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. 2010 Jul 1;33(7):968–972. doi: 10.1093/sleep/33.7.968

Upper Airway Sensory Function in Children with Obstructive Sleep Apnea Syndrome

Ignacio E Tapia 1, Preetam Bandla 1, Joel Traylor 1, Laurie Karamessinis 1, Jingtao Huang 1, Carole L Marcus 1,✉
PMCID: PMC2894439  PMID: 20614857

Abstract

Study Objectives:

Children with the obstructive sleep apnea syndrome (OSAS) have impaired responses to hypercapnia, subatmospheric pressure, and inspiratory resistive loading during sleep. This may be due, in part, to an impairment in the afferent limb of the upper airway sensory pathway. Therefore, we hypothesized that children with OSAS had diminished upper airway sensation compared to controls.

Design:

Case-control

Setting:

Academic hospital

Participants:

Subjects with OSAS aged 6–16 years, and age- and BMI-matched controls.

Interventions:

Two-point discrimination (TPD) was measured during wakefulness with modified calipers in the anterior tongue, right interior cheek, and hard palate.

Results:

Thirteen children with OSAS and 9 controls were tested. The age (mean ± SD) for OSAS and controls was 11 ± 4 vs. 13 ± 2 years (NS); OSAS BMI Z score 2.4 ± 0.5, controls 2.2 ± 0.5 (NS); OSAS apnea hypopnea index 31 ± 48, controls 0.4 ± 0.5 events/hour (P < 0.001). Children with OSAS had impaired TPD in the anterior tongue (median [range]) = 9 [3–14] mm, controls 3 [1–7], P = 0.002) and hard palate (OSAS 6 [3–9] mm, controls 3 [1–4], P < 0.001). TPD in the cheek was similar between the groups (P = 0.12).

Conclusion:

TPD in the anterior tongue and hard palate was impaired in children with OSAS during wakefulness. We speculate that this impairment might be due to a primary sensory function abnormality or secondary to nerve damage and/or hypoxemia caused by OSAS. Further studies after treatment of OSAS are needed.

Citation:

Tapia IE; Bandla P; Traylor J; Karamessinis L; Huang J; Marcus CL. Upper airway sensory function in children with obstructive sleep apnea syndrome. SLEEP 2010;33(7):968–972.

Keywords: Two-point, discrimination, palate

CHILDREN WITH THE OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) HAVE UPPER AIRWAY COLLAPSE AND RESULTANT OBSTRUCTIVE APNEA DURING sleep. This is the consequence of an imbalance between the upper airway structural load due to factors such as adenotonsillar hypertrophy, and upper airway neuromotor tone.1–3 The pharyngeal subatmospheric pressure, hypoxemia, and hypercapnia generated during these apneic episodes4 may activate the dilatory muscles of the upper airway, resulting in the reopening of the airway and termination of the obstructive apnea.3,5,6

Upper airway mucosal sensory receptors may have a role in the termination of an apnea by mediating upper airway tone.7–10 Previous studies in adults have demonstrated that attenuation of upper airway mucosal sensation by topical anesthesia increases the tendency to airway collapse.9,11 Furthermore, upper airway anesthesia also induces apneas and hypopneas during sleep in normal subjects8 and increases the frequency of obstructive events in snorers.7,10 The findings of these studies suggest that impairment of upper airway mucosal sensory function could contribute to upper airway collapse during sleep. In addition, previous studies performed in adult subjects have demonstrated impaired mucosal sensory function in subjects with OSAS.12–16 However, it is unknown whether children with OSAS have impaired upper airway sensory function.

Huang et al. recently analyzed cortical processing of afferent respiratory information by measuring respiratory-related evoked potentials during sleep in children with OSAS and controls.17 They found blunted respiratory-related evoked potentials responses in children with OSAS, indicative of impaired afferent processing. This may be due to impaired upper airway sensation. Hence, we hypothesized that children with OSAS had diminished airway mucosal sensation during wakefulness compared to controls. We therefore studied sensory function in the upper airway of children with OSAS compared to normal age-, gender-, and BMI-matched controls. Specifically, two-point discrimination during wakefulness was determined in the upper airway of subjects with OSAS compared to controls.

