- Email: [email protected]
Parental History of Adenotonsillectomy Is Associated with Obstructive Sleep Apnea Severity in Children with Snoring
Parental History of Adenotonsillectomy Is Associated with Obstructive Sleep Apnea Severity in Children with Snoring Emmanouel I. Alexopoulos, MD1, George Charitos, MD1, Georgia Malakasioti, MD1,2, Vasiliki Varlami, MD1, Konstantinos Gourgoulianis, MD1, Elias Zintzaras, MS, PhD3,4, and Athanasios G. Kaditis, MD1,2 Objective To test the hypothesis that history of adenoidectomy and/or tonsillectomy (AT) in at least 1 of the parents during childhood, is a risk factor for moderate-to-severe obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] >5 episodes/hour) in the offspring with snoring. Study design Data of children with snoring who were referred for polysomnography over 12 years by primary care physicians were reviewed. Results Data of 798 children without history of prior AT, neuromuscular, or genetic disorders or craniofacial abnormalities were analyzed. Of these children, 69.3% had tonsillar hypertrophy, 25.8% were obese, 26.8% had at least 1 parent with history of AT, and 22.1% had AHI >5 episodes/hour. Parental history of AT was significantly associated with moderate-to-severe OSA (logit model including sex, tonsillar hypertrophy, obesity, and physiciandiagnosed wheezing; OR [95% CI], 1.70 [1.18-2.46]; P < .01). When significant variables from the logit model (tonsillar hypertrophy, obesity, parental history of AT) were considered independently or in combination, tonsillar hypertrophy combined with history of AT in at least 1 of the parents had high specificity (84.4%) and the highest positive likelihood ratio (1.78) for identifying children with AHI >5 episodes/hour. Conclusions Among children with snoring who are referred for polysomnography by primary care physicians, those with tonsillar hypertrophy and parental history of AT have increased risk of moderate-to-severe OSA and represent 1 of the subgroups that should be prioritized for a sleep study in settings with limited resources. (J Pediatr 2014;164:1352-7). See related article, p 1346
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bstructive sleep-disordered breathing (SDB) in childhood represents an abnormal respiratory pattern during sleep resulting from increased upper airway resistance and/or pharyngeal collapsibility and manifested as snoring and increased work of breathing.1 When apnea, hypopnea, and gas exchange abnormalities also occur, the term obstructive sleep apnea (OSA) is applied which is the most severe form of obstructive SDB.2 Nocturnal polysomnography is the gold standard for the diagnosis of OSA, but fewer than 10% of children undergoing adenoidectomy and/or tonsillectomy (AT) for habitual snoring have a sleep study preoperatively to assess SDB severity because of the limited number of pediatric sleep laboratories in many health systems.3 Obesity, history of wheezing, prematurity, race, low socioeconomic status, and OSA diagnosed in first-degree relatives are clinical factors that predict severity of SDB in population-based studies and possibly contribute to the pathogenesis of the disorder either directly or indirectly.1,4-7 For instance, history of AT in parents has been recognized as a risk factor for pharyngeal lymphoid tissue hypertrophy and habitual snoring in the offspring.8 Because SDB is the most common indication for AT in childhood, especially during preadolescent years, parental history of AT can be used as a surrogate measure of clinically significant upper airway obstruction during sleep in the family.9,10 The primary aim of the current study was to assess the relationship between AT in parents and severity of OSA in children in an effort to make speculations about the pathogenesis of intermittent upper airway obstruction during sleep. Hence, we hypothesized that history of AT in at least 1 of the parents during their childhood was significantly associated with the presence of moderate-to-severe OSA (apnea-hypopnea index [AHI] >5 episodes/hour) in the offspring with snoring (>1 night/week). The secondary aim of this investigaFrom the Sleep Disorders Laboratory, School of tion was to evaluate the potential clinical usefulness of a positive parental history Medicine, University of Thessaly and Larissa University Hospital, Larissa, Greece; Pediatric Pulmonology Unit, of AT for the recognition of patients with symptoms of SDB who are at risk of Sleep Disorders Laboratory, First Department of moderate-to-severe OSA given that requests for polysomnography should be Pediatrics, School of Medicine, University of Athens and 1
2
AHI AT BMI OSA SDB
Apnea-hypopnea index Adenoidectomy and/or tonsillectomy Body mass index Obstructive sleep apnea Sleep-disordered breathing
Aghia Sophia Children’s Hospital, Athens, Greece; 3 Department of Biomathematics, School of Medicine, University of Thessaly, Larissa, Greece; and 4 Biostatistics Research Center, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, School of Medicine, Tufts University, Boston, MA The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.01.021
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Vol. 164, No. 6 June 2014 prioritized in health systems with limited resources. It is important to recognize children with AHI >5 episodes/ hour because they have low rate of spontaneous resolution of OSA, and they are at risk of cardiovascular morbidity, development of respiratory complications following AT, and persistent disease postoperatively.2,11-13
Methods Data of children with snoring ($1 night/week) referred for polysomnography to the Larissa University Hospital by their primary care physician from January 2001 to December 2012 for snoring were considered for analysis. Only data of subjects without history of AT, neuromuscular or genetic disorders, or craniofacial abnormalities were included in the analysis. This retrospective research protocol was approved by the Larissa University Hospital Ethics Committee. Information regarding history and physical examination and results of polysomnography were recorded in a special hospital form (sleep record) and archived in an electronic database within 1 week following the sleep study. Any missing data in the database were completed during the follow-up clinic visit. Since the establishment of the pediatric sleep laboratory in our hospital, all children arrive in late afternoon prior to polysomnography and parents undergo an interview with questions about their child’s health including: (1) symptoms of SDB; (2) history of AT; (3) history of physician-diagnosed wheezing treated with inhaled medications over the past year; (4) history of any chronic disease; and (5) history of AT in parents during their childhood. All children have a physical examination with measurement of height and body weight and calculation of body mass index (BMI) z score.14 Evaluation of tonsillar size by visual inspection of the oropharynx is completed by a single physician (E.A.) using a score ranging from 1+ to 4+.15 During the study period, overnight polysomnography was performed (Alice 4 or 5; Healthdyne, Marietta, Georgia). Polysomnography During the study period, overnight polysomnography was performed using the Alice 4 or 5 computerized systems (Healthdyne), and the following variables were recorded: (1) electroencephalogram (C3/A2, C4/A1, O1/A2); (2) right and left oculogram; (3) submental and tibial electromyogram; (4) body position; (5) electrocardiogram; (6) thoracic and abdominal wall motion (piezoelectric transducers); (7) oronasal airflow (3-pronged thermistor and nasal pressure transducer); and (8) oxygen saturation of hemoglobin. Arousals and sleep stages were assessed using standard criteria.16,17 Obstructive apnea was defined as the absence of airflow for at least 2 breaths in the presence of chest/abdominal wall motion.18 Apneas were considered of mixed type when there was both an obstructive and a central component. Hypopnea was defined as a reduction in the airflow signal amplitude of at least 50% compared with baseline in the presence of chest/ abdominal wall motion and associated with oxygen desaturation of hemoglobin equal to or greater than 4%, or with an
