Abbreviatioairway pressurbance index; R

* CorrespondE-mail addr

med.uni-tuebin1 Tel.: þ1 782 Tel.: þ49 73 Tel.: þ49 7

1087-0792/$ -doi:10.1016/j.

Sleep Medicine Reviews (2009) 13, 123e131

www.elsevier.com/locate/smrv

CLINICAL REVIEW

Interventions for obstructive sleep apneain children: A systematic review

Stefan Kuhle a,1, Michael S. Urschitz b,*, Steffen Eitner b,2,Christian F. Poets b,3

a School of Public Health, 650 University Terrace, University of Alberta,Edmonton, AB, Canada T6G 2T4b Department of Neonatology, University Children’s Hospital, Calwer Street 7,72076 Tubingen, Germany

KEYWORDSChild;Sleep;Sleep apnea;Obstructive;Therapeutics;Randomized controlledtrial

ns: AHI, apnea/hypopne; OSA, obstructive sleR, relative risk; SD, staing author. Tel.: þ49 7esses: stefan.kuhle@uagen.de (S. Eitner), chr

0 492 9087; fax: þ1 780071 2980877; fax: þ49071 2984742; fax: þ49

see front matter ª 200smrv.2008.07.006

Summary Background: Obstructive sleep apnea (OSA) is characterized byhabitual snoring, heavy breathing, sleep-related hypoxia and arousals from sleep,and is found in approximately 3% of children.Objective: To review the efficacy of medical, behavioral, mechanical and surgicalinterventions in improving OSA in children.Methods: Bibliographic databases, relevant conference proceedings and trial regis-ters were searched. Randomized controlled trials assessing interventions in chil-dren with objectively diagnosed OSA (as per polysomnography; apnea/hypopneaindex (AHI) or respiratory disturbance index (RDI)� 1/h) were considered.Results: The search identified 1690 potentially relevant studies. The five trials thatmet the inclusion criteria investigated seven different interventions (intranasalsteroids, adenotonsillectomy, maxillary distraction, temperature-controlled radio-frequency ablation, oral appliances, continuous and bilevel positive airway pres-sure therapy). Intranasal steroids had a significant advantage over placebo indecreasing the AHI (one study). Temperature-controlled radiofrequency ablationand adenotonsillectomy were equally effective in reducing the RDI (one study).Continuous and bilevel positive airway pressure therapy was equally effective in

ea index; ATE, adenotonsillectomy; 95% CI, 95% confidence interval; CPAP, continuous positiveep apnea; PSG, polysomnography; RCT, randomized controlled trial; RDI, respiratory distur-ndard deviation.

071 2980877; fax: þ49 7071 293969.lberta.ca (S. Kuhle), michael.urschitz@med.uni-tuebingen.de (M.S. Urschitz), steffen.eitner@istian-f.poets@med.uni-tuebingen.de (C.F. Poets).492 5521.

7071 293969.7071 293969.

8 Elsevier Ltd. All rights reserved.

124 S. Kuhle et al.

reducing the AHI (one study). There was insufficient evidence to support the use oforal appliances.Conclusions: Despite a broad array of treatment options for OSA, there is limitedevidence to support their use. More research is needed before general recommen-dations can be made.ª 2008 Elsevier Ltd. All rights reserved.

Background

Obstructive sleep apnea (OSA) in children is a formof sleep-disordered breathing characterized byepisodes of partial or complete upper airwayobstruction with a reduction in arterial hemoglobinoxygen saturation, hypercapnia and/or respira-tory-related arousal. Typical nighttime symptomsinclude snoring, restless sleep, and increasednumber of awakenings.1

The etiology of OSA is multifactorial: patency ofthe upper airways during sleep can be influencedby anatomic and neuromuscular factors.2 Themajority of cases of OSA in children are associatedwith adenotonsillar hyperplasia. Other factorsinclude craniofacial or neuromuscular abnormali-ties and obesity.3e5 Untreated OSA can result inserious morbidity including failure to thrive, corpulmonale, and mental retardation.6 Such severeconsequences are less common now due to earlierdiagnosis and treatment. Several reports havesuggested that children with OSA have neuro-cognitive deficits, such as poor learning, behav-ioral problems, and attention deficit hyperactivitydisorder.7e11

Clinically, OSA is commonly suspected basedon parental report of snoring, labored breathing,witnessed apnea, and/or daytime sleepiness aswell as impaired behavior.12 Definitive diagnosisis made by overnight polysomnography (PSG) ina sleep laboratory. The PSG criterion mostfrequently used for diagnosis is the apnea/hypopnea index (AHI) which allows to determineOSA severity in addition to establishing thediagnosis.

