Open Journal of Stomatology, 2011, 1, 150-157
doi:10.4236/ojst.2011.14022 Published Online December 2011 (http://www.SciRP.org/journal/ojst/
OJST
).
Published Online December 2011 in SciRes. http://www.scirp.org/journal/OJST
Immune function in Japanese schoolchildren with
sleep-disordered breathing: a preliminary study with analyses
of salivary markers
Hiroshi Ueda, Atsushi Horihata, Eka Matsumoto, Genki Watanabe, Myongsun Koh,
Kotaro Tanimoto, Kazuo Tanne
Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical Sciences, Hiroshima Univer-
sity, Hiroshima, Japan.
Received 25 August 2011; revised 6 October 2011; accepted 21 October 2011.
ABSTRACT
The aim of this study was to assess the prevalence of
sleep-disordered breathing (SDB) symptoms among
primary schoolchildren, and to objectively determine
the influence of SDB on the intra-oral environment
through the analysis of saliva. A questionnaire survey
was conducted among approximately 400 children
from a primary school in Hiroshima. Parents were
asked to complete the questionnaire and provide their
contact information if they allowed the collection of
saliva samples from their children. Thirty-eight chil-
dren agreed to participate in the saliva study. Habit-
ual snoring and cessation of breathing during sleep
were found in approximately 8% and 1% of children,
respectively. The present results showed significant
correlations between snoring and mouth breathing. A
significant association between excessive daytime sle-
epiness (EDS) and learning problems was found. Fur-
thermore, among children between the ages of 7 and
12 years, those with EDS and learning problems
tended to be older. SDB symptom scores were statisti-
cally significant only in relation to EDS. The present
study also demonstrated significantly higher levels of
salivary IgA and cortisol in children with sleep-re-
lated disorders. The present study determined the pre-
valence and characteristics of SDB among Japanese
primary schoolchildren and their effects on the oral
environment. Approximately 8% of primary school-
children with habitual snoring might need to be care-
fully monitored for SDB symptoms and immune sta-
tus to ensure proper psychological and physical deve-
lopment.
Keywords: Schoolchildren; Sleep-Disordered Breathing
Symptoms; Immune Function; Salivary Markers
1. INTRODUCTION
Sleep-disordered breathing (SDB), including sleep apnea
syndrome (SAS), is an important cause of morbidity for
both adults and children [1-5]. In children in particular,
SDB is of great concern because it can cause neurobe-
havioral and growth-related problems, and affect aca-
demic performance [6-9]. The estimated prevalence of
SAS in children ranges from 1% to 3% and the incidence
of habitual snoring has been reported to be 7% - 12% in
previous studies [10-13]. Therefore, the prevalence of
SDB and its influence on daily life are significant and
cannot be neglected in growing children.
In the fields of dentistry and orthodontics, mouth
breathing patients are known to have narrow upper den-
tition and long facial height resulting from the backward
and downward displacement of the mandible. This asso-
ciation has been explained by the fact that mouth brea-
thing causes reduced activity of the facial and mastica-
tory muscles, leading to the appearance of skeletal defor-
mities represented by an open bite with a small and dis-
tally located mandible. In addition, the descriptive term
“adenoid face”, consisting of narrow dentition, protrude-
ing teeth, and lip incompetence at rest has been docu-
mented in the literature for at least a century [14-16].
Over the last decades, the effect of SDB on the immu-
ne system has been reported frequently [17]. The meas-
urement of secretory immunoglobulin A (IgA) levels in
the saliva is a convenient and frequently used indicator
of immune status. SDB during childhood differs signify-
cantly from that in adults in terms of various parameters
such as symptoms and pathogenesis. Therefore, an appro-
priate differential study to discriminate SDB symptoms
in children is necessary.
The aim of this study was to assess the prevalence of
SDB symptoms in primary schoolchildren and to object-
tively determine its influence on the intra-oral environ-
ment by means of saliva analysis.

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 151
2. MATERIALS AND METHODS
2.1. Participants
A questionnaire survey was conducted among 412 chil-
dren (197 boys and 215 girls) from a primary school in
Hiroshima. All children were within normal range in bo-
th physical and psychological development and had no
significant systemic diseases. Each subject gave written
informed consent and the study protocol was approved
by the Ethical Review Board of Hiroshima University
Hospital.