arousal. AHI was the mean number of obstructive and mixed apneas and hypopneas per hour of total sleep time. All polysomnographies were scored by a single physician. Explanatory Variables of Interest and Outcome Variable AHI >5 episodes/hour (moderate-to-severe OSA) was the main outcome variable and parental history of AT (history of AT in at least 1 of the parents during childhood) was the main explanatory variable. Paternal history of AT, maternal history of AT, tonsillar hypertrophy (tonsillar size >2+), obesity (BMI in the 95th percentile or greater), sex, and physician-diagnosed wheezing over the past year treated with inhaled medications19 were other explanatory variables. Statistical Analyses Children without and with parental history of AT were compared in terms of demographic, clinical, and polysomnography variables. Children with both tonsillar hypertrophy and parental history of AT were also compared with all other participants regarding AHI and proportion of subjects with AHI >5 episodes/hour. Student t test was used for continuous variables that approached a normal distribution, Mann–Whitney U test for continuous variables that did not follow a normal distribution, and c2 test for categorical characteristics. The association between moderate-to-severe OSA and each explanatory variable was tested using Fisher exact test. The magnitude of association was expressed as OR and the corresponding 95% CI was calculated using Woolf estimate.20 Furthermore, the effect of parental history of AT and the other explanatory variables (sex, tonsillar hypertrophy, obesity, and physician-diagnosed wheezing) on OSA severity was assessed simultaneously by fitting a logit model.21 The significance of each variable in the model was evaluated using the respective change in deviance and the goodness-of-fit of the model was assessed using the residual deviance after fitting all explanatory variables.21 Two more logit models were fitted for evaluating the effect of paternal or maternal history of AT. The analysis was performed using R (www.r-project.com) and the logit models were fitted using GLIM 3.77 (Royal Statistical Society; London, United Kingdom). Sensitivity, specificity, positive and negative predictive values, and positive likelihood ratio of all explanatory variables that were significant in the logit models for prediction of moderate-to-severe OSA were calculated. Positive likelihood ratio was equal to sensitivity/(1 specificity). Similar calculations were carried out for combinations of parental history of AT with other significant explanatory variables.
Results A total of 798 children with history of snoring ($1 night/week) and without chronic disorders or prior AT underwent polysomnography during the study period. The median age of participants in the cohort was 5.8 years (range 2-15 years and IQR 4.5-7.7 years). Of all subjects, 553 (69.3%) had tonsillar hypertrophy, 206 (25.8%) were obese, and 214 (26.8%) had at least 1353
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1 parent who underwent AT in childhood. One hundred seventysix children (22.1% of 798 subjects) had AHI >5 episodes/hour. Children with parental history of AT did not differ from subjects without parental history of AT in terms of age, BMI z score, proportion of male subjects and frequencies of obesity, tonsillar hypertrophy, prematurity, or history of physiciandiagnosed wheezing treated with inhaled medications over the past year (Table I). The study group with history of AT in parents had significantly higher AHI compared with the group without such history (Table I). In addition, children with both tonsillar hypertrophy and history of AT in parents (n = 146) had significantly higher AHI than all other participants (n = 652): median 3.4 (IQR 1.5-6.6) episodes/ hour vs 2.1 (1-4.1) episodes/hour; P < .01. The former group differed significantly from the latter in the proportion of subjects with AHI >5 episodes/hour: 33.6% vs 19.5%; P < .01. Association of Parental History of AT with Moderate-to-Severe OSA Paternal, but not maternal history of AT, was significantly associated with the presence of moderate-to-severe OSA: OR (95% CI) = 1.51 (1.02-2.23), P = .04 and OR = 1.65 (0.98-2.78), P = .08, respectively. Parental history of AT was significantly related to AHI >5 episodes/hour: OR = 1.63 (1.13-2.33), P < .01 (Table II). The significant associations of paternal and parental history of AT with moderate-to-severe OSA persisted after fitting the logit models (Table II). The residual deviance of models 1 and 3 was significant (P < .01) indicating that additional risk factors should be incorporated in the models. Speculative Analysis In the primary analysis, it was assumed that all parents with history of AT (100%) underwent surgery as treatment for
Vol. 164, No. 6 SDB and the OR (95% CI) for moderate-to-severe OSA in their children was 1.63 (1.13-2.33) and P < .01. If SDB were the indication for surgery in only 70% of parents with history of AT and recurrent tonsillitis were the indication in the remaining parents (30%), provided that the margins of patient numbers with and without moderate-to-severe OSA and their ratio remained fixed (ie, equal to the observed ones), then OR would be 1.56 (1.04-2.33) and P = .03. Also, if only 50% of parents with history of AT underwent surgery for SDB and the remaining for recurrent tonsillitis, the OR for moderate-to-severe OSA in their children would be 1.54 (0.97-2.42) and P = .06. Sensitivity, Specificity, Positive and Negative Predictive Values, and Positive Likelihood Ratio of Parental History of AT and Other Explanatory Variables Significantly Associated with AHI >5 Episodes/hour Among the 4 significant explanatory variables in the logit models (tonsillar hypertrophy, obesity, parental history of AT, paternal history of AT), tonsillar hypertrophy had the highest sensitivity (81.8%) for finding AHI >5 episodes/ hour and the lowest specificity and positive likelihood ratio (Table III). Paternal and parental history of AT had lower sensitivity but higher specificity than tonsillar hypertrophy. When tonsillar hypertrophy was combined with parental history of AT, sensitivity was low but specificity and positive likelihood ratio were higher than those of tonsillar hypertrophy or obesity alone (Table III).
Discussion In the present cohort of children with snoring who had mostly tonsillar hypertrophy and a fairly low frequency of
Table I. Subjects’ characteristics and statistical comparisons of children without and with parental history of AT Variables Age, y Sex, male (%) BMI z score Obesity (%) Tonsillar hypertrophy (%) Physician-diagnosed wheezing treated with inhaled medications over the past year (%) Prematurity (<37 wk gestational age) Paternal history of adenoidectomy (%) Paternal history of tonsillectomy (%) Paternal history of AT (%) Maternal history of adenoidectomy (%) Maternal history of tonsillectomy (%) Maternal history of AT (%) AHI, episodes/h Respiratory arousal index, episodes/h Oxygen desaturation ($4%) of hemoglobin index, episodes/h % Sleep time with SpO2 <95% Subjects with AHI >5 episodes/h, %
Children without parental history of AT (n = 584) 6.3 2.4 342 (58.6) 0.7 1.4 153 (26.2) 407 (69.7) 257 (44) 9 (1.5) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2.1 (1-4.2) 0.9 (0.4-1.8) 2.6 (1.2-6) 1.1 (0.4-3.2) 115 (19.7)
Children with parental history of AT (n = 214) 6.3 2.7 125 (58.4) 0.7 1.4 53 (24.8) 146 (68.2) 98 (45.8) 3 (1.4) 90 (42.1) 127 (59.3) 168 (78.5) 61 (28.5) 53 (24.8) 75 (35) 2.8 (1.3-5.9) 1 (0.4-2.4) 3.3 (1.4-6.7) 1.5 (0.5-4.1) 61 (28.5)
P value .95 .97 .94 .68 .69 .62 .89 <.01 .14 .07 .10 <.01
SpO2, oxygen saturation of hemoglobin. Continuous variables are expressed as mean SD or median (IQR).
