SNORING AND OBSTRUCTIVE SLEEP APNEA IN YOUNG CHILDREN P E T E R

SNORING AND OBSTRUCTIVE
SLEEP APNEA IN YOUNG
CHILDREN
A 6-month follow-up study
PETER
NIEMINEN
Departments of Otorhinolaryngology,
Clinical Neurophysiology and
Paediatrics and
Institute of Dentistry,
University of Oulu
OULU 2002
PETER NIEMINEN
SNORING AND OBSTRUCTIVE
SLEEP APNEA IN YOUNG CHILDREN
A 6-month follow-up study
Academic Dissertation to be presented with the assent of
the Faculty of Medicine, University of Oulu, for public
discussion in the Auditorium 7 of the University Hospital
of Oulu, on May 3rd, 2002, at 12 noon.
O U L U N Y L I O P I S TO, O U L U 2 0 0 2
Copyright © 2002
University of Oulu, 2002
Reviewed by
Docent Markku Partinen
Docent Henrik Malmberg
ISBN 951-42-6655-2
(URL: http://herkules.oulu.fi/isbn9514266552/)
ALSO AVAILABLE IN PRINTED FORMAT
Acta Univ. Oul. D 673, 2002
ISBN 951-42-6654-4
ISSN 0355-3221
(URL: http://herkules.oulu.fi/issn03553221/)
OULU UNIVERSITY PRESS
OULU 2002
Nieminen, Peter, Snoring and obstructive sleep apnea in young children A 6-month
follow-up study
Departments of Otorhinolaryngology, Clinical Neurophysiology and Paediatrics, University of
Oulu, P.O.Box 5000, FIN-90014 University of Oulu, Finland, Institute of Dentistry, University of
Oulu, P.O.Box 5281, FIN-90014 University of Oulu, Finland
Oulu, Finland
2002
Abstract
Seventy-eight prepubertal children 3 to 10 years old (mean age 5,67 years, range 2.4 - 10.5 years),
with symptoms suggestive of obstructive sleep apnea syndrome (OSAS) were studied. Based on
overnight polysomnography (PSG) results, 32 children were classified as having OSAS, whereas 46
children were considered as primary snorers (PSs'), when an obstructive apnea-hypopnea index
(AHIO) of over one was considered abnormal. Symptoms, signs and findings in these two groups
were compared in a cross-sectional study. Fifty-eight of the children were retrieved for a follow-up
visit, which was scheduled six months from the first visit. The children with an initial AHIO of 2 or
over (n = 21) had been subjected to adenotonsillectomy swiftly after the first visit, whereas the others
(n = 37) were observed without intervention. The changes in symptoms, signs and findings were
analysed within and between these groups.
Relative risk (RR) ratios were calculated in order to find clinical symptoms and signs predicting
OSAS in snoring children. Observed apneas, restless sleep, constant snoring and tonsillar
hypertrophy were significantly associated with an increased risk of OSAS.
Dental arch measurements indicated that AHIO was significantly associated with the amount of
overjet, suggesting that altered breathing may affect the dentofacial morphology.
Nasalance measurements revealed no group differences between the OSAS children and PSs'.
Adenotonsillectomy had no significant influence on the nasalence scores. Measurements of nasalance
seem to contribute little to the diagnostics of OSAS in children.
At the first visit the mean circulating concentrations of insulin-like growth factor-1 (IGF-1) were
of the same magnitude in the OSAS children, the PSs' and the age-matched control group, but both
the OSAS children and the PSs' had lower IGF-binding protein-3 (IGFBP-3) concentrations than the
control subjects. At the second visit a significant increase of the peripheral concentrations of IGF-1
and IGFBP-3, along with increases in weight for height and BMI were observed in the surgically
treated children, whose respiratory parameters and symptoms had improved highly significantly, as
well. These results indicate that the growth of children with obstructed nighttime breathing is
potentially affected through impaired growth hormone secretion.
None of the primary snorers developed OSAS during the observation period, which finding
suggests a favorable prognosis for primary snoring in children.
Keywords: growth, children, snoring, obstructive sleep apnea, tonsillectomy
Acknowledgements
This work was carried out in the Departments of Otolaryngology, Clinical
Neurophysiology, Pediatrics and the Institute of Dentistry, University of Oulu, during the
years 1994-2002.
I wish to express my deep gratitude to Professor Kalevi Jokinen, M.D., Head of the
Department of Otolaryngology for his encouraging interest in my work throughout the
years, and to Emeritus Professor Antti Palva, M.D., who as the former Head of Department stimulated me in beginning of this study.
I am particularly grateful to the supervisor of my work, Docent Heikki Löppönen,
M.D., my friend, who has excellently taught me the scientific way of thinking and writing. His patience has been enormous, when he has guided me through the up- and downhills of this project. In spite of many other urgent matters he has always found the time to
discuss and help me with problems and he has considerably helped me in completing this
work.
I wish to express my gratefulness to Docent Uolevi Tolonen, M.D., of the Department
of Clinical Neurophysiology, who in addition to the enormous task of analyzing the sleep
recordings has also taken the time to guide me in scientific writing. His kind attitude,
constructive criticism and logic have made a great impression on me.
Docent Markku Partinen, M.D., University of Helsinki, the referee of this thesis, has
shown positive interest in my research. In the final stages of this study he provided me
with constructive criticism and advice, which I am deeply grateful for. I am indebted to
Docent Henrik Malmberg, M.D., University of Helsinki, the referee of this thesis, for his
thoroughness and constructive criticism in the process of reviewing.
I have been provided by very pleasant and skillful collaboration from my co-authors,
which as specialists in different clinical fields have been of utmost importance for this
study. I am deeply grateful to Dr. Tuija Löppönen, M.D., of the Department of Pediatrics,
who performed the anthropometric measurements and supervised me in study V. I wish to
express my sincere thankfulness to Kirsi Pirilä, DDS and Paula Tahvanainen, DDS, of the
Institute of Dentistry, and Professor Jan Huggare, DDS, who made the study II possible. I
also wish to thank phoniatricians Mirja Väyrynen, M.D., and Aulikki Tervonen, M.D., for
their supervision in study III. My warmest thanks go also to Docent Peter Lanning, M.D.,
for his assistance in study V. Professor Mikael Knip, M.D., helped me in designing and
finishing study V, for which I am deeply grateful.
I wish to thank the highly qualified staff of the ward 21 of the Department of Otolaryngology for their excellent and unselfish collaboration during this study. My thanks go also
to the Pediatric research laboratory and to the staff of the audiophoniatric department.
I sincerely thank all the children, parents and volunteers, who kindly participated in
this study. Without them this work would not have been possible.
I wish to thank all the senior colleagues of the Department of Otolaryngology for
teaching me in the field of Otolaryngology, and for fruitful comments and help with this
study. Docent Jukka Luotonen, M.D., has encouraged me on several occasions, and he
was one of the co-authors in study I.
My parents have supported and encouraged me during this work, for which I am grateful.
Finally, my dearest thanks go to my wife Anna-Lena and our daughters Erica and Henrietta. Thank you for all your patience with me during these years. Combining research,
clinical work and family life is not easy. Anna-Lena has always supported and encouraged me, and she has never questioned the time I have needed for my work. Anna-Lena, I
know you have had to carry out a lot of tasks without my help, besides your own studies.
You have still managed to be a wonderful mother and a dear wife. Erica and Henrietta
have been too young to understand the “book I am writing”, and are mainly eager to get
more time on the computer. Their happy laugh has given me a lot of strength.
This research has financially been supported by Korvatautien tutkimussäätiö, Helsinki, Finland, the Alma and K.A Snellman foundation, Oulu, Finland, and The Finnish
Medical Foundation, Helsinki, Finland.
Abbreviations
AHI
AHIO
BMI
CPAP
ECG
EDS
EEG
EMG
EOG
IGF-1
IGFBP-3
OSAS
Pcrit
PSG
RDI
REM
RIP
SBD
SWS
TST
UARS
apnea-hypopnea index
apnea-hypopnea index: obstructive
body mass index
continuous positive airway pressure
electrocardiography
excessive daytime somnolence
electroencephalography
electromyography
electro-oculogram
Insulin-like growth factor-1
Insulin-like growth factor binding protein-3
obstructive sleep apnea syndrome
critical closing pressure
polysomnography
respiratory disturbance index
rapid eye movement
respiratory inductive pletysmography
sleep-related breathing disorder
slow-wave sleep
total sleeping time
upper airway resistance syndrome
List of original communications
The thesis is based on the following communications which will be referred to in the text
by their Roman numerals.
I
Nieminen P, Tolonen U, Löppönen H, Löppönen T, Luotonen J & Jokinen K (1997)
Snoring children: factors predicting sleep apnea. Acta Otolaryngol (Stockh) Suppl
529:190-194
II
Pirilä K, Tahvanainen P, Huggare J, Nieminen P & Löppönen H (1995) Sleeping positions and dental arch dimensions in children with suspected obstructive sleep apnea
syndrome. Eur J Oral Sci 103:285-291
III Nieminen P, Löppönen H, Väyrynen M, Tervonen A & Tolonen U (2000) Nasalance
scores in snoring children with obstructive symptoms. Int J Pediatr Otorhinolaryngol
52:53-60
IV Nieminen P, Tolonen U & Löppönen H (2000) Snoring and obstructive sleep apnea in
children: a 6-month follow-up study. Arch Otolaryngol Head Neck Surg 126:481-486
V
Nieminen P, Löppönen T, Tolonen U, Lanning P, Knip M & Löppönen H (2002)
Growth and biochemical markers of growth in children with snoring and obstructive
sleep apnea. Pediatrics 109:e55
Contents
Abstract
Acknowledgements
Abbreviations
List of original communications
1 Introduction ................................................................................................................. 15
2 Review of the literature ............................................................................................... 16
2.1 History of sleep apnea among children ................................................................ 16
2.2 Normal sleep in 3 to 10 year old children ............................................................ 17
2.3 Definitions ............................................................................................................ 18
2.3.1 Primary snoring .......................................................................................... 18
2.3.2 Obstructive apneas .................................................................................... 18
2.3.3 Obstructive hypopneas .............................................................................. 19
2.3.4 Obstructive hypoventilation ...................................................................... 19
2.3.5 Central apneas ........................................................................................... 20
2.3.6 Mixed apneas ............................................................................................. 20
2.3.7 Desaturation ............................................................................................... 20
2.3.8 Arousals and sleep architecture ................................................................. 20
2.3.9 Autonomic arousals ................................................................................... 21
2.4 Classification of sleep-related airway obstruction ............................................... 22
2.4.1 UARS ........................................................................................................ 22
2.4.2 OSAS ......................................................................................................... 23
2.5 Diagnostic criteria for OSAS ............................................................................... 23
2.6 Diagnostic methods .............................................................................................. 24
2.6.1 Polysomnography ....................................................................................... 24
2.6.2 Clinical diagnosis ...................................................................................... 26
2.6.3 Pulseoximetry ............................................................................................ 27
2.6.4 Sleep sonography ...................................................................................... 27
2.6.5 Video and cardiorespiratory monitoring ................................................... 28
2.6.6 Radiology .................................................................................................. 28
2.6.7 Endoscopy ................................................................................................. 28
2.6.8 Nasal cannula/pressure transducer ............................................................ 29
2.7 Prevalence ............................................................................................................ 29
2.8 Pathophysiology ................................................................................................... 30
2.9 Etiology ................................................................................................................ 32
2.10Morphological and odonthological considerations .............................................. 34
2.11Clinical symptoms ................................................................................................ 34
2.11.1 Nighttime symptoms ................................................................................. 35
2.11.2 Daytime symptoms .................................................................................... 36
2.12Complications ...................................................................................................... 38
2.12.1 Failure to thrive ......................................................................................... 38
2.12.2 Cardiovascular complications ................................................................... 39
2.12.2.1 Cor pulmonale ............................................................................. 39
2.12.2.2 Hypertension ............................................................................... 39
2.12.2.3 Arrhythmias ................................................................................ 40
2.12.3 Developmental aspects .............................................................................. 40
2.13Treatment ............................................................................................................. 41
2.13.1Surgery ....................................................................................................... 41
2.13.1.1 Adenotonsillectomy .................................................................... 41
2.13.1.2 Maxillo-facial and related surgery .............................................. 42
2.13.1.3 Uvulo-palato-pharyngoplasty ...................................................... 42
2.13.1.4 Tracheotomy ............................................................................... 42
2.13.1.5 CPAP ........................................................................................... 43
2.13.2 Other .......................................................................................................... 43
2.14Treatment complications ...................................................................................... 44
2.15Natural history ...................................................................................................... 44
3 Aims of the present study ............................................................................................ 46
4 Subjects and methods .................................................................................................. 48
4.1 Subjects ................................................................................................................ 48
4.2 Methods ................................................................................................................ 49
4.2.1 Questionnaire .............................................................................................. 49
4.2.2 Clinical evaluation ..................................................................................... 49
4.2.3 Polysomnography ...................................................................................... 50
4.3 Symptoms and signs (studies I & IV) .................................................................. 51
4.4 Dental arch dimensions (study II) ........................................................................ 52
4.5 Nasalance studies (study III) ................................................................................ 52
4.6 Growth characteristics (study V) ......................................................................... 52
4.7 Protocol ................................................................................................................ 53
4.8 Statistics ............................................................................................................... 54
4.9 Ethical aspects ...................................................................................................... 54
5 Results and comments ................................................................................................. 55
5.1 First visit .............................................................................................................. 55
5.1.1 Polysomnography results ............................................................................ 55
5.1.1.1 Comments ................................................................................... 56
5.1.2 Symptoms and signs .................................................................................. 57
5.1.2.1 Comments ................................................................................... 59
5.1.3 Risk factors (Study I) ................................................................................ 60
5.1.3.1 Comments ................................................................................... 62
5.1.4 Dental arch dimensions (Study II) ............................................................. 62
5.1.4.1 Comments ................................................................................... 63
5.1.5 Nasalance scores (Study III) ...................................................................... 63
5.1.5.1 Comments ................................................................................... 63
5.1.6 Growth characteristics (Study V) .............................................................. 64
5.1.6.1 Comments ................................................................................... 66
5.2 Follow-up study ................................................................................................... 67
5.2.1 Polysomnography results ............................................................................ 67
5.2.1.1 Comments ................................................................................... 68
5.2.2 Symptoms (Study IV) ................................................................................ 69
5.2.2.1 Comments ................................................................................... 69
5.2.3 Impact on nasalence (study II) .................................................................. 69
5.2.3.1 Comments ................................................................................... 70
5.2.4 Effects on growth ...................................................................................... 70
5.2.4.1 Comments ................................................................................... 72
6 General discussion ....................................................................................................... 73
7 Conclusions ................................................................................................................. 76
References
Original communications
1 Introduction
Sleep related obstructive breathing disorders are relatively common in children. They
have a very large scale of symptoms, from plain harmless snoring to obstructive sleep
apnea syndrome (OSAS), a condition related to snoring with nighttime repetitive airway
patency disruptions. The mildest forms of sleep-related breathing disorders are probably
quite harmless to the children, whereas OSAS can even lead to life-threatening
complications in the pediatric population (1), hence there is a need for understanding the
syndrome.