2.2. Questionnaire
A questionnaire on self-reported symptoms for the eva-
luation of SDB was used according to the Tucson Chil-
dren’s Assessment of Sleep Apnea (TuCASA) study re-
ported previously by Goodwin et al. [18]. This screening
questionnaire was designed to assess the severity of sle-
ep-related symptoms irrespective of age and gender. The
questionnaire was translated into Japanese. Parents were
asked to answer 13 questions pertaining to their child’s
sleep habits (APPENDIX). These questions were scored
by the parent on a scale of “never”, “rarely”, “occasion-
ally”, “frequently”, “almost always”, or “don’t know”.
Each questionnaire informed the parent that we would
complete sleep studies on approximately 400 children.
The children who had all 3 symptoms (excessive day-
time sleepiness (EDS), witnessed apnea (WITAP), and
snoring) or more were selected and classified into the
SDB group and the children who had no symptoms at all
served as the control group according to the TuCASA
study.
The complete list of survey questions is shown in the
“APPENDIX”.
2.3. Saliva Sample Collection
Parents were asked to complete the questions and to pro-
vide their contact information if they agreed to allow
study personnel to call and schedule a saliva test for their
children. Of 412 children, 38 children (19 boys and 19
girls, ranging in age from 6.7 to 11.7 years) agreed to
participate in the saliva study. Before the start of the sa-
liva collection and analysis, informed consent in paper
form was obtained from the parents again. The same nu-
mber of children (19 boys and 19 girls) was selected for
the control group with similar distribution of sex and
age.
Saliva was collected from each participant and analy-
zed for IgA and cortisol levels according to the guide-
lines of Hanrahan et al. [19]. All subjects were requested
to collect the saliva sample within the first 20 min after
waking up. The samples were then taken to school on the
same day, collected by the study personnel and immedi-
ately frozen at –20˚C until their subsequent analysis.
2.4. SIgA and Cortisol Assay
Samples were recovered after thawing by centrifugation
at 1500 g for 15 min. Salivary IgA (μg/mL) and cortisol
(μg/dL) were quantified by means of an enzyme-linked
immunosorbent assay (ELISA) using the Salivary Sec-
retory IgA Indirect Enzyme Immunoassay Kit and High
Sensitivity Salivary Cortisol Enzyme Immunoassay Kit,
respectively (Salimetrics, LLC, State College, PA, USA).
A ready-to-use 96-well microtiter plate coated with
highly purified human SIgA was used to assess IgA lev-
els and for generating standard immunoglobulin level
curves. As a detecting antibody, goat anti-human SIgA
conjugated to horseradish peroxide was used. The first 2
columns of each plate contained blank controls and 6
dilutions of purified human SIgA (600, 200, 66.7, 22.2,
7.4, and 2.5 μg/mL) in duplicates. The rest of the plate
was filled with a high and low control, and diluted (1:
120) saliva samples in duplicates. After incubation for
90 min at room temperature with continuous mixing at
400 rpm, the wells were washed 6 times with wash buf-
fer (phosphate-buffered solution) and filled with TMB
solution (tetramethylbenzidine). After 5 min of mixing at
500 rpm and additional 40-min incubation in the dark at
room temperature, the wells were filled with an acidic
formulation stop solution. The plate was mixed at 500
rpm for 3 min and the developed color was measured at
an optical density of 450 nm on a microplate reader
(Model 550, Bio-Rad Laboratories, Hercules, CA, USA).
For the assessment of the salivary cortisol concentra-
tion, all samples were assayed in duplicate. Absorbance
was measured at an optical density of 450 nm on a mi-
croplate reader (Model 550, Bio-Rad Laboratories) and
the quantity was derived from the standard curve.
2.5. Data Analysis
Thirteen questionnaires for the evaluation of SDB sym-
ptoms and school activities were initially scored accord-
ing to frequency of occurrence as never (0), rarely (1),
sometimes (2), frequent (3), or always (4). Blanks were
regarded as missing data and “don’t know” was ne-
glected. Five principal subjective parameters regarding
respiration and sleep were analyzed and the findings were
compared with previous results obtained from the same
school in 2003.