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Table II. Associations of parental history of AT or other potential risk factors with presence of moderate-to-severe OSA (AHI >5 episodes/hour) in the child with snoring Risk factors
Subjects with mod/severe OSA (n = 176)
Male sex Yes No Tonsillar hypertrophy Yes No Obesity Yes No Physician-diagnosed wheezingz Yes No Paternal history of AT Yes No Maternal history of AT Yes No Parental history of AT Yes No
Subjects without mod/severe OSA (n = 622)
OR (95% CI)
P value*
Logit model 1 OR (95% CI)†
Logit model 2 OR (95% CI)†
Logit model 3 OR (95% CI)†
109 (61.9%) 67 (38.1%)
358 (57.6%) 264 (42.4%)
1.20 (0.85-1.69)
.34
1.20 (0.84-1.70)
1.16 (0.82-1.65)
1.18 (0.83-1.68)
144 (81.8%) 32 (18.2%)
409 (65.8%) 213 (34.2%)
2.34 (1.54-3.56)
<.01
2.48 (1.63-3.79)
2.39 (1.57-3.65)
2.46 (1.61-3.76)
55 (31.2%) 121 (68.8%)
151 (24.3%) 471 (75.7%)
1.42 (0.98-2.05)
.06
1.54 (1.06-2.24)
1.51 (1.04-2.20)
1.53 (1.05-2.24)
78 (44.3%) 98 (55.7%)
277 (44.6%) 344 (55.4%)
0.99 (0.71-1.38)
.95
0.96 (0.68-1.35)
1.00 (0.71-1.42)
0.97 (0.68-1.36)
47 (26.7%) 129 (73.3%)
121 (19.5%) 501 (80.5%)
1.51 (1.02-2.23)
.04
1.63 (1.09-2.42)
-
-
23 (13.1%) 153 (86.9%)
52 (8.4%) 570 (91.6%)
1.65 (0.98-2.78)
.08
-
1.63 (0.95-2.77)
-
61 (34.7%) 115 (65.3%)
153 (24.6%) 469 (75.4%)
1.63 (1.13-2.33)
<.01
-
-
1.70 (1.18-2.46)
*Fisher exact test. †A logit model was fitted to evaluate the effect of each explanatory variable on OSA severity simultaneously. zTreated with inhaled medications over the past year.
obesity, parental history of AT was significantly associated with OSA severity. Children with tonsillar hypertrophy and at least 1 parent with history of AT during childhood had significantly higher AHI relative to all other studied subjects. The presence of these 2 clinical factors in combination increases the odds of finding moderate-to-severe OSA when polysomnography is performed in children with snoring. Our findings are in accordance with the results of a study by Lundkvist et al based on the Swedish Hospital Discharge Register that has shown substantially increased standardized incidence ratios of adenotonsillar or tonsillar hypertrophy in boys or girls with a parent diagnosed with OSA in adulthood by polysomnography compared with subjects without such a history.10 Both the present report and the epidemiologic investigation by Lundkvist et al emphasize the importance of familial characteristics in the pathogenesis of OSA. Because the effects of tonsillar hypertrophy and obesity, defined by using the BMI, have been taken into account in the logit models, the calculated risk of moderate-to-severe OSA in children with snoring and parental history of AT
probably reflects the contribution of other familial factors to the pathogenesis of SDB such as body fat distribution, craniofacial characteristics, or control of the upper airway neuromotor tone.4,22 Obesity has been recognized as a risk factor for OSA in childhood in population-based studies and tonsillar hypertrophy has been shown to increase the risk of obstructive SDB in hospital-based reports.4,23,24 In addition, children with history of AT in parents, or adenotonsillar or tonsillar hypertrophy in siblings, have pharyngeal lymphoid tissue hypertrophy more frequently than children without such history.8,25 Therefore, familial characteristics may affect adenotonsillar tissue growth rate during preschool years, development of obesity, and their contribution to the pathogenesis of sleep apnea.4,8,24 A secondary goal of this study was to evaluate the clinical usefulness of parental history of AT for the recognition of patients with symptoms of obstructive SDB who are at risk of moderate-to-severe OSA. Unfortunately, patient selection and prioritization of requests for polysomnography
Table III. Sensitivity, specificity, positive and negative predictive values, and positive likelihood ratios of variables associated with moderate-to-severe OSA among children with snoring referred for polysomnography Predictors
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Positive likelihood ratio
Tonsillar hypertrophy Obesity Paternal history of AT Parental history of AT Tonsillar hypertrophy + parental history of AT Obesity + parental history of AT Tonsillar hypertrophy + obesity + parental history of AT
81.8% 31.3% 26.7% 34.7% 27.8% 8% 5.1%
34.2% 75.7% 80.5% 75.4% 84.4% 93.7% 96.6%
26% 26.7% 28% 28.5% 33.6% 26.4% 30%
86.9% 79.6% 79.5% 80.3% 80.5% 78.3% 78.3%
1.24 1.29 1.37 1.41 1.78 1.27 1.50
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may be necessary in health systems with limited resources.26 Paternal or parental history of AT has lower sensitivity but much higher specificity in detecting moderate-to-severe OSA than tonsillar hypertrophy. Presence of tonsillar hypertrophy and parental history of AT increases the odds of finding moderate-to-severe OSA on polysomnography (positive likelihood ratio of approximately 2). Thus, children with snoring, tonsillar hypertrophy, and parental history of AT should be prioritized for polysomnography. Some characteristics and limitations of the current retrospective study need to be discussed to facilitate interpretation of its findings and application of its conclusions. First, the majority of children in our cohort were of preadolescent age and had tonsillar hypertrophy, whereas obesity affected only one-quarter. In this way, their characteristics were similar to those of subjects recruited in the Childhood Adenotonsillectomy Trial, a multicenter, randomized, controlled investigation assessing the efficacy of AT in pediatric SDB.12 These study characteristics may provide an explanation as to why tonsillar size was a predictor of OSA in this report but not in other published studies.4,27 Second, characteristics of our cohort may have been affected by the referral practices of primary care physicians in our area who frequently consider a child at risk for OSA when there is a history of snoring for at least 1 night per week. Third, it should be recognized that although SDB is the most common indication for AT in childhood, some of the parents may have undergone surgery because of recurrent tonsillitis or other reasons.9 Nevertheless, in our speculative analysis the association between parental history of AT and moderate-to-severe OSA remained significant or approached statistical significance (P = .06) even when it was assumed that only 70% or 50% of parents, respectively, underwent surgery for SDB. In conclusion, among preadolescent children with snoring who are referred for polysomnography by primary care physicians, those with tonsillar hypertrophy and parental history of AT have increased risk of moderate-to-severe OSA and represent 1 of the subgroups that should be prioritized for a sleep study. Considering the coexistence of tonsillar hypertrophy and parental history of AT as a risk factor for moderate-to-severe OSA may allow more efficient use of polysomnography in settings with limited resources. n Submitted for publication Aug 26, 2013; last revision received Dec 9, 2013; accepted Jan 10, 2014. Reprint requests: Athanasios G. Kaditis, MD, First University Department of Pediatrics, Aghia Sophia Children’s Hospital, Thivon and Papadiamantopoulou St, Athens 11527, Greece. E-mail: [email protected]