Given the multifactorial nature of the disorderthere is no one-size-fits-all intervention for childrenwith OSA. Most children with OSA improve afteradenotonsillectomy (ATE).13 However, ATE is asso-ciated with surgical risks14 and may be unsuccessfulin abolishing OSA in some patients due to otherconcurrent underlying factors. There are a numberof adjunct or alternative interventions for pediatricOSA available such as anti-inflammatory drugs,15,16

weight reduction,12 continuous positive airwaypressure (CPAP)17 or oral appliances.18 Depending onthe duration and severity of the symptoms, the

anatomical and physiological findings, and the resultof the PSG assessment, the practitioner has tochoose which intervention will likely be most bene-ficial for the patient. To date, there has been nocomprehensive systematic review of the availableevidence on interventions for OSA. Therefore, we setout to review the efficacy of medical, behavioral,mechanical and surgical interventions in improvingOSA in children between 1 and 16 years of age.

Methods

Search strategy

Detailed individual search strategies for each ofthe following bibliographic databases were devel-oped: MEDLINE (1950epresent), EMBASE (1988epresent), Cochrane Central Register of ControlledTrials (CENTRAL) (1964epresent), CumulativeIndex to Nursing and Allied Health Literature(CINAHL) (1982epresent), Web of Science (1900epresent), and Literatura Latino-Americana e doCaribe de Informac~ao em Ciencias da Saude(LILACS) (1982epresent). For identification ofongoing clinical trials, controlled-trials.com, theInternational Federation of Pharmaceutical Manu-facturers & Associations (IFPMA) Clinical TrialsRegister, and the National Research Register (UK)were searched. A grey literature search was per-formed using SCOPUS. Conference proceedings ofthe American Thoracic Society, AssociatedProfessional Sleep Societies, European SleepResearch Society and European Respiratory Societyfor the years 2002e2007 were handsearched foreligible trials. Reference lists from eligible studiesand review articles were cross-checked to identifyadditional trials. Both English and non-Englishstudies were considered.

The detailed search strategy is available fromthe authors.

Study selection

Titles and abstracts of the records retrieved by theelectronic and hand searches were independentlyscreened by two reviewers (S.K., M.S.U.). The full-

Interventions for obstructive sleep apnea in children 125

text of potentially relevant articles was retrievedand assessed independently by two reviewers (S.K.,M.S.U.). All blinded and non-blinded randomizedcontrolled trials (RCTs) were considered for inclusionin the review. Children between 1 and 16 years of agewith objectively diagnosed OSA (as per PSG; AHI� 1/h or respiratory disturbance index (RDI)� 1/h) wereeligible for inclusion; pediatric studies with up to 20%of children being 17e18 years old were accepted.Exclusion criteria were malformation syndromes andneuromuscular disorders. All interventions aiming atthe reduction or cessation of OSA were considered.Comparisons were against placebo, no interventionor other medical, behavioral, mechanical, orsurgical interventions. The primary outcome was theAHI as measured by PSG. Where no AHI was reported,the RDI was accepted as the primary outcome.Secondary outcomes were the oxygen desaturationindex (as per PSG); respiratory arousal index (as perPSG); nadir of the arterial oxygen saturation (SpO2;as per PSG); mean SpO2 (as per PSG); % of children inwhom surgical treatment for OSA could be avoided(in ATE-na€ıve children); clinical symptom score(based on parent report of, e.g., snoring, witnessedapnea, daytime sleepiness, etc.); and % of childrenwith a decrease in tonsillar size.

