Sleep-Disordered Breathing In Obese Children.
Mecanisms, Diagnosis and Management

Author(s):

 Ha Trang Ha Trang
Paediatric Sleep Centre, Robert Debré University Hospital, Paris Diderot University, EA 7334 REMES, 48 boulevard Serurier, 75019 Paris (France)
View Author’s Full Biography

 

In order to develop normally, children spend long hours of the day sleeping, around 12-13 hours/day for pre-schoolers (age 3-5 years), 10-11 hours/day for school-aged (age 5-10 years) and 8-10 hours/day for adolescents (age 14-16 years). Although all the functions of sleep remain unfully understood, sleep is vital for restoration of body systems, energy conservation, brain development and memory consolidation, as shown by the adverse effects caused by sleep deprivation.

During sleep, the respiratory system, including control of breathing, control of respiratory muscles and respiratory mechanics, meets challenging conditions. Sleep-disordered breathing (SDB) may occur as a consequence of imbalance between the different forces controlling the adjustment of breathing during sleep. SDB comprises a wide spectrum of sleep-related breathing abnormalities, among which obstructive sleep apnoea syndrome (OSAS) that is defined as the presence of obstructive apneas or hypopneas caused by recurrent obstruction of the upper airway during sleep, and obesity-hypoventilation syndrome (OHS) that is defined as the association of obesity and chronic daytime hypercapnia (PaCO2 ≥ 45 mmHg) in the absence of other causes of hypoventilation [1-2].

OSAS is by far the most common form of SDB. In the general population, the prevalence rate of OSAS is estimated to be at 2% of the children, with a peak incidence between 2 and 8 years. The main cause is enlarged tonsils and adenoids. Unrecognized and untreated OSAS may affect nearly every major system, causing daytime fatigue, growth delay, cardiovascular dysfunction, behavior disorders, cognitive impairment, etc… [1-4]. In obese children, SDB encompasses OSAS and OHS. Obesity is recognized as an important risk factor for OSAS. It significantly affects its clinical presentation and its management scheme. OHS is thus far rarely reported in obese children but its prevalence is likely to be underestimated [5-8].

The present chapter focuses on the clinical aspects of SDB in children with common obesity and provides an overview on mechanisms, diagnosis and management. Aspects regarding syndromic or genetic obesity will not be addressed.

 

Mechanisms for SDB in Obese Children

The pathophysiological factors underlying OSAS can be grossly divided into anatomical factors that reduce upper airway internal calibre and those that control upper airway opening. OSAS occurs when factors that aim to maintain upper airway open are overwhelmed by those that obstruct or close the airway during sleep. Therefore, partial or total obstruction of upper airway may result in obstructive apneas or hypopneas (i.e. cessation or reduction of the airflow, respectively), subsequent periods of desaturation (defined as decrease of the oxygen saturation) over the night, sometimes associated with hypercapnia and sleep disruption [2].

sleep-disordered-breathing-in-obese-children-1

Figure 1. Multiple mechanisms involved in OSAS in the obese. Whereas enlarged tonsils and adenoids are the main cause found in the non-obese child, a number of additional factors likely contribute to generating OSAS in the obese.

 

 

In normally-weighted children, narrowed upper airway during sleep is mainly caused by anatomical obstacles such as large tonsils or adenoids. Figure 1 shows a number of additional factors thought to combine, further promoting OSAS in the obese. First, increased pharyngeal collapsibility, fat deposition in the subcutaneous tissue surrounding the airway in the cervical region, which reduces its internal caliber, laryngeal dysfunction-produced expiratory braking during sleep may contribute to an even more severe obstruction of the upper airway in the obese [9-13]. Second, obesity-related alterations in respiratory mechanisms further prompt impairment of gas exchange in case of disordered breathing. Restriction of lung volumes is mainly at the expense of functional residual capacity and expiratory reserve volume [14-15]. Fat deposition in the subcutaneous tissue surrounding the thorax and abdomen decreases chest wall compliance, increases intra-abdominal pressure, both factors limiting diaphragmatic excursion, thus producing shallow tidal breathing and increased work of breathing. Third, abnormalities of the central control of breathing have been demonstrated in mutant obese mice. Data remain inconsistent in humans, with studies showing decreased, unchanged or increased ventilatory responses to chemical stimuli [16-18]. Finally, one may hypothesize the role of epigenetic factors as obesity and OSAS share a number of candidate genes involved in the regulation of many pathways, metabolism, energy homeostasis, control of respiration and arousals [17-18]. However, the degree of responsibility of each of these factors in generating OSAS in the obese is more difficult to determine and requires further investigation.

