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CC BY-NC-ND 4.0 · Journal of Health and Allied Sciences NU 2022; 12(04): 356-360
DOI: 10.1055/s-0042-1742371
Review Article

Inflammatory Biomarkers for Children with Sleep Disorders: A Review

Nagashree Prabhu
1   Department of Pediatric and Preventive Dentistry, AB Shetty Memorial Institute of Dental Sciences, Nitte (Deemed to be University), Mangalore, Karnataka, India
,
Vabitha Shetty 
1   Department of Pediatric and Preventive Dentistry, AB Shetty Memorial Institute of Dental Sciences, Nitte (Deemed to be University), Mangalore, Karnataka, India
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Abstract

Introduction Obstructive sleep apnea (OSA) syndrome is a highly prevalent problem in children. Unfortunately sleep disorders in children remain largely unreported and underdiagnosed due to various reasons. Overnight in-laboratory polysomnography (PSG) is the gold standard diagnostic method for OSA; however, it has several drawbacks. Hence there is a need for simple alternative diagnostic methods, such as biomarkers. Children with OSA seem to have an inflammatory aspect to its pathophysiology; thus the rationale for evaluating inflammatory biomarkers.

Objective This narrative review aimed to evaluate the existing knowledge regarding inflammatory biomarkers for children with sleep disorders.

Materials and Methods An extensive search of all literature linked to the topic was performed in PubMed, Medline, EBSCOhost, Cochrane library database CENTRAL, and Google Scholar search engine. Keywords used in the search included combinations of the following: inflammation, sleep disorders, children, and biomarkers. Studies in the list of references of relevant literature were also included. A total of 155 articles published in the period from 1997 to 2021 were initially included in this review. Selected articles comprised original research, meta-analysis, and systematic reviews.

Results Studies have mainly centered their investigations on serum inflammatory biomarkers, namely interleukin-6, tumor necrosis factor-α, and C-reactive protein. Very few studies investigated salivary inflammatory biomarkers in children.

Conclusion Evidence suggests that children with sleep disorders have elevated levels of salivary as well as serum inflammatory biomarkers in comparison to normal healthy children. Also increased levels of these biomarkers correlate with disease severity. However, more studies are needed to determine the sensitivity and specificity of salivary inflammatory biomarkers for children with sleep disorders.

Keywords

inflammation - sleep disorders - children - biomarkers

Author's Contributions

V. Shetty has been conducting research in the field of sleep disorders in children since past 5 years. She has two published studies and one under review in this area of research. She has played a significant role in review of literature and article writing. N. Prabhu has played an active role in data collection and article writing.