Quality assessment

The quality of the included trials was indepen-dently assessed by two reviewers (S.K., M.S.U.).Allocation concealment of trials was evaluatedusing the criteria of Schulz et al.19 Study qualitywas assessed using the Jadad scale.20 Disagree-ment between the reviewers was resolved bydiscussion.

Data extraction

Data extraction was performed independently bytwo investigators (S.K., S.E.) using a pre-testedstandard paper form that captured details of studydesign, population, intervention, and outcomes.

Data analysis

The primary outcome as well as the oxygen desa-turation index, the respiratory arousal index, andthe clinical symptom score are reported as thepost-treatment mean difference with 95% confi-dence interval (95% CI). Avoidance of ATE anddecrease in tonsillar size is reported as a relativerisk. All point estimates and their 95% CI werecomputed using Review Manager 4.2.10.21

Where the mean and standard deviation (SD)were not available, they were imputed as follows:

when the median and range were available, thesepoints were used to reconstruct three points(minimum, median, and maximum) of the data set.Half of the remaining n� 3 data points were eachplaced at equidistant intervals between theminimum/maximum and the median. The meanand SD were then calculated for the reconstructeddata set. When the median and interquartile rangewere available, the mean was used instead of themedian (provided the data appeared not tooskewed) and the SD was calculated as interquartilerange divided by 1.35.22 In instances where onlythe baseline mean and the mean difference frombaseline had been provided, the post-treatmentmean was calculated from these values and thebaseline SD was used as the best approximation forthe post-treatment SD.

Given the heterogeneity of the study interven-tions, no pooling of results was attempted. Due tothe low number of studies, publication bias wasnot examined. For the same reasons, no sensitivityor subgroup analysis was performed.

Results

Study selection

All database searches were performed in August2007. A flow chart of the process of study identi-fication and inclusion/exclusion is shown in Fig. 1.

Independent review of the 86 potentially rele-vant studies identified five relevant studies.17,23e26

Eighty-one studies were excluded because they i)were not RCTs (n¼ 35); ii) studied adults or infantsonly (n¼ 15); iii) did not objectively diagnose OSAor included children with an AHI< 1 (n¼ 24); iv)were duplicate publications of the same study(n¼ 6); or v) included children with malformationsyndromes (n¼ 1). Three excluded studies27e29

fulfilled all inclusion criteria with the exception ofthe enrollment of an unknown fraction of childrenwith an AHI< 1.

A search of trial registers identified one relevantongoing trial.30 The study is investigating ina double-blind, placebo-controlled fashion theeffects of a 12-week course of the oral leukotrieneantagonist montelukast on PSG and radiologicalfindings in children with sleep-disorderedbreathing. The study start was in March 2005.Expected total enrollment is 50 children.

Study characteristics

All RCTs were published in the English language.Three RCTs were conducted in the US,17,23,24 one

Figure 1 Flow chart for study search and inclusion. Abbreviations: RCT, randomized controlled trial; OSA,obstructive sleep apnea; AHI, apnea/hypopnea index.

126 S. Kuhle et al.

in Canada,25 and one in Italy.26 All trials werepublished in the last 6 years. All RCTs were parallelarm trials. One study has only been published as anabstract for the Annual Meeting of the AssociatedProfessional Sleep Societies in 2006,24 theremainder were full-fledged journal publications.At the time of writing, unpublished data for theabstract were not available to the authors.

The five included studies investigated sevendifferent interventions (intranasal steroids, ATE,temperature-controlled radiofrequency ablation,oral appliances, and positive airway pressuretherapy) that fall into the broad categories ofmedical, mechanical, and surgical interventions.No study investigated a behavioral intervention.

Details on the study characteristics and themethodological quality of the five included trialsare summarized in Table 1.