Obesity is not associated in a straightforward manner with OSAS [13,19]. Worldwide studies show that not all obese subjects develop OSAS. This phenomenon suggests that susceptibility of the obese to OSAS may depend on individual physiological responses to obesity-induced physiological changes. Interestingly, a recent study shows that obese adolescents with OSAS exhibit a much less vigorous genioglossus muscular activity during sleep than those without OSAS, thus preventing the upper airway remain open [20]. Obese adolescents with OSAS or without OSAS have increased ventilatory responses to hypercapnia during wakefulness when compared to lean controls. However, during sleep, obese adolescents with OSAS show lower changes in response to hypercapnia of minute ventilation, inspiratory flow and inspiratory volume compared to those without OSAS. The authors hypothesized that central drive may play a significant role in adapting ventilation to hypercapnia [21].

OHS occurs when obesity is associated with daytime alveolar hypoventilation. In most of the cases, daytime hypoventilation comes in addition to chronic sleep hypoventilation caused by severe OSAS. In rare cases, it may involve predominantly altered central drive of breathing [5-8].

 

Obese Children are more exposed to SDB

Epidemiological studies show that obesity, defined as a body mass index (BMI) higher than 28 kg/m2, increases the risk for OSAS by 4-5 times in a group of 399 children aged 2-18 years. Beyond a normal BMI adjusted for age and gender, increases of 1 kg/m2 of the BMI increase the risk for OSAS by 12% and increase the number of apneas and hypopneas per hour of sleep by 3%. In the Cleveland Children Sleep and Health Study including 850 children from 8 to 11 years of age, the black American ethnicity is an additional risk for OSAS of 4-6 times in obese children. The presence of large tonsils in obese younger children, and a BMI higher than the 95th percentile in obese adolescents are predictors of significant OSAS [22-23].

Although obesity is recognized as a risk factor for OSAS, the real prevalence of OSAS remains difficult to determine in this specific population when considered as a whole. Early studies found that 24 to 60% of the obese children suffer from OSAS. However, these studies mostly included mono-center and/or small samples of patients, the latter being often referred for suspected respiratory disorders or having a morbid obesity (defined as a BMI >30 kg/m2 or weight >180% of the ideal weight) [24-26].

More recently, studies aiming to determine the prevalence of OSAS use community-based samples of obese children. A cross sectional prospective, multicenter study included 245 children (3-14 years of age, BMI higher than 95ème percentile adjusted for age and gender). Their mean age was 10.8 ± 2.6 years and BMI 28.0 ± 4.7 kg/m2. Using a cut-off value for presence of OSAS as an apnea-hypopnea index ≥ 3 /h of total sleep time, the prevalence rate was found at 21.5% [27].

 

Presentation of SDB in Obese Children

A constellation of clinical symptoms are suggestive of OSAS. Those found in obese children are not different from those in the non obese. Mechanisms underlying these symptoms are not equivocal. Moreover, a number of obesity-related co-morbidities may be associated (neurobehavioral, cardiovascular, metabolic disorders, etc…), thus further resulting in difficulties for the interpretation [28-29]. It is not uncommon that clinical symptoms are neglected or underestimated by children and their families, and often do not constitute reasons for consultation for most obese children. Therefore, it is important to search systematically in all children referred for obesity.

Typically, nocturnal and diurnal symptoms may be present in children suffering of OSAS. Parents most frequently report nocturnal snoring, sometimes notice periods of labored breathing type mouth breathing or breathing pauses followed by large movements of respiratory resumption and arousals. Nocturnal sweating and secondary enuresis are sometimes noticed. Night sleep can be agitated and restless, with nighttime awakenings. The morning awakening is slow, sometimes with headaches. There is a tendency for fatigue and daytime sleepiness, for behavioral problems or learning difficulties, type attention or memory deficit.