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Vol. 164, No. 6 3. Mitchell RB, Pereira KD, Friedman NR. Sleep-disordered breathing in children: survey of current practice. Laryngoscope 2006;116:956-8. 4. Bixler EO, Vgontzas AN, Lin HM, Liao D, Calhoun S, Vela-Bueno A, et al. Sleep disordered breathing in children in a general population sample: prevalence and risk factors. Sleep 2009;32:731-6. 5. Redline S, Tishler PV, Tosteson TD, Williamson J, Kump K, Browner I, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:682-7. 6. Rosen CL, Larkin EK, Kirchner HL, Emancipator JL, Bivins SF, Surovec SA, et al. Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity. J Pediatr 2003;142:383-9. 7. Goodwin JL, Vasquez MM, Silva GE, Quan SF. Incidence and remission of sleep-disordered breathing and related symptoms in 6- to 17-year old children–the Tucson Children’s Assessment of Sleep Apnea Study. J Pediatr 2010;157:57-61. 8. Kalampouka E, Moudaki A, Malakasioti G, PanaghiotopoulouGartagani P, Chrousos G, Kaditis AG. Family history of adenotonsillectomy as a risk factor for tonsillar hypertrophy and snoring in childhood. Pediatr Pulmonol 2013; http://dx.doi.org/10.1002/ppul.22830. Epub Date June 19, 2013. 9. Parker NP, Walner DL. Trends in the indications for pediatric tonsillectomy or adenotonsillectomy. Int J Pediatr Otorhinolaryngol 2011;75: 282-5. 10. Lundkvist K, Sundquist K, Li X, Friberg D. Familial risk of sleepdisordered breathing. Sleep Med 2012;13:668-73. 11. Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, Mitchell RB, Promchiarak J, Simakajornboon N, et al. Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study. Am J Respir Crit Care Med 2010;182: 676-83. 12. Marcus CL, Moore RH, Rosen CL, Giordani B, Garetz SL, Taylor HG, et al. A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med 2013;368:2366-76. 13. Nixon GM, Kermack AS, Davis GM, Manoukian JJ, Brown KA, Brouillette RT. Planning adenotonsillectomy in children with obstructive sleep apnea: the role of overnight oximetry. Pediatrics 2004;113: e19-25. 14. Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 2002;109:45-60. 15. Brodsky L. Modern assessment of tonsils and adenoids. Pediatr Clin North Am 1989;36:1551-69. 16. Rechtschaffen A, Kales A. A manual of standardized terminology: techniques and scoring systems for sleep stages of human subjects. Los Angeles: UCLA Brain Information Service/Brain Research Institute; 1968. 17. American Sleep Disorders Association. EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep 1992;15: 173-84. 18. American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med 1996; 153:866-78. 19. Kaditis AG, Kalampouka E, Hatzinikolaou S, Lianou L, Papaefthimiou M, Gartagani-Panagiotopoulou P, et al. Associations of tonsillar hypertrophy and snoring with history of wheezing in childhood. Pediatr Pulmonol 2010;45:275-80. 20. Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955;19:251-3. 21. McCullagh P, Nelder JA. Generalized linear models. 2nd ed. Boca Raton: Chapman and Hall/CRC; 1989. 22. Riha RL. Genetic aspects of the obstructive sleep apnoea/hypopnoea syndrome—is there a common link with obesity? Respiration 2009;78:5-17. 23. Kaditis AG, Lianou L, Hatzinikolaou S, Kalampouka E, GartaganiPanayiotopoulou P, Zintzaras E, et al. Tonsillar size in 2- to 14-yearold children with and without snoring. Pediatr Pulmonol 2009;44: 1216-22.
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June 2014 24. Papaioannou G, Kambas I, Tsaoussoglou M, PanaghiotopoulouGartagani P, Chrousos G, Kaditis AG. Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleepdisordered breathing. J Pediatr 2013;162:269-74.e4. 25. Friberg D, Sundquist J, Li X, Hemminki K, Sundquist K. Sibling risk of pediatric obstructive sleep apnea syndrome and adenotonsillar hypertrophy. Sleep 2009;32:1077-83.
ORIGINAL ARTICLES 26. Villa MP, Paolino MC, Castaldo R, Vanacore N, Rizzoli A, Miano S, et al. Sleep clinical record: an aid to rapid and accurate diagnosis of paediatric sleep disordered breathing. Eur Respir J 2013;41:1355-61. 27. Goodwin JL, Kaemingk KL, Mulvaney SA, Morgan WJ, Quan SF. Clinical screening of school children for polysomnography to detect sleep-disordered breathing—the Tucson Children’s Assessment of Sleep Apnea Study (TuCASA). J Clin Sleep Med 2005;1:247-54.
50 Years Ago in THE JOURNAL OF PEDIATRICS The Nature of Kidney Disease in Children Who Fail to Recover from Apparent Acute Glomerulonephritis Edelmann CM Jr, Greifer I, Barnett HLL. J Pediatr 1964;64:879-87
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his article reported the clinical course of 42 children with a diagnosis of acute glomerulonephritis: in 39 of the children, it occurred after a clinical course characteristic of postinfectious glomerulonephritis, and 3 of the children demonstrated atypical courses with failure to improve and the development of chronic kidney disease. The authors focused on these latter 3 cases and concluded that these 3 children likely had: (1) an unusually severe form of acute glomerulonephritis with rapidly progressive glomerular disease; (2) an exacerbation of previously unrecognized renal disease; or (3) superimposition of acute post streptococcal glomerulonephritis on preexisting renal disease. The authors favored the concept of preexisting renal disease. Of the 3 atypical cases, one was noted to have markedly thickened glomerular basement membranes with irregular nodular areas on a kidney biopsy; perhaps this child had membranoproliferative glomerulonephritis, which was later described by Clark West as a form of hypocomplementemic glomerulonephritis.1 Of the other 2 children, 1 presented with recurring episode of edema, hematuria, and proteinuria over several years; on a kidney biopsy, it was noted that the degree of renal damage was quite severe, with 80% of glomeruli demonstrating scarring, and the acute inflammatory process in the remaining glomeruli was interpreted as a recurrent inflammatory process. In the third child, it was noted that the onset of gross hematuria was only 6 days after a respiratory infection suggesting a short latent period. Perhaps these 2 children had IgA nephropathy as later described by Berger2—since IgA nephropathy is noted to have a relapsing remitting course and to have the onset of gross hematuria within days of an infection. The authors of this report were quite astute in their conclusion that these children likely had an acute exacerbation of previously unrecognized renal disease, and each of the authors has made enormous contributions to pediatric nephrology. Sharon P. Andreoli, MD Byron P. and Francis D. Hollett Professor of Pediatrics Division of Pediatric Nephrology James Whitcomb Riley Hospital for Children Indianapolis, Indiana http://dx.doi.org/10.1016/j.jpeds.2014.01.016
References 1. West CD, McAdams AJ, et al. Hypocomplementemic and normo-complementemic persistent (chronic) glomerulonephritis: clinical and pathologic characteristics. J Pediatr 1965;67:1089-112. 2. Berger J. IgA glomerular deposits in renal disease. Transpl Proc 1969;1:939-44.
