Remission and Incidence of Obstructive Sleep Apnea from Middle Childhood to Late Adolescence

Transcription

1 pii: sp REMISSION AND INCIDENCE OF OSA FROM MIDDLE CHILDHOOD TO LATE ADOLESCENCE Remission nd Incidence of Obstructive Sleep Apne from Middle Childhood to Lte Adolescence Jmes C. Spilsbury, PhD 1 ; Amy Storfer-Isser, PhD 2 ; Crol L. Rosen, MD 3 ; Susn Redline, MD 4 1 Center for Clinicl Investigtion, Cse Western Reserve University School of Medicine, Clevelnd, OH; 2 Sttisticl Reserch Consultnts, Schumburg, IL; 3 Deprtment of Peditrics, University Hospitls-Cse Medicl Center, Cse Western Reserve University School of Medicine, Clevelnd, OH; 4 Deprtment of Medicine, Hrvrd Medicl School, Brighm nd Women s Hospitl nd Beth Isrel Deconess Medicl School, Boston, MA Study Objective: To study the incidence, remission, nd prediction of obstructive sleep pne (OSA) from middle childhood to lte dolescence. Design: Longitudinl nlysis. Setting: The Clevelnd Children s Sleep nd Helth Study, n ethniclly mixed, urbn, community-bsed cohort, followed 8 y. Prticipnts: There were 490 prticipnts with overnight polysomnogrphy dt vilble t ges 8 11 nd y. Mesurements nd Results: Bseline prticipnt chrcteristics nd helth history were scertined from prent report nd US census dt. OSA ws defined s n obstructive pne- hypopne index 5 or n obstructive pne index 1. OSA prevlence ws pproximtely 4% t ech exmintion, but OSA lrgely did not persist from middle childhood to lte dolescence. Hbitul snoring nd obesity predicted OSA in crosssectionl nlyses t ech time point. Residence in disdvntged neighborhood, Africn-Americn rce, nd premture birth lso predicted OSA in middle childhood, wheres mle sex, high body mss index, nd history of tonsillectomy or denoidectomy were risk fctors mong dolescents. Obesity, but not hbitul snoring, in middle childhood predicted dolescent OSA. Conclusions: Becuse OSA in middle childhood usully remitted by dolescence nd most dolescent cses were incident cses, criteri other thn concern lone over OSA persistence or incidence should be used when mking tretment decisions for peditric OSA. Moreover, OSA s distinct risk fctors t ech time point underscore the need for lterntive risk-fctor ssessments cross peditric ges. The greter importnce of middle childhood obesity compred to snoring in predicting dolescent OSA provides support for screening, preventing, nd treting obesity in childhood. Keywords: dolescents, children, incidence, obstructive sleep pne, remission Cittion: Spilsbury JC, Storfer-Isser A, Rosen CL, Redline S. Remission nd incidence of obstructive sleep pne from middle childhood to lte dolescence. SLEEP 2015;38(1): INTRODUCTION Obstructive sleep pne (OSA) ffects 1 4% of children nd dolescents 1 4 nd is ssocited with behviorl, cognitive, nd physiologicl deficits. 5 7 Epidemiologicl dt, minly crosssectionl, hve identified severl peditric risk fctors: premture birth, Africn-Americn rce, obesity, nd residence in disdvntged neighborhood 2,8 ; denotonsillr hypertrophy 9 ; Hispnic ethnicity 10 ; crniofcil bnormlities 11 ; nd history of upper nd lower respirtory disese. 12 Longitudinl reserch ddressing the incidence nd vrition of OSA risk fctors cross peditric ges is reltively limited. 1,7,13 20 Previous longitudinl studies using polysomnogrphy (PSG) reported tht pproximtely 8 10% of children with primry snoring progress to OSA over 1- to 3-y period, 1,15,16 lthough recent community-bsed study of children with longer follow-up period (4.6 y on verge) reported tht more thn one-third progressed to OSA defined s n obstructive pne-hypopne index (OAHI) 1 event per hour. 21 A popultion-bsed study of 6- to 12-y-old children followed 5 yers reported sleep disordered brething (SDB) incidence A commentry on this rticle ppers in this issue on pge 11. Submitted for publiction Februry, 2014 Submitted in finl revised form My, 2014 Accepted for publiction June, 2014 Address correspondence to: Jmes C. Spilsbury, PhD, Center for Clinicl Investigtion, 2103 Cornell Rod, Office 6127, Clevelnd, OH ; Tel: (216) ; Emil: jcs5@cse.edu rte of 10%, defined s respirtory disturbnce index 1 event per hour. 18 Chrcteristics ssocited with SDB incidence or remission re not well understood. Mle sex hs been ssocited with risk of primry snoring 1,19,20 nd incident nd persistent SDB. 18 However, study of more thn 12,000 UK children followed from infncy to erly childhood reported tht over time, the ssocition of SDB symptoms with child-level fctors decresed, wheres fctors relted to socil conditions persisted. 17 Furthermore, lthough SDB predicts future body mss index (BMI), 18 only two longitudinl studies hve ddressed whether BMI predicts future OSA. The first study involved smll, clinic-bsed smple of primry snorers nd reported no significnt chnge in BMI in the smple t the pproximtely 2-y follow-up. 15 The second study, community-bsed smple, reported tht persistent obesity (obesity t both bseline nd 4.6-y follow-up) but not bseline obesity lone predicted OSA t follow-up. 21 However, the study smple once gin ws limited to primry snorers only. To improve understnding of OSA s epidemiology in children nd dolescents, we report the results of longitudinl study of objectively mesured OSA in community-bsed child cohort tht included substntil number of Africn Americns nd children born premturely, two groups with incresed risk for OSA during erly nd middle childhood. 2,22 The study s primry purpose ws to exmine OSA incidence nd remission from middle childhood (ge 8 11 y) through lte dolescence (ge y) nd ssess whether risk fctors for OSA in middle childhood remined so in dolescence. Becuse risk fctors my chnge with growth nd development, SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