Scores calculated from sleep questionnaires are shown not to predict the presence of OSAS, neither do they correlate with its severity. Larger neck circumference was found in obese children with OSAS than in those without it [23]. Waist-to-height ratio has been shown to distinguish OSAS from habitual snoring in obese children [30]. Presence of large tonsils is a strong predictor for OSAS. In contrast, lung function tests performed during wakefulness contribute poorly to prediction of OSAS. Awake sitting and supine respiratory resistance was found increased in most obese children; nevertheless they were associated neither with the presence nor with the severity of OSAS [31].

 

sleep-disordered-breathing-in-obese-children-2

Figure 2. Polysomnographic tracing showing repeated obstructive apnoeas during sleep, associated with respiratory muscles recruitment, desaturation, hypercapnia, bradycardia and micro-arousals. From top to bottom : C4A2/O2A2/C3A1, electroencephalogram ; REOG, LEOG, right and left electro-oculograms ; GG, genioglossus electromyogram ; EKG, electrocardiogram ; RR, cardiac period ; NBFL, naso-buccal airflow ; THO, ABD, thoracic and abdominal respiratory movements ; SaO2, oxygen saturation measured using pulse oximetry ; O2G, plethysmographic signal of SaO2 ; EtCO2, end-tidal CO2 ; CO2G, signal of capnography.

 

 

The key examination for diagnosis of OSAS is polysomnography (PSG). PSG is a test that simultaneously records neurophysiological parameters (electroencephalogram, electrooculogram, genioglossus electromyogram), respiration (airflow using pressure transducer and naso-oral thermistor, thoracic and abdominal respiratory movements, oxygen saturation using pulse oximetry, transcutaneous or end-tidal PCO2) and heart rate over a night period performed in a sleep centre. OSAS is confirmed by an increased obstructive apneas-hypopneas index (OIAH) (defined as the number of apneas and hypopneas per hour of total sleep time). Obstructive apnoea is a cessation of airflow associated with persistent or increased respiratory efforts (Figure 2). Hypopnoea is a decrease in the amplitude of the airflow associated with desaturation and/or arousal. Apnoeas and hypopnoeas occur predominantly during rapid eye movement sleep (Figure 3). A flow limitation breathing pattern may be caused by partial upper airway obstruction and is associated with the recruitment of accessory respiratory muscles. Respiratory efforts are evidenced by increased amplitude of out-of-phase respiratory movements of the thorax and the abdomen. Repetitive obstructive apnoeas or hypopnoeas may induce oxygen desaturation, and sometimes alveolar hypoventilation (hypercapnia). Sleep may be disrupted by frequent respiratory event-induced arousals or awakenings throughout the night (Figure 4). PSG not only allows identification of OSAS, but also assessment of its severity.

 

sleep-disordered-breathing-in-obese-children-3

Figure 3. Two obstructive apnoeas associated with out-of-phase respiratory movements of thorax and abdomen, desaturation, hypercapnia and movement arousals. See figure 2 for definitions of channels.

 

 

sleep-disordered-breathing-in-obese-children-4

Figure 4. Sleep data of one night showing the occurrence of many obstructive apnoeas-hypopnoeas, concomitant desaturation, and frequent awakenings during sleep. From top to bottom: SaO2, oxygen saturation; HR, heart rate; CA, central apnoea; OA, obstructive apnoea; MA, mixed apnoea, Stage of sleep; ACT, actimetry; REM, rapid eye movement sleep; EtCO2, end-tidal PCO2.

 

 

Some PSG-based studies reported that the degree of obesity correlates with the apnoea index and inversely correlates with the lowest value of oxygen saturation during sleep. Mean end-tidal PCO2 was found to be higher in children with a more severe obesity (body weight higher than 200% of its ideal value) than in the others. However, no significant correlations exist between PSG-based variables (respiratory event indices, percent of sleep time with oxygen saturation lower than 90%, percent of sleep time with end-tidal PCO2 higher than 50 mm Hg, arousal indices) and BMI, or age or gender [7,14,24-27].