Efficacy

Medical interventionsOne study assessed a 6-week course of intranasalsteroids.25 The study reported a significantimprovement of the AHI post-treatment compared

to the placebo group; the AHI in the treatmentgroup fell from 10.7/h to 5.7/h while it increasedfrom 11.0/h to 13.2/h in the placebo group(p¼ 0.04 for between-group difference; Table 2).Brouillette et al. also reported significantimprovements in the oxygen desaturation indexand in the parent-reported symptom score in theintervention group, while tonsillar size post-treatment was not different between groups (nomean values reported). The study found no changein nadir SpO2. The authors reported that 46% and75% of children in the intervention and placebogroup, respectively, proceeded to ATE during post-study follow-up. However, no time horizon for thefollow-up period was specified. The only adverseeffect that was possibly related to topical nasaltreatment was one nosebleed in the placebogroup.

Surgical interventionsCoticchia et al.23 compared temperature-controlled radiofrequency ablation of the tonsilswith conventional ATE. Both interventionssignificantly reduced the RDI at 3 months (from7.7 and 7.6/h to 0.3 and 1.6/h, respectively) as

Table

1St

udy

chara

cteri

stic

sand

meth

odolo

gica

lquality

of

the

five

incl

uded

tria

ls

Study

No.

enro

lled

Mean

age

[years

]% M

ale

OSA

definit

ion

Addit

ional

crit

eri

aIn

terv

enti

on

Com

pari

son

Desi

gnAlloca

tion

conce

alm

ent

Jadad

scale

Medic

al

Bro

uille

tte

et

al.

25

253.

856

AH

I>1

eIn

tranasa

lfluti

caso

ne

50mg

for

6w

eeks

Pla

cebo

Double

-blind

random

ized

contr

olled

A5

Surg

ical

Coti

cchia

et

al.

23

236.

461

RD

I>5

eTCRF

ATE

Random

ized

contr

olled

D2

Guille

min

ault

et

al.

24

326.

9n/a

AH

I>1

Narr

ow

maxi

lla

ATE

Maxi

llary

Dis

tract

ion

Random

ized

contr

olled

D1

Mech

anic

al

Villa

et

al.

26

327.

163

AH

I>1

Cro

ssbit

eO

ral

appliance

for

6m

onth

sN

oin

terv

enti

on

Random

ized

contr

olled

D0

Marc

us

et

al.

1726

10.4

81AH

I>1

Ineligi

bilit

yfo

rsu

rgery

CPA

Pfo

r6

month

sBiP

AP

for

6m

onth

sSi

ngl

e-b

lind

random

ized

contr

olled

B3

Abbre

viat

ions:

AH

I,apnea/h

ypopnea

index;

ATE,

adenoto

nsi

llect

om

y;BiP

AP,

bileve

lposi

tive

air

way

pre

ssure

;CPA

P,co

nti

nuous

posi

tive

air

way

pre

ssure

;n/a

,not

ava

ilable

;O

SA,

obst

ruct

ive

sleep

apnea;

RD

I,re

spir

atory

dis

turb

ance

index;

TCRF,

tem

pera

ture

-contr

olled

radio

frequency

abla

tion.

Interventions for obstructive sleep apnea in children 127

well as the snoring score (from 7.4 and 6.8 [ona visual analogue scale from 0 to 10] to 1.0 and0.9, respectively) and tonsillar size at 1 month(3.0e1.3 in the radiofrequency ablation group; nodata reported for the ATE group; Table 2).However, there was no statistically significantdifference in post-treatment RDI, snoring score ortonsillar size between the groups. There were nopostoperative complications such as apnea orhemorrhage in either group.

The study reported by Guilleminault et al.24

randomized children with OSA and narrow maxillato either ATE or maxillary distraction. Poly-somnography after 3 months showed residualevents severe enough to warrant the complemen-tary intervention in all children. No numericalvalues were reported.

Mechanical interventionsThe study by Villa et al.26 randomized childrenwith OSA and dysgnathia to either a personalizedjaw-positioning oral appliance for 6 months or nointervention. The authors reported that the AHI inthe intervention group decreased significantlyfrom 7.1 to 2.6/h. However, no AHI values werereported for the untreated group. Thus, no validgroup comparison of post-treatment AHIs waspossible. There was a trend towards a lower riskfor tonsillar hyperplasia (tonsil size> 2) in thetreatment group (relative risk (RR) 0.43; 95%confidence interval (CI) 0.17e1.11). Despite usinga clinical symptom score,31 the authors did notreport the overall score sum but only the break-down of the individual dichotomous items: the oralappliance significantly lowered parent-reportedsnoring (RR 0.18; 95% CI 0.06e0.55) and apnea (RR0.37; 95% CI 0.15e0.90). There was a trendtowards a lower risk for daytime sleepiness (RR0.64; 95% CI 0.11e3.78). A few patients in theintervention group reported excessive salivationthat subsided spontaneously. One child in theintervention group developed an uncontrollableviolent cough when the appliance was in situ, andeventually discontinued treatment.