To examine saliva data, the subjects were judged as
experiencing EDS if the parent reported that their child
was sleepy in the daytime “frequently” or more. WITAP
was present if the parent reported that their child stopped
or struggled to breath during sleep “frequently” or more.
Snoring was present if parents reported loud snoring
from their child “frequently” or more.
Data are presented as percentages. A similar study
with the same questionnaire was conducted in 2003, and
C
opyright © 2011 SciRes. OJST

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 152
the statistical significance of the symptom scores in the
previous and current surveys was examined with the
Mann-Whitney U test. A Spearman rank correlation ana-
lysis was used for non-parametric variables. To compare
the control and SDB symptom groups, Student’s t-test
was conducted. A p value < 0.05 was considered signifi-
cant.
3. RESULTS
3.1. Demographics of the Participants
Tables 1 and 2 show the demographic data of the pre-
vious survey in 2003 and of the present study. The num-
ber of participants in the present study was 69 (34 boys,
35 girls) in the first grade, 63 (29 boys, 34 girls) in the
second grade, 65 (30 boys, 35 girls) in the third grade,
72 (34 boys, 38 girls) in the fourth grade, 76 (37 boys,
39 girls) in the fifth grade, and 67 (33 boys, 34 girls) in
the sixth grade. The children ranged in age from 6 (first
grade) to 12 years (sixth grade), and the mean age was
9.6 (0.4) years. In addition, no significant differences in
the distribution of boys and girls were found between the
previous and current demographic data shown in Tables
1 and 2.
Table 1. The number of participants in the previous survey in
2003.
Boys Girls
Grade 1 46 21 25
Grade 2 80 41 39
Male 206
Grade 3 74 32 42
Grade 4 78 40 38
Grade 5 82 43 39
Total
418
Female 212
Grade 6 58 29 29
Table 2. The number of participants in the current survey.
Boys Girls
Grade 1 69 34 35
Grade 2 63 29 34
Male 197
Grade 3 65 30 35
Grade 4 72 34 38
Grade 5 76 37 39
Total
412
Female 215
Grade 6 67 33 34
3.2. SDB-Related Symptoms
The percentage of children reported to snore loudly “al-
most always”, “frequently”, and “occasionally” was 6.8%;
those reported to stop breathing during sleep “almost
always”, “frequently”, and “occasionally” were 1.3%, and
those reported to be daytime mouth breathers “almost
always” and “frequently” were 14.3%. Furthermore, in
association with school activities, the percentage of chil-
dren who answered that they were sleepy during the day-
time “almost always” and “frequently” were 3.9%, and
the percentage in those who had learning problems “almost
always”, “frequently”, and “occasionally” were 2.8%. In
the 2003 data, the percentage of children who answered
these questions similarly was almost the same (Table 3).
Table 4 shows the comparison of the distribution of
SDB problems after the children were divided into 2
groups based on their school grades. In the older group
comprising grade 4 - 6 children, the percentage of chil-
dren who reported daytime sleepiness and learning pro-
blems was higher than in the younger group, whereas the
percentage of children who reported snoring loudly was
lower in the older group than in the younger group.
As shown in Tabl e 5 , statistically significant correla-
tions were found among the 5 main questions. All signi-
ficant correlations were positive (r = 0.11 - 0.27). The
snoring scores were significantly correlated with most of
the other variables, excluding learning problems. On the
other hand, the learning problems score was significantly
correlated with that of EDS in both the previous and the
present surveys (p < 0.01).
With respect to the SDB symptom scores, the only
Table 3. Distribution of common SDB problems in the sleep
survey.
Question Responses
Previous
survey in
2003
(N = 418)
Current
survey
(N = 393)
Q1. How often
does your child
snore loudly?
Almost
always/Frequently/
Occasionally
8.8 6.8
Q2. How does
your child stop
breathing during
sleep?
Almost always/Frequently/
Occasionally 1.4 1.3
Q3. Is your child
a daytime mouth
breather?