Many physicians are still unaware of OSAS and its potential complications in children,
which may result in delayed diagnosis and unnecessary morbidity (2, 3). It may also be
difficult to separate the various levels of sleep disorders without objective measurements,
as there is a great deal of overlap of the symptoms across the continuum of sleep-related
obstructive disorders. Diagnostic challenges of the syndrome still remain to be overcome.
Due to the state of ongoing development, OSAS may affect children in specific ways
not encountered in adults. Some of the complications may have effects on later life and
possibly predispose to reappearing OSAS in adulthood.
The pathophysiology and etiology of OSAS in children are inadequately understood.
The complex process of airway closure during sleep is a dynamic phenomenon not
explained by mechanical factors alone. The multifaceted etiology of OSAS in children
explains why the method of choice- treatment, adenotonsillectomy, is not always curative.
The present investigation of snoring children with symptoms suggestive of OSAS was
designed to increase our knowledge of this disease and further give guidelines for
diagnostics and treatment of children suffering from OSAS.
2 Review of the literature
2.1 History of sleep apnea among children
Charles Dickens was probably the first to describe the features of sleep apnea in his
famous comic narrative The Posthumous Papers of the Pickwick Club (4). The fat boy
Joe was snoring heavily, he was falling constantly asleep and was described as having
slow perception. Damn that boy...! In 1889, William Hill (5) recognized the symptoms of
the syndrome, describing the stupid lazy-looking kid who frequently suffers from
headaches at school, breathes through his mouth instead of his nose, snores and is restless
at night. He speculated that some of their backwardness was secondary to some
hampering of the cerebral functions rather than deafness. Hill also found
adenotonsillectomy to be helpful for these children. In 1965 Menashe et al. (6) described
two children with cor pulmonale and other typical symptoms of OSAS secondary to
chronic upper airway obstruction formed by tonsils and adenoids, and regression of the
symptoms after tonsillectomy and adenoidectomy. The same year Noonan (7) presented
two children with right-sided ventricular hypertrophy, tremendous adenoids and tonsils
and snorting respiration. Radiation therapy to the nasopharynx caused the lymphoid
tissue to regress and the cardiopulmonary function to return to normal. Noonan stated that
“cor pulmonale from hypertrophied tonsils and adenoids” seems to constitute a valid but
rare medical indication for tonsillectomy and adenoidectomy. Further the same year, Cox
et al. (8) described a child with typical OSAS-symptoms and cor pulmonale resulting
from laryngomalacy, with clinical improvement after tracheotomy. All the authors saw
the connection between noisy respiration and hypersomnolence and heart changes. In
1967 Levy et al. (9) described how the symptoms of respiratory obstruction could be
alleviated by nasopharyngeal tubing.
The first continuous polygraphic night recordings of adult patients suffering from the
Pickwickian syndrome were performed by Jung & Kuhlo in 1965 (10). Pickwickian
syndrome, a terminological predecessor of OSAS, named after Dickens’ narrative of the
features of the fat boy Joe in the Pickwick Club (4), was described as consisting of
frequent diurnal episodes of spontaneous sleep with apnea, alveolar hypoventilation with
hypercapnia, and obesity (10). Jung & Kuhlo showed that occurrence of apneic intervals
17
is a prominent feature also during nocturnal sleep, and may occur before development of
obesity, so that the Pickwickian should have some central disturbance of respiration and
arousal, as shown by the CO2 tracing and EEG recordings of the sleeping subjects.
A further step towards the modern concept of OSAS was when Gastaut et al. (11) in
1966 also concluded that the loss of nocturnal sleep is responsible for diurnal
somnolence. Daytime drowsiness was shown not to be a consequence of acquired
hypoxia as was thought earlier. Polygraphic nocturnal recording showed heavily disturbed
sleep architecture with arousals at the termination of apneas and resaturation of the
arterial blood after resumption of breathing in an obese male.
The sleep apnea syndrome was described for the first time in 1973 in adults (12), and
1976 in children (13), in a pioneer article on the condition in the pediatric population with
a series of eight children. The symptoms, signs and complications of the syndrome were
described more thoroughly in a more comprehensive study with 50 children in 1981 (14),
when the first diagnostic criteria were introduced as well. The diagnostic criteria
resembled closely those developed for adults, but the adult criteria have later been found
not to be suitable for children (15) and have hence been modified (16).
In Finland, none of the earlier theses on obstructive sleep apnea (17-22) has focused
on OSAS in children from a surgical point of view.
2.2 Normal sleep in 3 to 10 year old children
The total amount of sleep needed by young children decreases annually with about one
hour to be about 12 hours at the age of five, at which age the afternoon naps have started
to disappear, and the frequency of night awakenings is low (23). By the age of ten,
children sleep 8 to 10 hours, and the sleep is quieter with less body movements than at
younger age. The sleep pattern usually follows a cycle of rapid movement through stages
1,2 and 3, before remaining in stage 4 for a longer time. Stage 4 gives way to stages 3 and
2 and a short period of stage one before REM sleep appears. The cyclic pattern is
repeated on the average four times during the night with less stage 4 sleep and increasing
amounts of REM sleep in the later periods (24). The change in children’s sleep stages
occurs smoothly and regularly in contrast to adults’ (24).
Between the first and fifth years of age, the percentage of REM sleep of the total
amount of sleep decreases from 30% to the adult level between 20 to 25% (25). In 6 to
11-year-old children, the amount of REM sleep remains constant at the 20 to 25% level of
sleep time (24, 26). The first REM period starts to appear somewhat earlier in older
children, within the first two hours of sleep, being quite short, about 15 minutes, whereas
the later periods have a tendency to become longer, up to 30 minutes, and more intense
toward the end of the night (26). Most of stage 3 and 4 sleep (slow-wave sleep, SWS) is
seen in the first third of the night (24), SWS accounting for ~ 22-26% of the total sleep
time (26), while REM sleep is more concentrated in the latter two third parts of the night,
especially in the latest part (24). With increasing age, the time spent in stage 2 non-REM
18
sleep increases at the expense of stage 4 non-REM sleep (slow-wave sleep), which
declines from about 18% in six-year-olds to 14% in ten-year-olds (26). Most sleep is
spent in stage 2, over 40% of the total sleeping time.
The breathing may be quite irregular during the night. Sighs, when a sharp increase of
respiratory movement amplitude occurs, contribute to reopening unventilated zones (27).
The respiratory frequency is highest during periods of wakefulness and in stage 1 nonREM sleep and lowest during stage 2 non-REM sleep of the last cycle of the night (28).
The mean highest and lowest respiratory rates have been reported to be 17 and 15 breaths
per minute accordingly (28). Later in childhood/adolescence the respiratory frequency
and variability is highest in REM sleep and lowest in stages 3–4 of non-REM sleep (29).
Apneas (see definitions below) may occur in normal children. Central apneas are
relatively common and normal phenomena, especially after movement (14, 28), occurring
mainly in stage 1 and 2 of non-REM sleep, and less in REM sleep (28, 29). Even up to
25-second-long central apneas have been recorded in normal children (28-30).
Obstructive apneas are less common, reported earlier as non-existent in normal children
(14, 28, 29). Later, obstructive apneas have been found to exist also in normal children,
but they are rare and only of short duration (16).
2.3 Definitions
2.3.1 Primary snoring
Children who snore, but are not found to have apneas, hypoventilation or excessive
arousals from sleep on polysomnography, have been called primary snorers (31, 32).
2.3.2 Obstructive apneas
In an obstructive apnea there is a continuing respiratory effort despite cessation of gas
exchange at the level of the mouth and nostrils. In Guilleminault et al.’s report from 1981
(14) the apnea as well as the hypopnea was defined to have to last at least 10 seconds to
be important. The same 10-seconds criterion was also used by Brouilette et al. in 1982
(33) as a part of the diagnostic procedure, and later by many other research groups. There
have been arguments against the adult criteria being extrapolated to children, since
children have smaller respiratory capacity and a faster respiratory rate (15). The 10second criterion has in many reports had to give way to shorter apneas, especially after
Marcus et al. in 1992 (16) published normal polysomnographic values for children. They
found no normal child to have obstructive apneas lasting more than ten seconds, and
apneas lasting 5-10 seconds were rare, which results are supported by others (28).
19
Obstructive apnea occurrence is usually greatest in REM sleep (34, 35), with up to 55%
of obstructive apneas occurring in REM sleep, and 36% in stage 2 sleep (35). Obstructive
apneas in SWS account for only about 5% to 10% of the total occurrences of apneas during the night in children (35, 36). The apneas occurring in REM sleep are also more severe
than apneas in other sleep stages (35). The apneas in REM sleep tend to increase in number and become more intense towards the latter part of the night (35), when the REM periods also become longer (26).
2.3.3 Obstructive hypopneas
In an obstructive hypopnea the gas exchange is reduced at the level of the mouth and
nostrils despite breathing effort. For hypopneas there exists a wide range of recording
techniques and definitions used in different sleep laboratories (37). In a survey study to
different accredited sleep laboratories it was found that no two laboratories used the same
definition and measures of hypopnea (37). In 54% (24/44) of the laboratories a 50%
reduction in the airflow was required to define a hypopnea, while in the rest of the 20/44
laboratories the requirement was less strict. Thirty-seven laboratories also included
oxygen desaturation as a part of their definition, but the degree of desaturation required to
meet the criteria for hypopnea varied widely. In 33 laboratories a sleep arousal was
needed to fulfil the definition of hypopnea, but there was no consistent definition of
arousal in response to the question. In a study on adults a 50% reduction in
thoracoabdominal movement lasting for 10 seconds was found to be the best definition of
hypopnea (38).
2.3.4 Obstructive hypoventilation
In children hypopneas often account for the most part of obstructive events (39, 40);
obstructive events are often periods of partial airway obstruction and prolonged
hypoventilation instead of clear-cut apneas (40), which are rather a culmination of the
”hypopnea”-syndrome (38). This is why many consider it important to measure the
amount of hypoventilation (16, 41, 42), rather than quantify the hypopneas. Brouilette et
al. (33) considered obstructive hypoventilation to be present when signs of partial airway
obstruction (paradoxical inward chest movement, snoring and use of accessory muscles)
were accompanied by hypercarbia. When Marcus et al. 1992 (16) introduced their normal
polysomnographic values for children and adolescents, they recommended that a peak
end-tidal CO2 over 53 mmHg, or end-tidal CO2 over 45 mmHg for more than 60 % of
total sleeping time (TST) should be considered abnormal. They also observed that the
peak end-tidal CO2 was frequently over 45 and occasionally even over 50 mmHg in
normal non-apneic children.