Marcus et al.17 compared continuous to bilevelpositive airway pressure therapy in children withOSA who were not candidates for ATE. Both ther-apies significantly lowered the AHI at 6 monthscompared to baseline (from 27 to 3/h for the totalgroup). However, there was no difference for anyof the outcomes between the groups. Therefore,the authors decided to report all outcome datacombined for the overall group. Side effects oftherapy were reported for both groups. At 48 h and5 months, 17% and 38% of patients, respectively,complained about nasal symptoms such as

128 S. Kuhle et al.

congestion and rhinorrhea. Recurrent epistaxisoccurred in two children. Nasal symptoms at 5months were more frequent in the continuous thanin the bilevel mode group (p¼ 0.02; no pointestimate given).

Discussion

The current review aimed to evaluate the avail-able evidence on interventions for OSA in children.Despite a broad array of available treatments,there is only limited evidence to support their use.Only five RCTs were identified using a comprehen-sive database search. The quality of the identifiedtrials was high in one study and medium to low inthe remainder.

There are a number of factors that may explainthe low number of trials included in this review.Firstly, only studies that used objective PSGcriteria for the diagnosis of OSA and the outcomeassessment were eligible for inclusion. Conse-quently, a number of potentially eligible studieswere excluded because they did not use sleepstudies for the assessment of their patients.Secondly, the nature of some treatment optionsfor OSA (such as ATE, maxillofacial surgery, oraljaw-positioning appliances, or positive airwaypressure therapy) makes an RCT with adequateblinding difficult if not impossible to conduct.Thirdly, historically, in the pre-Evidence BasedMedicine era the threshold for performing an ATEwas very low (slightly enlarged tonsils and/orrecurrent throat infections would usually suffice).

Table 2 Efficacy of interventions for OSA (primary and sedifference and relative risk, respectively, with 95% confide

Comparison Participants

Intranasal steroids vs. placebo25 n¼ 25Apnea/hypopnea indexOxygen desaturation indexRespiratory arousal indexNadir of SpO2

Mean SpO2

Avoidance of ATEClinical symptom scoreDecrease in tonsillar size

TCRF treatment vs. standard ATE23 n¼ 23RDISnoring score

Abbreviations: ATE, adenotonsillectomy; MD, mean difference; RRablation.A negative value (MD) or a value >1 (RR), respectively, favors thethree studies17,24,26 to determine the effect size estimates.

The frequent use of this intervention establishedthe method as the quasi-standard without everhaving been subjected to rigorous investigation.Finally, the field of pediatric sleep medicine is stillrelatively young; e.g., reference values for over-night PSG were established only relatively recen-tly.32e34 This is reflected in the observation thatmost of the studies included in this review werepublished only in the last 2 years.

Most concerning, there is very little data fromRCTs to support the use of ATE, the current quasi-standard and first-line treatment for OSA.12 Arecent Cochrane review35 found no RCTs on thetopic. The current review identified only two smallRCTs comparing ATE with temperature-controlledradiofrequency ablation23 and maxillary distrac-tion osteogenesis,24 respectively. Despite this lackof evidence, it is highly unlikely that an RCTcomparing ATE with a sham intervention is evergoing to be conducted. Therefore, a systematicreview of methodologically sound observationalstudies that used objective and blinded assess-ment of sleep before and after ATE is required toassess which patient groups are most likely tobenefit from surgery. Another implication of thepredominant position of ATE is that it has nowbecome difficult to enroll children with moderateto severe OSA into an RCT on OSA therapy unlessone arm is surgical therapy. Most studies in thisreview a priori excluded children with severe OSA.Parents of children with OSA may also be reluctantto enroll their children in an RCT evaluatingalternative treatments and instead choose the‘proven’ therapy.