Almost always/Frequently 14.3 14.3
Q4. Is your child
sleepy during the
daytime?
Almost always/Frequently 4 3.9
Q5. Does your
child ever have
learning prob-
lems?
Almost
always/Frequently/
Occasionally
2.4 2.8
%
C
opyright © 2011 SciRes. OJST

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 153
Table 4. Distribution of common SDB problems in sleep survey.
Grade 1, 2, 3 Grade 4, 5, 6
Question Responses
Previous survey
(N = 200) Current survey (N = 197)
Previous survey
(N = 218) Current survey (N = 215)
Q1. How often does your child snore loudly?
Almost
always/Frequently/
Occasionally
9.0 5.1 8.7 7.0
Q2. How does your child stop breathing
during sleep?
Almost
always/Frequently/
Occasionally
2.0 1.5 0.9 0.9
Q3. Is your child a daytime mouth breather? Almost always/
Frequently 14.0 12.7 20.6 14.4
Q4. Is your child sleepy during the daytime? Almost always/
Frequently 1.5 2.5 6.0 14.0
Q5. Does your child ever have learning
problems?
Almost
always/Frequently/
Occasionally
1.0 1.5 3.7 3.7
%
Table 5. Correlation coefficients between questions. Table 6. Descriptive statistics and comparisons between SDB
symptom scores in the 2 groups.
Q1 Q2 Q3 Q4 Q5
Q1
0.23**
0.10
0.27**
0.25**
0.18**
0.13**
0.09
0.07
Q2
0.21**
0.08
0.11*
−0.01
0.11*
0.03
Q3
0.08
0.25**
0.15**
0.07
Q4
0.13**
0.15**
Q5
2003
Grade 1, 2, 3 Grade 4, 5, 6
Med. 25% 75% Med. 25% 75% p
Q11 0 2 1 0 2 NS
Q20 0 0 0 0 0 NS
Q32 1 2 2 1 2 NS
Q40 0 1 1 0 1 *
Q51 1 2 1 1 2 NS
Med., median; 25%, 25th percentile; and 75%, 75th percentile. *Statistical
significance was defined as p < 0.05.
EDS question that was used in the previous and current
questionnaires showed a significantly large difference in
the score in the older group (Tables 6 and 7).
Table 7. Descriptive statistics and comparisons between SDB
symptom scores in the 2 groups.
2006
Grade 1, 2, 3 Grade 4, 5, 6
Med. 25% 75% Med. 25% 75% p
Q10 0 1 0 0 1 NS
Q20 0 0 0 0 0 NS
Q30 0 1 0 0 2 NS
Q40 0 1 1 0 2 *
Q50 0 0 0 0 0 NS
3.3. Saliva Analysis
Because no significant differences in IgA and cortisol
levels were found between boys and girls in both the
control and symptomatic groups, the means obtained
from 38 subjects in total were used for the following
statistical comparison.
Measurement of IgA levels showed that the symptom-
matic group had significantly higher levels than the con-
trols did (p < 0.05) (Figure 1). With respect to the corti-
sol levels, the symptomatic group also showed a consid-
erably higher level than the control group, although a sta-
tistically significant difference was not found (Figur e 2). Med., median; 25%, 25th percentile; and 75%, 75th percentile. *Statistical
significance was defined as p < 0.05.
OJST

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 154
0
200
400
600
800
Control groupSymptom group
＊
IgA
(μg/mL)
＊ ：significantly different (p < 0.05)
0
200
400
600
800
Control groupSymptom group
＊
IgA
(μg/mL)
＊ ：significantly different (p < 0.05)
Figure 1. Comparison of the IgA levels between control and
SDB symptom groups.
0.
5.0
10.0
15.0
20.0
25.0
Control groupSymptom group
Cortisol
(μg/dL)
0.