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bstructive sleep-disordered breathing (SDB) in childhood represents an abnormal respiratory pattern during sleep resulting from increased upper airway resistance and/or pharyngeal collapsibility and manifested as snoring and increased work of breathing.1 When apnea, hypopnea, and gas exchange abnormalities also occur, the term obstructive sleep apnea (OSA) is applied which is the most severe form of obstructive SDB.2 Nocturnal polysomnography is the gold standard for the diagnosis of OSA, but fewer than 10% of children undergoing adenoidectomy and/or tonsillectomy (AT) for habitual snoring have a sleep study preoperatively to assess SDB severity because of the limited number of pediatric sleep laboratories in many health systems.3 Obesity, history of wheezing, prematurity, race, low socioeconomic status, and OSA diagnosed in first-degree relatives are clinical factors that predict severity of SDB in population-based studies and possibly contribute to the pathogenesis of the disorder either directly or indirectly.1,4-7 For instance, history of AT in parents has been recognized as a risk factor for pharyngeal lymphoid tissue hypertrophy and habitual snoring in the offspring.8 Because SDB is the most common indication for AT in childhood, especially during preadolescent years, parental history of AT can be used as a surrogate measure of clinically significant upper airway obstruction during sleep in the family.9,10 The primary aim of the current study was to assess the relationship between AT in parents and severity of OSA in children in an effort to make speculations about the pathogenesis of intermittent upper airway obstruction during sleep. Hence, we hypothesized that history of AT in at least 1 of the parents during their childhood was significantly associated with the presence of moderate-to-severe OSA (apnea-hypopnea index [AHI] >5 episodes/hour) in the offspring with snoring (>1 night/week). The secondary aim of this investigaFrom the Sleep Disorders Laboratory, School of tion was to evaluate the potential clinical usefulness of a positive parental history Medicine, University of Thessaly and Larissa University Hospital, Larissa, Greece; Pediatric Pulmonology Unit, of AT for the recognition of patients with symptoms of SDB who are at risk of Sleep Disorders Laboratory, First Department of moderate-to-severe OSA given that requests for polysomnography should be Pediatrics, School of Medicine, University of Athens and 1
2
AHI AT BMI OSA SDB
Apnea-hypopnea index Adenoidectomy and/or tonsillectomy Body mass index Obstructive sleep apnea Sleep-disordered breathing
Aghia Sophia Children’s Hospital, Athens, Greece; 3 Department of Biomathematics, School of Medicine, University of Thessaly, Larissa, Greece; and 4 Biostatistics Research Center, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, School of Medicine, Tufts University, Boston, MA The authors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2014.01.021
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Vol. 164, No. 6 June 2014 prioritized in health systems with limited resources. It is important to recognize children with AHI >5 episodes/ hour because they have low rate of spontaneous resolution of OSA, and they are at risk of cardiovascular morbidity, development of respiratory complications following AT, and persistent disease postoperatively.2,11-13
Methods Data of children with snoring ($1 night/week) referred for polysomnography to the Larissa University Hospital by their primary care physician from January 2001 to December 2012 for snoring were considered for analysis. Only data of subjects without history of AT, neuromuscular or genetic disorders, or craniofacial abnormalities were included in the analysis. This retrospective research protocol was approved by the Larissa University Hospital Ethics Committee. Information regarding history and physical examination and results of polysomnography were recorded in a special hospital form (sleep record) and archived in an electronic database within 1 week following the sleep study. Any missing data in the database were completed during the follow-up clinic visit. Since the establishment of the pediatric sleep laboratory in our hospital, all children arrive in late afternoon prior to polysomnography and parents undergo an interview with questions about their child’s health including: (1) symptoms of SDB; (2) history of AT; (3) history of physician-diagnosed wheezing treated with inhaled medications over the past year; (4) history of any chronic disease; and (5) history of AT in parents during their childhood. All children have a physical examination with measurement of height and body weight and calculation of body mass index (BMI) z score.14 Evaluation of tonsillar size by visual inspection of the oropharynx is completed by a single physician (E.A.) using a score ranging from 1+ to 4+.15 During the study period, overnight polysomnography was performed (Alice 4 or 5; Healthdyne, Marietta, Georgia). Polysomnography During the study period, overnight polysomnography was performed using the Alice 4 or 5 computerized systems (Healthdyne), and the following variables were recorded: (1) electroencephalogram (C3/A2, C4/A1, O1/A2); (2) right and left oculogram; (3) submental and tibial electromyogram; (4) body position; (5) electrocardiogram; (6) thoracic and abdominal wall motion (piezoelectric transducers); (7) oronasal airflow (3-pronged thermistor and nasal pressure transducer); and (8) oxygen saturation of hemoglobin. Arousals and sleep stages were assessed using standard criteria.16,17 Obstructive apnea was defined as the absence of airflow for at least 2 breaths in the presence of chest/abdominal wall motion.18 Apneas were considered of mixed type when there was both an obstructive and a central component. Hypopnea was defined as a reduction in the airflow signal amplitude of at least 50% compared with baseline in the presence of chest/ abdominal wall motion and associated with oxygen desaturation of hemoglobin equal to or greater than 4%, or with an
arousal. AHI was the mean number of obstructive and mixed apneas and hypopneas per hour of total sleep time. All polysomnographies were scored by a single physician. Explanatory Variables of Interest and Outcome Variable AHI >5 episodes/hour (moderate-to-severe OSA) was the main outcome variable and parental history of AT (history of AT in at least 1 of the parents during childhood) was the main explanatory variable. Paternal history of AT, maternal history of AT, tonsillar hypertrophy (tonsillar size >2+), obesity (BMI in the 95th percentile or greater), sex, and physician-diagnosed wheezing over the past year treated with inhaled medications19 were other explanatory variables. Statistical Analyses Children without and with parental history of AT were compared in terms of demographic, clinical, and polysomnography variables. Children with both tonsillar hypertrophy and parental history of AT were also compared with all other participants regarding AHI and proportion of subjects with AHI >5 episodes/hour. Student t test was used for continuous variables that approached a normal distribution, Mann–Whitney U test for continuous variables that did not follow a normal distribution, and c2 test for categorical characteristics. The association between moderate-to-severe OSA and each explanatory variable was tested using Fisher exact test. The magnitude of association was expressed as OR and the corresponding 95% CI was calculated using Woolf estimate.20 Furthermore, the effect of parental history of AT and the other explanatory variables (sex, tonsillar hypertrophy, obesity, and physician-diagnosed wheezing) on OSA severity was assessed simultaneously by fitting a logit model.21 The significance of each variable in the model was evaluated using the respective change in deviance and the goodness-of-fit of the model was assessed using the residual deviance after fitting all explanatory variables.21 Two more logit models were fitted for evaluating the effect of paternal or maternal history of AT. The analysis was performed using R (www.r-project.com) and the logit models were fitted using GLIM 3.77 (Royal Statistical Society; London, United Kingdom). Sensitivity, specificity, positive and negative predictive values, and positive likelihood ratio of all explanatory variables that were significant in the logit models for prediction of moderate-to-severe OSA were calculated. Positive likelihood ratio was equal to sensitivity/(1 specificity). Similar calculations were carried out for combinations of parental history of AT with other significant explanatory variables.