2 especilly s irwy size nd centrl body ft increse while lymphoid tissue regresses, we hypothesized tht obesity would more strongly ssocite with OSA in dolescence compred to middle childhood. Secondry objectives were to exmine other subject chrcteristics relted to OSA in lte dolescence; ssess OSA incidence in primry snorers; nd explore how lterntive OSA definitions ffect incidence rtes. METHODS Smple The study smple consisted of prticipnts in the longitudinl Clevelnd Children s Sleep nd Helth Study cohort, 2 strtified rndom smple of 907 term nd preterm children born from t three mjor Clevelnd-re hospitls. Africn Americn nd former preterm children were intentionlly overrepresented to increse internl vlidity nd produce stble estimtes of ssocitions between OSA nd helth outcomes for these subgroups. This nlysis includes mesurements from two key developmentl time points: middle childhood (dt collected , child ge 8 11 y) nd lte dolescence (dt collected from , children ge y); 517 prticipted in both exmintions (Figure S1, supplementl mteril). Prticipnt nd fmily chrcteristics for who did (n = 517) nd did not (n = 390) prticipte in the lte dolescent follow-up exmintion were similr except tht greter proportion of youth prticipting in both exmintions hd cregivers with eduction greter thn high school: 59% versus 41%, P = 0.02 (Tble S1, supplementl mteril). Procedures Prents (or legl gurdins) nd dolescents (18 y or older) provided informed, written consent. Children provided ssent. The University Hospitls of Clevelnd s institutionl review bord pproved the study. Middle Childhood Assessment Dt collection detils hve been described previously. 2 Assessments occurred in prticipnts homes. Demogrphic nd medicl dt were obtined by prent-completed, stndrdized questionnire. 23 In-home sleep pne monitoring ws conducted with Type III sleep monitor recording thorcic nd bdominl excursions nd estimted tidl volume, pulse oximetry, hert rte, nd body position (PT-2 system, SensorMedics, Yorb Lind, CA). Respirtory events were scored if 8 sec (or two or more missed respirtory cycles). Obstructive pnes were scored when chest nd bdominl efforts were synchronous nd estimted tidl volume ws bsent or nerly bsent, irrespective of ssocited desturtion. Hypopnes were scored when respirtory efforts were ccompnied by 50% reduction in estimted tidl volume nd ccompnied by 3% oxyhemoglobin desturtion. Adolescent Assessment Overnight PSG nd physiologicl nd nthropometric ssessments, including physicin-dministered physicl exmintion, followed stndrdized protocol t the reserch center, beginning t pproximtely 17:00 nd ending the following dy t 11:00. 24,25 The PSG recording (Compumedics E-series; Compumedics, Abbotsford, Austrli) consisted of mesurement of two electroencephlogrms (C 3 /C 2 nd C 4 / C 1 ), bilterl electrooculogrms, bipolr submentl electromyogrm, thorcic nd bdominl respirtory inductnce plethysmogrphy, irflow (nsl orl thermocouple nsl pressure recording), finger-pulse oximetry, electrocrdiogrm, body position, nd bilterl leg movements. Obstructive pnes were scored when complete or nerly complete bsence of irflow occurred on the thermistry chnnel for 10 sec in ssocition with respirtory effort. Hypopnes were identified s n pproximtely 50% reduction in irflow or summed respirtory excursions ssocited with n oxygen desturtion 3% (see supplementl methods for dditionl protocol informtion). For both exmintions, the OAHI ws defined s ll obstructive or mixed pnes nd hypopnes with 3% desturtion per sleep hour. Study Mesures Prticipnt chrcteristics such s rce/ethnicity (Africn Americn versus other); history of OSA, tonsillectomy or denoidectomy; physicin-dignosed sthm; mternl smoking; hbitul snoring ( 1 2 times per week during the pst month); nd cregiver eduction were obtined from prent or dolescent. Preterm sttus (gesttionl ge < 37 w) ws obtined from hospitl birth records. Tonsil size ws scertined by physicin exm using five-point scle (see supplementl methods). Residence in socioeconomiclly distressed neighborhood ws determined using US census dt per estblished procedures (see supplementl methods). 8,26 BMI (kg/ m 2 ), bsed on direct height nd weight mesurement, ws converted into ge- nd sex-djusted percentiles ( cdc.gov/growthchrts/). Obesity ws defined s BMI 95th percentile for ge nd sex. The primry study outcome, OSA, ws defined s n OAHI 5 or n obstructive pne index (OAI) 1. Secondry outcomes were: (1) SDB, defined s OSA, hbitul snoring, or both; nd (2) OSA defined s n OAHI 1. Sttisticl Anlyses Study vribles were summrized using mens (M) nd stndrd devitions (SD) for normlly distributed vribles, medins nd interqurtile rnges for mrkedly nonnormlly distributed vribles, counts nd proportions for ctegoricl vribles, nd included two-smple t-tests, Wilcoxon rnk-sum tests, nd chisqure tests. The concordnce of OSA (nd SDB) in middle childhood nd dolescence were exmined using McNemr test. Log-binomil models ssessed the reltion of previously identified risk fctors with OSA in dolescence; reltive risk rtios (RR) nd 95% confidence intervls (95% CI) re presented. Models were estimted without covrite djustment nd fter djusting for BMI z-score t either ge 8 11 y or y. Secondry nlyses exmined ssocitions restricted to full-term births or nonobese prticipnts t ge 8 11 y, nd ssocition of hbitul snoring in middle childhood with incident OSA t ge y. Logistic regression nlyses exmined the crosssectionl ssocition of prticipnt chrcteristics with OSA (see supplementl methods); odds rtios (OR) nd 95% CI re reported. Anlyses were performed using SAS (SAS Institute, Inc., Cry, NC). SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