20
2.3.5 Central apneas
A central apnea occurs when there is a lack of breathing effort concomitant with loss of
gas exchange. Stradling et al. (43) have suggested that any event, regardless of the
duration, with an over 4% decrease in arterial oxygen saturation exceeding the frequency
of 3/hour should be considered abnormal. The role of the central apneas in OSAS is,
however, unclear (44), and many different standards have been applied. To be scored,
there may be a demand of co-joint deep desaturation (below 90%) (16), a lower time limit
(20 sec) with co-incident desaturation (45) and/or bradykardia (32), or central apneas may
be ignored (31). It seems that central apneas are more common in OSAS-children than in
primary snorers (46).
2.3.6 Mixed apneas
A mixed apnea begins with a central apnea proceeding with an obstructive component.
Mixed apneas are usually included in the category of obstructive apneas.
2.3.7 Desaturation
A decrease in the blood oxygenation level, desaturation, may follow all types of apnea.
Desaturations may also occur in non-snoring children. The mean arterial oxygen
saturation during the night in normal children is ~ 96% (43, 47). Brief over 4%
desaturations may occur in normal children at a rate less than 3 times per hour (43), and
occasional deep desaturations below 90 % in normal children have been reported (48),
even below 80% (30). As for normative criteria, Marcus et al. (16) recommended that
saturation values below 92% should be considered abnormal in the pediatric population.
In their study population with normal children there were nevertheless found
desaturations below this level. However, many children with clear apneas never desaturate
below 92% (31, 49).
2.3.8 Arousals and sleep architecture
An EEG-arousal in sleep is defined as an abrupt shift in EEG frequency, lasting for 3
seconds or more, which may include theta, alpha and/or frequencies greater than 16Hz
but not spindles (50). The adult criteria have been modified for children so that EEG
frequency shifts greater than 1 second are considered (51). An arousal is usually linked
with the termination of obstructive apnea in adults, whereas this is often not the case in
children (15, 52, 53). There are no standardized criteria for arousal detection in infants
and children (51, 53), and only few reports have documented regular occurrence of
21
arousal at the end of sleep-related obstructive events in infants and children (51, 54). EEG
arousals are probably not an important mechanism in the termination of respiratory events
in children (31, 35, 46, 53, 55, 56), as less than 40% of the respiratory events are
terminated with an arousal, and the EEG arousal index has been found to be relatively
alike between OSAS-children and normal controls (31, 53, 55), or only slightly higher
(46). It has, however, been pointed out that spontaneous arousals (movement or EEG
arousals) without any relation to apneas should be assessed as respiratory arousals, since
they are possibly associated with aggravated inhalation (57).
The percentages of REM sleep and slow-wave sleep seem to be quite equal in OSAS
children compared with normal subjects (35, 51, 52), so the sleep macrostructure in
OSAS children is preserved compared with normal children (35, 56, 57). Bandla et Gozal
(58) demonstrated that in apneas not associated with an arousal, the delta frequency was
decreased during the apnea followed by increase after the termination of the apnea. The
authors speculated that this phenomenon might represent subtle evidence of arousal and
sleep fragmentation. According to the Atlas Task Force (1992) (50) the delta wave bursts
might be indicative of arousals, but the evidence is limited.
2.3.9 Autonomic arousals
It is possible that arousals not detected by current definitions can occur without visible
EEG changes. Nocturnal sound provocations causing increase in blood pressure but no
visible EEG changes have been shown to cause increased daytime sleepiness in adults
(59). Instead of EEG arousals, children rather tend to have movement arousals. Mograss
et al. (51) reported that the majority of apneas in children were terminated by a short
movement arousal, which often did not result in sleep-stage change, but did re-establish
airway patency. The arousals were often shorter than 3 seconds. Praud et al. (60) reported
that 88% of non-REM apneas were terminated by movement arousal, 12% with an EEG
arousal. All the apneas in REM sleep were ended with a movement arousal, which was
defined as an increase in EMG on any channel, accompanied by a change in pattern on
any additional channel lasting for at least 2 seconds.
Overnight ECG monitoring in OSAS children has revealed reduced R-R intervals
beginning a few seconds after initiation of obstruction, followed by increased R-R
intervals when breathing resumed (61). Mograss et al. (51) found that 84% of all
movement arousals in children could be detected using cardio-respiratory montage. The
movement arousal is identified with tachycardia, increased amplitude and irregularity of
respiratory inductive pletysmography signals, and distortion of the pulse waveform. A
pulse increase linked to the obstructive event evidently indicates subcortical reactions
(62). Children with OSAS have also been found to have higher sympathetic activity
throughout the night than normal children (63).
22
2.4 Classification of sleep-related airway obstruction
The severity of upper airway obstruction can be considered to have a spectrum with
increasing severity, from mild obstruction causing only snoring to the culmination of
repetitive complete closures of the upper airways (apneas) (Fig. 1) (64). Primary snoring,
UARS and OSAS seem to lie on a continuum (46), with a great deal of syndrome overlap
(65). Due to the resembling symptomatology, the syndromes are hardly separated based
on the symptoms and orocraniofacial information (65).
Increasing intensity
of airway obstruction
Snoring
Sleep disruption
(possibly UARS)
Hypoventilation and
blood-gas changes
Repetitive complete closures of
airway (apneas)
Fig. 1. The schematic spectrum of the severity of airway obstruction in children.
2.4.1 UARS
Fragmented sleep due to repetitive arousals secondary to increased inspiratory effort has
been blamed as the cause of the daytime symptoms of children with snoring but no
apneas. In adults this is called the upper airway resistance syndrome (UARS), where
inspiratory negative pressure increase causes a cortical arousal leading to an abrupt
opening of the airways before an apnea occurs (66). However, excessive daytime
somnolence, personality changes and neurocognitive impairments have been shown to
occur in children with heavy snoring, restless sleep and large negative esophageal
23
pressure changes in the absence of apneas, desaturations or cortical arousals (67).
Downey et al. (46) found no significant difference in the arousal index between snorers
and children they felt to have UARS, whereas Guilleminault et al. (65) found no
significant difference in the number of arousals in children with UARS and OSAS. The
role of arousals in pediatric UARS is unclear (56), as is the best method of identifying
UARS, since many children will not tolerate the esophageal catheter used to monitor the
esophageal pressure required for detecting respiratory effort-related arousals, which
method has been thought to be the best for recognizing abnormal breathing patterns
during sleep (65). A recent finding suggests that a nasal cannula/pressure transducer
could be a non-invasive reproducible detector of all events in sleep-disordered breathing,
detecting also the same events as esophageal manometry (68), which can help to clarify
the role of this syndrome in children.
2.4.2 OSAS
OSAS can be considered as the culmination of sleep-related obstructive disorders in
children. OSAS arises from a series of events which repeat themselves during the night,
and which can lead to daytime symptoms and development of health-related
complications. A total collapse of the upper airway leads to an obstructive apnea, with no
gas exchange at the level of mouth and nostrils. If the collapse is incomplete, an
obstructive hypopnea with reduced gas exchange or a prolonged hypoventilation period
occurs. Instead of repetitive discrete obstructive apneas, children often exhibit a pattern of
partial obstructive hypoventilation characterized by snoring, paradoxical ribcage motion,
phasic desaturations and hypercapnia (33, 40, 69). Though sometimes called the
obstructive hypoventilation syndrome, this type of obstruction pattern is included under
OSAS in children.
2.5 Diagnostic criteria for OSAS
Diagnostics of pediatric OSAS is difficult at least for two reasons: lack of universally
accepted criteria for the syndrome and the unique demands of the children. Children will
not always easily tolerate complex recording apparatus in and around them, which obviously is a problem from the technical point of view. For most of the information regarding
the child’s symptoms one has to rely on the parents, who perhaps do not notice their
child’s nocturnal symptoms unless their own sleep is disturbed.
The most accurate and comprehensive method of diagnosing OSAS is nocturnal polysomnography (70). The diagnostic criteria used for adults are found not to be suited for
children (15, 16, 40). Basically in the studies of pediatric OSAS the children have the
same clinical symptomatology, but may be differently classified due to different criteria
and the recording methods used. The diagnostic criteria are usually based on a certain
apnea/hypopnea index (AHI), but desaturations, hypercapnic episodes, and arousals may
24
be included in the criteria, then often called the respiratory disturbance index (RDI),
either as their own parameters or in association with apnea or hypopnea (71). Different
approaches to measuring RDIs may contribute to substantial variability in the identification and classification of the disorder (71).
Marcus et al. (16) have studied 50 normal children and adolescents and given
recommendations for normal polysomnographic criteria (Table 1). Marcus et al. (16)
found obstructive apneas to be very rare in normal children, whereas in older (pubertal)
children are apneas perhaps not as uncommon (48). Most authors use lower indexes and
shorter apnea times as criterion for pediatric OSAS than the index 5 and apnea duration
10 seconds originally presented by Guilleminault et al. (14).
Table 1. Abnormal polysomnographic criteria for children according to Marcus et al.
(1992)
Abnormal polysomnographic criteria
a) more than one obstructive apnea of any length per hour of sleep
b) central apneas associated with desaturation below 90% irrespective of the length of the apnea
c) peak end-tidal CO2 pressure > 53mmHg or end-tidal CO2 pressure > 45 mmHg for more than 60 % of
total sleeping time
d) arterial oxygen saturation values < 92%
In the consensus statement of the American Thoracic Society (70) for standards and
indications for cardiopulmonary sleep studies in children, only broad guidelines to
determine abnormality for the respiratory events could be given.
2.6 Diagnostic methods
2.6.1 Polysomnography
(PSG) is the gold standard recommended for diagnostic investigation also in children
(41). In the consensus statement of the American Thoracic Society (70), PSG is
recommended to differentiate between primary (benign) snoring and snoring associated
with either partial or complete airway obstruction, hypoxemia and sleep disruption.
According to the consensus statement, polysomnography is indicated as a diagnostic tool
in a variety of situations, most importantly: 1) for evaluating the child with disturbed
sleep patterns, excessive daytime sleepiness, cor pulmonale, failure to thrive, or
polycythemia unexplained by other factors or conditions, especially if the child also
snores; 2) in the child who has clinically significant airway obstruction during sleep as
observed by medical personnel, or documented by audiovideo recording. 3) Since
children with OSAS are at a higher risk of postoperative complications (72), PSG is
recommended if the surgeon is uncertain whether the clinical observation of obstructed
breathing is sufficient to warrant surgery.
25
The exceptional demands of children make the pediatric PSG perhaps more
demanding than for adults. Pediatric PSG should be as little invasive as possible so as not
to disrupt the child’s usual sleeping pattern. Also, the surroundings should be appropriate
for age and to accommodate a parent.
The measurements are obtained to assess the adequacy of ventilation, to differentiate
between the obstructive and central apneas and to evaluate the severity and physiological
consequences of the breathing disturbance (70). Usually a central apnea is scored when
there are flat tracings simultaneously from strain gauges and the thermistor, and an
obstructive apnea when continuous deflections are obtained from strain gauges while
there is a simultaneous flat recording from the thermistor (23).
There are several parameters measured with PSG. The airflow is usually measured
with an oro-nasal thermistor and/or a nasal CO2 sampling catheter, which both can
provide a qualitative airflow signal (42). The thermistor registers the airflow both from
the mouth and the nostrils, but in order to do this, it must be attached to the upper lip.
Quantitative measurements of airflow require an oro-nasal mask (pneumotachograph), or
tracheotomy tube, and are therefore used mainly in research settings. The limitations of
both methods can perhaps be circumvented with a recently introduced system for
detection of respiratory events, the nasal cannula/pressure transducer (73).
The ventilation can be measured semiquantitatively with respiratory inductive
pletysmography (RIP), where two bands measure the separate contributions of chest and
abdomen to the tidal volume. When compared with pneumotachographic airflow
measurement, RIP has been shown to have a 0.96 or greater correlation coefficient (74).
Calibrated RIP can detect obstructive apneas and hypopneas (38). RIP may also prove to
be useful in non-invasive diagnostics of UARS (75). The advantage of RIP is that it does
not require attachments to the face.
The oxygenation of blood is usually measured with pulse oxymetry, which rapidly
responds to changes in the blood oxygen partial pressures, with only the circulation time
to the periphery as a systemic artifact. The oxymetry sensor is convenient but sensitive to
movement artifacts and may easily be pulled off. The pulse waveform should also be
monitored on a separate channel adjacent to the ECG signal to help to determine the
accuracy of the saturation reading (70). Transcutaneous oxygen tension measurement has
a long response time to rapid decrease in arterial oxygen saturation, so the decrease of
oxygen tension with apnea may be difficult to quantitate (76).
The effective way to detect periods of hypoventilation is to measure the end-tidal CO2,
which is thought to reflect the alveolar CO2 (42). The CO2 pressure may also be
measured transcutaneously, but then only a trend rather than transient changes can be
measured (42).
