800,000 computational cells. This 3D mesh was exported and read into a custom Reynolds Average Navier Stokes computational fluid dynamics solver based on OpenFOAM 2.0.1 (OpenCFD Ltd/ESI Group, Paris, France).

The following were boundary conditions that were set to the model:

  1. A pressure outlet at the outlet surface in the larynx of −20 Pa.

  2. A pressure inlet at the inlet surface at the nostrils of 0 Pa.

  3. Nonimpermeable walls (no-slip conditions) for the sides of the upper airway.

Pressure-based boundary conditions were used because this enables the simulation of the flow demand for the wide range of patient ages and sizes. Second-order discretization schemes were used and the pressure velocity coupling was solved using the SIMPLE scheme. A steady, laminar simulation of the inspiratory airflow was then performed until convergence of the mass flow rate through the upper airway was achieved. From the outcome of the computational fluid dynamics analysis the resistance of the upper airway was calculated. Some patients expressed an obstruction during the CT scan. Therefore, this value was transformed to the inverse of the resistance and defined as the conductance. Computational fluid dynamics analysis of the children without a history of tonsillectomy at baseline was used to characterize computational fluid dynamics endpoints with OSA severity.

Choice of Treatment

A pediatric otolaryngologist made the decision about the need and type of surgery by using the combination of a detailed history, clinical assessment, PSG data, and DISE. DISE was performed in the surgical theater by a single pediatric otolaryngology-head and neck surgeon (BA). All children were sedated on the operating table by a pediatric anesthesiologist with a mixture of sevoflurane and oxygen. The desired level of sedation and spontaneous breathing was obtained by intravenous propofol. The examination was performed when the child was in lying supine position and the head in neutral position. A flexible fibrotic laryngoscope was passed into one nostril up to the level of the nasopharynx when there was a stable respiratory pattern. Treatment decisions were based on a multidisciplinary agreement between pediatric pulmonologist, otolaryngology-head and neck surgeon, and the child's pediatrician. As described earlier, AT is the first-line treatment of OSA in children. In this study, only children with AT as treatment were included for the analysis to characterize treatment outcome. A second PSG was performed after 3 to 12 months after AT, and children without a second PSG were excluded. The response of treatment was expressed as the percentage change in oAHI before and after treatment. Surgical treatment was considered successful when a reduction in oAHI of at least 50% was obtained. However, a complete cure of OSA was defined as an oAHI < 2 events/h.

Statistical Analysis

Statistical analyses were conducted with SPSS version 24 (IBM Corp, Armonk, New York, United States). Sample mean, median, and standard deviations were tabulated. Normally distributed data are presented as mean ± standard deviation and skewed data as median and range. Different degrees of OSA at baseline and differences between children with improvement of greater than 50% of oAHI and children with less than 50% of oAHI were compared using Mann-Whitney U test/Jonckheere-Terpstra test or χ2 test. Comparison of the upper airway between European (EU) and non-European (N-EU) children was done using Mann-Whitney U test. Spearman correlations were performed between the imaging and/or computational fluid dynamics analyses and OSA severity before and after the treatment. All analyses are two-tailed and significance was set at P < .05.

RESULTS

Patients Characteristics at Baseline

A total of 33 children with DS received a diagnosis of OSA by PSG and were included for the baseline analyses. The group consisted of 18 males and 15 females, age 4.3 ± 2.3 years and mean BMI z-score was 0.6 (−2.9 to 3.0). Most of the children were within a healthy BMI range, with 12% of those age 2 years or older classified as overweight or obese. A history of allergy was reported in two children and a history of wheezing in seven children. Most of them (74%) had a Brodsky tonsil score of 3 or 4. There was no history of tonsillectomy or AT. Median oAHI was 15.7 (3 to 70) events/h. Five of these children had mild OSA (15%), 9 had moderate OSA (27%), and 19 had severe OSA (58%). Patient and upper airway characteristics are compared between the different categories of OSA severity in Table 1. The minimal cross-sectional area was significantly smaller in children with more severe OSA (P = .03).

Baseline patient characteristics according to increasing categories of OSA severity.

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Table 1

Baseline patient characteristics according to increasing categories of OSA severity.

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No correlations were observed between oAHI and upper airway imaging/FRI, clinical assessment (tonsil score), or age. However, there was a positive correlation between minimal oxygen saturation during PSG and upper airway volume zone 3 (r = .37, P = .04), conductance (r = .47, P = .01) and minimal cross-sectional area (r = .41, P = .02). There was a negative correlation between minimal oxygen saturation during PSG and tonsil Brodsky score (r = −.36, P = .05). There was no correlation between minimal oxygen saturation during PSG and BMI z-score or age.