MATERIAL AND METHODS

Study Group

Children between 6–16 years of age were included. The younger age limit was selected to exclude children who could not understand and cooperate with testing. The older age limit was chosen to avoid overlap with adult OSAS. Patients with OSAS were recruited from the Sleep Center at The Children's Hospital of Philadelphia following a recent clinical polysomnogram. Normal controls were recruited from the general community by means of advertisements. For screening purposes, controls completed the validated Pediatric Sleep Questionnaire18 to exclude those with suspected sleep disordered breathing. Those who passed the screening underwent a polysomnogram to ensure normalcy. Other exclusion criteria for OSAS and controls included significant medical conditions other than OSAS, medications that could interfere with sensory perception (such as benzodiazepines and opiates), and a history of upper airway surgery. The control and OSAS groups were matched for age, gender, and BMI z-scores. The Institutional Review Board of The Children's Hospital of Philadelphia approved the study. Informed consent was obtained from the parents/guardians of subjects, and assent from the children.

Polysomnography

Subjects were studied in the sleep laboratory at The Children's Hospital of Philadelphia as previously described.19 Polysomnography data were digitally recorded using Rembrandt (Medcare, Buffalo, NY). The electroencephalogram was recorded using scalp electrodes (C3/A2, C4/A1, O1/A2, and O2/A1), and right and left electroculograms were recorded. Muscle tone of the chin was measured by submental electromyography. Oxyhemoglobin saturation (SpO2) was measured by pulse oximetry (Masimo Rad-9, Irvine, CA) that was set at 2-second averaging. Nasal pressure was measured by cannula (Pro-Tech, Mukilteo, WA). As a back-up, oronasal airflow was measured by an oronasal thermistor (Pro-Tech, Mukilteo, WA). End-tidal CO2 was measured by sidestream sample (Novametrix Medical Systems, Wallingford, CT). Movements of the chest and abdomen were measured by respiratory inductive plethysmography (SensorMedics, Yorba Linda, CA). The electrocardiograph was recorded by a modified lead 1. Leg movements were recorded by electromyography leads placed over the anterior tibialis muscles of both legs. Sleep stages were determined by the criteria of Rechtschaffen and Kales.20 Arousals were scored according to standards set by the American Sleep Disorders Association.21 Scoring of respiratory variables was performed on the basis of standards set by the American Thoracic Society and previously published data on children.22,23 In order to avoid overlap between groups, subjects with OSAS were included if they had an apnea hypopnea index (defined as the sum of obstructive and mixed apneas and hypopneas, divided by total sleep time) ≥ 5/hr, and controls were included if their apnea hypopnea index was ≤ 1.5/hour.24,25

Sensory Function Testing

OSAS and controls underwent two-point discrimination testing during wakefulness with the child seated comfortably. Two-point discrimination was tested using the method of limits26 in the posterior hard palate, the buccal mucosa of the right cheek, and the anterior tongue, using a caliper with smooth, rounded wire tips (Figure 1). The soft palate was not tested to avoid eliciting a gag reflex in these young children.27 The cheek was selected as a control site because it is innervated by the buccal nerve, which is the only sensory branch of the anterior division of the trigeminal mandibular nerve,28 and has not been described as an afferent of the upper airway negative pressure reflex.29 Testing was performed under direct visualization with the child opening the mouth and protruding the tongue without tensing it. Either one or both ends of the compass were placed in contact with the mucosa for 2 seconds, with sufficient pressure to slightly indent the mucosa without causing bleeding or discomfort. The stimulus was randomly alternated between 1 and 2 points while establishing the threshold to keep the subject focused. A 10-second rest between each measurement was provided to prevent extinction. The subject was instructed to indicate 1 versus 2 points by holding up the appropriate number of fingers. Testing began using the largest inter-prong distance that spatial constraints allowed, which was decreased by 2-mm increments to the smallest inter-prong distance that the subject/control could perceive as 2 points. Eighty-two percent of the children were tested by one observer (I.T.). The testers were not blinded to the OSAS status of the children.

Figure 1.

Figure 1

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Two-point discrimination was tested with this modified caliper with blunted points.

Data Analysis

Statistical analysis was performed with SigmaStat 3.0 (Systat Software Inc., San Jose, CA). The Kolmogorov-Smirnov test was used to test for normalcy. Normally distributed data are presented as mean ± standard deviation (SD). Differences in demographics and two-point discrimination in the tongue and hard palate between groups were compared with the unpaired t-test. Differences in two-point discrimination in the cheek between groups were examined using the Mann-Whitney rank sum test. A P value < 0.05 was required for significance.

RESULTS

Study Group Characteristics

The subjects' characteristics are shown in Table 1. Subjects had moderate to severe OSAS by pediatric standards. As the OSAS group tended to be obese, equally obese controls were recruited.

Table 1.