condary outcomes), expressed as post-treatment meannce interval

Statistical method Effect size (95% CI)

MD �7.30 [�15.57, 0.97]MD �2.50 [�7.67, 2.67]MD �1.20 [�5.24, 2.84]MD �1.90 [�5.98, 2.18]MD 0.00 [�0.83, 0.83]RR 1.62 [0.63, 4.16]MD �2.90 [�5.25, �0.55]RR 1.85 [0.74, 4.58]

MD 3.00 [�1.39, 7.39]MD 0.10 [�0.85, 1.05]

, relative risk; TCRF, temperature-controlled radiofrequency

intervention. Insufficient data were provided in the remaining

Interventions for obstructive sleep apnea in children 129

However, there are some alternatives to ATE intreating OSA. Temperature-controlled radio-frequency ablation is a new surgical technique thatuses radiofrequency energy to reduce tonsillarsize. It is less traumatic than conventional ATE andcan be performed in an office setting. If thistechnique proves to be as effective as conven-tional ATE, it may save resources for the healthcare system. The investigators were able to showthat both techniques were equally effective inimproving OSA. However, due to the omission ofdouble-blinding and the small sample size (n¼ 23),evidence from this study can only be consideredpreliminary. Further studies are needed beforea recommendation can be made.

As adenoids and tonsils consist of lymphoidtissue, there has recently been an increasedinterest in the use of anti-inflammatory medica-tions to reduce the size of the lymphoid tissuethereby abolishing nocturnal airway obstruction.The one RCT that investigated the efficacy ofintranasal steroids25 showed a statisticallysignificant reduction of the AHI. However, thereare a number of caveats: first, treatment resul-ted only in a reduction in the number of apneasin most children, not in their complete cessation.Also, the nadir SpO2 did not change in the study.Thus, the children continued to have sleep-related hypoxia of the same magnitude asbefore. Furthermore, the study did not investi-gate the long-term effects and potential harmsof the intervention. Long-term use of steroidsmay lead to systemic side effects such as growthsuppression.36 Another important factor to takeinto account is whether ATE can eventually beavoided by the use of intranasal steroids.Brouillette et al. reported a lower percentage ofchildren undergoing ATE in the treatment arm.However, this was not an a priori specifiedoutcome and the length of the follow-up periodwas not described. It is possible that intranasalsteroids are more effective in specific subsets ofchildren (e.g., those with concurrent allergies/asthma). Unfortunately, the small sample size ofthe trial did not allow for a subgroup analysis. Asit stands, intranasal steroids can only be rec-ommended for short-term use to amelioratesymptoms in children with OSA, e.g., while onthe waiting list for ATE. Of note, another RCTcomparing intranasal steroids against placebo inchildren with sleep-disordered breathing wasrecently completed. Published interim resultsshowed objective ameliorations in sleep frag-mentation and respiratory disturbance in childrenreceiving budesonide for 6 weeks.29 However,the trial also included children with an AHI< 1,

and was thus not eligible for inclusion in thepresent review.

As abnormalities of the maxillo-mandibularanatomy (such as dysgnathia) can contribute to theetiology of OSA by reducing the pharyngeal space,in some patients correct alignment of the jawusing an oral appliance may be successful intreating OSA. The trial assessing the effectivenessof an oral jaw-positioning appliance for thetreatment of OSA in children with dysgnathia26

showed that the intervention resulted in a signifi-cant reduction of the AHI 6 months after treat-ment. However, the trial suffers significantmethodological shortcomings such as inappro-priate randomization and lack of an intention-to-treat analysis (nine out of 32 patients withdrewfrom the study). Further, the authors failed tocompare the post-treatment AHIs in the twogroups and incorrectly concluded (based on theirbeforeeafter analysis of the treatment group) thatan oral appliance is more effective than no inter-vention in reducing the AHI. Another significantproblem is the high frequency of non-compliancewith the intervention; five out of 19 children in thetreatment group dropped out because theyrefused to wear the appliance.