Results A total of 798 children with history of snoring ($1 night/week) and without chronic disorders or prior AT underwent polysomnography during the study period. The median age of participants in the cohort was 5.8 years (range 2-15 years and IQR 4.5-7.7 years). Of all subjects, 553 (69.3%) had tonsillar hypertrophy, 206 (25.8%) were obese, and 214 (26.8%) had at least 1353
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1 parent who underwent AT in childhood. One hundred seventysix children (22.1% of 798 subjects) had AHI >5 episodes/hour. Children with parental history of AT did not differ from subjects without parental history of AT in terms of age, BMI z score, proportion of male subjects and frequencies of obesity, tonsillar hypertrophy, prematurity, or history of physiciandiagnosed wheezing treated with inhaled medications over the past year (Table I). The study group with history of AT in parents had significantly higher AHI compared with the group without such history (Table I). In addition, children with both tonsillar hypertrophy and history of AT in parents (n = 146) had significantly higher AHI than all other participants (n = 652): median 3.4 (IQR 1.5-6.6) episodes/ hour vs 2.1 (1-4.1) episodes/hour; P < .01. The former group differed significantly from the latter in the proportion of subjects with AHI >5 episodes/hour: 33.6% vs 19.5%; P < .01. Association of Parental History of AT with Moderate-to-Severe OSA Paternal, but not maternal history of AT, was significantly associated with the presence of moderate-to-severe OSA: OR (95% CI) = 1.51 (1.02-2.23), P = .04 and OR = 1.65 (0.98-2.78), P = .08, respectively. Parental history of AT was significantly related to AHI >5 episodes/hour: OR = 1.63 (1.13-2.33), P < .01 (Table II). The significant associations of paternal and parental history of AT with moderate-to-severe OSA persisted after fitting the logit models (Table II). The residual deviance of models 1 and 3 was significant (P < .01) indicating that additional risk factors should be incorporated in the models. Speculative Analysis In the primary analysis, it was assumed that all parents with history of AT (100%) underwent surgery as treatment for
Vol. 164, No. 6 SDB and the OR (95% CI) for moderate-to-severe OSA in their children was 1.63 (1.13-2.33) and P < .01. If SDB were the indication for surgery in only 70% of parents with history of AT and recurrent tonsillitis were the indication in the remaining parents (30%), provided that the margins of patient numbers with and without moderate-to-severe OSA and their ratio remained fixed (ie, equal to the observed ones), then OR would be 1.56 (1.04-2.33) and P = .03. Also, if only 50% of parents with history of AT underwent surgery for SDB and the remaining for recurrent tonsillitis, the OR for moderate-to-severe OSA in their children would be 1.54 (0.97-2.42) and P = .06. Sensitivity, Specificity, Positive and Negative Predictive Values, and Positive Likelihood Ratio of Parental History of AT and Other Explanatory Variables Significantly Associated with AHI >5 Episodes/hour Among the 4 significant explanatory variables in the logit models (tonsillar hypertrophy, obesity, parental history of AT, paternal history of AT), tonsillar hypertrophy had the highest sensitivity (81.8%) for finding AHI >5 episodes/ hour and the lowest specificity and positive likelihood ratio (Table III). Paternal and parental history of AT had lower sensitivity but higher specificity than tonsillar hypertrophy. When tonsillar hypertrophy was combined with parental history of AT, sensitivity was low but specificity and positive likelihood ratio were higher than those of tonsillar hypertrophy or obesity alone (Table III).
Discussion In the present cohort of children with snoring who had mostly tonsillar hypertrophy and a fairly low frequency of
Table I. Subjects’ characteristics and statistical comparisons of children without and with parental history of AT Variables Age, y Sex, male (%) BMI z score Obesity (%) Tonsillar hypertrophy (%) Physician-diagnosed wheezing treated with inhaled medications over the past year (%) Prematurity (<37 wk gestational age) Paternal history of adenoidectomy (%) Paternal history of tonsillectomy (%) Paternal history of AT (%) Maternal history of adenoidectomy (%) Maternal history of tonsillectomy (%) Maternal history of AT (%) AHI, episodes/h Respiratory arousal index, episodes/h Oxygen desaturation ($4%) of hemoglobin index, episodes/h % Sleep time with SpO2 <95% Subjects with AHI >5 episodes/h, %
Children without parental history of AT (n = 584) 6.3 2.4 342 (58.6) 0.7 1.4 153 (26.2) 407 (69.7) 257 (44) 9 (1.5) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2.1 (1-4.2) 0.9 (0.4-1.8) 2.6 (1.2-6) 1.1 (0.4-3.2) 115 (19.7)
Children with parental history of AT (n = 214) 6.3 2.7 125 (58.4) 0.7 1.4 53 (24.8) 146 (68.2) 98 (45.8) 3 (1.4) 90 (42.1) 127 (59.3) 168 (78.5) 61 (28.5) 53 (24.8) 75 (35) 2.8 (1.3-5.9) 1 (0.4-2.4) 3.3 (1.4-6.7) 1.5 (0.5-4.1) 61 (28.5)
P value .95 .97 .94 .68 .69 .62 .89 <.01 .14 .07 .10 <.01
SpO2, oxygen saturation of hemoglobin. Continuous variables are expressed as mean SD or median (IQR).
