Sleep-Disordered Breathing, Obesity, and Airway Inflammation in Children and Adolescents

doi:10.1378/chest.08-0535

Chest

Volume 134, Issue 6, December 2008, Pages 1169-1175

https://doi.org/10.1378/chest.08-0535 Get rights and content

Background

To investigate the relationship between obstructive sleep apnea syndrome (OSAS) and exhaled nitric oxide (eNO) in overweight children and adolescents without asthma or atopy and to assess whether obesity per se is associated with increased airway inflammation.

Methods

Consecutive overweight subjects without symptoms of asthma or allergy were recruited at a pediatric obesity clinic. A normal-weight control group without OSAS and asthma or allergy was also recruited. All subjects underwent polysomnography and two measurements of eNO (afternoon and morning after polysomnography).

Results

Controlling for age, the mean (± SD) afternoon eNO concentration was significantly higher in the snoring group (14.1 ± 1.1 parts per billion [ppb]) compared with the normal-weight group (10.1 ± 0.8 ppb; p = 0.03) and with the overweight group with normal polysomnography findings (8.9 ± 0.8 ppb; p = 0.007). The afternoon eNO concentration was also different between the OSAS group (11.9 ± 1.0 ppb) and the overweight group with normal polysomnography findings (p = 0.03). Morning eNO values were higher in the OSAS group (12.3 ± 1.1 ppb) than in the normal weight group (9.9 ± 0.8 ppb; p = 0.047) and in the overweight control group (9.7 ± 0.7 ppb; p = 0.02). BMI z score was not significantly correlated with afternoon eNO concentration or with morning eNO concentration.

Conclusion

This study illustrates that both habitual snoring and OSAS are associated with increased airway inflammation in overweight children as assessed by higher eNO levels. Furthermore, it was demonstrated that childhood obesity in the absence of sleep-disordered breathing is not associated with increased airway inflammation.

Section snippets

Study Population

Consecutive overweight or obese children and adolescents aged 6 to 17 years were recruited between March 2005 and October 2007 at the Pediatric Obesity Clinic of the Antwerp University Hospital. Normal-weight children were also recruited as part of a previously published study²³ regarding normative data on SDB in children and adolescents. The exclusion criteria were a history of asthma, chronic lung disease, neuromuscular disease, laryngomalacia, any genetic or craniofacial syndrome, and the

Patient Characteristics

Subject characteristics are presented in Table 1. The study population included 13 normal-weight children, 17 overweight children with normal sleep study findings, 7 overweight children with habitual snoring, and 11 overweight children with OSAS.

Overweight children with habitual snoring had a significantly lower FEV₁, FEV₁/vital capacity (VC) ratio, and maximal expiratory flow at 50% (MEF₅₀) than their overweight peers with normal polysomnography findings. Only one subject in the habitual

Discussion

In the present study, we illustrated that both habitual snoring and OSAS are associated with increased airway inflammation, as assessed by higher eNO level, in overweight children and adolescents without asthma or atopy. Furthermore, we could demonstrate that childhood obesity as such is not associated with increased airway inflammation.

Our present study using eNO levels confirmed previous reports12, 13 using other techniques that SDB in children is associated with increased airway

Acknowledgment

The authors thank the staff of the Lung Function Laboratory of Antwerp University Hospital for obtaining the lung function and eNO measurements for this study.

References (42)

American Thoracic Society
Standards and indications for cardiopulmonary sleep studies in children
Am J Respir Crit Care Med
(1996)
MG Greene et al.
Consequences of sleep-disordered breathing in childhood
Curr Opin Pulm Med
(1997)
L Brunetti et al.
Prevalence of obstructive sleep apnea syndrome in a cohort of 1,207 children of southern Italy
Chest
(2001)
W Anuntaseree et al.
Snoring and obstructive sleep apnea in Thai school-age children: prevalence and predisposing factors
Pediatr Pulmonol
(2001)
T Gislason et al.
Snoring, apneic episodes, and nocturnal hypoxemia among children 6 months to 6 years old: an epidemiologic study of lower limit of prevalence
Chest
(1995)
NJ Ali et al.
Snoring, sleep disturbance, and behaviour in 4–5 year olds
Arch Dis Child
(1993)
SL Verhulst et al.
The prevalence, anatomical correlates and treatment of sleep-disordered breathing in obese children and adolescents
Sleep Med Rev
(2008)
CO Olopade et al.
Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea
Chest
(1997)
GE Carpagnano et al.
Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome
Transl Res
(2008)
M Petrosyan et al.
Exhaled breath markers in patients with obstructive sleep apnoea
Sleep Breath
(2008)

A Depalo et al.

Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects

J Intern Med

(2008)

AM Li et al.

Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea

Thorax

(2007)

AD Goldbart et al.

Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome

Chest

(2006)

RJ Hancox et al.

Sex differences in the relation between body mass index and asthma and atopy in a birth cohort

Am J Respir Crit Care Med

(2005)

S Guerra et al.

Persistence of asthma symptoms during adolescence: role of obesity and age at the onset of puberty

Am J Respir Crit Care Med

(2004)

FD Gilliland et al.

Obesity and the risk of newly diagnosed asthma in school-age children

Am J Epidemiol

(2003)

DR Gold et al.

Body-mass index as a predictor of incident asthma in a prospective cohort of children

Pediatr Pulmonol

(2003)

JA Castro-Rodriguez et al.

Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years

Am J Respir Crit Care Med

(2001)

PM Matricardi et al.

The asthma-obesity link in childhood: open questions, complex evidence, a few answers only

Clin Exp Allergy

(2007)

G Fantuzzi

Adipose tissue, adipokines, and inflammation

J Allergy Clin Immunol

(2005)

SR Lucas et al.

Paediatric asthma and obesity

Paediatr Respir Rev

(2006)

Cited by (62)

WRISTOX<inf>2</inf> is a reliable tool to diagnose obstructive sleep apnoea syndrome
2021, International Journal of Pediatric Otorhinolaryngology
Overnight pulse oximetry is an alternative to polysomnography (PSG) in diagnosing obstructive sleep apnoea syndrome, but its sensitivity is reported to be low.
To determine the (a) diagnostic accuracy, interobserver reliability and reliable oxygen desaturation index of 4% (ODI₄) score at diagnosing obstructive sleep apnoea syndrome in children and (b) correlation between the apnoea hypopnoea index (AHI) with ODI₄ and oxygen nadir between both PSG and oximetry.
This cross-sectional study included children aged 1–18 years old, undergoing a fully attended overnight PSG for suspected obstructive sleep apnoea syndrome. The Nonin 3150 WristOx₂ ™ [Fig. 2] was worn simultaneously during the PSG. Poor oximetry recordings were excluded. Pulse oximetry was scored using the McGill Oximetry Score (MOS) whereby a score of 2–4 was positive for OSAS. Specificity, sensitivity, positive predictive values (PPV), negative predictive values (NPV) and interobserver reliability of the WristOx₂ were calculated.
One hundred and sixty-two children with a mean (SD) age of 9.3 (±3.5) years (range 2 years 6 months old - 17 years old) were included after excluding 18 children (poor oximetry data [n = 16] and incomplete PSG [n = 2]). Interobserver agreement of the WristOx₂ was 0.8763 (95% CI:0.80, 0.95). WristOx₂ had a sensitivity 50%, specificity 96.7%, PPV 96% and NPV 53% at diagnosing OSAS. ODI₄ ≥ 2 events/hour in oximetry had a sensitivity of 97.6% and negative predictive value of 85.7% at diagnosing OSA.
Overnight pulse oximetry with the Nonin 3150 WristOx₂ ™ is an accurate and reliable tool in diagnosing significant OSAS in children.
Risk factors analysis and intervention of lung dysfunction in children with obstructive sleep apnea: A retrospective case series study
2021, International Journal of Pediatric Otorhinolaryngology
To establish an optimized airway management process to improve preoperative lung dysfunction in obstructive sleep apnea (OSA).
The study included 483 children (319 males and 164 females; 6y to14y years) with OSA who underwent an adenotonsillectomy from November 2017 to December 2018. Children with OSA and who had abnormal airway function were identified by lung function test, and the risk factors for abnormal lung function were assessed. Next, the children received individualized atomization intervention based on the severity of their abnormal lung function, and the improvement in lung function was evaluated.
Lung function tests revealed that 45 patients had obstructive ventilation dysfunction, and histories of chronic cough or asthma were identified as risk factors for perioperative abnormal lung function. The FEV1% pre exceeded 80% after 2 days of atomization intervention in 27 of 28 mild cases, 4 of 13 moderate cases, but in none of the 4 moderate-severe cases. After 4 days of atomization intervention, the FEV1%pre of the remaining 14 patients in the three groups all increased up to 80%. Other indicators of lung function (e.g., FEV1/FVC% pre, MEF50% pre, MEF25% pre, and MMEF% pre) were also greatly improved following the improvement of FEV1% pre. No perioperative airway complications occurred.
Prior to performing surgery on children with OSA and who have risk factors associated with abnormal lung function, it is potentially beneficial to establish an optimized airway management process to improve lung function before adenotonsillectomy.
Comparison of two exhaled biomarkers in children with and without sleep disordered breathing
2018, Sleep Medicine
Citation Excerpt :
Unlike biomarkers of oxidative stress, airway inflammation as measured by FENO levels is not always reported to be high in patients with OSA [40–42]. Verhulst et al. reported that non-atopic children with OSA had higher morning FENO levels than either normal-weight or overweight controls [19]. Furthermore, they also found that the high FENO levels in subjects who snored habitually were comparable to those observed in subjects with OSA, Verhulst et al. hypothesized that airway inflammation may be induced by soft-tissue damage during snoring rather than by obstructive events during sleep [19].
Airway oxidative stress and inflammation are likely to be involved in sleep disordered breathing (SDB) in children. We aimed to measure concentrations of 8-isoprostane (8-IsoP) in the exhaled breath condensate (EBC) and exhaled nitric oxide (FE_NO) in patients with SBD and healthy children, in order to assess the relationship between these two biomarkers, disease severity, and overnight changes.
Patients with SDB (n = 46) and healthy controls (n = 20) aged 4.5–15.1 years (M/F: 36/30) underwent exhaled measurements. Patients with SDB underwent standard polysomnography to define primary snoring (PS: AHI < 1) and obstructive sleep apnea (OSA). Upon awakening the following morning, FE_NO was measured and EBC was collected for the measurement of EBC 8-IsoP.