Study group characteristics

OSAS Controls P value
N 13 9 NS
Males (N (%)) 7 (54) 4 (44) NS
Age (years) 11 ± 4 13 ± 2 NS
BMI Z-score 2.4 ± 0.5 2.2 ± 0.5 NS
Sleep efficiency (%TST) 80 ± 12 86 ± 6 NS
Arousal index (N/hour) 23 ± 16 15 ± 10 0.01
Stage 1 (% TST) 10 ± 5 7 ± 4 NS
Stage 2 (% TST) 50 ± 12 50 ± 5 NS
SWS (% TST) 23 ± 12 23 ± 9 NS
REM (% TST) 17 ± 6 20 ± 4 NS
AHI (N/hour) 31 ± 48 0.4 ± 0.5 < 0.001
SpO2 nadir (%) 82 ± 9 94 ± 2 0.002
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Values are displayed as mean ± SD. BMI, body mass index; AHI, apnea hypopnea index; TST, total sleep time; SWS, slow wave sleep; SpO2, oxyhemoglobin saturation

Two-Point Discrimination

Children with OSAS had impaired two-point discrimination in the anterior tongue (Figure 2). This impairment was even greater in the palate (Figure 3). However, the degree of two-point discrimination impairment was not influenced by age or severity of OSAS at either site (Table 2). No difference was found between OSAS subjects and controls when testing two-point discrimination in the cheek (P = 0.12). There was no significant difference in the results based on who tested the subjects.

Figure 2.

Figure 2

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Two-point discrimination in the tongue for children with obstructive sleep apnea syndrome (OSAS) compared to controls. The Y axis represents the inter-prong distance in mm. The box represents the interquantile range; the central line represents the median; the whiskers represent the 5th and 95th percentiles; and the dots represent the outliers. Subjects with OSAS had decreased two-point discrimination compared to controls (P = 0.002).

Figure 3.

Figure 3

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Two-point discrimination in anterior palate for children with the obstructive sleep apnea syndrome (OSAS) compared to controls. The Y axis represents the inter-prong distance in mm. The box is the interquantile range; the central line is the median; the whiskers are the 5th and 95th percentiles; and the dots are the outliers. The two-point discrimination in the palate was impaired in OSAS subjects compared to controls with a P value lower than 0.001.

Table 2.

Pearson correlation coefficient results between two-point discrimination in the tongue and hard palate vs. age and AHI

TPD tongue Correlation coefficient (P value) TPD palate P value
Age 0.23 0.45 0.32 0.29
AHI 0.35 0.25 −0.15 0.63
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TPD, two-point discrimination; AHI, apnea hypopnea index

DISCUSSION

This study analyzed the sensory function in the upper airway of children with OSAS and controls. We found that subjects with OSAS had impaired detection of two-point discrimination in the tongue and palate compared to age-, gender, and BMI-matched controls. These findings prove that subjects with OSAS have impairment in upper airway sensation during wakefulness at an early age.

The upper airway is a complex neuromuscular area with more than 30 pairs of muscles responsible for coordinated activities such as breathing, swallowing, and coughing.30 The role of the upper airway neuromotor tone in OSAS has been studied during natural sleep by measuring the change in maximal inspiratory airflow in response to increasing levels of subatmospheric pressure applied via a nasal mask.2,7 Normal controls show reflex neuromotor activation, manifested by upper airway dilation in response to nasal subatmospheric pressure. This helps maintain upper airway patency in the presence of subatmospheric pressure. In addition, investigations in adults have shown reduced upper airway muscle activation, measured by genioglossus electromyography, during wakefulness13,31 and sleep31 after applying topical anesthesia to the upper airway. Specifically, the nasal branch of the trigeminal, facial, vagus, and glossopharyngeal nerves have been described as the afferent innervation of the upper airway negative pressure reflex.29 The hypoglossal and glossopharyngeal nerves have been described as the efferent loop.29 Impairments in both afferent and/or efferent loops can result in increased upper airway collapsibility. In the present study the hard palate, tongue, and cheek were tested. The palate is innervated by the nasopalatine nerve (branch of the trigeminal) and the anterior palatine nerve (branch of the facial nerve). The tongue is innervated by the lingual nerve.32,33 The cheek was selected as a control site because it is innervated by the buccal nerve, which is the only sensory branch of the anterior division of the trigeminal mandibular nerve,28,34 and has not been described as an afferent of the upper airway negative pressure reflex29 in contrast to the palate and tongue.