Publication History

Received: 27 August 2021

Accepted: 07 December 2021

Article published online:
09 February 2022

© 2022. Nitte (Deemed to be University). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Gislason T, Benediktsdóttir B. Snoring, apneic episodes, and nocturnal hypoxemia among children 6 months to 6 years old. An epidemiologic study of lower limit of prevalence. Chest 1995; 107 (04) 963-966
    CrossrefPubMedGoogle Scholar
  • 2 Redline S, Tishler PV, Schluchter 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 (5 Pt 1): 1527-1532
    CrossrefPubMedGoogle Scholar
  • 3 Huynh NT, Morton PD, Rompré PH, Papadakis A, Remise C. Associations between sleep-disordered breathing symptoms and facial and dental morphometry, assessed with screening examinations. Am J Orthod Dentofacial Orthop 2011; 140 (06) 762-770
    CrossrefPubMedGoogle Scholar
  • 4 Dayyat E, Kheirandish-Gozal L, Gozal D. Childhood obstructive sleep apnea: one or two distinct disease entities?. Sleep Med Clin 2007; 2 (03) 433-444
    CrossrefPubMedGoogle Scholar
  • 5 Owens JA. The practice of pediatric sleep medicine: results of a community survey. Pediatrics 2001; 108 (03) E51
    CrossrefPubMedGoogle Scholar
  • 6 Marcus CL, Brooks LJ, Draper KA. et al; American Academy of Pediatrics. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2012; 130 (03) e714-e755
    CrossrefPubMedGoogle Scholar
  • 7 Gozal D. Serum, urine, and breath-related biomarkers in the diagnosis of obstructive sleep apnea in children: is it for real?. Curr Opin Pulm Med 2012; 18 (06) 561-567
    CrossrefPubMedGoogle Scholar
  • 8 Lamm C, Mandeli J, Kattan M. Evaluation of home audiotapes as an abbreviated test for obstructive sleep apnea syndrome (OSAS) in children. Pediatr Pulmonol 1999; 27 (04) 267-272
    CrossrefPubMedGoogle Scholar
  • 9 Sivan Y, Kornecki A, Schonfeld T. Screening obstructive sleep apnoea syndrome by home videotape recording in children. Eur Respir J 1996; 9 (10) 2127-2131
    CrossrefPubMedGoogle Scholar
  • 10 Andreu AL, Chiner E, Sancho-Chust JN. et al. Effect of an ambulatory diagnostic and treatment programme in patients with sleep apnoea. Eur Respir J 2012; 39 (02) 305-312
    CrossrefPubMedGoogle Scholar
  • 11 Atkinson Jr AJ, Colburn WA, DeGruttola VG. et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinl pharmacol Ther 2001; 69 (03) 89-95
    CrossrefPubMedGoogle Scholar
  • 12 Friberg D. Heavy snorer's disease: a progressive local neuropathy. Acta Otolaryngol 1999; 119 (08) 925-933
    CrossrefPubMedGoogle Scholar
  • 13 Ibáñez-Del Valle V, Navarro-Martínez R, Ballestar-Tarín ML, Cauli O. Salivary inflammatory molecules as biomarkers of sleep alterations: a scoping review. Diagnostics (Basel) 2021; 11 (02) 278
    CrossrefPubMedGoogle Scholar
  • 14 Suzuki YJ, Jain V, Park A-M, Day RM. Oxidative stress and oxidant signaling in obstructive sleep apnea and associated cardiovascular diseases. Free Radic Biol Med 2006; 40 (10) 1683-1692
    CrossrefPubMedGoogle Scholar
  • 15 Lavie L. Sleep-disordered breathing and cerebrovascular disease: a mechanistic approach. Neurol Clin 2005; 23 (04) 1059-1075
    CrossrefPubMedGoogle Scholar
  • 16 McCord JM. The evolution of free radicals and oxidative stress. Am J Med 2000; 108 (08) 652-659
    CrossrefPubMedGoogle Scholar
  • 17 Haddad JJ. Pharmaco-redox regulation of cytokine-related pathways: from receptor signaling to pharmacogenomics. Free Radic Biol Med 2002; 33 (07) 907-926
    CrossrefPubMedGoogle Scholar
  • 18 Zhang D, Sun M, Samols D, Kushner I. STAT3 participates in transcriptional activation of the C-reactive protein gene by interleukin-6. J Biol Chem 1996; 271 (16) 9503-9509
    CrossrefPubMedGoogle Scholar
  • 19 Schäfer H, Pauleit D, Sudhop T, Gouni-Berthold I, Ewig S, Berthold HK. Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Chest 2002; 122 (03) 829-839
    CrossrefPubMedGoogle Scholar
  • 20 Htoo AK, Greenberg H, Tongia S. et al. Activation of nuclear factor kappaB in obstructive sleep apnea: a pathway leading to systemic inflammation. Sleep Breath 2006; 10 (01) 43-50
    CrossrefPubMedGoogle Scholar
  • 21 Yamauchi M, Tamaki S, Tomoda K. et al. Evidence for activation of nuclear factor kappaB in obstructive sleep apnea. Sleep Breath 2006; 10 (04) 189-193
    CrossrefPubMedGoogle Scholar
  • 22 Archontogeorgis K, Nena E, Papanas N, Steiropoulos P. Biomarkers to improve diagnosis and monitoring of obstructive sleep apnea syndrome: current status and future perspectives. Pulm Med 2014; 2014: 930535
    CrossrefPubMedGoogle Scholar
  • 23 Kheirandish-Gozal L, Gozal D. Sleep Disordered Breathing in Children. New York: Springer; 2012
    CrossrefGoogle Scholar
  • 24 Tillett WS, Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of Pneumococcus. J Exp Med 1930; 52 (04) 561-571
    CrossrefPubMedGoogle Scholar