OSA patients yielded higher awakening levels of 8-IsoP in EBC than PS patients and control subjects. The 8-IsoP levels, though not FE_NO, correlated with AHI (r = 0.40, p = 0.003) and SaO2 (r = −0.50, p = 0.001). Cut-off levels of 8-IsoP predicted OSA with a high AUC value (0.84, p = 0.000). Sensitivity and specificity for 8-IsoP levels above the percentile 50 (33.3 pg/mL) were 76.5% and 78.1%, respectively. 8-IsoP levels did not change from the evening to morning session, whereas morning FE_NO levels rose significantly only in patients with mild OSA (p = 0.03).
Levels of 8-IsoP, though not FE_NO, distinguish children with OSA from those with PS or healthy, correlate with disease severity and closely predict OSA in the whole sample.
Sleep endoscopy findings in children with persistent obstructive sleep apnea after adenotonsillectomy
2018, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
This can account for narrowing of the retrolingual airway in the obese. Verhulst [11,12] also provides information that may contribute to an explanation for why obese children with sleep apnea are more likely to have adenoid regrowth. They found that levels of expired nitric oxide, associated with airway inflammation, were elevated in children who were obese and had sleep apnea, when compared to normal weight children with sleep apnea and obese children without sleep apnea.
Describe the patterns of obstruction in persistent pediatric OSA and their relationship with patient weight.
Retrospective review.
All pediatric DISE procedures performed at a tertiary care hospital between October 2010 and October 2015 were reviewed. Patients had polysomnography after adenotonsillectomy that confirmed persistent obstructive sleep apnea (OSA). Variables included age, gender, co-morbidities, and AHI. DISE findings focused on inferior turbinates, adenoid, tongue base, epiglottis, aryepiglottic (AE) folds, arytenoids, lingual tonsil and their contributions to obstruction.
34 patients were included with mean age of 7.85 (2–16) years, mean BMI of 23.15 (13.6–44.8) and mean AHI of 6.34 (1.5–25.2) events per hour. Obstruction occurred at the level of the epiglottis in 97%, with retropositioning by tongue base (73.6%) or lingual tonsil enlargement (70.5%). Obstruction occurred at the inferior turbinates in 76.5%, the adenoid in 64.7% and the palate in 58.8%. Shortened AE folds were less often identified (15%). Multiple sites of partial or complete obstruction were found in 97% of patients. Overweight or obese patients had a mean of 3 sites of complete obstruction and 4.69 sites of partial or complete obstruction as compared to 2.33 and 4.52 in underweight or normal weight children. Overweight or obese children were more likely to have obstruction at the lingual tonsil or adenoid than normal/underweight children.
Multiple sites of obstruction in persistent pediatric OSA were found. Children with higher BMIs had slightly different findings, suggesting that attention to adenoid regrowth and lingual tonsil hypertrophy is important.
Peri-operative management of overweight and obese children and adolescents
2017, The Lancet Child and Adolescent Health
Obesity has become endemic, even in children. Systemic complications associated with obesity include metabolic syndrome, cardiovascular disease, and respiratory compromise. These comorbidities require adequate investigation, targeted optimisation, and, if surgery is required, specific management during the peri-operative period. Specific peri-operative strategies should be used for paediatric patients who are overweight or obese to prevent postoperative complications, and optimising the respiratory function during surgery is particularly crucial. This Review aims to provide up-to-date information on peri-operative management for physicians who are caring for children and adolescents (usually younger than 18 years) who are overweight or obese undergoing surgery, including bariatric surgery. We have particularly focussed on the physiological consequences of obesity—namely, obstructive sleep apnoea, respiratory compromise, and pharmacological considerations.
The effect of body weight on distal airway function and airway inflammation
2016, Obesity Research and Clinical Practice
Obesity is a global health problem that adversely influences the respiratory system. We assessed the effects of body mass index (BMI) on distal airway function and airway inflammation.
Impulse oscillometry (IOS) as a measure of distal airway function, together with spirometry, were assessed in adults with a range of different BMIs. Airway inflammation was assessed with the fraction of exhaled nitric oxide (FeNO) and participants exhaled at various exhalation flows to determine alveolar and bronchial NO.
In total 34 subjects were enrolled in the study; 19 subjects had a normal BMI (18.50–24.99), whilst 15 subjects were overweight (BMI 25.00–29.99), or obese (BMI ≥30). All subjects had normal spirometry. However, IOS measures of airway resistance (R) at 5 Hz, 20 Hz and frequency dependence (R_5–20) were elevated in overweight/obese individuals, compared to subjects with a normal BMI (median (interquartile range)); 5 Hz: 0.41 (0.37, 0.45) vs. 0.32 (0.30, 0.37) kPa/l/s; 20 Hz: 0.34 (0.30, 0.37) vs. 0.30 (0.26, 0.33) kPa/l/s; R_5–20: 0.06 (0.04, 0.11) vs. 0.03 (0.01, 0.05) kPa/l/s; p < 0.05), whereas airway reactance at 20 Hz was decreased in overweight/obese individuals (20 Hz: 0.07 (0.03, 0.09) vs. 0.10 (0.07, 0.13) kPa/l/s, p = 0.009; 5 Hz: −0.12 (−0.15, −0.10) vs. −0.10 (−0.13, −0.09) kPa/l/s, p = 0.07). In contrast, within-breath IOS measures (a sign of expiratory flow limitation) and FeNO inflammatory measures, did not differ between groups (p > 0.05).
Being overweight has significant effects on distal and central airway function as determined by IOS, which is not detected by spirometry. Obesity does not influence airway inflammation as measured by FeNO. IOS is a reliable technique to identify airway abnormalities in the presence of normal spirometry in overweight people.