Electroencephalogram should be included in PSG for sleep staging, together with
electrooculogram to record rapid eye movements (70). Scoring arousals from an all-night
EEG recording is a laborious manual process, so a recent finding suggests that an
automated analysis of arousals implied from blood pressure rises could be a convenient
alternative to EEG scoring (77). Submental or chin electromyogram (EMG) discharges
can indicate changes in respiratory effort, whereas intercostal EMG used by some may
allow monitoring of the diaphragmatic effort (41). Tibialis EMG monitoring is used to
detect periodical leg movements. It can also help to quantitate movement arousals during
PSG assessment of cardiopulmonary function (70).
26
The cardiac rate and rhythm should be monitored with electrocardiogram (70) to
reveal cardiac consequences of obstructed breathing (39, 61).
Daytime nap studies should be interpreted with caution due to the circadian rhythm of
many functions and the relative lack of REM sleep (41), as obstructive apneas and
hypopneas are more common during REM than non-REM sleep (35, 53, 78). Nap studies
seem to underestimate the degree of obstructed breathing, though they may have a
screening value, since the positive predictive value of nap studies compared with
overnight studies has been found to be 100% and the negative predictive value 17% (79).
There is often big discrepancy between PSG results and the clinical diagnosis score in
children with strongly suspected OSAS (49), and it has been suggested that the diagnosis
should be based on a combination of factors gathered from these forms of assessment
(49). Reliance on EEG as an indicator may also be misleading by giving an underestimate
of the clinical severity of sleep-disordered breathing in children (53). PSG is perhaps not
necessary in all children with strong clinical evidence of OSAS, since PSG is so
expensive and the availability may be poor (80). Sleep studies do, however, contribute to
the clinical impression when assessing the need for operation or possible postoperative
complications (81).
The first-night effect or night-to night variability may influence the PSG-results (82),
but there is no data on the reproducibility, sensitivity and specificity of a single-night PSG
for children of different ages. In adults, the first-night effect on apneas and hypopneas is
not significant (83).
The automated sleep analyses or computer-based scoring systems are not yet very
reliable, and tend to overestimate the respiratory disturbances (84). The smaller oro-nasal
airflow and respiratory movement signals as well as a displaced thermistor may be
misinterpreted by the computer as apneas/hypopneas (84).
2.6.2 Clinical diagnosis
Many physicians have to base their diagnosis of OSAS on the clinical symptoms and
signs of the children. The accuracy of clinical diagnosis of pediatric OSAS has been
evaluated in a series of studies (31, 85-88), in which only half or less of the children
proved to have OSAS despite symptoms strongly suggesting the condition. The results
are fairly constant in spite of slightly different criteria used for OSAS in the studies.
Scoring and screening methods for guidelines of diagnosis-making have been developed,
both for the pediatric (89) and adult population (90, 91). Brouilette et al. (89) derived a
symptom score which according to their research classified correctly all controls and 22
out of 23 OSAS patients. Observed apneas, constant snoring and difficulty in breathing
during sleep were found to be fairly predictive of OSAS. Later the OSA score has been
shown to misclassify a substantial number of patients (31), and to be even less accurate
than clinical subjective impression (92). Goldstein et al. (88) found clinical diagnosis to
have a 92% sensitivity and 29% specificity for right diagnosis of OSAS, and a 50%
positive predictive value and 83% negative predictive value when compared to PSGresults. Parental information of apneas is reported to have high specificity (94%), but
27
relatively low sensitivity (44%) (93), and the predictive accuracy of witnessed apneas was
in one study found to be only 32% (85). A health-related quality of life (HRQL) survey
has been proposed as a mean of determination of OSAS severity in children (94). In the
study, the scores of the survey were significantly associated with the apnea-hypopnea
score.
Some orofaciocranial features are found to be highly suggestive of breathing disorders
during sleep when associated with specific clinical symptoms: a small chin, a steep
mandibular plane, a retroposition of the mandible, a long face, a high hard palate, and an
elongated soft palate (65). Guilleminault et al. (65) found a high score on a visual clinical
orocraniofacial scale to be equally common in UARS and OSAS children, but if a child
also scored high on tonsil-size grading OSAS was a more likely diagnosis than UARS.
2.6.3 Pulseoximetry
In adults, starting treatment based on results of nocturnal oxymetry suggestive of sleep
apnea hypopnea syndrome has been suggested to be a way of decreasing the need for
PSG (95). The clear disadvantage of the method is though, that it cannot differentiate
between central and obstructive apneas and hypopneas. Lately, Brouilette et al. (96)
demonstrated that a positive nocturnal oximetry trend graph including at least three or
more desaturation clusters and at least three desaturations to under 90%, had at least a
97% positive predictive value in a child suspected of having OSAS. According to the
authors oxymetry could be used as a definitive diagnostic test for straightforward OSAS
attributable to adenotonsillar hypertrophy or for identifying children with obstructive
symptoms who could require PSG. A negative oxymetry cannot rule out OSAS, so a high
clinical suspicion warrants further investigations (97).
2.6.4 Sleep sonography
Sleep sonography, where the breathing sounds are recorded and analysed through
computer processing, cannot differentiate between central and obstructive apnea, which is
clearly a drawback of the method (98). Still, sonography may have value as a cheap
screening method (98). Lamm et al. (99) found in their study of 29 children that findings
on a home audiotape, where the presence of struggled sound and respiratory pauses are
analysed manually, can be suggestive of OSAS, but they are not sufficiently specific to
reliably distinguish between OSAS and primary snoring. Tracheal sound recordings
together with O2 measurement have been reported to be a reliable method of detecting
respiratory events in adults (100). This method is not suitable for children either, as
children often exhibit continuous snoring with hypoventilation/hypopneas instead of clear
apneas (stop in breathing and sound) (40, 101).
28
2.6.5 Video and cardiorespiratory monitoring
Video-recording of the first 60 minutes of a child’s sleep has been suggested to be helpful
in demonstrating sleep apnea (43, 102). Video recording can also be used to evaluate the
time spent moving to measure sleep disturbance (43). Video-recording has been shown to
be valuable as a part of cardiorespiratory video montage, where movement/arousals can
be identified sensitively with the aid of cardiovascular channels and video recording,
which helps to delete induced arousals (51) and to distinguish sleep from wakefulness,
thereby reducing the need for EEG recording in pediatric polysomnography (78).
2.6.6 Radiology
Anteroposterior and lateral radiographs of the airway are the most common radiological
examinations of children with suspected airway obstruction (103). But the airway
obstruction is a dynamic phenomenon, and lateral neck radiography does not provide
sufficient information on which to base a decision to perform adenotonsillectomy to
relieve airway obstruction during sleep in children (104). The plain radiographs will
nevertheless reveal anatomic abnormalities (103).
(Video)fluoroscopy has been performed on children to study the pathophysiology of
OSAS (33, 105, 106). Videofluoroscopy can provide additional information to lateral
radiographs and PSG in children with minor adenotonsillar enlargement or with predisposing factors (101).
Virtual endoscopy has proved to effectively show fixed lesions in the upper airways,
but it is not sensitive enough to detect dynamic movements leading to obstruction (107).
Magnetic resonance imaging of the upper airways may reveal structural abnormalities
in OSAS children (108).
2.6.7 Endoscopy
Flexible fiberoscopy has been shown to identify reliably the site of obstruction in children
with anomalous upper airways with obstructive symptoms even when awake (109). Sleep
nasoendoscopy combined with rigid laryngo-bronchoscopy has been suggested to be
valuable in detecting the site of obstruction in children with residual symptoms after
adenotonsillectomy (110).
29
2.6.8 Nasal cannula/pressure transducer
A recent finding suggests that a nasal cannula/pressure transducer could be a non-invasive
reproducible detector of all events in sleep disordered breathing, detecting also the same
events as esophageal manometry (68). The nasal cannula system consists of a standard
oxygen cannula placed in the nares and attached to a sensitive pressure transducer that
detects pressure fluctuations caused by inspiration and expiration. The pressure reading is
taken from the distal end of the oxygen cannula with prongs that extend into the nose,
thus measuring the pressure inside the nose. The flow signal is measuring a pressure drop
across a relatively constant resistance at the inlet of the nose (73). The nasal cannula
system permits the analysis of both flow and its morphology (111, 112), and may even
detect snoring (112). The nasal cannula system seems to be more sensitive in detecting
apneas and hypopneas than the thermistor (73). The system may be especially useful in
identifying increased upper airway resistance and the presence of flow limitation (68, 73,
113). In conjunction with EEG, analysis of the shape of the nasal cannula flow signal,
when transient inspiratory flattening suggests flow limitation, can be used to replace
esophageal manometry in detecting respiratory-related arousals (68).
2.7 Prevalence
The prevalence of regular snoring in children is reported to vary between 3.2 and 11%
(114-118). Irregular snoring is present in 17 to 27% of all children (116, 119). The
prevalence of OSAS in the pediatric population has been reported to be 0.7–3.4 % in the
epidemiological studies of the subject (114-116, 120).
The prevalence estimates may be affected by variability in respiratory event
identification across laboratories (71). In groups of children with predisposing factors,
such as morphological anomalies (ex. Mb Down) (121), allergy (122), and obesity (92,
123-125) the prevalence of sleep-related breathing disorders (SBD) is often higher.
Passive smoking and smoking in pregnancy seem also to increase the risk for OSAS
(118). Racial differences may also influence the prevalence of SBD’s, Afro-American and
far-east Asians being at higher risk (120, 125-127). In contrast to adults, OSAS is equally
common in both genders (15, 116, 120). More studies assessing the prevalence seem to be
needed.
The prevalence of UARS is unclear, though it has been suggested that it may be as common as or more common than OSAS, based on a study where children with anomalies/
syndromes were included (65).
30
2.8 Pathophysiology
The upper airway area, which is controlled by 30 muscles, has to serve many functions: it
must enable speaking and swallowing and it must keep an open airway. The key force
causing the closure of the upper airway is the suction pressure created by the inspiratory
effort (128). A narrowed airway leads to higher inspiratory effort to maintain airflow into
the lower airways, and when a so-called critical closing pressure (Pcrit) is reached (129),
the muscle contraction force keeping the airway patent in the collapsible upper airway is
overcome by the pharyngeal suction force, and subsequently a closure occurs (130). As in
adults (131), the upper airway in children has been shown to behave in accordance with
the Starling resistor model; when a collapsible segment is situated between two noncollapsible segments with fixed diameters, resistances and pressures (nasal and tracheal),
closure in the collapsible segment occurs when the pressure surrounding the airway
becomes greater than the pressure in the airway (Pcrit) (Fig. 2) (129). The model predicts
that under conditions of flow limitation the maximal inspiratory airflow is determined by
the pressure changes upstream (nasal) to a collapsible locus of the upper airway and is
independent of the downstream (tracheal) pressure generated by the diaphragm. In adults
it has been shown that Pcrit is higher in patients with OSAS than in primary snorers
(132), and decreases after treatment (uvulopalatoplasty) in those who respond in a
clinically favourable way (133). There is some evidence that this would also be the case
in children, as Marcus et al. (129) found in a study with a small material that Pcrit for
OSAS children declined after treatment and clinical improvement, but was still higher
than in primary snorers. The Pcrit is similar in children and adults with OSAS (129, 132),
but markedly lower in children than adults with primary snoring, suggesting a less
collapsible upper airway in children (129, 134). Children seem to respond to
subatmospheric pressure loading by neuromuscular activation far better than adults,
preventing airway collapse (135). Isono et al. (134) found children with sleep-disordered
breathing to have positive closing pressures, while normal control children had
subatmospheric closing pressures when fully paralysed with muscle relaxant. The closing
pressure was found to be highest at adenoidal/tonsillar level, whereas in control children
the soft palate and retroglossal areas were the primary sites of closure. These areas also
closed with higher pressures in the obstructed than in the control children. In adults it has
been shown that normal men develop obstructive apneas of different intensity in sleep
when subjected to application of subathmospheric pressures (136), whereas children seem
to be able to better maintain the upper airway patency when subjected to subatmospheric
pressures (135).
31
Resistance
upstream
Pressure surrounding the
airway (Pcrit)
Pressure
upstream
Upstream
segment (nasal)
Resistance
downstream
Pressure
downstream
Pharyngeal segment
Downstream
segment
(tracheal)
Fig. 2. The Starling resistor model of upper airway. The airway is represented by a tube with a
collapsible segment (pharynx) between two rigid segments with fixed diameters, resistances and
pressures (nasal and trachel segments). The airway collapses when the pressure surrounding
the airway becomes greater than the pressure within the airway.
Despite the fact that the adenoids and tonsils have been pointed out as the cause of OSAS
in children in the majority of cases (14, 33, 36), there must be an underlying tendency to
airway obstruction, as reviewed above, since many children with enormous tonsils have
no respiratory problems, while some children with OSAS without exceptionally large
tonsil and adenoid tissue (101, 137) with perhaps subtle predisposing conditions (138) get
cured with tonsillectomy (139), but may have underlying predisposing conditions. Airway
obstruction and OSAS are dynamic phenomena resulting from a combination of structural
and neuromotor abnormalities that may occur in some children. Loss in sleep of
neuromuscular control reflexes of upper airway muscles that are intact during
wakefulness has been shown to happen in adult OSAS patients significantly more than in
controls (140), and is obviously the case also in children, as they do not snore while
awake.