This study population consisted of 12 N-EU children (origin of these children: 6 from Morocco, 3 from Turkey, 2 from South-Africa and 1 from Asia). N-EU children were matched for sex and age with a subgroup of 18 EU children. There was no difference in OSA severity between EU and N-EU children. However, N-EU children had significantly more total airway obstruction compared to the EU children (67% versus 22%, P = .02).

Treatment

Combination of a detailed history, clinical assessment, PSG data, and DISE-directed treatment decisions resulted in different surgical and nonsurgical treatments (Figure 3). Although AT is the most commonly used treatment in children with OSA, in this study, 21 of the 33 children underwent AT.

Various surgical and nonsurgical treatments.

AT = adenotonsillectomy, CPAP = continuous positive airway pressure, DS = Down syndrome, OSA = obstructive sleep apnea, PSG = polysomnography.

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Figure 3

Various surgical and nonsurgical treatments.

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Nineteen children underwent a second PSG after AT. Persistent OSA, defined as oAHI ≥ 2 events/h, was found in 79% (7 children with moderate OSA and 8 children with severe OSA). However, 79% of these 19 children had a decrease of greater than 50% in oAHI after treatment. Table 2 shows the differences between children with and without a decrease of more than 50% in oAHI after AT. Most of them (81%) had a tonsil score of more than 3 and (33% and 50%) had their minimal cross-sectional area located in zone 3 during upper airway imaging. Children with a decrease greater than 50% in oAHI had a significantly higher volume of zone 4 and zone 5 compared to children without a decrease of greater than 50% (Figure 4 and Figure 5).

Differences in patient, polysomnographic and imaging characteristics among children with and without a decrease of more than 50% in oAHI after treatment.

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Table 2

Differences in patient, polysomnographic and imaging characteristics among children with and without a decrease of more than 50% in oAHI after treatment.

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Image of a child's upper airway with a decrease of more than 50% in oAHI after AT.

AT = adenotonsillectomy, oAHI = obstructive apnea-hypopnea index.

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Figure 4

Image of a child's upper airway with a decrease of more than 50% in oAHI after AT.

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Image of a child's upper airway with a decrease of less than 50% in oAHI after AT.

AT = adenotonsillectomy, oAHI = obstructive apnea-hypopnea index.

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Figure 5

Image of a child's upper airway with a decrease of less than 50% in oAHI after AT.

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There was a strong positive correlation between the improvement in oAHI after treatment and oAHI at baseline (r = .84, P < .001) (Figure 6). Difference in oAHI before and after treatment correlated with upper airway zone 4 (r = .51, P = .03) and zone 5 (r = .51, P = .03) as well. There was no correlation between oAHI after treatment and FRI or tonsil score.

Correlation between the improvement in oAHI after treatment and oAHI at baseline.

oAHI = obstructive apnea-hypopnea index.

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Figure 6

Correlation between the improvement in oAHI after treatment and oAHI at baseline.

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DISCUSSION

To our best knowledge, this is the first study that used upper airway imaging by CT combined with computational fluid dynamics to describe treatment outcome in children with DS and OSA. At baseline, children with more severe OSA had a smaller minimal cross-sectional area of the upper airway. In addition, a smaller volume of the overlap region between adenoids and tonsils, a lower upper airway conductance during imaging, and a higher tonsil score were correlated with a lower minimal oxygen saturation. Persistent OSA was seen in 79% of our patients who underwent AT. Most of them (79%) had a decrease of greater than 50% in oAHI after treatment. A smaller volume of the upper airway in the regions below the tonsils was associated with a less favorable response to AT.

At baseline, children with more severe OSA had a smaller minimal passage through the upper airway, probably due to more obstruction in the adenoid/tonsil region. First, there were no correlations between OSA severity as expressed by oAHI and FRI. This could be due to (multilevel) collapse in the upper airway during sleep that cannot be visualized by our scanning protocol during wakefulness. Second, there was no correlation between oAHI and tonsil score as well. This is comparable to two large previous studies,5,17 whereas another study by de Miguel-Diez et al. concluded that tonsillar hypertrophy was associated with sleep-disordered breathing.27 In other words, the minimal cross-sectional area was correlated with more severe OSA whereas no correlation was found with clinical assessment (tonsil score).

