Skip to main content
Top
Published in: Sleep and Breathing 1/2016

01-03-2016 | Original Article

Nasal nitric oxide in sleep-disordered breathing in children

Authors: Guy Gut, Riva Tauman, Michal Greenfeld, Keren Armoni-Domany, Yakov Sivan

Published in: Sleep and Breathing | Issue 1/2016

Login to get access

Abstract

Background

Inflammation plays a role in the pathogenesis and consequences of sleep-disordered breathing (SDB). The nasal mucosa and paranasal sinuses produce high levels of nitric oxide (NO). In asthma, exhaled NO is a marker of airway inflammation. There is only limited information whether nasal NO (nNO) accompanies also chronic upper airway obstruction, specifically, SDB. The objective of this study was to investigate nNO levels in children with SDB in comparison to healthy non-snoring children.

Methods

Nasal NO was measured in children who underwent overnight polysomnographic studies due to habitual snoring and suspected SDB and in healthy non-snoring controls.

Results

One hundred and eleven children participated in the study: 28 with obstructive sleep apnea (OSA), 60 with primary snoring (PS), and 23 controls. Nasal NO levels were significantly higher in children with OSA and PS compared to controls (867.4 ± 371.5, 902.0 ± 330.9, 644.1 ± 166.5 ppb, respectively, p = 0.047). No difference was observed between children with OSA and PS. No correlations were found between nNO levels and any of the PSG variables, nor with age, BMI percentile or tonsils size.