In normal children (infants) there is very little movement of the pharyngeal soft tissues
in sleep (141). Videofluoroscopical studies have demonstrated how the inspiratory
obstruction may involve forward movement of the retropharyngeal soft tissues, medial
movement of the lateral pharyngeal walls, inferior and posterior displacement of tonsils,
posterior displacement of tongue and posterior movement of the mandible (33, 101, 105).
In some children the soft palate is found to be sucked into the airway, though less
constantly (101). These same changes have been demonstrated through endoscopical
studies during sleep in children with anomalous upper airways (109). Genioglossus
hypotonia is unlikely pathogenesis for OSAS in children, as genioglossus activation
increases during partially obstructed breathing (142). Praud et al. (143) found no decrease
in genioglossus or diaphragmatic EMG activity in children with obstructed breathing due
to enlarged tonsils at the onset of obstructive apnea, but instead a significant increase in
the genioglossus EMG activity preceding the end of the apneas.
32
The pharyngeal dilating muscles, which relax in sleep, are controlled by various
reflexes and stimuli. What is the main reason for imbalance in these reflexes in OSAS
children is unknown. Increased neuromotor tone of the pharyngeal dilating muscles has
been shown to be a compensatory mechanism for narrowing of the upper airways in
adults, but due to the invasive methods required, similar studies have not been performed
on children (144). The upper airway muscles are muscles accessory to respiration, and
have in animal models proved to be prone to activation by chemical stimuli (145). The
ventilatory drive in children seems to be fairly normal in contrast to adults (135), in
whom the ventilatory responses to hypercapnia and hypoxia are significantly decreased in
OSAS patients (146), but normalized after treatment (147). Breathing responses to
exposed hypoxia and hypercarbia have been compared between OSAS children and
healthy controls, and no significant difference was found between the children during
wakefulness (148) nor during sleep (55). The sleeping children had slightly blunted
arousal response to hypercapnia, correlating with the apnea index (55). Hypoxia was
found to be a poor stimulus to arousal. Artificial CO2 increase resulted in decreased
airway obstruction. OSAS children have also been found to have blunted arousal
threshold to inspiratory resistive loading, suggesting together with the responses to
hypercapnia that children with OSAS may have a generalised deficit of arousal in
response to respiratory stimuli (149).
Functional magnetic resonance imaging has revealed respiratory loading to cause
significant signal increase in discrete brain regions (150).
In OSAS children sympathetic activity has been found to be higher and the
parasympathetic activity lower throughout the night when compared with normal children
(63). It is unknown, whether obstructive apneas cause increased sympathetic activity or
increased sympathetic activity is the predisposing factor for development of apneas.
2.9 Etiology
In most reports, hypertrophy of the tonsils and adenoids is considered as the major cause
of OSAS in children (14, 33, 36, 93, 101, 151). The size of the palatine tonsils is not
necessarily decisive, though usually children with OSAS have larger adenoids and tonsils
compared with other children (108, 152). Magnetic resonance imaging of the upper
airways has shown that OSAS children have smaller volume of the upper airways than
matched control children (108). There exists no study where the relationship between the
tonsils and adenoids in order of importance as the etiological factor of OSAS would have
been systematically studied. The adenoids and tonsils are often considered as a “bulk”,
and the treatment has then been described in many reports as tonsillectomy or
adenoidectomy or both. The role of the adenoid in producing nighttime apneas and
hypoventilation is probably smaller than that of oropharyngeal tissues; bare
adenoidectomy is not always a curative treatment of OSAS in otherwise normal children,
even if it can give temporary relief, while tonsillectomy then relieves the obstruction
(116). Croft et al. (93) found no relationship between the nasal airway patency and the
degree of snoring/apneas, whereas there was a significant relationship between tonsillar
33
position and size and sleep grade. The thickness of the pad of adenoids in lateral
cephalometry was not important. Mahboubi et al. (104) stated that the radiologically
assessed adenoidal size would not give much information about the degree of airway
obstruction, whereas Fernbach et al. (101) found hardly any OSAS-children to have an
adenoidal-nasopharyngeal ratio greater than two standard deviations above the mean
value of normal controls. In one study has the adenoid size been found to correlate to the
severity of apneic periods but not to the number of episodes of obstructive apnea in
children (153). Brodsky et al. (154) reported that the velopharyngeal sphincter, one of the
key sites of obstruction in adult OSAS, seems to be enlarged in children with large
obstructing tonsils due to a shorter soft palate. The authors concluded that the obstruction
is not at the nasopharyngeal level, but rather in a small diameter oropharynx, which gets
crowded with low density/high volume tonsils. In another study Brodsky et al. (151)
demonstrated that much of the smaller distance between the medial tonsillar surface in
children with obstruction compared with those without obstruction is explained by the
smaller diameter between the lateral pharyngeal walls.
Any anatomical abnormality which can affect the upper airway may potentially impair
nocturnal respiration. In the early report by Guilleminault et al. (14) 26 out of the 50
children had so-called secondary OSAS; 14 children had either micrognathiaretrognathia, Pierre-Robin syndrome, Crouzon disease, Treacher-Collins syndrome,
trisomy 21 (Downs syndrome), webbed pharynx or obstruction secondary to surgery for
cleft palate. Other contributing underlying diseases may be arthrogryposis multiplex,
temporomandibular joint ankylosis, Larsen syndrome (33) or Goldenhar syndrome (155).
Hypoplasia of the skeletal and cartilaginous tissues and/or hyperplasia and hypotonia of
soft tissues such as relative macroglossia and glossoptosis (156), and lingual tonsil
hypertrophy (157) may also contribute to upper airway obstruction. Bower et Gungor
(158) have listed 48 syndromes/diseases which may predispose to OSAS. Any
neurological or muscular (neuromuscular) deficiency affecting the muscle tone in the
upper airways or the breathing muscles can also predispose to OSAS (14, 33, 159).
In contrast to adults, only the minority of OSAS children are obese (15). Obesity may
increase the risk of OSAS (92, 120, 123, 124, 153, 160), especially in morbidly obese children (ideal body weight exceeded by 200%) (161). In a study of 32 massively obese children, 93% had abnormal sleep study (nap study)(161). In another study with a similar type
of patients, 32% (13/41) of the obese children had mildly abnormal PSG, while two had
seriously abnormal PSG (160). In unselected material are OSAS children, however, not
markedly more obese than children with primary snoring (31).
Allergy seems to be associated with an increased risk of snoring and OSAS in children
(117, 122). Children with sinus problems and persistent wheeze as an indication of asthma
are also at increased risk of developing obstructive sleep disorders (120).
The importance of familial predisposition in developing OSAS in adults has been
pointed out (3, 120, 162-164). There has also been seen increased risk of OSAS in infants
with familial predisposition (165).
Ethnicity may be a risk factor in OSAS. Redline et al. (120) have found Afro-American
children to be at higher risk of developing obstructive sleep disorders. Far-East-Asian men
seem to have more severe OSAS than white men though being usually non-obese, probably due to craniofacial anatomical differences (127).
34
Though tonsillar and adenoidal hypertrophy is the major cause of OSAS in children, it
is important to be aware of the possible predisposing factors when inspecting and
examining children with suspected OSAS. The natural history of OSAS may be different
in children with underlying conditions and treatment modalities may be more demanding
(155).
2.10 Morphological and odonthological considerations
The developing facial skeleton may be influenced by obstruction and mouth breathing
caused by adenoidal and tonsillar hypertrophy (166). By the age of four, the facial
skeleton has attained 60% of adult size and by the age of 12, 90%. There is a continuous
interaction between airway patency during sleep and maxillo-mandibular growth (167).
Obstructed breathing leading to an extended position of the head has been shown to affect
even the morphology of the first vertebra (atlas) (168). Children with obstructed nocturnal
breathing seem to alter the posture of the head to improve the airflow (54), which affects
the soft tissues which mould the facial skeleton. Children with OSAS seem to have a
narrower width of maxilla and longer dental arches than non-obstructed children (169).
Guilleminault et al. (65) found that a small chin, a steep mandibular plane, a retroposition
of the mandible, a long face, a high hard palate, and an elongated soft palate were
common among children with obstructed breathing. In addition to significantly reduced
mandibular protusion, the hyoid bone has been found to be significantly lower in OSAS
children than in age matched controls (152).
It has been shown that children with tonsillar obstruction have a lot of bite anomalies,
like open bite and lateral cross bite, which diminish or disappear over two years after
treating the obstruction (170). The authors speculated that early treatment of obstruction
might development of OSAS in adulthood. The dental/facial irregularities seem to worsen
during periods of fast growth and rarely reverse spontaneously (171).
2.11 Clinical symptoms
Symptoms of OSAS in children differ in several ways from those in adults, and may be
only nocturnal (Table 2). Despite a troublesome struggle throughout the night, the
children may be quite symptomless in the daytime, at least in the initial stages of the
syndrome. Excessive daytime somnolence, the hallmark of OSAS in adults, is
encountered only in a minority of children with OSAS (15, 172).
35
Table 2. Comparison of the symptoms and some other features of OSAS in adults and
children
Children
Adult
Snoring
Often continuous, snorting
Loud, alternating with pauses
Predominant respiratory pattern
Mixture of obstructive, mixed and
central apneas and hypoventilation
Obstructive apneas predominate
Sleep structure
Normal macrostructure
Sleep pattern disruption
Arousal on apnea termination
Usually not
Nearly always
Nighttime mouth-breathing
Common
Common
Restless sleep
Common
Common
Sweating during sleep
Common
Common
Odd sleeping positions
Common
Not common
Excessive daytime sleepiness (EDS) Minority of patients, rather
hyperactivity, behavioral changes
Main presenting symptom
Daytime mouth breathing
Common
Not common
Cognitive impairment
May be present, poor school
performance
May be present
Obesity
Minority of patients
Majority of patients
Growth or weight retardation
Not rare
No
Gender
Male-female 1:1
Male-female 8-10:1
Enlarged tonsils and adenoids
Most common
Uncommon
Complications
Cardiopulmonary, growth,
behavioral, developmental
Mainly cardiopulmonary and
complications of EDS
Surgical treatment
Adenotonsillectomy curative in
most cases
Only in selected cases
2.11.1 Nighttime symptoms
Snoring has in most studies been found to be the most common symptom of pediatric
OSAS (Table 3). While in all reports most OSAS children are found to snore every night,
only in the early report by Guilleminault et al. (14) were all children observed to snore
constantly. The snoring is typically interrupted by pauses and associated by snorts. The
respiratory effort is frequently increased during obstructed breathing, observed as
retractions, use of accessory muscles and paradoxical breathing (158). Detected apneas
by the parents have been found to have high specificity (94%), but relatively low
sensitivity (44%) (93), which last number is fairly well in line with the figures in Table 3.
The other common symptoms mentioned in many reports are restless sleep, mouth
breathing, profuse sweating, nightmares and enuresis (Table 3). Some of these symptoms,
at least enuresis, may be influenced by age. Reappearing enuresis after toilet training
probably has greater significance as a significant symptom than enuresis per se (14).
36
Table 3. Most common nighttime symptoms of pediatric OSAS and their prevalence in
various reports.
Authors
Guilleminault et al.
1981
n
50
Difficulty Observed
Snoring
(every/most breathing apneas
in sleep
nights)
(%)
(%)
(%)
100
84
Brouilette et al. 1984
23
96
Ahlqvist-Rastad et al.
1988
93
83
82
Leach et al. 1992
34
76
47
Schlüter et al. 1993
15
93
Carrol et al. 1995
35
97
Suen et al. 1995
35
100
Guilleminault et al.
1996
104
83/96
Wang et al. 1998
25
92
96
Restless
sleep
Sweating
Enuresis
(%)
(%)
(%)
Night
terror/
mares
(%)
84
96
18
24
50
8
13
55%
34
22
78
60
89
0
0
-/4
38/62
33
74
94/42
88
75/87
44
Other night time symptoms reported are awakenings, cyanosis, insomnia (1, 31, 87, 89).
Sometimes the symptoms connected with bedtime, such as struggling, bed resistance,
sleep-walking, sleep-talking, nightmares and restless sleep, may be due to behavioural
disorders, which can accompany OSAS (173).
2.11.2 Daytime symptoms
Excessive daytime sleepiness (EDS), the hallmark of OSAS in adults, is not common in
children (15, 36, 126, 172). Though reported in many papers as a possible symptom of
pediatric OSAS (1, 87, 89, 174, 175), only in two studies by Guilleminault et al. (14, 65)
has EDS been the most commonly presented complaint (84% and 86%). In a recent study,
where a multiple sleep latency test was performed on 54 prepubertal OSAS children, less
than 15% of the children exhibited EDS (172). In a survey study with 782 pre-school-age
children regular snorers were found to have higher risk of EDS, but over the two-year
follow-up period daytime overall sleepiness decreased from 20.7 to 11.2%, though the
prevalence of snoring remained constant (114, 115). This indicates perhaps some age
dependency of sleepiness in children. The children must also often follow the hectic time
schedules of their parents, which may lead to an insufficient amount of sleep, especially
in the younger ones, which can be a difficult parameter to control in clinical trials.