3 RESULTS Smple Chrcteristics The nlytic smple consisted of 490 prticipnts for whom PSG dt were vilble both t middle childhood (M = 9.5, SD = 0.8 y) nd lte dolescence (M = 17.7, SD = 0.4 y). The men time between visits ws 8.2 y (SD = 0.7 y). Approximtely hlf of the smple ws mle, 36.5% were Africn Americn, nd 44.1% were premture t birth (see supplementl results for detils). At the middle childhood exmintion, 22.1% lived in distressed neighborhood, 15.1% were obese, 7.1% hd history of tonsillectomy or denoidectomy, nd 19.6% reported doctor s dignosis of sthm. At the lte dolescence exmintion, obesity prevlence incresed to 19.4%; tonsillectomy or denoidectomy to 12.0%, nd n sthm dignosis to 28.8%. OSA Prevlence, Remission, nd Incidence From Middle Childhood to Lte Adolescence OSA prevlence ws 4.7% mong 8- to 11-y-olds nd 4.3% mong 16- to 19-y-olds. OSA did not persist from middle childhood to lte dolescence. Only two of the 23 prticipnts (8.7%) with OSA t ge 8 11 y hd OSA t ge y (P = 0.75) (Figure 1). Five of the 21 children whose OSA remitted by dolescence underwent tonsillectomy or denoidectomy between exmintions (Figure 1). Of the 467 children without OSA in middle childhood, 19 (4.0%) hd incident OSA t lte dolescence. Predictors of OSA in Middle Childhood nd Lte Adolescence As we reported before, 2,8 comprison of children with nd without OSA t 8 11 y reveled tht significntly greter proportion of children with OSA were Africn Americn, of preterm birth, living in distressed neighborhood, nd hbitul snorers (Tble 1). However, none of these chrcteristics predicted OSA t y in undjusted nlyses (Tbles 1 nd 2) or in BMI-djusted nlyses (Tble 2). Similr results were observed in secondry nlyses strtified by term sttus (Tble S2, supplementl mteril) nd secondry nlyses restricted to nonobese prticipnts (Tble S3, supplementl mteril). Child chrcteristics t ge 8 11 y tht were ssocited with OSA t ge yers were mle sex, obesity, higher BMI z-score, nd history of tonsillectomy or denoidectomy (Tble 1). Cross-sectionl, undjusted nlyses of chrcteristics t ge y reveled tht BMI z-score, obesity, mle sex, history of tonsillectomy or denoidectomy, sthm, nd hbitul snoring were positively ssocited with dolescent OSA (Tbles 3 nd 4). After djusting for BMI z-score, mle sex nd history of tonsillectomy or denoidectomy remined significnt (Tble 4). In secondry BMI-djusted nlyses restricted to full-term prticipnts, mles nd prticipnts with sthm hd significntly incresed odds of dolescent OSA (Tble S4, supplementl mteril). Hbitul Snoring nd OSA Hbitul snoring t ge 8 11 y ws not significntly ssocited with incident OSA t ge y. Among the 68 children without OSA who hbitully snored t 8 11 y, 5 (7.3%) developed OSA t ge y. In comprison, 14 of the 397 individuls without OSA who were nonsnorers (3.5%) developed Figure 1 Incidence nd remission of OSA from middle childhood to lte dolescence. Middle Childhood Exm 8 11 yers Group 23 with OSA 467 without OSA Tonsillectomy or denoidectomy before middle childhood exm Adolescence Exm yers 2 with OSA 21 without OSA b 19 with OSA c 448 without OSA d Tonsillectomy or denoidectomy between exms 0 1 b 2 5 c 7 1 d No children were receiving CPAP therpy t the time of the middlechildhood exm. At the dolescent exm, 5 children hd been prescribed CPAP, but none were using it. OSA (undjusted RR = 2.09; 95% CI: 0.78, 5.60; BMI-djusted RR = 1.55; 95% CI: 0.57, 4.27). Among the 513 prticipnts with vilble snoring dt (cregiver or self-report) t both time points, 16.2% of the 8- to 11-y-olds nd 22.4% of the dolescents were hbitul snorers. Hlf (50.6%) of the hbitul snorers t ge 8 11 y remined so t ge y (P = 0.003). Seventeen percent of the 430 nonsnorers t ge 8 11 y developed hbitul snoring by ge y. Alterntive OSA nd SDB Definitions Undjusted nlyses using broder definition of SDB (PSGmesured OSA, hbitul snoring, or both) showed tht SDB in dolescence ws ssocited with dolescent BMI z-score, mle sex, Africn Americn bckground, previous tonsillectomy or denoidectomy, nd sthm (Tble S5, supplementl mteril). All covrites except sthm retined significnce in model djusted for ll chrcteristics simultneously. Sensitivity nlyses redefining OSA using threshold of OAHI 1 showed tht 47.2% of the 53 children now clssified s hving OSA t ge 8 11 y lso hd OSA t ge y (P < 0.001), nd 27.7% of the 437 children without OSA t 8 11 y developed OSA by y. Moreover, 31.7% of the children with hbitul snoring but not OSA t 8 11 y developed OSA t ge y, using the redefinition of OSA t both time points. DISCUSSION Knowledge bout OSA s nturl history during childhood nd dolescence is scnt, limiting clinicl decision-mking. SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

4 Tble 1 Prticipnt chrcteristics by OSA sttus, t middle childhood (ge 8 11 y) nd lte dolescent exmintions (ge y) (N = 490); Clevelnd Children s Sleep nd Helth Cohort. OSA Age 8 11 y OSA Age y Child Chrcteristics (Age 8 11 y) No (n = 467) Yes (n = 23) No (n = 469) Yes (n = 21) Age t bseline, y 9.5 ± ± ± ± 0.9 Mle 237 (50.8%) 9 (39.1%) 225 (48.0%) 21 (100%) b Africn Americn 164 (35.1%) 15 (65.2%) b 168 (35.8%) 11 (52.4%) Preterm 201 (43.0%) 15 (65.2%) 206 (43.9%) 10 (47.6%) BMI z-score 0.28 ± ± ± ± 1.34 b Obese (BMI 95 th percentile) 71 (15.2%) 3 (13.0%) 65 (13.9%) 9 (42.9%) b Hbitul loud snoring 68 (14.6%) 13 (56.5%) b 75 (16.1%) 6 (28.6%) Tonsillry size grde c 0 or (35.6%) 146 (31.3%) %) 26 (5.6%) 3 (13.0%) 7 (30.4%) 12 (52.2%) 1 (4.4%) 162 (34.6%) 148 (31.6%) 133 (28.4%) 25 (5.3%) 7 (33.3%) 5 (23.8%) 7 (33.3%) 2 (9.5%) History of tonsillectomy 18 (3.9%) 1 (4.4%) 16 (3.4%) 3 (14.3%) History of tonsillectomy or denoidectomy 33 (7.1%) 2 (8.7%) 28 (6.0%) 7 (33.3%) b Neighborhood distress 95 (20.3%) 13 (56.5%) b 102 (21.8%) 6 (28.6%) Doctor dignosis of sthm 90 (19.3%) 6 (26.1%) 89 (19.0%) 7 (33.3%) Prent history of OSA 25 (5.4%) 3 (13.0%) 27 (5.8%) 1 (4.8%) P < b P < c Grde 0 = tonsils bsent, within tonsillr foss, or just outside of the tonsillr foss; grde 1 = tonsils occupy 25% of the orophryngel width; grde 2 = tonsils occupy 26 50% of the orophryngel width; grde 3 = tonsils occupy 51 75% of the orophryngel width; grde 4 = tonsils occupy > 75% of the orophryngel width. BMI, body mss index; OSA, obstructive sleep pne. Tble 2 Undjusted nd body mss index-djusted reltive risk of obstructive sleep pne t ge y. Erly, ggressive OSA dignosis in erly childhood my be pproprite if OSA persists or progresses over time. However, if OSA usully remits, then erly dignosis my be less criticl thn ongoing evlution of OSA-relted symptoms nd signs cross childhood. The Childhood Adenotonsillectomy Tril s recent report estimted tht 49% of 5- to 9-y-old tonsillectomy cndidtes rndomized to wtchful witing hd remission of PSG evidence for OSA fter 7 mo. 27 To our knowledge, this is the first report of OSA s nturl history from middle childhood to dolescence nd its ssocited risks bsed on objectively determined OSA sttus