Conclusions

Compared to healthy controls, nNO is increased in children with SDB, but it is not correlated with disease severity. This is probably due to the local mechanical processes and snoring.
Literature
1.
go back to reference Tal A (2014) Obstructive sleep apnea syndrome: pathophysiology and clinical characteristics. In: Sheldon SH, Ferber R, Kryger MH, Gozal D (eds) Principles and practice of pediatric sleep medicine, 2nd edn. Elseveir, London, pp 215–220 Tal A (2014) Obstructive sleep apnea syndrome: pathophysiology and clinical characteristics. In: Sheldon SH, Ferber R, Kryger MH, Gozal D (eds) Principles and practice of pediatric sleep medicine, 2nd edn. Elseveir, London, pp 215–220
2.
go back to reference Kim J, Hakim F, Kheirandish-Gozal L, Gozal D (2011) Inflammatory pathways in children with insufficient or disordered sleep. Respir Physiol Neurobiol 178:465–474CrossRefPubMedPubMedCentral Kim J, Hakim F, Kheirandish-Gozal L, Gozal D (2011) Inflammatory pathways in children with insufficient or disordered sleep. Respir Physiol Neurobiol 178:465–474CrossRefPubMedPubMedCentral
3.
go back to reference Gozal D, Kheirandish L (2006) Oxidant stress and inflammation in the snoring child: confluent pathways to upper airway pathogenesis and end-organ morbidity. Sleep Med Rev 10:83–96CrossRefPubMed Gozal D, Kheirandish L (2006) Oxidant stress and inflammation in the snoring child: confluent pathways to upper airway pathogenesis and end-organ morbidity. Sleep Med Rev 10:83–96CrossRefPubMed
4.
go back to reference Goldbart AD, Tal A (2008) Inflammation and sleep disordered breathing in children: a state-of-the-art review. Pediatr Pulmonol 43:1151–1160CrossRefPubMed Goldbart AD, Tal A (2008) Inflammation and sleep disordered breathing in children: a state-of-the-art review. Pediatr Pulmonol 43:1151–1160CrossRefPubMed
5.
go back to reference Hatipoğlu U, Rubinstein I (2003) Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 70:665–671CrossRefPubMed Hatipoğlu U, Rubinstein I (2003) Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis. Respiration 70:665–671CrossRefPubMed
6.
go back to reference Kent BD, Ryan S, McNicholas WT (2011) Obstructive sleep apnea and inflammation: relationship to cardiovascular co-morbidity. Respir Physiol Neurobiol 178:475–481CrossRefPubMed Kent BD, Ryan S, McNicholas WT (2011) Obstructive sleep apnea and inflammation: relationship to cardiovascular co-morbidity. Respir Physiol Neurobiol 178:475–481CrossRefPubMed
7.
go back to reference Rubinstein I (1995) Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 105:175–177CrossRefPubMed Rubinstein I (1995) Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 105:175–177CrossRefPubMed
8.
go back to reference Salerno FG, Carpagnano E, Guido P, Bonsignore MR, Roberti A, Aliani M, Vignola AM, Spanevello A (2004) Airway inflammation in patients affected by obstructive sleep apnea syndrome. Respir Med 98:25–28CrossRefPubMed Salerno FG, Carpagnano E, Guido P, Bonsignore MR, Roberti A, Aliani M, Vignola AM, Spanevello A (2004) Airway inflammation in patients affected by obstructive sleep apnea syndrome. Respir Med 98:25–28CrossRefPubMed
10.
go back to reference Sekosan M, Zakkar M, Wenig BL, Olopade CO, Rubinstein I (1996) Inflammation in the uvula mucosa of patients with obstructive sleep apnea. Laryngoscope 106:1018–1020CrossRefPubMed Sekosan M, Zakkar M, Wenig BL, Olopade CO, Rubinstein I (1996) Inflammation in the uvula mucosa of patients with obstructive sleep apnea. Laryngoscope 106:1018–1020CrossRefPubMed
11.
go back to reference Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ (2004) Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med 170:541–546CrossRefPubMed Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ (2004) Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med 170:541–546CrossRefPubMed
12.
go back to reference Philippe C, Boussadia Y, Prulière-Escabasse V, Papon JF, Clérici C, Isabey D, Coste A, Escudier E, d’Ortho MP (2015) Airway cell involvement in intermittent hypoxia-induced airway inflammation. Sleep Breath 19:297–306CrossRefPubMed Philippe C, Boussadia Y, Prulière-Escabasse V, Papon JF, Clérici C, Isabey D, Coste A, Escudier E, d’Ortho MP (2015) Airway cell involvement in intermittent hypoxia-induced airway inflammation. Sleep Breath 19:297–306CrossRefPubMed
13.
go back to reference Goldbart AD, Goldman JL, Li RC, Brittian KR, Tauman R, Gozal D (2004) Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection. Chest 126:13–18CrossRefPubMed Goldbart AD, Goldman JL, Li RC, Brittian KR, Tauman R, Gozal D (2004) Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection. Chest 126:13–18CrossRefPubMed
14.
go back to reference Li AM, Hung E, Tsang T, Yin J, So HK, Wong E, Fok TF, Ng PC (2007) Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea. Thorax 62:75–79CrossRefPubMedPubMedCentral Li AM, Hung E, Tsang T, Yin J, So HK, Wong E, Fok TF, Ng PC (2007) Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea. Thorax 62:75–79CrossRefPubMedPubMedCentral
15.
go back to reference Goldbart AD, Krishna J, Li RC, Serpero LD, Gozal D (2006) Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome. Chest 130:143–148CrossRefPubMed Goldbart AD, Krishna J, Li RC, Serpero LD, Gozal D (2006) Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome. Chest 130:143–148CrossRefPubMed