5.0
10.0
15.0
20.0
25.0
Control groupSymptom group
Cortisol
(μg/dL)
Figure 2. Comparison of the cortisol levels between control
nd SDB symptom groups.
a
4. DISCUSSION
In the present study, a consciousness survey was con-
ducted for the assessment of SDB symptoms and prob-
lem behaviors among primary schoolchildren. The influ-
ence of these factors on salivary secretory immuno-
globulin A and cortisol levels was also examined. Sleep
apnea syndrome (SAS) has been of increasing concern
among the middle-aged population in Japan in recent
years, and the physical and psychological development
of children is considered to be greatly influenced by sle-
ep quality [2-4]. Mental retardation from chronic hypo-
xia, low stature from hyposecretion of growth hormones,
and slow learning due to daytime sleepiness are listed as
examples of the association between SDB and physical
and psychological development; hence, children in pri-
mary school were defined as the target of the present
study.
4.1. Prevalence of SDB Symptoms
In this study, habitual snoring and cessation of breathing
during sleep were found in approximately 8% and 1% of
children, respectively. Several studies from other coun-
tries have reported the prevalence of sleep problems in a
population-based sample of children. Gozal and Pope re-
ported that the mean prevalence of snoring among 1588
children was 9% in the United States [7]. A similar pre-
valence of snoring among children was reported in Fr-
ance (10%) [20] and in Italy (7.3%) [12]. The overall
snoring prevalence in the previous and current surveys
from our group was at the upper limit of the range re-
ported by others.
With respect to cessation of breathing, the present re-
sults were similar to those of previous studies reporting
that SAS affects approximately 1% - 2% children [2,
10,13]. Cessation of breathing during sleep is not the
same as diagnostic SAS. However, apneic symptoms
such as cessation of breathing, difficulty in periodic
breathing, and nocturnal choking might be the indicators
of the presence of SAS.
The present results showed significant correlations
between snoring and mouth breathing. Mouth breathing
is one of the characteristic SAS symptoms [13]. Fur-
thermore, nasal influences on mouth breathing, snoring,
and sleep apnea have been reported [21]. Therefore, it is
reasonable to assume that mouth breathing caused by
nasal obstruction leads to loud snoring, apneic breathing,
and disturbed sleep.
In this study, a strong association between EDS and
learning problems was detected. This finding suggests
that poor sleep quality such as sleep fragmentation and
nocturnal hypoxemia might induce EDS, which ulti-
mately influences academic performance and ability. In
agreement with our results, EDS, as well as various be-
havioral problems such as inattention, hyperactivity, and
aggression in school were reported in association with
sleep-related disorders in previous studies [7-9]. Inter-
estingly, Gozal demonstrated that improvements in scho-
ol performance could be induced by remediation of SAS
in first-grade children with substantial academic impair-
ment in school-related activities [6].
Furthermore, among children between 7 and 12 years
of age, those with EDS and learning problems were more
likely to be older than those without. Our data regarding
SDB symptom scores were statistically significant only
with respect to EDS. This may be due to the difference
in mean sleep times between older and younger children,
which were 9 h 18 min (32 min) (first grade) and 7 h 38
min (56 min) (sixth grade), respectively (data not sho-
wn). The current lifestyle of Japanese children, which
includes longer study periods after school and the resul-
ting delay in bedtime, might be a significant factor affec-
ting children’s sleep.
The Tucson Children’s Assessment of Sleep Apnea
(TuCASA) study is a prospective cohort study that was
designed to determine the prevalence of objectively do-
cumented SDB in preadolescent children and to investi-
gate its relationship to symptoms, performance on neuro-
behavioral measures, and physiologic and anatomic risk
factors [18]. Although screening questionnaires for chil-
dren can easily show bias, most TuCASA components
C
opyright © 2011 SciRes. OJST

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 155
are regarded as standard questions that are found in
sleep-habit questionnaires pertaining to SDB in children.
4.2. Association of SDB Symptoms with Salivary
Immune Factors
The results of the present study showed significantly hi-
gher levels of salivary IgA and cortisol in children with
sleep-related disorders. Secretory IgA, which is meas-
ured in the saliva, is the predominant antibody detected
in bodily secretions. IgA levels are believed to indicate
the functional status of the entire mucosal immune sys-
tem [22]. As a source of biological fluid for physical
examination, saliva has several advantages. Collection of
saliva is less intrusive and easier than that of urine or
blood, especially for children.