in community-bsed cohort with substntil representtion of Africn Americn nd former preterm children, groups previously ssocited with incresed OSA risk. 2 In this study, pproximtely 4% of children nd dolescents met conservtive criterion for OSA (OAHI 5) t ech time point. However, different children were ffected during middle childhood nd dolescence, indicting tht OSA identified in Adjusted for BMI z-score t Age 8 11 Adjusted for BMI z-score t Age y Undjusted Subject Chrcteristics t Age 8 11 y Africn Americn 1.91 (0.83, 4.41) 1.66 (0.72, 3.84) n/e Preterm 1.15 (0.50, 2.66) 1.28 (0.56, 2.93) 1.21 (0.54, 2.71) Neighborhood distress 1.41 (0.56, 3.56) 1.32 (0.53, 3.28) 1.15 (0.48, 2.79) BMI z-score 1.77 (1.18, 2.67) n/ n/e P < BMI, body mss index; CI, confidence intervl; n/, not pplicble; n/e, not estimble; OSA, obstructive sleep pne; RR, reltive risk. community-bsed smple rrely persists from middle childhood through lte dolescence: During our 8-y period, 91% of middle childhood cses remitted. Most dolescents with OSA were incident cses, occurring in individuls without either OSA or hbitul snoring erlier in childhood. Hbitul snoring displyed greter persistence: hlf of hbitul snorers in middle childhood remined so in dolescence, lthough most of them did not progress to OSA t lte dolescence, using our conservtive criterion for OSA. Persistence nd lck of progression of hbitul snoring hs been reported elsewhere. 14,19 However, recent report from Chinese community-bsed cohort of 6- to 13-y-old children with primry snoring followed pproximtely 4 y found tht 37.1% of the children progressed from primry snoring to OSA, using liberl OSA definition (OAHI 1). 21 We obtined similr result (31.7%) when we used this OSA definition in sensitivity nlyses. The clinicl significnce of the temporl concordnce of these milder SDB forms is uncler. SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

5 Tble 3 Prticipnt chrcteristics by obstructive sleep pne sttus, t the lte dolescent exmintion (ge y) (N = 515). Adolescent Chrcteristics OSA Age y (Age y) No (n = 491) Yes (n = 24) Age, y 17.7 ± ± 0.5 Mle 238 (48.5%) 22 (91.7%) b Africn Americn 180 (36.7%) 11 (45.8%) Preterm 211 (43.0%) 11 (45.8%) BMI z-score 0.56 ± ± 1.13 b Obese (BMI 95 th percentile) 86 (17.5%) 14 (58.3%) b Hbitul loud snoring 104 (21.3%) 10 (41.7%) Tonsillry size grde c 0 or (59.7%) 145 (31.1%) 51 (10.9%) 1 (0.2%) 17 (70.8%) 5 (27.8%) 1 (5.6%) 0 (0%) History of tonsillectomy 33 (6.7%) 6 (25.0%) b History of tonsillectomy or 41 (10.4%) 10 (41.7%) b denoidectomy Doctor dignosis of sthm 132 (28.0%) 12 (50.0%) Prent history of OSA 50 (11.2%) 1 (4.8%) P < b P < c Grde 0 = tonsils bsent, within tonsillr foss, or just outside of the tonsillr foss; grde 1 = tonsils occupy 25% of the orophryngel width; grde 2 = tonsils occupy 26%-50% of the orophryngel width; grde 3 = tonsils occupy 51%- 75% of the orophryngel width; grde 4 = tonsils occupy > 75% of the orophryngel width. Our observed rtes for OSA persistence (8.7%) nd incidence (4% over 8.2 y) were much lower thn those reported from southwestern US cohort of White nd Hispnic children ge 6 to 17 y (Tucson Children s Assessment of Sleep Apne Study, or TuCs), which found 29% SDB persistence from bseline (M = 8.5 y) to follow-up (M = 14.7 y) nd 10% incidence over 5 y. 18 The lrge rte differences between the two longitudinl studies underscore the sensitivity of OSA to the event definitions used (TuCs used threshold of one event per hour nd included centrl events). When we explored using n OSA definition similr to TuCs (OAHI 1), our OSA incidence incresed from 4.0% to 27.7%, nd persistence incresed from 8.7% to 47.2%. Similr to findings in children followed from infncy to erly childhood, 17 our findings reveled little overlp in OSA risk fctors in middle childhood compred to lte dolescence. Congruent with our previous reports, 2,8 Africn Americn rce, preterm sttus, nd neighborhood distress were risk fctors for OSA t ge 8 11 y, but not in dolescence. In contrst, new risk fctors emerged: mle sex nd history of tonsillectomy or denoidectomy. Additionlly, dolescents with OSA hd greter BMI compred to their peers without OSA both t dolescence nd t middle childhood, even though most of them did not hve OSA when younger. The ssocition of obesity with development of OSA hs been similrly reported mong children with primry snoring. 21 Although the ssocition between sthm nd OSA ws prtilly confounded with obesity nd sex, higher OSA rte in children with sthm is consistent Tble 4 Cross-sectionl odds rtios of obstructive sleep pne t ge y (N = 515; n = 24 with obstructive sleep pne). Subject Chrcteristics t Age y Undjusted Adjusted for BMI z-score t Age y BMI z-score 2.67 (1.68, 4.24) b n/ Mle (2.72, 50.27) b (2.45, 46.16) b Africn Americn 1.46 (0.64, 3.33) 1.07 (0.46, 2.53) Preterm 1.12 (0.49, 2.56) 1.19 (0.51, 2.76) Neighborhood distress 1.18 (0.46, 3.04) 1.03 (0.39, 2.73) History of tonsillectomy 4.63 (1.72, 12.44) b 3.37 (1.18, 9.62) History of tonsillectomy 6.16 (2.60, 14.59) b 4.81 (1.96, 11.85) b or denoidectomy Asthm 2.58 (1.13, 5.88) 2.14 (0.91, 5.03) Hbitul loud snoring 2.65 (1.14, 6.13) 1.60 (0.66, 3.88) P < b P < BMI, body mss index; CI, confidence intervl. with prior dt. 28 Explortory nlyses strtified the smple by obesity or by full-term/preterm sttus. Although smple sizes were smll, observed ssocitions were generlly similr to those for the full smple, except for possibly stronger ssocitions between OSA nd history of tonsillectomy or denoidectomy mong former preterm prticipnts, nd between OSA nd sthm mong full-term prticipnts (Tbles S2-S4). The identifiction of mle sex s n dolescent OSA risk fctor mirrors previous reports. 18,20 Sex effects hve been reported to be weker in prepubertl children. 