OSAS in obese children differ in many aspects from that in obese adults. Excessive daytime somnolence which is a hallmark of obese adults with SDB is rarely noticed in obese children. Sleep latency objectively measured by the multiple sleep latency tests is found to be normal in obese children with OSAS [32-33].

More recently, a study reported the utility of a portable recording device for screening OSAS in a group of 25 obese adolescents [34]. These devices only record respiratory parameters (airflow, respiratory movements, and oxygen saturation) and heart rate. They do not record neurophysiological parameters, therefore sleep data are not available. The validity and effectiveness of these partial diagnostic tools are yet to be determined in larger sample of patients.

OHS with daytime hypercapnia is a clinical presentation found in a number of obese adults (xxx), but has been reported in a few obese children only [5-8].

The exploding rate of obesity in children worldwide in the last decadeshas dramatically impacted the prevalence of SDB worldwide. These results in anincrease in the prevalenceofmorbiditiesassociated with obesity, including metabolic,cardiovascularand respiratory diseases.

 

Management of SDB in Obese Children

Management of obese children with OSAS must be comprehensive. Co-morbidities should be identified and treated. Weight loss is the primary goal and depends on complying with dietary hygiene. In a study performed in a group of children and adolescents with severe obesity (mean BMI z-score 2.7), weight loss achieved during 5 months resulted in a reduction of BMI z-score by 0.9 and significantly decreased the severity of OSAS [35]. Tonsillectomy and/or adenoidectomy may be recommended if tonsils and/or adenoids are hypertrophied, but may induce a certain increase in BMI. Postoperative complications are more frequent in obese children than the non-obese, largely secondary to mechanical problems. Postoperative hospital surveillance is recommended in severely obese children. Adenoido-tonsillectomy has been shown to be effective in obese children with OSAS, however the rate of OSAS relapse is higher than in normally-weighted children [36-40]. When weight loss is not possible or in case of persisted OSAS after tonsillectomy, noninvasive ventilation on nasal mask continuous positive airway pressure has proved its feasibility and effectiveness to normalize gas exchange. It can be conducted in the child’s home, under control by a specialized pediatric team [1,7].

 

Conclusion

Obesity increases prevalence of SDB in children and affects outcomes. Polysomnography is the key examination for identifying SDB and rating its severity. Weight loss should be the main objective, associated with tonsillectomy and/or non-invasive ventilation.

Management of obesity in children should include identification and treatment of SDB. A body of evidence is now available showing that sleep duration shortening and sleep fragmentation induced by SDB not only negatively impact on daytime vigilance and cognitive function, but may in turn favor obesity and its maintenance [41-42].

 

Abbreviations

AHI, apnoea-hypopnoea index;

BMI, body mass index;

OAHI, obstructive apnoea-hypopnoea index;

OHS, obesity-hypoventilation syndrome;

OSAS, obstructive sleep apnoea syndrome;

SDB, sleep-disordered breathing

 