The most likely explanation for the significantly high
concentration of salivary IgA in the symptom group is
that sleep-related disorders negatively affect immune
functions and increase IgA levels for protection against
certain infections. The release of salivary IgA could be
an indicator of intra-oral and upper airway inflammation.
Therefore, salivary IgA provides a major defense against
potential pathogens by preventing colonization and rep-
lication on the mucosal surfaces of the oral cavity and
the upper respiratory tract. Previous studies demonstra-
ted that recurrent upper respiratory infection was associ-
ated with increased prevalence of SDB symptoms in
children [12,23,24].
The use of self-reported stress as a measurement me-
thod can be associated with bias and variation in study
results [25]. The psychological status of patients can be
reflected in their stress level. Cortisol is a stress hormone
that indicates hypothalamic-pituitary-adrenal (HPA) axis
activity and is a reliable biomarker of stress that is easily
measured in saliva [26]. The cortisol awakening re-
sponse, which is measured during the first 30 - 45 min
after waking up in the morning, is an especially reliable
marker of HPA axis activity [27]. Yehuda et al. demon-
strated that a single salivary cortisol sample taken im-
mediately after waking up can provide an accurate esti-
mate of urinary cortisol and mean salivary cortisol thr-
oughout the day [28]. The present results indicated that
SDB symptoms can constitute a stressor capable of ele-
vating cortisol levels, and suggested that children in pri-
mary school with greater adrenocortical reactivity might
have a considerable level of psychological stress.
In the field of dentistry, especially orthodontics, many
studies have shown the influence of breathing disorders
caused by respiratory obstruction with the large soft pal-
ate, tonsils, tongue, and nasal inflammation on craniofa-
cial morphology. Animal studies demonstrated that spe-
cific skeletal and dental changes, including an increased
lower facial height, anterior downward tipping of the
occlusal plane, and dual bites, crossbite, and open bites
occur within 24 months after nasal obstruction in mon-
keys [29,30]. Bresolin et al. investigated the relation-
ship between mouth breathing in allergic children and
dento-facial development [29], and demonstrated that
mouth breathers had longer faces with narrower maxilla
and retrognathic mandibles [31]. These studies show that
breathing disorders are strongly correlated with cranio-
facial morphology. Moreover, a small oral cavity with
narrow dentition associated with retrognathism due to
undergrowth of the mandible could induce SDB. There-
fore, anatomical disorders carry a certain risk in terms of
predisposition to the development of respiratory disor-
ders such as SAS.
In conclusion, the present study determined the pre-
valence and characteristics of SDB among Japanese
primary schoolchildren and its influence on the oral en-
vironment. Approximately 8% of primary schoolchildren
with habitual snoring might need to be carefully moni-
tored for SDB symptoms and immune status to ensure
appropriate psychological and physical development.
REFERENCES
[1] American Academy of Pediatrics (2002) Clinical practice
guideline: Diagnosis and management of childhood sleep
apnea syndrome. Pediatrics, 109, 704-712.
doi:10.1542/peds.109.4.704
[2] Ali, N.J., Pitson, D.J. and Stradling, J.R. (1993) Snoring,
sleep disturbance and behaviour in 4 - 5 year olds. Ar-
chives of Disease in Childhood, 68, 360-366.
doi:10.1136/adc.68.3.360
[3] Gottlieb, D.J., Vezina, R.M., Chase, C., Lesko, S.M., Hee-
ren, T.C., Weese-Mayer, D.E., Auerbach, S.H. and Corwin,
M.J. (2003) Symptoms of sleep-disordered breathing in
5-year-old children are associated with sleepiness and
problem behaviors. Pediatrics, 112, 870-877.
doi:10.1542/peds.112.4.870
[4] Schechter, M.S. (2001) Section on pediatrics pulmonol-
ogy subcommittee obstructive sleep apnea syndrome.