17 These findings indicte tht sex differences my differentilly modulte OSA risk in children in peripubertl nd postpubertl periods Africn Americn rce ws more strongly ssocited with OSA in younger compred to older children, for uncler resons. Africn Americn rce likely represents combintion of socioculturl, environmentl, nd genetic risk fctors whose influence my vry in ssocition with growth nd development. Perhps the OR = 1.91 for Africn Americn rce for dolescent OSA, though elevted, filed to rech significnce given the reltively smll number of children with OSA in this community-bsed smple. The significnt ssocition observed between SDB nd Africn Americn rce mong dolescents supports this notion. Hbitul snoring ws ssocited with OSA t ech time point. However, snoring during middle childhood did not predict dolescent OSA using our conservtive definition of OSA, indicting the greter importnce of middle childhood obesity compred to snoring in predicting dolescent OSA, nd providing further support for preventing nd treting obesity in childhood. Also, snoring, though reltively stble cross the ges of 8 18 y nd ssocited with OSA cross-sectionlly, did not by itself strongly predict incident OSA, finding congruent with tht reported for smll clinicl smple of younger children. 15 Antomicl nd developmentl chnges my prtilly explin shifts in OSA risk fctors from childhood through dolescence. Across childhood, lrge chnges occur in upper irwy ntomy nd phryngel irwy collpsibility, 32 nd in body SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

6 ft distribution, tonsillr size, lung size, nd hormonl levels. Younger children my be more sensitive to environmentl irritnts nd to the effects of smller lung volumes or centrl ventiltory instbility ssocited with premturity, wheres older children with lrger lung volumes nd phryngel dimensions my be more susceptible to influences ssocited with obesity nd mle sex, reflecting the dynmic complexity of fctors influencing irwy size nd ptency cross childhood. Of note, history of tonsillectomy or denoidectomy ws n OSA risk fctor t ge y. OSA in children who hve hd tonsillectomy hs been ssocited with fmilil risk of OSA 33 nd suggests tht history of tonsillectomy my identify children t risk for OSA becuse of fctors extending beyond lymphoid hypertrophy 34 (i.e., history of tonsillectomy or denoidectomy is functioning s mrker of other risk fctors). Furthermore, children whose tonsils nd/or denoids were removed my not hve been cured, especilly if they were obese or Africn Americn, two groups in whom symptoms re less likely to resolve fter surgery. 12,33 Study limittions should be noted. First, certin methodologicl spects of the study might hve underestimted or overestimted OSA. For exmple, technologicl ssessments of OSA differed cross time points, nd results of recent study compring overnight polysomnogrphy with respirtory polygrphy (similr to our in-home method) indicte tht AHI clculted in home studies my be underestimted becuse of (1) missed hypopnes cusing rousls without desturtion nd (2) use of totl recording time s the denomintor insted of totl sleep time, which cn be derived from polysomnogrphy. 35 Also, pproximtely 20% of prticipnts t ech time point hd sthm. Children with sthm re more likely to experience desturtions (especilly in rpid eye movement), which re likely cused by their lung condition nd underlying sleep neurobiology, not obstruction per se, 36 potentilly leding to n over-estimtion of OSA in this popultion. Regrding misestimtions, we cn note tht in our study, smple of children studied with both in-lbortory nd in-home studies showed good greement in AHI mesured using both techniques, 2 nd it ws unlikely tht use of two techniques resulted in identifying unique groups of children t ech exmintion. Second, using common definition for OSA in peditric popultions is chllenging. Our primry nlysis used conservtive definition to mximize comprbility nd clinicl relevnce in dolescents. Secondry nlyses showed tht prevlence nd incidence rtes incresed mrkedly s thresholds for bnormlity were lowered. Third, representtion of Hispnic nd Asin children ws smll, limiting generlizbility. Fourth, over the 8-y follow-up period, only of the originl cohort ws studied. However, prticipnts who were nd were not followed up were similr, except tht cregiver eduction ws lower for those who were not followed up. Finlly, the reltively few OSA cses limited power to detect weker risk fctors nd precluded djusting for multiple confounders. In conclusion, study findings suggest tht dolescents present with more dult-like OSA profile, 37 which hs importnt implictions for peditric screening for OSA through clinicl history: specificlly, screening must be tilored to specific ge rnges. Perhps estblishing ge-bsed cutoffs of AHI scores for dignosis of OSA (e.g., more liberl cutoff for younger ges, nd more conservtive cutoff for older ges) might lso be pproprite. At this point in time, more reserch is needed to identify the most pproprite cutoffs for dverse helth outcomes in children, teens, nd young dults. Findings lso underscore the need to prevent obesity in erly childhood, which my reduce the likelihood of dolescent OSA. Children who hve hd tonsillectomy or denoidectomy re t incresed risk for dolescent OSA becuse they likely hve dditionl risk fctors for OSA nd should be monitored for OSA symptoms nd signs. In the community, untreted OSA in middle childhood usully does not persist. Similrly, hbitul snoring usully does not progress to OSA from middle childhood to dolescence. However, this lck of progression does not men tht hbitul snoring is unimportnt or hrmless. Ultimtely, concerns bout ptients current symptoms nd sequele should guide decisions regrding surgery for the full spectrum of peditric SDB, not just concerns over persistence or incidence of OSA. ACKNOWLEDGMENTS The uthors grtefully cknowledge the fmilies prticipting in the CCSHS, whose generosity mde this study possible. DISCLOSURE STATEMENT This ws not n industry supported study. The study ws supported by NIH HL07567, HL60957, UL1-RR024989, the Cse Western Reserve University Trnsdisciplinry Reserch in Energetics nd Cncer Center (1U54CA116867) nd Hrvrd Trnsdisciplinry Reserch in Energetics nd Cncer Center (1U54CA155626). Dr. Spilsbury hs received reserch grnt support from the Ntionl Institutes of Helth nd the Willim T. Grnt Foundtion. Dr. Redline reports tht Brighm nd Women s Hospitl