View all citing articles on Scopus

: The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

: Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

View full text

Chest

Original ResearchSleep MedicineSleep-Disordered Breathing, Obesity, and Airway Inflammation in Children and Adolescents

Background

Methods

Results

Conclusion

Section snippets

Study Population

Patient Characteristics

Discussion

Acknowledgment

Standards and indications for cardiopulmonary sleep studies in children

Am J Respir Crit Care Med

Consequences of sleep-disordered breathing in childhood

Curr Opin Pulm Med

Prevalence of obstructive sleep apnea syndrome in a cohort of 1,207 children of southern Italy

Chest

Snoring and obstructive sleep apnea in Thai school-age children: prevalence and predisposing factors

Pediatr Pulmonol

Snoring, apneic episodes, and nocturnal hypoxemia among children 6 months to 6 years old: an epidemiologic study of lower limit of prevalence

Chest

Snoring, sleep disturbance, and behaviour in 4–5 year olds

Arch Dis Child

The prevalence, anatomical correlates and treatment of sleep-disordered breathing in obese children and adolescents

Sleep Med Rev

Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea

Chest

Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome

Transl Res

Exhaled breath markers in patients with obstructive sleep apnoea

Sleep Breath

Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects

J Intern Med

Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea

Thorax

Inflammatory mediators in exhaled breath condensate of children with obstructive sleep apnea syndrome

Chest

Sex differences in the relation between body mass index and asthma and atopy in a birth cohort

Am J Respir Crit Care Med

Persistence of asthma symptoms during adolescence: role of obesity and age at the onset of puberty

Am J Respir Crit Care Med

Obesity and the risk of newly diagnosed asthma in school-age children

Am J Epidemiol

Body-mass index as a predictor of incident asthma in a prospective cohort of children

Pediatr Pulmonol

Increased incidence of asthmalike symptoms in girls who become overweight or obese during the school years

Am J Respir Crit Care Med

The asthma-obesity link in childhood: open questions, complex evidence, a few answers only

Clin Exp Allergy

Adipose tissue, adipokines, and inflammation

J Allergy Clin Immunol

Paediatric asthma and obesity

Paediatr Respir Rev

Original Research
Sleep Medicine
Sleep-Disordered Breathing, Obesity, and Airway Inflammation in Children and Adolescents