16.
go back to reference Benedek P, Lazar Z, Bikov A, Kunos L, Katona G, Horvath I (2013) Exhaled biomarker pattern is altered in children with obstructive sleep apnoea syndrome. Int J Pediatr Otorhinolaryngol 77:1244–1247CrossRefPubMed Benedek P, Lazar Z, Bikov A, Kunos L, Katona G, Horvath I (2013) Exhaled biomarker pattern is altered in children with obstructive sleep apnoea syndrome. Int J Pediatr Otorhinolaryngol 77:1244–1247CrossRefPubMed
17.
go back to reference Malakasioti E, Alexopoulos C, Befani K, Tanou V, Varlami D, Ziogas D, Liakos P, Gourgoulianis K, Kaditis AG (2012) Oxidative stress and inflammatory markers in the exhaled breath condensate of children with OSA. Sleep Breath 16:703–718CrossRefPubMed Malakasioti E, Alexopoulos C, Befani K, Tanou V, Varlami D, Ziogas D, Liakos P, Gourgoulianis K, Kaditis AG (2012) Oxidative stress and inflammatory markers in the exhaled breath condensate of children with OSA. Sleep Breath 16:703–718CrossRefPubMed
18.
go back to reference Kaditis AG, Ioannou MG, Chaidas K, Alexopoulos EI, Apostolidou M, Apostolidis T, Koukoulis G, Gourgoulianis K (2008) Cysteinyl leukotriene receptors are expressed by tonsillar T cells of children with obstructive sleep apnea. Chest 134:324–331CrossRefPubMed Kaditis AG, Ioannou MG, Chaidas K, Alexopoulos EI, Apostolidou M, Apostolidis T, Koukoulis G, Gourgoulianis K (2008) Cysteinyl leukotriene receptors are expressed by tonsillar T cells of children with obstructive sleep apnea. Chest 134:324–331CrossRefPubMed
19.
go back to reference Dayyat E, Serpero LD, Kheirandish-Gozal L, Goldman JL, Snow A, Bhattacharjee R, Gozal D (2009) Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest 135:1142–1149CrossRefPubMedPubMedCentral Dayyat E, Serpero LD, Kheirandish-Gozal L, Goldman JL, Snow A, Bhattacharjee R, Gozal D (2009) Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest 135:1142–1149CrossRefPubMedPubMedCentral
20.
go back to reference Goldbart AD, Goldman JL, Veling MC, Gozal D (2005) Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 172:364–370CrossRefPubMedPubMedCentral Goldbart AD, Goldman JL, Veling MC, Gozal D (2005) Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 172:364–370CrossRefPubMedPubMedCentral
21.
go back to reference Goldbart AD, Greenberg-Dotan S, Tal A (2012) Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics 130:e575–e580CrossRefPubMed Goldbart AD, Greenberg-Dotan S, Tal A (2012) Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics 130:e575–e580CrossRefPubMed
22.
go back to reference Almendros I, Acerbi I, Puig F, Montserrat JM, Navajas D, Farré R (2007) Upper-airway inflammation triggered by vibration in a rat model of snoring. Sleep 30:225–227PubMed Almendros I, Acerbi I, Puig F, Montserrat JM, Navajas D, Farré R (2007) Upper-airway inflammation triggered by vibration in a rat model of snoring. Sleep 30:225–227PubMed
23.
go back to reference Barnes PJ, Dweik RA, Gelb AF, Gibson PG, George SC, Grasemann H, Pavord ID, Ratjen F, Silkoff PE, Taylor DR, Zamel N (2010) Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest 138:682–692CrossRefPubMed Barnes PJ, Dweik RA, Gelb AF, Gibson PG, George SC, Grasemann H, Pavord ID, Ratjen F, Silkoff PE, Taylor DR, Zamel N (2010) Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest 138:682–692CrossRefPubMed
24.
go back to reference Lundberg JO, Rinder J, Weitzberg E, Lundberg JM, Alving K (1994) Nasally exhaled nitric oxide in humans originates mainly in the paranasal sinuses. Acta Physiol Scand 152:431–432CrossRefPubMed Lundberg JO, Rinder J, Weitzberg E, Lundberg JM, Alving K (1994) Nasally exhaled nitric oxide in humans originates mainly in the paranasal sinuses. Acta Physiol Scand 152:431–432CrossRefPubMed
25.
go back to reference Corbelli R, Hammer J (2007) Measurement of nasal nitric oxide. Paed Resp Rev 8:269–672 Corbelli R, Hammer J (2007) Measurement of nasal nitric oxide. Paed Resp Rev 8:269–672
26.
go back to reference Struben VM, Wieringa MH, Feenstra L, de Jongste JC (2006) Nasal nitric oxide and nasal allergy. Allergy 61:665–670CrossRefPubMed Struben VM, Wieringa MH, Feenstra L, de Jongste JC (2006) Nasal nitric oxide and nasal allergy. Allergy 61:665–670CrossRefPubMed
27.
go back to reference Arnal JF, Didier A, Rami J, M’Rini C, Charlet JP, Serrano E, Besombes JP (1997) Nasal nitric oxide is increased in allergic rhinitis. Clin Exp Allergy 27:358–362CrossRefPubMed Arnal JF, Didier A, Rami J, M’Rini C, Charlet JP, Serrano E, Besombes JP (1997) Nasal nitric oxide is increased in allergic rhinitis. Clin Exp Allergy 27:358–362CrossRefPubMed
28.
go back to reference Baraldi E, Azzolin NM, Carra S, Dario C, Marchesini L, Zacchello F (1998) Effect of topical steroids on nasal nitric oxide production in children with perennial allergic rhinitis: a pilot study. Respir Med 92:558–561CrossRefPubMed Baraldi E, Azzolin NM, Carra S, Dario C, Marchesini L, Zacchello F (1998) Effect of topical steroids on nasal nitric oxide production in children with perennial allergic rhinitis: a pilot study. Respir Med 92:558–561CrossRefPubMed