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Table II. Associations of parental history of AT or other potential risk factors with presence of moderate-to-severe OSA (AHI >5 episodes/hour) in the child with snoring Risk factors
Subjects with mod/severe OSA (n = 176)
Male sex Yes No Tonsillar hypertrophy Yes No Obesity Yes No Physician-diagnosed wheezingz Yes No Paternal history of AT Yes No Maternal history of AT Yes No Parental history of AT Yes No
Subjects without mod/severe OSA (n = 622)
OR (95% CI)
P value*
Logit model 1 OR (95% CI)†
Logit model 2 OR (95% CI)†
Logit model 3 OR (95% CI)†
109 (61.9%) 67 (38.1%)
358 (57.6%) 264 (42.4%)
1.20 (0.85-1.69)
.34
1.20 (0.84-1.70)
1.16 (0.82-1.65)
1.18 (0.83-1.68)
144 (81.8%) 32 (18.2%)
409 (65.8%) 213 (34.2%)
2.34 (1.54-3.56)
<.01
2.48 (1.63-3.79)
2.39 (1.57-3.65)
2.46 (1.61-3.76)
55 (31.2%) 121 (68.8%)
151 (24.3%) 471 (75.7%)
1.42 (0.98-2.05)
.06
1.54 (1.06-2.24)
1.51 (1.04-2.20)
1.53 (1.05-2.24)
78 (44.3%) 98 (55.7%)
277 (44.6%) 344 (55.4%)
0.99 (0.71-1.38)
.95
0.96 (0.68-1.35)
1.00 (0.71-1.42)
0.97 (0.68-1.36)
47 (26.7%) 129 (73.3%)
121 (19.5%) 501 (80.5%)
1.51 (1.02-2.23)
.04
1.63 (1.09-2.42)
-
-
23 (13.1%) 153 (86.9%)
52 (8.4%) 570 (91.6%)
1.65 (0.98-2.78)
.08
-
1.63 (0.95-2.77)
-
61 (34.7%) 115 (65.3%)
153 (24.6%) 469 (75.4%)
1.63 (1.13-2.33)
<.01
-
-
1.70 (1.18-2.46)
*Fisher exact test. †A logit model was fitted to evaluate the effect of each explanatory variable on OSA severity simultaneously. zTreated with inhaled medications over the past year.
obesity, parental history of AT was significantly associated with OSA severity. Children with tonsillar hypertrophy and at least 1 parent with history of AT during childhood had significantly higher AHI relative to all other studied subjects. The presence of these 2 clinical factors in combination increases the odds of finding moderate-to-severe OSA when polysomnography is performed in children with snoring. Our findings are in accordance with the results of a study by Lundkvist et al based on the Swedish Hospital Discharge Register that has shown substantially increased standardized incidence ratios of adenotonsillar or tonsillar hypertrophy in boys or girls with a parent diagnosed with OSA in adulthood by polysomnography compared with subjects without such a history.10 Both the present report and the epidemiologic investigation by Lundkvist et al emphasize the importance of familial characteristics in the pathogenesis of OSA. Because the effects of tonsillar hypertrophy and obesity, defined by using the BMI, have been taken into account in the logit models, the calculated risk of moderate-to-severe OSA in children with snoring and parental history of AT
probably reflects the contribution of other familial factors to the pathogenesis of SDB such as body fat distribution, craniofacial characteristics, or control of the upper airway neuromotor tone.4,22 Obesity has been recognized as a risk factor for OSA in childhood in population-based studies and tonsillar hypertrophy has been shown to increase the risk of obstructive SDB in hospital-based reports.4,23,24 In addition, children with history of AT in parents, or adenotonsillar or tonsillar hypertrophy in siblings, have pharyngeal lymphoid tissue hypertrophy more frequently than children without such history.8,25 Therefore, familial characteristics may affect adenotonsillar tissue growth rate during preschool years, development of obesity, and their contribution to the pathogenesis of sleep apnea.4,8,24 A secondary goal of this study was to evaluate the clinical usefulness of parental history of AT for the recognition of patients with symptoms of obstructive SDB who are at risk of moderate-to-severe OSA. Unfortunately, patient selection and prioritization of requests for polysomnography
Table III. Sensitivity, specificity, positive and negative predictive values, and positive likelihood ratios of variables associated with moderate-to-severe OSA among children with snoring referred for polysomnography Predictors
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Positive likelihood ratio
Tonsillar hypertrophy Obesity Paternal history of AT Parental history of AT Tonsillar hypertrophy + parental history of AT Obesity + parental history of AT Tonsillar hypertrophy + obesity + parental history of AT
81.8% 31.3% 26.7% 34.7% 27.8% 8% 5.1%
34.2% 75.7% 80.5% 75.4% 84.4% 93.7% 96.6%
26% 26.7% 28% 28.5% 33.6% 26.4% 30%
86.9% 79.6% 79.5% 80.3% 80.5% 78.3% 78.3%
1.24 1.29 1.37 1.41 1.78 1.27 1.50
Parental History of Adenotonsillectomy Is Associated with Obstructive Sleep Apnea Severity in Children with Snoring
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may be necessary in health systems with limited resources.26 Paternal or parental history of AT has lower sensitivity but much higher specificity in detecting moderate-to-severe OSA than tonsillar hypertrophy. Presence of tonsillar hypertrophy and parental history of AT increases the odds of finding moderate-to-severe OSA on polysomnography (positive likelihood ratio of approximately 2). Thus, children with snoring, tonsillar hypertrophy, and parental history of AT should be prioritized for polysomnography. Some characteristics and limitations of the current retrospective study need to be discussed to facilitate interpretation of its findings and application of its conclusions. First, the majority of children in our cohort were of preadolescent age and had tonsillar hypertrophy, whereas obesity affected only one-quarter. In this way, their characteristics were similar to those of subjects recruited in the Childhood Adenotonsillectomy Trial, a multicenter, randomized, controlled investigation assessing the efficacy of AT in pediatric SDB.12 These study characteristics may provide an explanation as to why tonsillar size was a predictor of OSA in this report but not in other published studies.4,27 Second, characteristics of our cohort may have been affected by the referral practices of primary care physicians in our area who frequently consider a child at risk for OSA when there is a history of snoring for at least 1 night per week. Third, it should be recognized that although SDB is the most common indication for AT in childhood, some of the parents may have undergone surgery because of recurrent tonsillitis or other reasons.9 Nevertheless, in our speculative analysis the association between parental history of AT and moderate-to-severe OSA remained significant or approached statistical significance (P = .06) even when it was assumed that only 70% or 50% of parents, respectively, underwent surgery for SDB. In conclusion, among preadolescent children with snoring who are referred for polysomnography by primary care physicians, those with tonsillar hypertrophy and parental history of AT have increased risk of moderate-to-severe OSA and represent 1 of the subgroups that should be prioritized for a sleep study. Considering the coexistence of tonsillar hypertrophy and parental history of AT as a risk factor for moderate-to-severe OSA may allow more efficient use of polysomnography in settings with limited resources. n Submitted for publication Aug 26, 2013; last revision received Dec 9, 2013; accepted Jan 10, 2014. Reprint requests: Athanasios G. Kaditis, MD, First University Department of Pediatrics, Aghia Sophia Children’s Hospital, Thivon and Papadiamantopoulou St, Athens 11527, Greece. E-mail: [email protected]