In this study, the risk of more severe OSA was equally distributed between sexes, comparable with the results of two other studies.17,28 However, Hill et al. and de Miguel-Diez et al. found that males are at higher risk for the development of OSA.5,27 Hill et al. suggested male sex as a risk factor, although predictive power was reduced after controlling for other variables such as age and tonsillar hypertrophy. These conflicting results could be due to the relatively small population of our study and the study of Austeng et al. or because of the different measurement techniques to diagnose OSA.28 Almost all children in the study of Hill et al. underwent cardiorespiratory polygraphy instead of full overnight laboratory PSG. Thereby, Hill et al. also included children without OSA.

We did not find a correlation between BMI z-score and OSA severity, comparable with six previous studies.3,5,2831 whereas two other studies reported a correlation.27,32 This is probably due to differences in age and obesity percentages between studies.

Ethnicity has been suggested as an important risk factor for OSA in children. Dudley and Patel concluded that African American children and obesity were associated with more severe OSA in children.31 Tamanyan et al. determined whether demographic or clinical factors predict OSA severity in 301 Australian children. They concluded that non-Caucasian children were more likely to have a diagnosis of moderate to severe OSA than Caucasian children.33 To our knowledge, there are no studies that have investigated the influence of ethnicity in children with DS and OSA, nor are there studies that have compared the upper airway of EU and N-EU children. In our study, no difference was observed between OSA severity or treatment response between different ethnicities. However, children from N-EU had more total obstruction in the upper airway at baseline. This suggests some differences in upper airway morphology in children from N-EU countries. Our study had a limited sample size, and the relationship between ethnicity and OSA severity in children with DS needs to be addressed in larger future studies.

After AT, 19 children underwent a second PSG. Persistent OSA, defined as oAHI ≥ 2 events/h, was found in 79%. Previous literature reported some different percentages of outcome after surgical treatment, about 30% to 50%.14,16,17 These percentages are based on different methods compared to our study. Some studies compared a combination of some surgical treatments (adenoidectomy, tonsillectomy, AT, tonsillar pillar plication, uvulopalatopharyngoplasty or anterior tongue reduction) and one study only AT. The cutoff value in the majority of studies is oAHI > 5 events/h. In our study, 42% had oAHI > 5 events/h after AT. Shott et al. investigated 15 children and 87% had persistent OSA (oAHI > 2 events/h).16 Maris et al. investigated 34 children and 82% had persistent OSA (oAHI > 2 events/h).17

Children with more severe OSA had a larger decline of oAHI after treatment. This was described earlier by Maris et al.17 There was no correlation between oAHI after treatment and FRI or tonsil score.

Furthermore, children with a decrease of greater than 50% in oAHI had a significantly higher volume of zone 4 and zone 5 (region below the tonsils) compared to children without a decrease of more than 50%. Tongue base collapse or hypotonia were not seen during DISE in children with less favorable response to AT. Therefore, baseline CT scans of these children showed enlargement of the uvula, enlargement of the tonsils with narrowing of hypopharynx, and enlargement of Waldeyer tonsillar ring. A drawback of the current study is the lack of post-AT CT scans. In previous studies, the size of the tongue was measured by MRI. There was no measurement for glossoptosis or macroglossia in our study, which could also be a possible reason for a smaller volume of zone 4 and zone 5 in these children. Another possible reason for less volume in zone 4 and zone 5 is gastroesophageal reflux. Children with DS are commonly associated with gastroesophageal reflux.34 Gastric acid can cause inflammation and swelling of the soft tissues around zones 4 and 5.

Children with DS are likely to have macroglossia, glossoptosis, and enlargement of lymphoid tissue. However, there are still children who have these risk factors and benefit from AT (decrease of greater than 50% in oAHI). This study suggests that upper airway imaging could probably report some objective values for treatment selection by creating cutoff values of volumes below the tonsils. There were not enough patients in the current study to determine these cutoff values; therefore, more research is needed.

Two previous imaging studies investigated the reason of persistent OSA in children with DS by cine MRI.10,19 Fricke et al. compared lingual tonsil size among 52 children with OSA (20 of 52 children with DS) and 37 controls by cine MRI. They concluded that enlargement of lingual tonsils is relatively common in children with persistent OSA, particularly in patients with DS. Admittedly, these children were older compared to our study (mean age of 12.1 ± 6.4 years).10 Donnelly et al. evaluated the causes of persistent OSA in 27 children with DS (mean age 9.9 years) by cine MRI as well. They concluded that the most common causes of persistent OSA include marcoglossia, glossoptosis, recurrent enlargement of the adenoid tonsils, and enlarged lingual tonsils.19 Flexible laryngoscopy is required for examination of the lingual tonsils. However, Fricke et al. concluded that enlarged lingual tonsils are often identified on MRI sleep studies and not on physical examination.10 Therefore, imaging or DISE may be indicated for the evaluation of the lingual tonsils prior to surgery in these children. DISE shows some information about tonsillar obstruction, tongue base and epiglottis collapse. Although there are some limitations of both methods, MRI is invasive in young children because of the sedation and CT requires radiation. Children are also sedated during DISE, although DISE could be performed in combination with surgery. DISE is limited because there could be more obstruction in sedated children. A systematic review about the effects of anesthesia and opioids on the upper airway concluded that 4 of 12 published studies showed a decrease in airway cross-sectional area with increasing propofol dosage. They concluded that the level of obstruction was highest at the base of the tongue.35