References

  1. Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012 Sep;130(3):576-84. doi: 10.1542/peds.2012-1671. Epub 2012 Aug 27.
  2. Arens R, Marcus CL Pathophysiology of upper airway obstruction: a developmental perspective..Sleep. 2004 Aug 1;27(5):997-1019.
  3. Sans-Capdevila O, Gozal D.Neurobiological consequences of sleep apnea syndrome in children].Rev Neurol. 2008 Dec 16-31;47(12):659-64. Review. Spanish.
  4. Bhattacharjee R, Kheirandish-Gozal L, Pillar G, Gozal D. Cardiovascular complications of obstructive sleep apnea syndrome: evidence from children. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):416-33. doi: 10.1016/j.pcad.2008.03.002. Review.
  5. Bourne RA, Maltby CC, Donaldson JD: Obese hypoventilation syndrome of early childhood requiring ventilatory support. Int J Pediatr Otorhinolaryngol 1988;16:61–68.
  6. Riley DJ, Santiago TV, Edelman NH: Complications of obesity-hypoventilation syndrome in childhood. Am J Dis Child 1976;130:671–674.
  7. Tauman R, Gozal D. Obesity and obstructive sleep apnea in children. Paediatr Respir Rev. 2006 Dec;7(4):247-59. Epub 2006 Oct 30. Review.
  8. Berger KI, Ayappa I, Chatr-Amontri B, Marfatia A, Sorkin IB, Rapoport DM, Goldring RM: Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. Chest 2001;120:1231–1238.
  9. Verhulst SL, Van Gaal L, De Backer W, Desager K. The prevalence, anatomical correlates and treatment of sleep-disordered breathing in obese children and adolescents. Sleep Med Rev. 2008;12(5):339-346.
  10. Huang J, Pinto SJ, Yuan H, et al. Upper airway collapsibility and genioglossus activity in adolescents during sleep. Sleep 2012;35(10):1345-1352.
  11. Yuan H, Schwab RJ, Kim C, et al. Relationship between body fat distribution and upper airway dynamic function during sleep in adolescents. Sleep 2013;36(8):1199-207.
  12. Tuck SA, Dort JC, Remmers JE. Braking of expiratory airflow in obese pigs during wakefulness. Respir Physiol 2001; 128: 241-245
  13. Slaats MA, Van Hoorenbeeck K, Van Eyck A, et al. Upper airway imaging in pediatric obstructive sleep apnea syndrome. Sleep Med Rev 2014. pii: S1087-0792(14)00082-3. doi: 10.1016/j.smrv.2014.08.001.
  14. Marcus CL, Curtis S, Koerner CB, Joffe A, Serwint JR, Loughlin GM. Evaluation of pulmonary function and polysomnography in obese children and adolescents. Pediatr Pulmonol 1996;21:176–183.
  15. Inselman LS, Milanese A, Deurloo A: Effect of obesity on pulmonary function in children. Pediatr Pulmonol 1993;16:130-137
  16. Tankersley C, Kleeberger S, Russ B, Schwartz A, Smith P: Modified control of breathing in genetically obese (ob/ob) mice. J Appl Physiol 1996;81:716–723.
  17. O’Donnell CP, Tanskerley CG, Polotsky VP, Schwartz AR, Smith PL: Leptin, obesity, and respiratory function. Respir Physiol 2000;119:173–180.
  18. Phipps PR, Starritt E, Caterson I, Grunstein RR: Association of serum leptin with hypoventilation in human obesity. Thorax 2002;57:75–76.
  19. Kohler MJ, van den Heuvel CJ. Is there a clear link between overweight/obesity and sleep disordered breathing in children? Sleep Med Rev 2008 Oct;12(5):347-361.
  20. Huang J, Pinto SJ, Yuan H, Katz ES, Karamessinis LR, Bradford RM, et al. Upper airway collapsibility and genioglossus activity in adolescents during sleep. Sleep. 2012;35(10):1345-1352.
  21. Yuan H, Pinto SJ, Huang J, et al. Ventilatory responses to hypercapnia during wakefulness and sleep in obese adolescents with and without obstructive sleep apnea syndrome. Sleep 2012;35(9):1257-1267.
  22. Redline S, Tishler PV, Schluter M, Aylor J, Clark K, Graham G: Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med 1999;159:1527–1532.
  23. Goodwin JL, Kaemingk KL, Fregosi RF, Rosen GM, Morgan WJ, Sherrill DL, Quan SF. Clinical outcomes associated with sleep-disordered breathing in Caucasian and Hispanic children–the Tucson Children’s Assessment of Sleep Apnea study (TuCASA). Sleep. 2003;26(5):587-591.