References 1. Katz ES, D’Ambrosio CM. Pathophysiology of pediatric obstructive sleep apnea. Proc Am Thorac Soc 2008;5:253-62. 2. Kaditis A, Kheirandish-Gozal L, Gozal D. Algorithm for the diagnosis and treatment of pediatric OSA: a proposal of two pediatric sleep centers. Sleep Med 2012;13:217-27. 1356
Vol. 164, No. 6 3. Mitchell RB, Pereira KD, Friedman NR. Sleep-disordered breathing in children: survey of current practice. Laryngoscope 2006;116:956-8. 4. Bixler EO, Vgontzas AN, Lin HM, Liao D, Calhoun S, Vela-Bueno A, et al. Sleep disordered breathing in children in a general population sample: prevalence and risk factors. Sleep 2009;32:731-6. 5. Redline S, Tishler PV, Tosteson TD, Williamson J, Kump K, Browner I, et al. The familial aggregation of obstructive sleep apnea. Am J Respir Crit Care Med 1995;151:682-7. 6. Rosen CL, Larkin EK, Kirchner HL, Emancipator JL, Bivins SF, Surovec SA, et al. Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity. J Pediatr 2003;142:383-9. 7. Goodwin JL, Vasquez MM, Silva GE, Quan SF. Incidence and remission of sleep-disordered breathing and related symptoms in 6- to 17-year old children–the Tucson Children’s Assessment of Sleep Apnea Study. J Pediatr 2010;157:57-61. 8. Kalampouka E, Moudaki A, Malakasioti G, PanaghiotopoulouGartagani P, Chrousos G, Kaditis AG. Family history of adenotonsillectomy as a risk factor for tonsillar hypertrophy and snoring in childhood. Pediatr Pulmonol 2013; http://dx.doi.org/10.1002/ppul.22830. Epub Date June 19, 2013. 9. Parker NP, Walner DL. Trends in the indications for pediatric tonsillectomy or adenotonsillectomy. Int J Pediatr Otorhinolaryngol 2011;75: 282-5. 10. Lundkvist K, Sundquist K, Li X, Friberg D. Familial risk of sleepdisordered breathing. Sleep Med 2012;13:668-73. 11. Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, Mitchell RB, Promchiarak J, Simakajornboon N, et al. Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study. Am J Respir Crit Care Med 2010;182: 676-83. 12. Marcus CL, Moore RH, Rosen CL, Giordani B, Garetz SL, Taylor HG, et al. A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med 2013;368:2366-76. 13. Nixon GM, Kermack AS, Davis GM, Manoukian JJ, Brown KA, Brouillette RT. Planning adenotonsillectomy in children with obstructive sleep apnea: the role of overnight oximetry. Pediatrics 2004;113: e19-25. 14. Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 2002;109:45-60. 15. Brodsky L. Modern assessment of tonsils and adenoids. Pediatr Clin North Am 1989;36:1551-69. 16. Rechtschaffen A, Kales A. A manual of standardized terminology: techniques and scoring systems for sleep stages of human subjects. Los Angeles: UCLA Brain Information Service/Brain Research Institute; 1968. 17. American Sleep Disorders Association. EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. Sleep 1992;15: 173-84. 18. American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir Crit Care Med 1996; 153:866-78. 19. Kaditis AG, Kalampouka E, Hatzinikolaou S, Lianou L, Papaefthimiou M, Gartagani-Panagiotopoulou P, et al. Associations of tonsillar hypertrophy and snoring with history of wheezing in childhood. Pediatr Pulmonol 2010;45:275-80. 20. Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet 1955;19:251-3. 21. McCullagh P, Nelder JA. Generalized linear models. 2nd ed. Boca Raton: Chapman and Hall/CRC; 1989. 22. Riha RL. Genetic aspects of the obstructive sleep apnoea/hypopnoea syndrome—is there a common link with obesity? Respiration 2009;78:5-17. 23. Kaditis AG, Lianou L, Hatzinikolaou S, Kalampouka E, GartaganiPanayiotopoulou P, Zintzaras E, et al. Tonsillar size in 2- to 14-yearold children with and without snoring. Pediatr Pulmonol 2009;44: 1216-22.
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June 2014 24. Papaioannou G, Kambas I, Tsaoussoglou M, PanaghiotopoulouGartagani P, Chrousos G, Kaditis AG. Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleepdisordered breathing. J Pediatr 2013;162:269-74.e4. 25. Friberg D, Sundquist J, Li X, Hemminki K, Sundquist K. Sibling risk of pediatric obstructive sleep apnea syndrome and adenotonsillar hypertrophy. Sleep 2009;32:1077-83.
ORIGINAL ARTICLES 26. Villa MP, Paolino MC, Castaldo R, Vanacore N, Rizzoli A, Miano S, et al. Sleep clinical record: an aid to rapid and accurate diagnosis of paediatric sleep disordered breathing. Eur Respir J 2013;41:1355-61. 27. Goodwin JL, Kaemingk KL, Mulvaney SA, Morgan WJ, Quan SF. Clinical screening of school children for polysomnography to detect sleep-disordered breathing—the Tucson Children’s Assessment of Sleep Apnea Study (TuCASA). J Clin Sleep Med 2005;1:247-54.
50 Years Ago in THE JOURNAL OF PEDIATRICS The Nature of Kidney Disease in Children Who Fail to Recover from Apparent Acute Glomerulonephritis Edelmann CM Jr, Greifer I, Barnett HLL. J Pediatr 1964;64:879-87
T
his article reported the clinical course of 42 children with a diagnosis of acute glomerulonephritis: in 39 of the children, it occurred after a clinical course characteristic of postinfectious glomerulonephritis, and 3 of the children demonstrated atypical courses with failure to improve and the development of chronic kidney disease. The authors focused on these latter 3 cases and concluded that these 3 children likely had: (1) an unusually severe form of acute glomerulonephritis with rapidly progressive glomerular disease; (2) an exacerbation of previously unrecognized renal disease; or (3) superimposition of acute post streptococcal glomerulonephritis on preexisting renal disease. The authors favored the concept of preexisting renal disease. Of the 3 atypical cases, one was noted to have markedly thickened glomerular basement membranes with irregular nodular areas on a kidney biopsy; perhaps this child had membranoproliferative glomerulonephritis, which was later described by Clark West as a form of hypocomplementemic glomerulonephritis.1 Of the other 2 children, 1 presented with recurring episode of edema, hematuria, and proteinuria over several years; on a kidney biopsy, it was noted that the degree of renal damage was quite severe, with 80% of glomeruli demonstrating scarring, and the acute inflammatory process in the remaining glomeruli was interpreted as a recurrent inflammatory process. In the third child, it was noted that the onset of gross hematuria was only 6 days after a respiratory infection suggesting a short latent period. Perhaps these 2 children had IgA nephropathy as later described by Berger2—since IgA nephropathy is noted to have a relapsing remitting course and to have the onset of gross hematuria within days of an infection. The authors of this report were quite astute in their conclusion that these children likely had an acute exacerbation of previously unrecognized renal disease, and each of the authors has made enormous contributions to pediatric nephrology. Sharon P. Andreoli, MD Byron P. and Francis D. Hollett Professor of Pediatrics Division of Pediatric Nephrology James Whitcomb Riley Hospital for Children Indianapolis, Indiana http://dx.doi.org/10.1016/j.jpeds.2014.01.016
References 1. West CD, McAdams AJ, et al. Hypocomplementemic and normo-complementemic persistent (chronic) glomerulonephritis: clinical and pathologic characteristics. J Pediatr 1965;67:1089-112. 2. Berger J. IgA glomerular deposits in renal disease. Transpl Proc 1969;1:939-44.
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