  • 25 Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018; 9: 754
    CrossrefPubMedGoogle Scholar
  • 26 Du Clos TW, Mold C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res 2004; 30 (03) 261-277
    CrossrefPubMedGoogle Scholar
  • 27 Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340 (06) 448-454
    CrossrefPubMedGoogle Scholar
  • 28 Ciubotaru I, Potempa LA, Wander RC. Production of modified C-reactive protein in U937-derived macrophages. Exp Biol Med (Maywood) 2005; 230 (10) 762-770
    CrossrefPubMedGoogle Scholar
  • 29 Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Kim J. C-reactive protein and obstructive sleep apnea syndrome in children. Front Biosci (Elite Ed) 2012; 4: 2410-2422
    CrossrefPubMedGoogle Scholar
  • 30 Tauman R, Ivanenko A, O'Brien LM, Gozal D. Plasma C-reactive protein levels among children with sleep-disordered breathing. Pediatrics 2004; 113 (06) e564-e569
    CrossrefPubMedGoogle Scholar
  • 31 Larkin EK, Rosen CL, Kirchner HL. et al. Variation of C-reactive protein levels in adolescents: association with sleep-disordered breathing and sleep duration. Circulation 2005; 111 (15) 1978-1984
    CrossrefPubMedGoogle Scholar
  • 32 Kheirandish-Gozal L, Capdevila OS, Tauman R, Gozal D. Plasma C-reactive protein in nonobese children with obstructive sleep apnea before and after adenotonsillectomy. J Clin Sleep Med 2006; 2 (03) 301-304
    CrossrefPubMedGoogle Scholar
  • 33 Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations and systemic inflammation in obstructive sleep apnea among nonobese and obese prepubertal children. Am J Respir Crit Care Med 2008; 177 (10) 1142-1149
    CrossrefPubMedGoogle Scholar
  • 34 Li AM, Chan MH, Yin J. et al. C-reactive protein in children with obstructive sleep apnea and the effects of treatment. Pediatr Pulmonol 2008; 43 (01) 34-40
    CrossrefPubMedGoogle Scholar
  • 35 Ingram DG, Matthews CK. Effect of adenotonsillectomy on c-reactive protein levels in children with obstructive sleep apnea: a meta-analysis. Sleep Med 2013; 14 (02) 172-176
    CrossrefPubMedGoogle Scholar
  • 36 Bhattacharjee R, Kheirandish-Gozal L, Kaditis AG, Verhulst SL, Gozal D. C-reactive protein as a potential biomarker of residual obstructive sleep apnea following adenotonsillectomy in children. Sleep (Basel) 2016; 39 (02) 283-291
    CrossrefPubMedGoogle Scholar
  • 37 Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 1975; 72 (09) 3666-3670
    CrossrefPubMedGoogle Scholar
  • 38 Seymour HE, Worsley A, Smith JM, Thomas SH. Anti-TNF agents for rheumatoid arthritis. Br J Clin Pharmacol 2001; 51 (03) 201-208
    CrossrefPubMedGoogle Scholar
  • 39 Ghosh S. Anti-TNF therapy in Crohn's disease. Novartis Found Symp 2004; 263: 193-205 , discussion 205–218
    CrossrefPubMedGoogle Scholar
  • 40 Nadeem R, Molnar J, Madbouly EM. et al. Serum inflammatory markers in obstructive sleep apnea: a meta-analysis. J Clin Sleep Med 2013; 9 (10) 1003-1012
    CrossrefPubMedGoogle Scholar
  • 41 Kheirandish-Gozal L, Gozal D. Obstructive sleep apnea and inflammation: proof of concept based on two illustrative cytokines. Int J Mol Sci 2019; 20 (03) 459
    CrossrefPubMedGoogle Scholar
  • 42 Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997; 82 (05) 1313-1316
    CrossrefPubMedGoogle Scholar
  • 43 Gozal D, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Khalyfa A, Tauman R. Sleep measures and morning plasma TNF-α levels in children with sleep-disordered breathing. Sleep 2010; 33 (03) 319-325
    CrossrefPubMedGoogle Scholar
  • 44 Khalyfa A, Serpero LD, Kheirandish-Gozal L, Capdevila OS, Gozal D. TNF-α gene polymorphisms and excessive daytime sleepiness in pediatric obstructive sleep apnea. J Pediatr 2011; 158 (01) 77-82
    CrossrefPubMedGoogle Scholar
  • 45 Driessen C, Plomp RG, van der Spek PJ. et al. Is there an effect of obstructive sleep apnea syndrome on oxidative stress and inflammatory parameters in patients with craniofacial anomalies?. J Craniofac Surg 2013; 24 (06) 1908-1913
    CrossrefPubMedGoogle Scholar
  • 46 Alexopoulos EI, Theologi V, Malakasioti G. et al. Obstructive sleep apnea, excessive daytime sleepiness, and morning plasma TNF-α levels in Greek children. Sleep (Basel) 2013; 36 (11) 1633-1638
    CrossrefPubMedGoogle Scholar
  • 47 Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 2014; 6 (10) a016295
    CrossrefPubMedGoogle Scholar
  • 48 Hirani N, Antonicelli F, Strieter RM. et al. The regulation of interleukin-8 by hypoxia in human macrophages–a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS). Mol Med 2001; 7 (10) 685-697
    CrossrefPubMedGoogle Scholar
  • 49 LaVoy EC, Palmer CA, So C, Alfano CA. Bidirectional relationships between sleep and biomarkers of stress and immunity in youth. Int J Psychophysiol 2020; 158: 331-339
    CrossrefPubMedGoogle Scholar