received grnt from ResMed Foundtion nd ResMed Inc. nd equipment from both ResMed Inc nd Philips-Respironics for use in clinicl trils. The other uthors hve indicted no finncil conflicts of interest. REFERENCES 1. Anuntseree W, Kusirikul S, Suntornlohnkul S. Nturl history of snoring nd obstructive sleep pne in Thi school-ge children. Peditr Pulmonol 2005;39: Rosen CL, Lrkin EK, Kirchner HL, et l. Prevlence nd risk fctors for sleep-disordered brething in 8- to 11-yer-old children: ssocition with rce nd premturity. J Peditr 2003;142: Schlud M, Urschitz MS, Urschitz-Duprt PM, Poets CF. The Germn study on sleep-disordered brething in primry school children: epidemiologicl pproch, representtives of study smple, nd preliminry screening results. Peditr Perint Epidemiol 2004;18: Sogut A, Altin R, Uzun L, et l. Prevlence of obstructive sleep pne syndrome nd ssocited symptoms in 3-11-yer old Turkish children. Peditr Pulmonol 2005;39: Owens JA. Neurocognitive nd behviorl impct of sleep disordered brething in children. Peditr Pulmonol 2009;44: Mitchell RB, Kelly J. Behvior, neurocognition, nd qulity-of-life in children with sleep-disordered brething. Int J Peditr Otorhinolryngol 2006;70: Bonuck KA, Prikh S, Bssil M. Growth filure nd sleep disordered brething: review of the literture. Int J Pedit Otorhinolryngol 2006;70: Spilsbury JC, Storfer-Isser A, Kirchner HL, et l. Neighborhood disdvntge s risk fctor for peditric obstructive sleep pne. J Peditr 2006;149: SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

7 9. Mrcus CL, Brooks LJ, Drper KR, et l. Dignosis nd mngement of childhood obstructive sleep pne syndrome. Peditrics 2012;130:e Goodwin JL, Bbr SI, Kemingk KL, et l. Symptoms relted to sleep-disordered brething in White nd Hispnic children: the Tucson children s ssessment of sleep pne study. Chest 2003;124: Ckirer B, Hns MG, Grhm G, Aylor J, Tishler PV, Redline S. The reltionship between crniofcil morphology nd obstructive sleep pne in Whites nd in Africn-Americns. Am J Respir Crit Cre Med 2001;163: Redline SS, Tishler PV, Schluchter M, Aylor J, Clrk K, Grhm G. Risk fctors for sleep-disordered brething in children: ssocitions with obesity, rce, nd respirtory problems. Am J Respir Crit Cre Med 1999;159: Ali NJ, Pitson D, Strdling JR. Nturl history of snoring nd relted behviour problems between the ges of 4 nd 7 yers. Arch Dis Child 1994;71: Chervin RD, Ruzick DL, Archbold KH, Dillon JE. Snoring predicts hyperctivity four yers lter. Sleep 2005;28: Mrcus CL, Hmer A, Loughlin GM. Nturl history of primry snoring in children. Peditr Pulmonol 1998;26: Topol HI, Brooks LJ. Follow-up of primry snoring in children. J Peditr 2001;138: Bonuck KA, Chervin RD, Cole TJ, et l. Prevlence nd persistence of sleep disordered brething symptoms in young children: 6-yer popultion-bsed cohort study. Sleep 2011;34: Goodwin JL, Vsquez MM, Silv GE, Qun SF. Incidence nd remission of sleep-disordered brething nd relted symptoms in 6- to 17-yer old children--the Tucson children s ssessment of sleep pne study. J Peditr 2010;157: Urschitz MS, Guenther A, Eitner S, et l. Risk fctors nd nturl history of hbitul snoring. Chest 2004;126: Snchez-Armengol A, Ruiz-Grci A, Crmon-Bernl C, et l. Clinicl nd polygrphic evolution of sleep-relted brething disorders in dolescents. Eur Respir J 2008;32: Li AM, Zhu Y, Au CT, et l. Nturl history of primry snoring in schoolged children: 4-yer follow-up study. Chest 2013;143: Weinstock TG, Mrcus CL, Amin RS, et l. Obstructive sleep pne severity nd ssocited co-morbidities in cndidtes for denotonsillectomy: the Childhood Adenotonsillectomy (CHAT) Study. Am J Respir Crit Cre Med 2012:A Kump K, Whlen C, Tishler PV, et l. Assessment of the vlidity nd utility of sleep-symptom questionnire. Am J Respir Crit Cre Med 1994;150: Redline S, Storfer-Isser A, Rosen CL, et l. Assocition between metbolic syndrome nd sleep-disordered brething in dolescents. Am J Respir Crit Cre Med 2007;176: Weiss A, Xu F, Storfer-Isser A, Thoms A, Ievers-Lndis CE, Redline S. The ssocition of sleep durtion with dolescents ft nd crbohydrte consumption. Sleep 2010;33: O Hre W, Mther M. The growing number of kids in severely distressed neighborhoods: evidence from the 2000 Census. Bltimore, MD: the Annie E. Csey Foundtion nd Popultion Reference Bureu, Accessed June 24, Avilble t: journls/cye/13_2/reprints13_2/kidsindistressedneighborhoods/ SeverelyDistressedNeighborhoods.pdf 27. Mrcus C, Moore R, Rosen C, et l. A rndomized tril of denotonsillectomy for childhood sleep pne (CHAT). N Engl J Med 2013;368: Ross KR, Hrt MA, Storfer-Isser A, et l. Obesity nd obesity relted co-morbidities in referrl popultion of children with sthm. Peditr Pulmonol 2009;44: Cistulli P, Grunstein R, Sullivn C. Effect of testosterone dministrtion on upper irwy collpsibility during sleep. Am J Respir Crit Cre Med 1994;149: Fuentes-Prder MA, Snchez-Armengol A, Cpote-Gil F, et l. Effects of sex on sleep-disordered brething in dolescents. Eur Respir J 2004;23: Lin CM, Dvidson TM, Ancoli-Isrel S. Gender differences in obstructive sleep pne nd tretment implictions. Sleep Med Rev 2008;12: Arens R, Mrcus CL. Pthophysiology of upper irwy obstruction: developmentl perspective. Sleep 2004;27: Morton S, Rosen C, Lrkin E, Tishler P, Aylor J, Redline S. Predictors of sleep-disordered brething in children with history of tonsillectomy nd/or denoidectomy. Sleep 2001;54: Guilleminult C, Hung Y, Glmnn C, Li K, Chn A. Adenotonsillectomy nd obstructive sleep pne in children: prospective survey. Otolryngol Hed Neck Surg 2007;136: Tn HL, Gozl D, Rmirez HM, Bndl HPR, Kheirndish-Gozl L. Overnight polysomnogrphy versus respirtory polygrphy in the dignosis of peditric obstructive sleep pne. Sleep 2014;37: Perez GF, Gutierrez MJ, Shhlnoor H, et l. Oximetry signl processing identifies REM sleep-relted vulnerbility trit in sthmtic children. Sleep Disord 2013;2013:Article ID , 6 pges, org/ /2013/ Dyyt E, Kheirndish-Gozl L, Gozl D. Childhood obstructive sleep pne: one or two distinct disese entities? Sleep Med Clin 2007;2: SLEEP, Vol. 38, No. 1, Remission nd Incidence of Peditric OSA Spilsbury et l.