Technical report: Diagnosis and management of child-
hood obstructive sleep apnea syndrome. Pediatrics, 109,
e69. doi:10.1542/peds.109.4.e69
[5] Matsumoto, E., Tanaka, E., Tabe, H., Wakisaka, N., Na-
kata, Y., Ueda, H., Hori, T., Abe, T. and Tanne K. (2007)
Sleep architecture and the apnea-hypopnea index in chil-
dren with obstructive-sleep apnea syndrome. Journal of
Oral Rehabilitation, 34, 112-120.
doi:10.1111/j.1365-2842.2006.01676.x
[6] Gozal, D. (1998) Sleep-disordered breathing and school
performance in children. Pediatrics, 102, 616-620.
doi:10.1542/peds.102.3.616
[7] Gozal, D. and Pope, D.W. (2001) Snoring during early
childhood and academic performance at ages thirteen to
fourteen years. Pediatrics, 107, 1394-1399.
doi:10.1542/peds.107.6.1394
[8] Owens, J., Opipari, L., Nobile, C. and Spirito, A. (1998)
Sleep and daytime behavior in children with obstructive
C
opyright © 2011 SciRes. OJST

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 156
OJST
sleep apnea and behavioral sleep disorders. Pediatrics,
102, 1178-1184. doi:10.1542/peds.102.5.1178
[9] Downey, R., Perkin, R.M. and MacQuarrie, J. (1993)
Upper airway resistance syndrome: Sick, symptomatic
but unrecognized. Sleep, 16, 620-623.
doi:10.1378/chest.107.4.963
[10] Gislason, T. and Benediktsdottir, B. (1995) Snoring, ap-
neic episodes, and nocturnal hypoxemia among children
6 months to 6 years old: An epidemiologic study of lower
limit of prevalence. Chest, 107, 963-966.
[11] Brunetti, L., Rana, S., Lospalluti, M.L., Pietrafesa, A.,
Francavilla, R., Fanelli, M. and Armenio, L. (2001)
Prevalence of obstructive sleep apnea syndrome in a co-
hort of 1207 children of southern Italy. Chest, 120,
1930-1935. doi:10.1378/chest.120.6.1930
[12] Corbo, G.M., Fuciarelli, F. and Foresi, A. (1989) Snoring
in children: Association with respiratory symptoms and
passive smoking. British Medical Journal, 299, 1491-
1494. doi:10.1136/bmj.299.6714.1491
[13] Carrol, J.L., McColley, S.A., Marcus, C.L., Curtis, S. and
Loughlin, G.M. (1995) Inability of clinical history to dis-
tinguish primary snoring from obstructive sleep apnea
syndrome in children. Chest, 108, 610-618.
doi:10.1378/chest.108.3.610
[14] Linder-Aronson, S. (1970) Adenoids: Their effect on
mode of breathing and nasal airflow and their relation-
ship to characteristic of the facial skeleton and the denti-
tion. Acta Otolaryngologica Supplementum, 265, 1-132.
[15] Harvold, E.P., Vargervik, K. and Chierici, G. (1973) Pri-
mate experiments on oral sensation and dental malocclu-
sions. American Journal of Orthodontics, 63, 494-508.
doi:10.1016/0002-9416(73)90162-0
[16] Proffit, W.R. and Fields, H.W. (1993) The etiology of
orthodontic problem. Contemporary Orthodontics, 2nd
Edition, Mosby, St. Louis, 105-138.
[17] O’Leary, A. (1990) Stress, emotion, and human immune
function. Psychological Bulletin, 108, 363-383.
doi:10.1037/0033-2909.108.3.363
[18] Goodwin, J.L., Babar, S.I., Kaemingk, K.L., Rosen, G.M.,
Morgan, W.J., Sherrill, D.L. and Quan, S.F. (2003) Symp-
toms related to sleep-disordered breathing in White and
Hispanic children. The Tucson Children’s Assessment of
Sleep Apnea Study Chest, 124, 196-203.
[19] Hanrahan, K., McCarthy, A.M., Kleiber, C., Lutgendorf,
S. and Tsalikian, E. (2006) Strategies for salivary cortisol
collection and analysis in research with children. Applied
Nursing Research, 19, 95-101.
doi:10.1016/j.apnr.2006.02.001
[20] Teculescu, D.B., Caillier, I. and Perrin, P. (1992) Snoring
in French preschool children. Pediatric Pulmonology, 13,
239-244. doi:10.1002/ppul.1950130412
[21] Olsen, K. and Kern, E.B. (1995) Nasal influences on
snoring and obstructive sleep apnea. Mayo Clinic Pro-
ceedings, 65, 1095-1105.