Anyhow, in the study, daytime sleepiness increased significantly across the snoring
categories (115).
37
The characteristics of pediatric OSAS with periods of prolonged hypoventilation or
hypopneas with no necessity of abundant EEG arousals is probably one explanation for
the relative rarity of EDS in pediatric OSAS. The possible autonomic reactions seem not
to disturb the macrostructure of sleep (57). However, obesity and very high apnea indexes
seem to increase the risk for EDS (172). Another explanation is that sleepiness in young
children may be difficult to distinguish. Rather than being sleepy, children may show
behavioural deterioration or outbursts, and increased activity (176). Indeed, externalizing
behaviour problems such as hyperactivity, irritability, bizarre behaviour, personality
changes, bed resistance, school and learning problems and morning headaches are
frequently reported symptoms of OSAS in children, but none is patognomonous for
OSAS, and the reported prevalence of these symptoms is usually well below 50% (14, 89,
174). Authors who have reported the highest incidence of these symptoms in OSAS
children have included children with serious facial dysmorfia, neuromuscular disorder or
general medical problems in their study material (14), which obviously explains the
difference in reported frequency of daytime symptoms compared with other reports.
Goldstein et al. (177) reported abnormal behaviour in 28% of children scheduled for
adenotonsillectomy due to chronic upper airway obstruction, with obvious improvement
after treatment.
Even in mild forms of obstructive sleep disturbances, aggression, inattention and
hyperactivity have been found to improve after adenotonsillectomy, along with a positive
effect on vigilance, reflectiveness and impulsivity (178). On the other hand, Harvey et al.
(179) did not find successful treatment of OSAS to result in any significant changes in
overall development or temperament.
Sometimes the daytime symptoms in OSAS children may be secondary to primary
behavioural sleep disorders, as children with OSAS and co-morbid behavioural sleep
disorders have been found to have significantly more daytime behaviour problems than
OSAS-children without the accompanying condition (173). Children with adenotonsillar
hypertrophy and signs of upper airway obstruction have also been found to have less
daytime behavioural problems than children with attention-deficit disorder (180).
School problems may lead educators to request clinical investigations of abnormally
behaving children (14). Besides behavioural problems, obstructive sleep disorders may
also adversely affect learning performance; poor academic scores of first-grade children
with nighttime obstructed breathing have been found to improve significantly after
treatment (181). In obese children, the number of apneic/hypopneic events has been
found to significantly and inversely correlate with memory and learning abilities (123).
Most of the studies concerning neurocognitive and behavioural functions in sleeprelated breathing disorders lack objective measurements, and are mainly based on
parental reports. Professional educators may also have a different evaluation of the child’s
behaviour than the parents. Ali et al. found (178) found children with obstructed
nighttime breathing to, after adenotonsillectomy, improve statistically significantly in all
three behaviour subscales (aggressiveness, inattention and hyperactivity) on Conner’s
behaviour scale of the parent questionnaire, while the teachers, who completed the same
questionnaire, had not observed any obvious changes, despite a significant improvement
was found in the children postoperatively when objective tests measuring attention,
38
reflectiveness and impulsivity were performed. Interestingly, the children considered as
plain snorers scored also significantly better on the objective tests 3 to 6 months after
surgery.
It has been mentioned in many reports, that children with OSAS suffer from frequent
upper airway infections (89, 167, 174). In fact, Brouilette et al. (89) found a highly
significant difference in the frequency of upper airway infections in children with OSAS
and the control group, with 83% of the children having frequent infections, and increased
difficulty breathing during the infections. Carroll et al. (31) found no difference in the
frequency of “runny nose” between OSAS children and primary snorers (33% each).
2.12 Complications
OSAS may lead to serious, even life-threatening complications in children (182). What is
the level of apneic events and duration of OSAS needed to increase the risk leading to
complications is unknown. Evidence exists that even mild forms of sleep disturbance may
have deleterious effects affecting the daytime functioning of the child (178). On the other
hand, PSG-defined severity of apneas or development of cardiovascular complications
has not been found to have a clear relationship with the duration of symptomatology (36).
Frank et al. (36) reported that many OSAS children had had symptoms lasting up to five
years without progression in severity or development of complications, whereas some
children developed severe symptoms and complications in just a few weeks.
2.12.1 Failure to thrive
Children with OSAS may show slowed weight- and height-gain. Typically children start
falling from their weight and height curves, and after the relief of their airway obstruction
they experience a rapid “catch-up growth”, the weight increase being especially rapid (8,
33, 43, 67, 102, 183-186). High prevalence of failure to thrive, 52% (67) and 27% (33),
have been found in studies where children with anatomic abnormalities or other
handicaps have been included in the study material. The causes of poor growth are not
known. Suggested causes for underheight and -weight are poor appetite and recurrent
tonsillitis (43), difficulties in feeding, increased work of respiration and of caloric
expenditure (102, 186), abnormal nocturnal growth hormone secretion (1, 187), and
nocturnal acidemia impairing end-organ response to growth factors (183). In a recent
study it was shown that the respiratory improvement after adenotonsillectomy in children
with OSAS is associated with a significant increase both in serum Insulin-like growth
factor-1 (IGF-1) levels and weight (188). IGF-1 is thought to be the main mediator of the
growth-promoting actions of GH (189), reflecting the daily mean GH levels, and is
thought to correlate well with physiological changes in GH secretion (190).
39
Probably depleted GH-secretion is not the only cause of failure to thrive, since OSASchildren may also be obese (14, 160, 161), but, in contrast to adults, only the minority
(15). On the other hand, obesity has been found to be linked with higher risk of obstructive
sleep disorders in children also (120).
2.12.2 Cardiovascular complications
2.12.2.1 Cor pulmonale
Cor pulmonale due to chronic upper airway obstruction in children has been well reported
(14, 33, 183, 191-193). Already before OSAS was recognized as a clinical entity, case
reports of children with obstructing tonsils and adenoids who had cor pulmonale were
published (6-9). Children with apparent OSAS suffering from congestive heart-failure
and even pulmonary oedema, which resolved after treatment, have been described (9,
192).
The prevalence, the needed severity or duration of the syndrome leading to cor
pulmonale is not known. Most of the reports of pediatric cor pulmonale secondary to
OSAS are case-reports, with only the early reports presenting a high incidence in bigger
series (14, 33). In a study with stringent criteria for OSAS no abnormal electro- or
echocardiograms were found in any of the studied 30 OSAS children (88).
Cardiac changes may take place without evident clinical features, with reversal after
treatment (194, 195). The right ventricular ejection fraction has been found to be reduced
in some children with clinically diagnosed OSAS, despite normal physical examination,
chest radiography and ECG (194). Changes in the internal ventricular dimensions
correlating with the degree of peak negative inspiratory pressure have also been found in
snoring children without daytime evidence of cardiovascular complications (195).
2.12.2.2 Hypertension
In adults hypertension is a common complication of OSAS. As regards children there
exist somewhat controversial findings. Only the minority seem to have clearly abnormal
blood pressure (14, 88). Marcus et al. (196) found the mean blood pressure to be elevated
in OSAS-children compared to primary snorers and age-appropriate normative data. The
diastolic blood pressure, especially in sleep, was found to be significantly higher in
OSAS children than in primary snorers, who both had relatively high blood pressure
compared with normative data, though the majority of the children were within the
normative range. Tracheotomy has been found to eliminate hypertension in children with
OSAS (197).
40
The etiology for hypertension secondary to OSAS has been widely studied in adults,
with sympathetic nervous system activation secondary to arousal and/or hypoxemia and
changes in cardiac output secondary to increased intrathoracic pressure as the probable
causes (196). Parasympathetic dysfunction in OSAS patients may also be linked with cardiovascular morbidity (198). Cardiac reactions due to autonomic nervous system changes
triggered by subcortical arousals (51) have been suggested as the cause of development of
OSAS-related arterial hypertension in children (196).
2.12.2.3 Arrhythmias
Serious cardiac arrhythmias in OSAS-children are found to be infrequent (39, 44). In the
study by D´Andrea et al. (39), no evidence of life-threatening cardiac arrhythmias were
found among 12 children with serious desaturations. The average heart rate during
obstructive periods decreased statistically significantly, but the change was small, only
about 5%. In another study OSAS was found to alter the beat-to-beat variation in a
characteristic fashion, more pronounced at slow heart rates, but in this study either no
serious arrhythmias were found (61). OSAS-children have in one study been found to
have significantly higher overnight pulse frequency than matched children, presumably
due to hypoxemia rather than arousals, according to the authors (43). Baharav et al. (63)
found changes in heart rate variability in power spectrum analysis of instantaneous
fluctuations, with low frequency power being higher in OSAS patients than controls for
all sleep stages. The differences were less obvious on visual inspection.
2.12.3 Developmental aspects
Behavioural disorders, which have been reported in OSAS children (14, 33, 173), may
have negative long-term consequences for the children, if they last for a longer period
(199). Learning problems may occur at school age. In a study by Gozal (181), first-grade
pupils with academic scores ranked in the lowest 10th percentile with sleep-associated gas
exchange abnormalities, were found to get clearly improved grades after adenotonsillectomy, while those not operated on had no change in their grades. There is also a risk of
“learning debt”, since based on a large survey study there are indications that young children who snore loudly and frequently during their sleep are at higher risk of exhibiting
lower grades in school several years after the snoring has resolved (200). Aggression,
inattention and hyperactivity have been found to improve after adenotonsillectomy in
children with mild sleep disturbance according to a parent questionnaire. Surgery also
had a positive effect on vigilance, reflectiveness and impulsivity. (178) In a preliminary
study of obese children, the number of apneic/hypopneic events was found to be significantly and inversely correlated with memory and learning abilities (123).
41
2.13 Treatment
2.13.1 Surgery
2.13.1.1 Adenotonsillectomy
Tonsillectomy and/or adenoidectomy has proved to be a curative treatment of pediatric
OSAS in most cases of normally developed children, where the most likely cause is
adenotonsillar hypertrophy (14, 33, 39, 56, 86, 88, 93, 139, 170, 174, 201), even if the
tonsils and/or adenoids would not be seemingly enlarged (101, 139, 174, 202). As
mentioned earlier, different anomalies or concomitant diseases may predispose to OSAS,
and in such cases adenotonsillectomy is not necessarily a satisfactory treatment (33, 155,
156, 203), though in many cases of “secondary OSAS” adenotonsillectomy has proved to
be effective (14, 159). Relapses may nevertheless occur in adolescence, probably due to
morphological causes and hormonal changes in boys (204). Persistent or reappearing
OSAS later in childhood/adolescence seems to be strongly correlated with obesity and
Afro-American ethnicity (125).
Adenotonsillectomy has also been shown to be an effective treatment of children
suspected of having UARS (67).
Adenoidectomy is not always a curative treatment even though the adenoid is enlarged
and a supposed site of obstruction (116, 183). Levy et al. (9) reported that the symptoms
of a child with obvious OSAS were alleviated by adenoidectomy, but the pulmonary
pressure remained abnormally high. The authors did not consider tonsillectomy.
Tonsillotomy has recently been advocated as an alternative to tonsillectomy due to less
postoperative pain and shorter convalescence, with results fairly well comparable to
conventional tonsillectomy (205, 206).
The predominant cause of adenoidectomy and tonsillectomy is recurrent infections
(207), but there has been a dramatic increase in OSAS as a significant indication for
surgery (208). Tonsillectomy is reluctantly performed on children under three years of
age: sleep apnea seems to be the leading cause for operation in this age group (209, 210).
The incidence of OSAS in children is feared to increase, as the total amount of these
operations is declining due to increased use of antibiotics (211), although tonsillectomy
and adenoidectomy currently are the most common pediatric surgical procedures
performed. Tonsillectomy decreases effectively the frequency of throat infections (207),
during which the prevalence of snoring has been shown to increase, and obstructive
symptoms are expected to worsen (119). The prevalence of pediatric OSAS is probably
regionally unequal, as there are great regional differences in tonsillectomy rates due to
different criteria for surgery (207). Interestingly, all ear, nose and throat-consultants or
general practitioners do not recognize OSAS as indication for tonsillectomy (2, 3).
Parental pressure may also sometimes influence decisions about surgery (2).
42
2.13.1.2 Maxillo-facial and related surgery
Obstructed breathing may affect the development of facial morphology just as the
abnormal facial morphology may be the etiology explaining obstructed breathing.
Treatment of OSAS has been shown to improve dentofacial deformities (138, 202).
Maxillofacial surgery is rare in children, and obviously applied only in OSAS cases with
upper airway anomalies, where adenotonsillectomy is either insufficient or
contraindicated. Possible operations are mandibular and/or maxillary osteotomy, tonguehyoid suspension, maxillary expansion combined with soft-tissue reduction procedures
(44, 155, 212).