Previous studies in children with OSAS have shown impairment of the upper airway dilation reflex response to negative pressure,2,7 manifested as increased upper airway collapsibility compared to normal controls during wakefulness35 and sleep.2,7 In addition, children with OSAS have diminished arousal responses to hypercapnia,4,36 and inspiratory resistive loading37 but normal acoustic arousal responses38 during sleep. The hypercapneic response and two-point discrimination from the head and face have different afferent pathways. The ventral trigeminothalamic tract is the pathway for two-point discrimination from the tested sites. The main site of CO2 chemoreception is the ventrolateral medulla oblongata.39 Specifically, the cholinergic muscarinic receptors found in this brainstem area appear to have an important modulatory role on the ventilatory response to hypercapnia.40 CO2-sensitive neurons have been found in other areas of the brain but their role in hypercapneic response is still unclear.39,41 Therefore, it is reasonable to infer that the central integration of different respiratory afferent inputs may be defective in subjects with OSAS, rather than the afferent receptors themselves. Furthermore, Huang et al. recently demonstrated blunted respiratory-related evoked potentials response during sleep in OSAS indicative of impaired afferent processing.19 Further research is warranted.

Obesity and overweight were not inclusion criteria of the present study; however, it was not surprising that the mean BMI Z-score in our OSAS group was 2.4 because the prevalence and severity of pediatric obesity has increased significantly over the past decades, all over the world.42 In the United States, the prevalence of overweight children aged 6 to 11 years doubled between 1980 and 2000. During the same period of time, the prevalence of overweight children aged 12 to 17 years tripled.43,44 Furthermore, recent publications have stressed the role of obesity as a risk factor for OSAS in children.45–47 Specifically, Redline et al. found that obese children were 4–5 times most likely to have sleep disordered breathing.48

To our knowledge, there are no publications analyzing the effects of obesity on the sensory function in the upper airway. However, Horner et al. demonstrated that obese adults have large deposits of fat in the soft palate and fat streaks in the tongue.49 Nevertheless, the impaired sensation noted in the children with OSAS in the current study was not due to obesity alone, as the controls were equally obese. Furthermore, in the current study, children with OSAS had decreased sensation in the hard palate as well as the tongue, although fat is not usually deposited in the hard palate.

The palate TPD results are in agreement with those reported in adults by Kimoff,12 Guilleminault,13 and Jobin,14 which could suggest that a selective deficit in upper airway sensory perception can be present even after the relatively shorter duration of OSAS in children. A sensory neuropathy in the upper airway of adult patients with OSAS has been described by Friberg et al.50–52 They reported signs of neurogenic damage in palatopharyngeal muscle biopsies of adults with OSAS that were more severe in those with more severe OSAS. However it is still unknown whether this finding is secondary to vibrational nerve damage or to a more generalized neurologic disorder or is a combination of both. Moreover, the sole publication analyzing palatopharyngeal muscle biopsies in children with OSAS compared to normal controls and snorers failed to find histopathological differences between the three groups, although the techniques used cannot eliminate the presence of a neuropathy.53 Hence, the etiology of the sensory function deficit in OSAS has yet to be clarified.

The limitations of the present study include the unknown duration of OSAS because families could not describe an accurate time of onset of symptoms. In addition, the clinical history has proved to be of limited value in the diagnosis of childhood OSAS.54 Another limitation to be considered is that psychophysical methods, such as two-point discrimination testing, require the active participation of the subject. Therefore, results can be affected by psychological confounding factors. However, when carried out accurately and in a standardized manner, these methods can be as valid as the more invasive neurophysiological techniques.55 Hence, we do not think that subjective issues affected the children's response to upper airway testing. Despite the challenges of testing two-point discrimination with a caliper in the upper airway in children, such as spatial constraints, short attention span, and possible gagging, all of our subjects could be tested without issues following standard and reproducible methods.26,56,57 Stimuli were presented in a random order to ensure that results were not affected by potential observer's bias, the child's behavior, or attention span. Children tolerated the testing well. Specifically, no gag reflex was elicited in any subject. Similarly, the difference in TPD in tongue and palate between the groups cannot be explained by cognitive impairment in OSAS subjects,58–60 because otherwise we would have found differences in the control site as well.

CONCLUSIONS

This study has shown that children with OSAS have impaired two-point discrimination perception in the tongue and palate compared to age-, gender-, and BMI-matched normal controls despite a relatively short duration of OSAS. However, it is unknown whether the findings are secondary to a congenital abnormality of sensory perception or secondary to selective nerve damage due to chronic snoring and possibly mouth breathing. Further studies post-treatment are needed to clarify the pathophysiology of the upper sensory function in children with OSAS.

DISCLOSURE STATEMENT

This was not an industry supported study. Dr. Marcus has received research support from Respironics. The other authors have indicated no financial conflicts of interest.

ACKNOWLEDGMENTS

The authors thank the children participating in this study and their families, and the sleep laboratory technicians for their invaluable help. This research was supported by the National Institutes of Health R01 HL58585.

ABBREVIATIONS

OSAS

obstructive sleep apnea syndrome

TPD

two-point discrimination

AHI

apnea hypopnea index

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