[22] Mestecky, J. (1993) Saliva as a manifestation of the
common mucosal immune system. Annals of the New
York Academy of Sciences, 694, 184-194.
doi:10.1111/j.1749-6632.1993.tb18352.x
[23] Frank, Y., Kravath, R., Pollak, C.P. and Weitzman, E.D.
(1983) Obstructive sleep apnea and its therapy: Clinical
and polysomnographic manifestations. Pediatrics, 71,
737-742.
[24] Brouillette, R.T., Fernbach, S.K. and Hunt, C.E. (1982)
Obstructive sleep apnea in infants and children. Journal
of Pediatric, 100, 31-40.
doi:10.1016/S0022-3476(82)80231-X
[25] Suter, P.M., Maire, R., Holtz, D. and Vetter, W. (1997)
Relationship between self-perceived stress and blood pres-
sure. Journal of Human Hypertension, 11, 171-176.
doi:10.1038/sj.jhh.1000409
[26] Kirschbaum, C. and Hellhammer, D.H. (1994) Salivary
cortisol in psychoneuroendocrine research: Recent de-
velopments and applications. Psychoneuroendocrinology,
19, 313-333. doi:10.1016/0306-4530(94)90013-2
[27] Prussner, J.C., Wolf, O.T., Hellhammer, D.H., Buske-
Kirschbaum, A., Von Auer, K., Jobst, S., Kaspers, D. and
Kirschbaum, C. (1997) Free cortisol levels after awak-
ening: A reliable biological marker for the assessment of
adreno-cortical activity. Life Sciences, 61, 2539-2549.
doi:10.1016/S0024-3205(97)01008-4
[28] Yehuda, R., Halligan, S.L., Yang, R.K., Guo, L.S., Ma-
kotkine, I., Singh, B. and Pickholtz, D. (2003) Relation-
ship between 24-hour urinary-free cortisol excretion and
salivary cortisol levels sampled from awakening to bed-
time in healthy subjects. Life Sciences, 73, 349-358.
doi:10.1016/S0024-3205(03)00286-8
[29] Yamada, T., Tanne, K., Miyamoto, K. and Yamauchi, K.
(1997) Influences of nasal respiratory obstruction on cra-
niofacial growth in young Macaca fuscata monkeys.
American Journal of Orthodontics and Dentofacial Or-
thopedics, 111, 38-43.
doi:10.1016/S0889-5406(97)70300-7
[30] Miller, A.J., Vargervik, K. and Chierici, G. (1984) Ex-
perimentally induced neuromuscular changes during and
after nasal airway obstruction. American Journal of Or-
thodontics, 85, 385-392.
doi:10.1016/0002-9416(84)90159-3
[31] Bresolin, D., Sharpiro, P.A., Sharpiro, G.G., Chapko, M.K.
and Dassel, S. (1983) Mouth breathing in allergic chil-
dren: Its relationship to dentofacial development. Ameri-
can Journal of Orthodontics, 83, 334-343.
doi:10.1016/0002-9416(83)90229-4

H. Ueda et al. / Open Journal of Stomatology 1 (2011) 150-157 157
APPENDIX
Screeni n g Questionnaire
1) Does your child stop breathing during sleep?
2) Does your child struggle to breathe during sleep?
3) Do you ever shake your child during sleep to make
him/her breathe again?
4) Do your child’s lips ever turn blue or purple while
he/she is sleeping?
5) Are you ever concerned about your child’s breath-
ing during sleep?
6) How often does your child snore loud?
7) How often does your child have a sore throat?
8) Does your child complain of morning headaches?
9) Is your child a daytime mouth breather?
10) Is your child sleepy during the daytime?
11) Does your child fall asleep at school?
12) Does your child fall asleep while watching televi-
sion?
13) Does your child have learning problems?
Possible Responses
1) Almost always
2) Frequently
3) Occasionally
4) Rarely
5) Never
6) Don’t know
C
opyright © 2011 SciRes. OJST