In children with anomalies or neuromuscular compromises, methods shown to be
effective in adults have been applied to children with good results (155, 156, 212).
Burnstein et al. (155) launched the “Airway zone concept” stressing the importance of
recognizing the multifactorial etiology of OSAS in these children. Since the treatment is
usually quite straightforward in children, adenotonsillectomy is still usually the
preliminary procedure before more advanced surgical procedures (tongue reduction,
tongue-hyoid suspension and jaw surgery). It is important to be aware of anatomical
abnormalities, such as long soft palate, subclinical mandibular or lingual displacements,
which may explain residual symptoms seen in some after tonsillectomy (34). Recurrence
of symptoms requiring treatment occurring in adolescence in some boys is probably due
to underlying craniofacial morphological changes (204). A small percentage of children
with adenotonsillar hypertrophy but no other risk factors for OSAS are not cured by
adenotonsillectomy (86), and may require further treatment, for example CPAP (213).
2.13.1.3 Uvulo-palato-pharyngoplasty
The initially very promising treatment of OSAS in adults (214) has later been shown to
require accurate diagnosis to be effective treatment of OSAS. In children this operation is
rare, but obviously effective, when the criteria are right, though usually preceded by
(adeno)tonsillectomy (44, 138, 155).
2.13.1.4 Tracheotomy
Tracheotomy is hardly an alternative in cases where adenotonsillar hypertrophy is the
leading cause of OSAS, due to risks of substantial decreases in the quality of life (215).
In the early reports of pediatric OSAS, tracheotomy was not an uncommon therapeutic
alternative (13, 14, 33). Tracheotomy to a child is a heavy treatment, and problems like
inaccurately fitting tubes, granulation, infections and depression have to be overcome
(14). The need for tracheotomy has diminished due to developed new treatments, such as
CPAP (203, 213, 216), and vigorous surgery (155). According to Cohen et al. (215),
parents of children with performed tracheotomy due to OSAS found 95% of the
43
controlled parameters worse than the parents of children who had undergone even
extensive surgery for OSAS. In serious cases of OSAS where nothing else gives a
satisfactory result, tracheotomy is curative, since the obstruction is by-passed.
2.13.1.5 CPAP
Continuous positive airway pressure (CPAP) is an effective treatment of OSAS also in
children, especially in cases of congenital malformations, when in the past tracheotomy
usually had to be performed, if adenotonsillectomy failed to relieve a serious obstruction
(203). Many of the technical problems with the device and poorly fitting nasal masks
(203) have been overcome (213), and nasal CPAP has been found to be an effective and
generally well-tolerated therapy (216). In the multicenter retrospective study by Marcus
et al. (213), data was obtained from 94 patients evenly divided between different age
categories. The compliance rate to CPAP treatment was estimated to be between 50 to
100%, the younger children being more compliant. Of the patients with adequate
compliance, CPAP was effective in treating OSA in all but one case.
In the multicenter study the main reasons for CPAP treatment was associated obesity
(27%), craniofacial anomalies (25%), idiopathic OSAS (persisting after adenotonsillectomy) (18%) and Down syndrome (13%). All centres still recommended adenotonsillectomy as primary treatment, in case contraindications to surgery did not exist. In the study
by Waters et al. (216) only 5% of the 82 children needing CPAP after adenotonsillectomy
had idiopathic OSAS, whereas upper airway structural and functional abnormalities
accounted for 62% of the cases where CPAP was used. The success rate for treatment was
86%. CPAP therapy may be of value when preparing children with serious OSAS for operation (216, 217).
2.13.2 Other
OSAS-children are rarely seriously overweight (15). Obesity is, however, shown to be
linked with higher incidence of PSG abnormalities (160, 161), and possibly even higher
prevalence of OSAS (92, 126), so, in case of overweight, reduction will not be harmful.
Radiofrequency volumetric tissue reduction of the soft palate is a promising method of
treating snoring in adults (218, 219). The method has few adverse effects, but there is no
experience of its use on children.
Supplemental oxygen has been shown to improve the oxygenation of OSAS children
with significant hypoxemia without necessarily blunting the hypoxic ventilatory drive
(220), though the number or duration of apneas is not affected (221). This method is suggested to be used temporarily when waiting for definitive treatment in children in a serious
situation (220).
Corticosteroids have been shown to be ineffective in the treatment of OSAS; prednison
did not diminish the adenotonsillar hypertrophy nor symptomatology (201).
44
Radiation therapy, used to regress the lymphoid tissue in the two cases presented by
Noonan (7), belongs inevitably to the past.
2.14 Treatment complications
The most common complication after pediatric adenotonsillectomy is local bleeding, with
a reported incidence 2–4%, requiring operative re-intervention in 0.06–2% of all the children operated on (222, 223). The more serious complication is airway obstruction, occurring in ~1%–2% of unselected operative child material (209, 223). Rosen et al. (217)
found the risk of postoperative airway complications to be very high among OSAS-children with underlying medical conditions in addition to enlarged tonsils and adenoids to
explain the presence of OSAS. The high-risk clinical characteristics were found to be
young age, craniofacial anomalies, failure to thrive, hypotonia, morbid obesity, large
extent of operation, high RDI and serious desaturations. McColley et al. (72) found 23%
(16/69) of OSAS-children to have severe respiratory compromise after adenotonsillectomy, defined as intermittent or continuous desaturation to 70% or less and/or hypercapnia.
Young age (under three years) and high obstructive event index (>10) were found to be
the most important risk factors. In one study children with mild OSAS were found to
have a small improvement rather than worsening of their respiratory status on the night
following adenotonsillectomy (224). The results should not be extrapolated to children
with more serious OSAS though, since they were not studied.
Pulmonary oedema has been reported as a possible complication following relief of
acute (225) or chronic airway obstruction (226). In chronic airway obstruction there is
probably an underlying cardiac complication (cor pulmonale, even right cardiac failure)
predisposing to oedema when the airway obstruction is suddenly relieved (226).
Inhalation halothane anesthesia induction may provoke airway obstruction, so intravenous access should be established even before the child is asleep (224). Extreme caution
has been warranted after surgery for children with serious OSAS (224), and in general
children with OSAS should undergo inpatient surgery (32, 102).
2.15 Natural history
The natural history of OSAS is unknown (44). In severe cases it may be poor, with
serious complications developing (33, 36). What is the level of obstructive disorders and
the needed time for serious complications to develop are so far unknown. The PSGdefined severity of apneas or the development of cardiovascular complications have not
been found to have a clear relationship with the duration of symptomatology (36). Many
OSAS children may have symptoms lasting up to five years without progression in
severity or development of complications, whereas some children developed severe
symptoms and complications in just a few weeks (36). Recent studies indicate though that
even mild forms of sleep disturbance have measurable effects on children’s daytime
45
behaviour and neurocognitive functions (178, 227). There may often be a long delay
between the onset of symptoms and treatment, during which time the children/parents can
experience severe and discomforting symptoms (3, 36). In Richards & Ferdman’s study
(3) 82% of the children had a delay over one year, 51% over two years and 13% over as
many as six years.
Is there a trend in children that snoring and obstruction tends to get worse over time as
in adults? Snoring has been shown to have a stable prevalence in preschool-age children in
two studies by Ali et al. (114, 115). In their studies initially four to five-year-old children
were studied two years later. Twelve per cent of the children snored regularly at both
times, but half of the children who had snored regularly at the time of the first study no
longer did so at the time of the second study. This would suggest that as snoring may be
self-limiting in children, also obstructive disorders could be at least in some cases temporary. In children primary snoring seems rarely to progress to OSAS over the years, and if
so, the syndrome is mild (32, 228). Guilleminault et al. (204) noticed that in some boys the
obstructive disorders reappear in puberty, despite initially successful treatment with adenotonsillectomy. The reason was thought to be hormonal changes linked with puberty.
However, the prevalence of OSAS seems not to be significantly higher in 12 to 16-yearold adolescents than in younger children (229).
It might be that early treatment of obstruction could prevent and reverse facial morphology changes and inhibit development or recurrence of OSAS in adulthood (204). As there
seems to be familial aggregation of OSAS (163), early recognition and treatment of children with SBD and familial tendency to disproportionate facial morphology could be
important in a preventive sense (65).
3 Aims of the present study
The investigation was undertaken to increase the knowledge about OSAS in children,
focusing on symptoms, signs, etiology, diagnosis, effects of treatment, prognosis and
complications. The ultimate goal is to find children at risk of serious OSAS.
Six hypotheses were studied based on prior knowledge derived from the literature.
1. Certain symptoms and signs in snoring children are more prevalent in children with
OSAS.
Children with OSAS may have few daytime symptoms and therefore receive a
delayed diagnosis, predisposing them to sneaking complications. The symptoms may
resemble those of children with primary snoring. Finding factors linked with
increased risk of OSAS would be clinically valuable.
2. Dentofacial differences exist between children with and without OSAS.
Occlusal and morphological abnormalities have been recognized in children with
abnormal night time breathing. Some of these changes seem not to be inherited.
Obstructed breathing and abnormal sleeping positions can be suspected to affect the
development of the dentofacial skeleton.
3. Children with OSAS have a different ratio of acoustic energy emitted through the
nose and mouth (nasalance) compared with children without OSAS.
Hyponasality is often considered as a sign of adenotonsillar hypertrophy. Accordingly, children with OSAS could be assumed to have lower nasalance scores than
other children.
4. Adenotonsillectomy is a curative treatment of OSAS in children.
The main etiology of OSAS in children is adenotonsillar hypertrophy. Adenotonsillectomy should therefore cure OSAS in the absence of underlying predisposing conditions. If successful treatment leads to the reversal of symptoms, will complications
already developed also be reversed?
47
5. Primary snoring will progress to OSAS if untreated.
The natural history of less severe obstructive sleep disorders in children has been
little studied. Whether children with primary snoring tend to develop OSAS, and
whether mild OSAS has a tendency to progress to more serious stages needs to be
studied.
6. Growth hormone secretion is impaired in children with OSAS.
Growth failure is a reported complication of pediatric OSAS. Growth hormone and
its mediators are the strongest growth-promoting factors in humans. Therefore, disturbed growth hormone secretion could be thought to cause the growth impairment in
children with OSAS.
4 Subjects and methods
4.1 Subjects
The study population consists of prepubertal (3–10-year old) children with regular
nighttime obstructive symptoms suggestive of OSAS. The lower age-limit was chosen for
technical reasons and the higher to avoid pubertal hormonal changes possibly affecting
the results (study V). The children were in the first phase selected from the referrals from
primary health care to the Department of Otorhinolaryngology in the Oulu University
Hospital during the years 1994-1997 regarding the necessity of treatment due to nighttime
snoring, apneas or difficult breathing. At this point, children with known upper airway
anomalies, abnormal development, chronic infections, asthma or perennial allergy were
excluded. Children with seasonal allergy were accepted for the study if they had
obstructive nighttime breathing disorders also outside the allergy season.
Secondly, the parents of all children with OSAS completed a detailed questionnaire
regarding their child’s diurnal symptoms. The parents were asked to follow their child’s
sleep for two weeks before completing the questionnaire.
After a review of the questionnaires, children with regular obstructive symptoms for
more than six months were invited for an ear, nose and throat evaluation and a thorough
update of patient history. The facial morphology was controlled. Earlier adenoidectomy
was not an exclusion criterion.
Seventy-eight snoring children constituted the source of subjects for five separate studies. They all had symptoms suggestive of OSAS, they were regular snorers and/or were
observed to have apneas during sleep. Due to co-operation problems, non-availability of
some laboratory functions at times or technical reasons the number of subjects is unequal
in the different studies (Studies I–V, Table 4). Of the 78 children in studies III–V 43 were
boys. One girl assessed in the study I did not participate in further studies, while a boy was
included in the study material after study I. The mean age of the study subjects was 5.67
years, median 5.4 years, range 2.4–10.5 years.
49
Table 4. The number of OSAS children and primary snorers successfully measured and
evaluated in the diverse studies. PS = primary snorers.
Study
Visit I
Visit II
Visit II
OSAS
PS
OSAS
PS
n
n
n
n
Surgery
AHIO >2
n
No surgery
AHIO < 2
n
Study I
29
49
Study II
5
21
StudyIII
19
34
12
24
9
27
Study IV
27
31
27
31
21
37
Study V
30
40
23
30
19
34
Thirty normal subjects, (17 of them boys), mean age 7.1 years, range 4.2–10.9 years,
offspring of hospital personnel, were recruited to constitute a control group for the
establishment of normative data for PSG measurements.
4.2 Methods
4.2.1 Questionnaire
The questionnaire completed by the parents included 31 questions. The questionnaire
included questions concerning the regularity and duration of snoring, detected apneas,
sleeping disturbances, oral breathing day- and nighttime, eating habits and daytime
symptoms described as being typical of OSAS. The answering alternatives were
formulated in the same manner as in the Basic Nordic Sleep Questionnaire (230) as:
always (every night/day), every other night/day (3 to 5 times a week), weekly, less than
weekly or never. When possible, the alternatives yes or no were used.