8 SUPPLEMENTAL MATERIAL SUPPLEMENTAL METHODS Sleep Study Scoring Middle-childhood ssessment In-home, sleep-pne monitoring ws conducted with Type III sleep monitor recording thorcic nd bdominl excursions nd estimted tidl volume, pulse oximetry, hert rte, nd body position (PT-2 system, SensorMedics, Yorb Lind, CA). Respirtory events were scored if 8 sec long (or two or more missed respirtory cycles). The use of n 8-sec durtion ccounted for children s fster respirtory rte thn in dults (or lte dolescents) nd lower functionl residul cpcity, which cn led to more rpid desturtion with short respirtory events. Obstructive pnes were scored when chest nd bdominl efforts were synchronous nd estimted tidl volume ws bsent or nerly bsent, irrespective of ssocited desturtion. Hypopnes were scored when respirtory efforts were ccompnied by 50% reduction in estimted tidl volume nd ccompnied by 3% oxyhemoglobin desturtion. Adolescent ssessment Overnight polysomnogrphy (PSG) nd physiologicl nd nthropometric ssessments, including physicin-dministered physicl exm, followed stndrdized protocol t the reserch center, beginning t pproximtely 17:00 nd ending the following dy t 11:00. 1,2 The PSG recording (Compumedics E-series; Compumedics, Abbotsford, Austrli) consisted of mesurement of two electroencephlogrms (C 3 /C 2 nd C 4 /C 1 ), bilterl electrooculogrms, bipolr submentl electromyogrm, thorcic nd bdominl respirtory inductnce plethysmogrphy, irflow (nsl orl thermocouple nsl pressure recording), finger-pulse oximetry, electrocrdiogrm, body position, nd bilterl leg movements. Obstructive pnes were scored when complete or nerly complete bsence of irflow occurred on the thermistry chnnel for 10 sec in ssocition with respirtory effort. Hypopnes were identified s n pproximtely 50% reduction in irflow or summed respirtory excursions ssocited with n oxygen desturtion of 3%. For both exmintions, the obstructive pne-hypopne index (OAHI) ws defined s ll obstructive or mixed pnes nd hypopnes with 3% desturtion per sleep hour. Comprbility of dt from the middle childhood to lte dolescent exmintion A smple of 112 children underwent both in-home sleep pne testing nd full in-lbortory PSG (sleep stging, nslorl irflow, respirtory effort, oximetry, nd electrocrdiogrphy). In subsmple of 55 children who underwent both tests within 3 mo of the other, the men OAHI index ws 2.6 ± 8.0 nd 2.9 ± 7.5 for lbortory versus home studies, respectively (intrclss correltion coefficient = 0.85). Furthermore, there ws no evidence tht inclusion of rousls in the definitions of hypopnes pprecibly ltered the AHI estimtes. In the group of 112 children with in-lbortory PSG t the middle school exmintion, the men (pired) difference in AHI for the index Tble S1 Bseline prticipnt chrcteristics (ge 8 11 y) by prticiption t follow-up (ge y). Prticipted (n = 517) Did not prticipte (n = 390) Subject Chrcteristics Age, men (SD), y 9.5 (0.8) 9.5 (0.8) Sex Femle (n = 451) Mle (n = 456) Rce Non Africn- Americn (n = 576) Africn Americn (n = 331) Term sttus Full-term (n = 490) Preterm (n = 417) 60% 54% 40% 46% BMI z-score, men (SD) 0.29 (1.22) 0.30 (1.21) Prent eduction High school or less (n = 228) > High school (n = 666) Neighborhood distress No (n = 708) Yes (n = 192) Tonsils removed No (n = 840) Yes (n = 41) Tonsils or denoids removed No (n = 805) Yes (n = 67) Doctor s dignosis of sthm No (n = 724) Yes (n = 183) Prent history of OSA No (n = 805) Yes (n = 67) Hbitul snoring Yes (n = 146) No (n = 747) PSG Mesures SDB ctegory Apne (OAHI 5 or OAI 1; n = 40) Hbitul snorer, no pne (n = 120) No pne or snoring (n = 678) 50% 59% 59% 46% 52% 56% 52% 59% SDB (OAHI 5 or OAI 1 or hbitul snorer) Yes (n = 164) No pne or snoring (n = 678) 59% Apne (OAHI 5 or OAI 1) Yes (n = 40) No (n = 810) OAHI 1 Yes (n = 89) No (n = 761) 60% 50% 41% 41% 54% 48% 44% 48% 41% 41% 40% Dt re presented s number (row %) unless otherwise indicted. P < BMI, body mss index; OAHI, obstructive pne-hypopne index; OAI, obstructive pne index; PSG, polysomnogrphy; SD, stndrd devition; SDB, sleep disordered brething. SLEEP, Vol. 38, No. 1, A Remission nd Incidence of Peditric OSA Spilsbury et l.

9 Tble S2 Undjusted reltive risk of obstructive sleep pne t ge y strtified by term sttus. Preterms N = 216; n = 10 with OSA Full-terms N = 274; n = 11 with OSA Subject Chrcteristics t Age 8 11 y Africn-Americn 1.67 (0.50, 5.58) 2.16 (0.68, 6.88) Neighborhood distress 0.79 (0.17, 3.60) 2.22 (0.67, 7.33) BMI z-score 1.45 (0.86, 2.42) 2.37 (1.24, 4.53) P < BMI, body mss index; CI, confidence intervl; OSA, obstructive sleep pne; RR, reltive risk. Tble S3 Undjusted reltive risk of obstructive sleep pne t ge y mong nonobese prticipnts only. derived by scoring hypopnes with corroborting desturtion only compred to hypopnes scored with either desturtion or rousl, ws (stndrd devition = 0.19), nd the mximum difference ws The mesures were highly correlted: Spermn r = 0.99 (P < ), with miniml observed differences between the two mesures. Prentl Notifiction of Sleep Study Results In both the middle childhood nd dolescent exmintions, prents of ll prticipnts received letter from the investigtors describing the results of the sleep study. In cses where the children exhibited five or more brething puses per hour, the letter recommended tht prents contct their child s doctor so tht the child s brething could be rechecked. Mesurement of Tonsillry Size Tonsillr hypertrophy ws ssessed using five-point scle 3 with scores of 0 to 4: Grde 0 = tonsils bsent or within the tonsillr foss; Grde 1 = tonsils just outside of the tonsillr foss nd occupy 25% of the orophryngel width; Grde 2 = tonsils occupy 26%-50% of the orophryngel width; Grde 3 = tonsils occupy 51%-75% of the orophryngel width; Grde 4 = tonsils occupy > 75% of the orophryngel width. For nlytic purposes, Grdes 0 nd 1 were combined into one ctegory, which represents miniml tissue present in the irwy. Determintion of Residence in Distressed Neighborhood Residence in socioeconomiclly distressed neighborhood ws determined by mtching prticipnts residentil ddresses t the first exmintion to the corresponding 2000 US Census trct, nd then ctegorizing neighborhood of residence s distressed if the census trct hd vlues 1 stndrd devition bove the men for ll US census trcts on t lest three of the four following mesures: poverty rte, proportion of fmilies with relted children heded by single femles, high school dropout BMI < 95 th %tile t ge 8 11 y N = 415; n = 12 with OSA rte, nd proportion of civilin, noninstitutionlized, working ge (16 64 y) mles unemployed or not in the lbor force. 