The sample size of the current study was too small to evaluate the predictive capability of a logistic regression model incorporating clinical and FRI to predict the outcome of treatment. Further studies including larger samples of patients before treatment are needed to validate a model to predict treatment outcome. Virtual surgery by FRI may also guide the surgeon in choosing an effective surgical strategy as already described by Mylavarapu et al.36 A recent study by Mylavarapu et al. used computational fluid dynamics to perform virtual surgery and assess airflow changes in patients with DS and persistent OSA. Virtual surgeries were performed on 10 patients with moderate to severe OSA. Actual surgery was successful (defined by postoperative oAHI < 5 events/h) in 6 of 10 patients. Changes in oAHI and upper airway resistance, as calculated by computational fluid dynamics for preoperative and postoperative modeling, matched well for 8 of 10 patients. Limitations of this study were that the authors did not describe the influence of age and did not compare the virtual surgery with surgical changes in anatomy by MRI after treatment. However, this technique could also be helpful for treatment selection.37

Two other studies used imaging in children with DS to investigate upper airway morphology. Uong et al.38 investigated the anatomical differences by MRI (size and shape of the upper airway in relation to surrounding tissue) among 11 children with DS without OSA and 14 controls without DS and OSA (mean age of 3 years). Adenoid and tonsil volume was significantly smaller in the children with DS. However, tongue, soft-palate, pterygoid, and parapharyngeal fat pads were similar. There was a smaller upper airway size in children with DS, and the authors suggested that this was caused by soft-tissue crowding within a smaller middle and lower face skeleton.38 Another imaging study investigated the stiffness of the airway wall from MRI by a noninvasive method in 21 children with DS and OSA. Airway changes were evaluated by continuous positive airway pressure. The localized airway and tissue elasticity were found to increase with increasing OSA severity. They concluded that elasticity-based patient phenotyping can potentially assist clinicians in decision making on the level of continuous positive airway pressure.39

Our study has several limitations that should be acknowledged. First, as already stated, the sample size was rather limited, which prevented the use of logistic regression and the comparison of FRI against clinical markers. Further validation studies should include larger samples of patients with a wider range of age groups to optimize a predictive model incorporating these different markers. Second, we decided to use DISE before treatment to make the selection of treatment because of the added value of DISE as described before,20 resulting in less patients who had AT as treatment. Third, CT scanning results in exposure to radiation. However, radiation is reduced to ranges between 0.2–0.4 mSv (depending on the age) and the maximal suggested value for radiation is 3 mSv per year. Finally, no sedation was needed in these children to perform the CT scan which makes it also less invasive, with the consequence that the upper airway was not assessed during sleep.

CONCLUSION

In summary, this is the first study that characterized treatment outcome in young children with DS and OSA by upper airway imaging by CT combined with computational fluid dynamics. Thirty-three children with DS and OSA were included in this study. At baseline, children with more severe OSA had a smaller minimal passage through the upper airway. After treatment, persistent OSA after AT was seen in 79%; however, 79% had a decrease of greater than 50% in oAHI after treatment. This study suggests that upper airway imaging could have an influence in treatment selection. Children with less favorable response had a smaller volume of the zones below the tonsils that was probably due to enlargement of the lingual tonsils, glossoptosis, or macroglossia which are not treated by AT.

DISCLOSURE STATEMENT

Monique Slaats is supported by a Special Research Fund (BOF) of University of Antwerp and Stijn Verhulst is supported by a Senior Clinical Investigator Grant from the Research Foundation Flanders (FWO). The authors report no conflicts of interest.

ABBREVIATIONS

AT

adenotonsillectomy

CI

confidence interval

CPAP

continues positive airway pressure

CT

computed tomography

DISE

drug induced sleep endoscopy

DS

Down syndrome

EU

European

FRI

functional respiratory imaging

MRI

magnetic resonance imaging

N-EU

non-European

oAHI

obstructive apnea-hypopnea index

OSA

obstructive sleep apnea

PSG

polysomnography

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