Positive airway pressure therapy to maintainpatency of the upper airway during sleep is thetreatment of choice for OSA in adults. Due to thedifferent pathophysiology of OSA in children andthe low attractiveness of the intervention, positiveairway pressure therapy has been reserved formoderate to severe cases of pediatric OSA who arenot eligible for ATE. Marcus et al.17 comparedcontinuous to bilevel positive airway pressuretherapy in children with OSA who were not candi-dates for ATE. Both therapies significantly loweredthe AHI at 6 months compared to baseline.However, there was no difference in any outcomebetween the groups. Adherence was a major issuein this study. Unfortunately, there was nodescription of the nine drop-outs from this study(31%), and no intention-to-treat analysis was per-formed. Based on the available data, no recom-mendation regarding the use of positive airwaypressure therapy for the treatment of OSA inchildren can be made.

The results from this systematic review mayhave some implications for further research in thisarea. Most importantly, there is a lack of evidenceon the appropriate treatment for OSA in children.High-quality research evaluating the varioustreatment options is urgently needed to be able tomake evidence-based recommendations for themanagement of these children. A substantialnumber of potentially eligible trials had to be

Research agenda

1. Randomized controlled trials comparingdifferent kinds of otolaryngologic interven-tions for OSA in children (e.g., adenotomy,tonsillotomy, tonsillectomy, adeno-tonsillotomy, and adenotonsillectomy) with

130 S. Kuhle et al.

excluded from this review because of the lack ofsleep studies to verify the presence of OSA. Theuse of sleep studies to objectively measure treat-ment efficacy would greatly enhance the quality ofresearch in children with OSA. There is also a needfor more rigorous standards for the assessment ofsleep studies to facilitate between-studycomparisons.

placebo or sham procedure are needed.2. Non-surgical interventions for OSA in chil-

dren should be compared to placebo/shamprocedure and to an effective otolaryngo-logic intervention.

3. Studies on interventions for OSA in chil-dren without adenotonsillar hyperplasiawho are not compliant with ventilation areurgently needed.

4. For the future, outcomes of randomizedcontrolled trials on interventions for OSAin children should include i) polysomno-graphically confirmed severity of OSA, ii)treatment-related side effects andadverse events, iii) compliance withtherapy (if applicable), and iv) improve-ments in disease-related morbidity andquality of life.

Conclusions

Despite a broad array of available treatments forOSA in children, there is only limited evidence tosupport their use. Most concerning, there is verylittle data from RCTs to support the use of ATE, thecurrent quasi-standard and first-line treatment forOSA. Intranasal steroids appear to have a short-termbeneficial effect on the AHI in children with mild tomoderate OSA. However, long-term safety data arenot available. Surgical therapies for OSA (ATE,temperature-controlled radiofrequency ablation)and positive airway pressure therapy have not beentested against no intervention or sham procedures.There is insufficient data to support the use of oralappliances in children with OSA. Carefully designedRCTs are urgently needed to evaluate the varioustreatment options for OSA in children. A substantialnumber of potentially eligible trials had to beexcluded because no sleep studies were performedto verify the presence of OSA. The use of sleepstudies to objectively measure treatment efficacywould greatly enhance the quality of research inchildren with OSA.

Practice points

1. Evidence from well-designed randomizedcontrolled trials for interventions for OSAin children is sparse.

2. Although adenotonsillectomy is the widelyaccepted first-line intervention for OSA inchildren, randomized controlled trialscomparing adenotonsillectomy againstplacebo, sham procedure, or adenotomyare lacking.

3. Most of the non-surgical interventions forOSA in children have not been comparedagainst adenotonsillectomy.

4. Among the non-surgical interventions forOSA in children, nasal steroids are promisingcandidates. However, potential side effectsof steroids, such as growth or adrenalsuppression, need to be considered.

Conflict of interest statement

None to declare.

Acknowledgements

The authors would like to thank Lisa Tjosvold fromthe Cochrane Child Health Field, University ofAlberta, for her help with putting together thesearch strategy.

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