4,5 Description of Logistic Regressions Four sets of logistic regression models were fitted to exmine dolescent risk fctors ssocited with sleep disordered brething (SDB) t ge y: (1) undjusted; (2) djusted for body mss index (BMI) z-score t ge y; nd 3) djusted for known risk fctors: BMI z-score, mle sex, Africn Americn rce, preterm sttus, neighborhood distress, history of tonsillectomy, physicin-dignosed sthm; (4) sme s (3) except djusted for history of tonsillectomy or denoidectomy. SUPPLEMENTAL RESULTS BMI < 95 th %tile ge y N = 395; n = 8 with OSA RR (95%CI) Subject Chrcteristics t Age 8 11 y Africn-Americn 0.96 (0.29, 3.14) 1.20 (0.29, 4.93) Preterm 1.72 (0.56, 5.34) 0.77 (0.19, 3.18) Neighborhood distress 0.73 (0.16, 3.28) 1.25 (0.26, 6.09) BMI z-score 1.14 (0.64, 2.01) 2.20 (0.79, 6.11) BMI, body mss index; CI, confidence intervl; OSA, obstructive sleep pne; RR, reltive risk. Rce/Ethnicity nd Premture Birth Detils The smple ws 36.5% Africn Americn, nd 63.5% other, with other consisting lmost entirely of white prticipnts (93%), followed by 4% multircil/bircil, nd 2% Hispnic. The men gesttionl ge of the former preterm prticipnts ws 31 ± 3 w, men birth weight ws 1517 ± 568 g, nd 21.3% weighed < 1000 g t birth. SUPPLEMENTAL REFERENCES 1. Redline S, Storfer-Isser A, Rosen CL, et l. Assocition between metbolic syndrome nd sleep-disordered brething in dolescents. Am J Respir Crit Cre Med 2007;176: Weiss A, Xu F, Storfer-Isser A, Thoms A, Ievers-Lndis CE, Redline S. The ssocition of sleep durtion with dolescents ft nd crbohydrte consumption. Sleep 2010;33: Brodsky L. Modern ssessment of tonsils nd denoids. Peditr Clin North Am 1989;36: O Hre W, Mther M. The growing number of kids in severely distressed neighborhoods: evidence from the 2000 Census. Bltimore, MD: the Annie E. Csey Foundtion nd Popultion Reference Bureu; Spilsbury JC, Storfer-Isser A, Kirchner HL, et l. Neighborhood disdvntge s risk fctor for peditric obstructive sleep pne. J Peditr 2006;149: SLEEP, Vol. 38, No. 1, B Remission nd Incidence of Peditric OSA Spilsbury et l.

10 Tble S4 Cross-sectionl odds rtios of obstructive sleep pne t ge y restricted to full-term children (N = 293; n = 13 with obstructive sleep pne). Subject Chrcteristics t Age y Undjusted Adjusted for BMI z-score t Age y BMI z-score 2.00 (1.12, 3.57) n/ Mle (1.65, ) b (1.63, ) Africn Americn 1.54 (0.51, 4.72) 1.07 (0.33, 3.49) Neighborhood distress 1.84 (0.55, 6.21) 1.66 (0.48, 5.74) History of tonsillectomy 2.51 (0.29, 21.44) 2.25 (0.26, 19.89) History of tonsillectomy or denoidectomy 2.81 (0.58, 13.72) 2.39 (0.48, 11.96) Asthm 3.90 (1.26, 12.02) 3.24 (1.03, 10.25) Hbitul loud snoring 1.12 (0.30, 4.21) 0.73 (0.19, 2.90) P < b P < BMI, body mss index; CI, confidence intervl; n/, not pplicble; OR, odds rtio. Tble S5 Cross-sectionl odds rtios of sleep disordered brething (obstructive sleep pne or hbitul loud snoring) t ge y (N = 513; n = 128 with sleep disordered brething). Model 1 undjusted Model 2 djusted for BMI z-score t ge y OR (95%CI) Model 3 full model with history of tonsillectomy Model 4 full model with history of tonsillectomy or denoidectomy b Subject Chrcteristics t Age y BMI z-score 1.85 (1.50, 2.28) d n/ 1.78 (1.43, 2.22) d 1.77 (1.42, 2.21) d Mle 2.12 (1.40, 3.20) d 2.10 (1.37, 3.22) d 2.20 (1.39, 3.48) d 2.19 (1.38, 3.47) d Africn-Americn 2.58 (1.72, 3.89) d 2.33 (1.53, 3.56) d 3.44 (1.99, 5.95) d 3.24 (1.87, 5.62) d Preterm 1.05 (0.70, 1.57) 1.10 (0.72, 1.67) 1.06 (0.67, 1.67) 1.00 (0.63, 1.59) Neighborhood distress 1.36 (0.85, 2.16) 1.27 (0.78, 2.07) 0.64 (0.34, 1.18) 0.67 (0.36, 1.25) History of tonsillectomy 2.25 (1.15, 4.40) c 1.87 (0.92, 3.81) 2.35 (1.09, 5.07) c n/ History of tonsillectomy 2.99 (1.72, 5.18) d 2.62 (1.47, 4.67) d n/ 2.78 (1.49, 5.21) d or denoidectomy Asthm 1.62 (1.06, 2.50) c 1.48 (0.95, 2.33) 1.23 (0.76, 1.99) 1.24 (0.76, 2.00) Adjusted for ll covrites listed except history of tonsillectomy or denoidectomy. b Adjusted for ll covrites listed except history of tonsillectomy. c P < d P < BMI, body mss index; CI, confidence intervl; n/, not pplicble; OR, odds rtio. SLEEP, Vol. 38, No. 1, C Remission nd Incidence of Peditric OSA Spilsbury et l.

11 Time point #1 Middle Childhood Exmintion 907 Prticipnts 8 11 y of ge 16 previously requested no further contct 157 lost to follow-up 217 Declined not interested - 40 lck of time - 14 helth resons - 4 equipment fer (needles, PSG) - 4 moved out of re 27 Excluded: missing dt - 23 unknown OSA sttus time point #1-2 unknown OSA sttus time point #2-2 missing residentil ddress; neighborhood distress not clculted 734 contcted Time point #2 Adolescent Exmintion 517 consented nd prticipted 490 comprised nlytic smple Figure S1 Clevelnd Children Sleep nd Helth Study: prticipnt flowchrt between study time points. OSA, obstructive sleep pne; PSG, polysomnogrphy. SLEEP, Vol. 38, No. 1, D Remission nd Incidence of Peditric OSA Spilsbury et l.