  24. Mallory GB, Fiser DH, Jackson R: Sleep-associated breathing disorders in morbidly obese children and adolescents. J Pediatr 1989;115:892–897.
  25. Silvestri JM, Weese-Mayer DE, Bass MT, Kenny AS, Hauptman SA, Pearsall SM: Polysomnography in obese children with a history of sleep-associated breathing disorders. Pediatr Pulmonol 1993;16:124–129.
  26. Chay OM, Goh A, Abisheganaden J, Tang J, Lim WH, Chan YH, Wee MK, Johan A, John AB, Cheng HK, Lin M, Chee T, Rajan U, Wang S, Machin D: Obstructive sleep apnea syndrome in obese Singapore children. Pediatr Pulmonol 2000;29:284–290.
  27. Alonso-Álvarez ML, Cordero-Guevara JA, Terán-Santos J, et al. Obstructive sleep apnea in obese community-dwelling children: the NANOS study. Sleep. 2014 May 1;37(5):943-9. doi: 10.5665/sleep.3666.
  28. Xanthopoulos MS, Gallagher PR, Berkowitz RI, Radcliffe J, Bradford R, Marcus CL. Neurobehavioral Functioning in Adolescents With and Without Obesity and Obstructive Sleep Apnea.   Sleep 2014 Oct 17. pii: sp-00197-14. [Epub ahead of print].
  29. Westerståhl M, Hedvall Kallerman P, Hagman E, Ek AE, Rössner SM, Marcus C. Nocturnal blood pressure non-dipping is prevalent in severely obese, prepubertal and early pubertal children. Acta Paediatr. 2014;103(2):225-30.
  30. de Sousa Caixêta JA, Saramago AM, de Cácia Pradella-Hallinan ML, Moreira GA, Tufik S, Fujita RR. Waist-to-height ratio distinguish obstructive sleep apnea from primary snoring in obese children. Sleep Breath. 2014 May 9. [Epub ahead of print].
  31. Trang H, Frelut ML, Navarro J, Gaultier C: Absence of correlation between clinical score, respiratory resistance, and obstructive sleep apnea in children with morbid obesity (abstract). 16th Congress of the European Sleep Research Society, Reykjavik, 2002.
  32. Gozal D, Kheirandish-Gozal L. Obesity and excessive daytime sleepiness in prepubertal children with obstructive sleep apnea. Pediatrics 2009 ;123(1):13-8.
  33. Moraleda-Cibrián M, O’Brien LM. Sleep duration and body mass index in children and adolescents with and without obstructive sleep apnea. Sleep Breath. 2014;18(3):555-61.
  34. Lesser DJ, Haddad GG, Bush RA, Pian MS .The utility of a portable recording device for screening of obstructive sleep apnea in obese adolescents. J Clin Sleep Med. 2012 Jun 15;8(3):271-7. doi: 10.5664/jcsm.1912.
  35. Verhulst SL, Franckx H, Van Gaal L, De Backer W, Desager K. The effect of weight loss on sleep-disordered breathing in obese teenagers. Obesity (Silver Spring). 2009;17(6):1178-83.
  36. Shine NP, Lannigan FJ, Coates HL, Wilson A. Adenotonsillectomy for obstructive sleep apnea in obese children: effects on respiratory parameters and clinical outcome. Arch Otolaryngol Head Neck Surg. 2006 Oct;132(10):1123-7.
  37. Chan DK, Jan TA, Koltai PJ. Effect of obesity and medical comorbidities on outcomes after adjunct surgery for obstructive sleep apnea in cases of adenotonsillectomy failure. Arch Otolaryngol Head Neck Surg. 2012;138(10):891-6.
  38. Soultan Z, Wadowski S, Rao M, Kravath RE: Effect of treating obstructive sleep apnea by tonsillectomy and/or adenoidectomy on obesity in children. Arch Pediatr Adolesc Med 1999;153:33–37.
  39. Kang KT, Chou CH, Weng WC, Lee PL, Hsu WC. Associations between adenotonsillar hypertrophy, age, and obesity in children with obstructive sleep apnea. PLoS One. 2013;8(10):e78666. doi: 10.1371/journal.pone.0078666. eCollection 2013.
  40. Nafiu OO, Prasad Y, Chimbira WT. Association of childhood high body mass index and sleep disordered breathing with perioperative laryngospasm. Int J Pediatr Otorhinolaryngol. 2013 Dec;77(12):2044-8.
  41. Van Cauter E, Knutson KL. Sleep and the epidemic of obesity in children and adults. Eur J Endocrinol. 2008 Dec;159 Suppl 1:S59-66.
  42. Wang Y, Carreras A, Lee S, et al. Chronic sleep fragmentation promotes obesity in young adult mice. Obesity (Silver Spring). 2014 Mar;22(3):758-62.

 

0 Comments

Leave a reply

Your email address will not be published. Required fields are marked *

*

Send this to a friend