29.
go back to reference Palm JP, Alving K, Lundberg JO (2003) Characterization of airway nitric oxide in allergic rhinitis: the effect of intranasal administration of l-NAME. Allergy 58:885–892CrossRefPubMed Palm JP, Alving K, Lundberg JO (2003) Characterization of airway nitric oxide in allergic rhinitis: the effect of intranasal administration of l-NAME. Allergy 58:885–892CrossRefPubMed
30.
go back to reference Maniscalco M, Sofia M, Carratu L, Higenbottam T (2001) Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis. Eur J Clin Invest 31:462–466CrossRefPubMed Maniscalco M, Sofia M, Carratu L, Higenbottam T (2001) Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis. Eur J Clin Invest 31:462–466CrossRefPubMed
31.
go back to reference Petrosyan M, Perraki E, Simoes D, Koutsourelakis I, Vagiakis E, Roussos C, Gratziou C (2008) Exhaled breath markers in patients with obstructive sleep apnoea. Sleep Breath 12:207–215CrossRefPubMed Petrosyan M, Perraki E, Simoes D, Koutsourelakis I, Vagiakis E, Roussos C, Gratziou C (2008) Exhaled breath markers in patients with obstructive sleep apnoea. Sleep Breath 12:207–215CrossRefPubMed
32.
go back to reference Brodsky L, Adler E, Stanievich JF (1989) Naso- and oropharyngeal dimensions in children with obstructive sleep apnea. Int J Pediatr Otorhinolaryngol 17:1–11CrossRefPubMed Brodsky L, Adler E, Stanievich JF (1989) Naso- and oropharyngeal dimensions in children with obstructive sleep apnea. Int J Pediatr Otorhinolaryngol 17:1–11CrossRefPubMed
33.
go back to reference Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of Pediatrics (2002) Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 109:704–712CrossRef Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome. American Academy of Pediatrics (2002) Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 109:704–712CrossRef
34.
go back to reference Marcus CL, Omlin KJ, Basinki DJ, Bailey SL, Rachal AB, Von Pechmann WS, Keens TG, Ward SL (1994) Normal polysomnographic values for children and adolescents. Am J Respir Crit Care Med 149:715–721CrossRefPubMed Marcus CL, Omlin KJ, Basinki DJ, Bailey SL, Rachal AB, Von Pechmann WS, Keens TG, Ward SL (1994) Normal polysomnographic values for children and adolescents. Am J Respir Crit Care Med 149:715–721CrossRefPubMed
35.
go back to reference Uliel S, Tauman R, Greenfeld M, Sivan Y (2004) Normal polysomnographic respiratory values in children and adolescents. Chest 125:872–878CrossRefPubMed Uliel S, Tauman R, Greenfeld M, Sivan Y (2004) Normal polysomnographic respiratory values in children and adolescents. Chest 125:872–878CrossRefPubMed
36.
go back to reference American Thoracic Society; European Respiratory Society (2005) ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 171:912–930CrossRef American Thoracic Society; European Respiratory Society (2005) ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 171:912–930CrossRef
37.
go back to reference Carpagnano GE, Spanevello A, Sabato R, Depalo A, Turchiarelli V, Foschino Barbaro MP (2008) Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome. Transl Res 151:45–50CrossRefPubMed Carpagnano GE, Spanevello A, Sabato R, Depalo A, Turchiarelli V, Foschino Barbaro MP (2008) Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome. Transl Res 151:45–50CrossRefPubMed
38.
go back to reference Culla B, Guida G, Brussino L, Tribolo A, Cicolin A, Sciascia S, Badiu I, Mietta S, Bucca C (2010) Increased oral nitric oxide in obstructive sleep apnoea. Respir Med 104:316–320CrossRefPubMed Culla B, Guida G, Brussino L, Tribolo A, Cicolin A, Sciascia S, Badiu I, Mietta S, Bucca C (2010) Increased oral nitric oxide in obstructive sleep apnoea. Respir Med 104:316–320CrossRefPubMed
39.
go back to reference Puig F, Rico F, Almendros I, Montserrat JM, Navajas D, Farre R (2005) Vibration enhances interleukin-8 release in a cell model of snoring induced airway inflammation. Sleep 28:1312–1316PubMed Puig F, Rico F, Almendros I, Montserrat JM, Navajas D, Farre R (2005) Vibration enhances interleukin-8 release in a cell model of snoring induced airway inflammation. Sleep 28:1312–1316PubMed
40.
go back to reference Marcus CL, Brooks LJ, Draper KA, Gozal D, Halbower AC, Jones J, Schechter MS, Ward SD, Sheldon SH, Shiffman RN, Lehmann C, Spruyt K, American Academy of Pediatrics (2012) Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 130:e714–e755CrossRefPubMed Marcus CL, Brooks LJ, Draper KA, Gozal D, Halbower AC, Jones J, Schechter MS, Ward SD, Sheldon SH, Shiffman RN, Lehmann C, Spruyt K, American Academy of Pediatrics (2012) Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 130:e714–e755CrossRefPubMed
Metadata
Title
Nasal nitric oxide in sleep-disordered breathing in children
Authors
Guy Gut
Riva Tauman
Michal Greenfeld
Keren Armoni-Domany
Yakov Sivan
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Sleep and Breathing / Issue 1/2016
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-015-1189-8

Other articles of this Issue 1/2016

Sleep and Breathing 1/2016 Go to the issue

Sleep Breathing Physiology and Disorders • Letter to the Editors

Auto-CPAP: saving money as a single tool for OSA

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.