4.2.2 Clinical evaluation
A thorough clinical ear, nose and throat examination was done. Previous adenoidectomy
was registered. The palatine tonsils were graded on a scale from I to IV on a clinical basis
slightly modified from the standardised evaluation system recommended by Brodsky et
al. (231) as follows: Grade (Gr.) I tonsils within tonsillar fossa, Gr. II tonsils not reaching
the midline between anterior faucial pillar and uvula, Gr. III tonsils medially from the
midline and Gr. IV tonsils with maximally four millimetres in between. Tonsils graded III
and IV were considered enlarged in this study.
50
4.2.3 Polysomnography
In all studies the children were subjected to overnight polysomnography. The PSGmonitoring was performed in the hospital under the surveillance of a trained nurse. The
children were accompanied by a parent through the night in the room.
A six-channel computerised polygraph developed by the Department of Clinical Neurophysiology with leads for an oronasal thermistor (qualitative measurement of oronasal
airflow), a thoracoabdominal strain gauge (measurement of thoracoabdominal movement),
a pulseoximeter (oxygen saturation, pulse, pulse waveform), a body-position sensor, leg
EMG (exclusion of myoclonus) and a static charge-sensitive bed (SCSB) was used (Figure
3). The children’s sleep was also videotaped to ascertain their sleep in addition to the
nurse’s diaries. Although the analysis programme included a possibility of automatic analysis of the night’s events, all recordings were manually checked by a clinical neurophysiologist. All obstructive apneas, hypopneas and mixed apneas were scored, as well as
central apneas. An obstructive apneic episode was defined as total cessation of oronasal
airflow as detected by the thermistor in the presence of continuous breathing efforts
revealed by the thoracoabdominal strain gauge or the SCSB, and hypopnea as at least 50%
reduction in the airflow signal. A central apnea was defined as a cessation of airflow in the
absence of breathing efforts. Central apneas preceded by a deep sigh were disregarded.
The apneas lasting 5–10 seconds and apneas lasting more than 10 seconds were scored
separately. Mixed apneas were included into the obstructive episodes category. The baseline oxygen saturation was determined at the beginning of sleep. The number of oxygen
desaturation events to below 4% from the baseline value per hour of sleep was calculated,
as well as the number of over 10% desaturations. The saturation distribution was analysed
as the width of the saturation range of the night when the time spent with the highest and
lowest values (10% each) had been cut off. This parameter describes the variability of the
oxygen saturation during the night. Obstructive apnea-hypopnea index (AHIO) of one or
higher with events lasting 10 seconds or more was considered pathological in this study
according to normative data (16), (study IV). Mixed apneas were included in the index,
whereas central apneas were not. Children with an AHIO of one or higher were considered
as having OSAS, while children with an AHIO of less than one were considered as primary snorers. Successful PSG recording was mandatory for all children in order to be
evaluated in the study. Due to the lack of EEG, EOG or chin EMG-tracing sleep staging or
recording of cortical arousals could not be performed. Tachycardic episodes linked to the
termination of intervals of periodic hypopneas with less than 50% decrease in oronasal
signal amplitude were scored. These respiratory-induced pulse increases likely indicate
subcortical arousals (144) and may be linked to the increased upper airway resistance syndrome (UARS).
51
Fig. 3. Polysomnographic and video equipment for the recording of sleep patterns during one
overnight observation period
4.3 Symptoms and signs (studies I & IV)
As the first task the questionnaire answers were used to compare the symptoms between
the children with OSAS and primary snoring. In order to find symptoms and signs linked
with increased risk of OSAS, cumulative relative risk (RR) ratios of having OSAS were
calculated for each level of the answer alternatives with 95% confidence intervals (CI).
Relative risk ratios for predicting OSAS were also calculated for the tonsillar size and
previous history of adenoidectomy.
The OSA-score developed and presented by Brouilette and co-workers (89) was also
tested in this study (Study IV). There is one reservation about the analysis of the OSAscores in this study, since we used laborious breathing instead of breathing difficulties during sleep as in the original formula.
52
4.4 Dental arch dimensions (study II)
Dental impressions were taken using alginate impression material and cast in blue dental
stone. The wax index was used to record the intercuspal relationship. The linear
dimensions of the dental arches were measured manually. Nine variables were measured
from the plaster casts using a calibrated digital sliding calliper. In this part of the study
children with AHIO of 4 or more were categorised as having OSAS.
4.5 Nasalance studies (study III)
The objectively measured nasal air escape in speech, nasalance, was assessed as a
nasalance score obtained with a commercially available Nasometer, Model 6200 (Kay
Elemetrics, Pine Brook, NJ, USA). The Nasometer uses a sound separator to differentiate
between oral and nasal acoustic waveforms, after which each waveform is filtered with a
300-Hz band-pass filter that has a centred frequency at 500Hz. The separator plate rests
against the upper lip with microphones on both sides for measuring the acoustic energy
emitted through the nasal and oral passages. The intensity of the filtered energy is then
converted into a ratio (nasal/nasal+oral), which is, after multiplication by 100, expressed
as a nasalence percentage that reflects the relative proportion of nasal to nasal + oral
acoustic energy. Four standardised sentences in Finnish, for which reference values for
mean nasalance and its standard deviation in normal Finnish speech have been developed
(232), were used to obtain the nasalance scores. One sentence only contains nasal
consonants, with high nasalance score in normal speech. The three other sentences
contain mainly oralised sound segments with low nasalance scores in normal speech. The
nasalence scores of the OSAS children and primary snorers were compared with the
Finnish reference values (232). A mean of three consecutive measurements was
calculated when the coefficient of variation was approximately 20% or less. The children
had to produce the test phrases in a natural manner.
4.6 Growth characteristics (study V)
The children were subjected to anthropometric measurements. Height was measured to
the nearest 1.0 mm with a Harpenden wall mounted stadiometer (Holtain Limited,
Crymtch, Dyfed, Britain), and weight with an electronic scale to the nearest 0.1 kg.
Relative height and relative weight were assessed from Finnish growth charts (233).
Target height representing the relative midparental height was calculated as follows: TH
(standard deviation score, SDS) = [(height (cm) of mother + father)/2–171] / 10 (234).
The target height deficit was target height minus relative height at final evaluation. The
data on parental height was collected by means of a questionnaire (235). The biceps,
triceps and subscapular skin folds were measured to the nearest 0.1 mm with a Harpenden
skin fold calliper (John Bull, British Indicators Ltd., St. Albans, Herts, UK) (236). The
53
body mass index (BMI) was calculated (weight (kg) divided by height squared (m2)).
Finnish age- and gender-matched references were used to assess the relative BMI in SDS`
(237). The body density was calculated from the combined triceps and subscapular skin
fold thickness results according to the method devised by Parizkova (238). The
percentage of body fat was calculated by the method described by Keys and Brozek
(239). All the anthropometric measurements were performed three times and the mean
value was subsequently used.
The stage of puberty (Tanner I) was ascertained according to Tanner and Whitehouse
(240). The radiological bone age was determined according to Greulich and Pyle (1959).
Insulin-like growth factors were measured from peripheral blood samples. Circulating
concentrations of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP3) are strongly related to diurnal GH secretion, reflecting mean daily GH levels, and
thought to correlate well with physiological changes in GH secretion (190, 241). IGF-1 is
perceived as the main mediator of the growth-promoting actions of GH (189). The samples were taken in the morning following the PSG. Plasma IGF-I concentrations were analyzed with a radioimmunoassay using commercial reagents (Incstar Corporation,
Stillwater, Minnesota, USA), with a sensitivity of 1.0 nmol/l. The serum IGFBP-3 concentrations were determined radioimmunologically (Diagnostic Systems Laboratories Inc,
Webster, Texas, USA), with a sensitivity of 30 µg/l. The methods have intra-assay coefficients of variation less than 5%. Both samples from the same individual were analyzed in
the same assay to exclude the effect of interassay variation.
4.7 Protocol
The study was prospective, with aimed two visits six months apart. At the first visit
polysomnographically verified children with OSAS and primary snorers were compared
for symptoms, clinical findings, acoustic airway patency and growth parameters. Agematched control groups were generated or existing normative data applied (Studies II–V).
At the second visit six months later (visit two) PSG and all the other studies were
repeated for all children available (Studies III–V), except for the odontological studies.
The parents completed the same questionnaire regarding their child’s symptoms. 58 children had a successful second PSG study. Fifteen children did not participate in the second
part of the study, in four cases there was a protocol violation and in one case technical
problems. As for visit 1, the number of subjects is unequal in the different studies due to
co-operation problems, non-availability of some laboratory functions at times or technical
reasons (Table 4). According to the study protocol, children with AHIO of two or higher
underwent surgical therapy (adenotonsillectomy), unless there were contraindications,
shortly after the first visit. Children with AHIO of less than two constituted the follow-up
group. Two children with AHIO over 2 were included in the follow-up group due to contraindications for surgery. The effect of adenotonsillectomy as treatment of OSAS was
assessed subjectively through the symptoms as reported by the parents, OSA-score and
symptom score, as well as objectively with PSG (study IV). The effects of surgery on
54
acoustic airway patency (study III) and on growth parameters (study V) were also
assessed. The same parameters were also assessed in the follow-up group to obtain natural
history in children with primary snoring or mild OSAS. In both groups the children served
as their own controls, and the children were compared within and between the groups.
4.8 Statistics
The data was stored and processed with the SPSS for Windows software® (SPSS Inc.,
Chicago, Ill., USA). Students t-test for two independent samples and paired samples were
applied for normally distributed data. The non-parametric Mann-Whitney U-test and
Wilcoxon’s signed rank tests were utilized for data with skewed distribution. Chi-square
analyses were used for nominal and ordinal variables. Correlation coefficients were
calculated with the Pearson 2-tailed test. Regression analysis was applied when the
dependent and independent variables were continuous, and the residuals ranged from –3
to 3 without obvious skewness.
Relative risk (RR) ratios with 95% confidence intervals were calculated using CIA
software (242).
4.9 Ethical aspects
The study protocol was approved by the Ethics Committee, Medical Faculty, University
of Oulu. The study was conducted according to the Declaration of Helsinki.
5 Results and comments
5.1 First visit
5.1.1 Polysomnography results
Thirty-two children were classified as having OSAS whereas 46 children were considered
as primary snorers based on the PSG results (Table 5). Of all the obstructive events
lasting 10 seconds or more, hypopneas accounted for 78.6% in the OSAS- and 92.5% in
the primary snorers group. Short obstructive events (5 to 10 seconds) were much less
common than those lasting for 10 seconds or more in both groups. Inclusion of the
shorter apneas in the AHIO would not have changed the grouping. The main PSG-results
are given in Table 5, where the OSAS children and the primary snorers are also compared
with the control group. Significant differences could be noted between the OSAS children
and primary snorers for all the main parameters except for the mean saturation
distribution (p = .11) and the central apnea index (p = .07). The primary snorers had
significantly higher mean obstructive indexes than the control children, whereas the total
apnea index was not significantly higher in the primary snorers due to equal central apnea
indexes.
56
Table 5. The polysomnography findings of the whole study material. The data are mean,
(SD)(range).
OSAS (n = 32)
p1
Primary snorers
(n = 46)
p2 Controls (n = 30) p3
Obstructive apnea-hypopnea
index (>10 sec)
5.15 (5.2)
(1.0–14.6)
.00
0.14 (0.26)
(0–0.89)
.001
0
.00
Obstructive hypopnea index
(>10 sec)
4.15 (3.7)
(0.41–14.48)
.00
0.12 (0.23)
(0–0.79)
.001
0
.00
Obstructive apnea-hypopnea
index (>5 sec)
6.28 (4.91)
(1.1-19.1)
.00
0.18 (0.28)
(0-0.95)
.002
0
.00
Central apnea index (>10
sec)
0.66 (1.1)
(0–5.78)
.07
0.29 (0.3)
(0–1.28)
.96
0.28 (0.26)
(0–0.86)
.09
Total apnea index (>10 sec)
5.73 (4.4)
(0.26–16.77)
.00
0.43 (0.4)
(0–1.8)
.13
0.28 (0.26)
(0–0.86)
.00
Saturation distribution % (90
- 10)
3.17 (1.6)
(0.8–10.2)
.11
2.7 (0.7)
(1.7–4.5)
.27
2.4 (0.7)
(0.3–3.7)
.02
4% desaturation index
3.9 (6.4)
(0–30)
.002
0.8 (2.0)
(0–13)
.03
0.12 (0.22)
(0–1.0)
.00
Periods with tachycadia associated with partial hypopnea
(min/hour)
1.2 (1.1)
(0.2–4.6)
.00
0.57 (0.6)
(0–2.37)
.00
0.16 (0.24)
(0–1.2)
.00
p1 indicates the statistical difference between the children with OSAS and the primary snorers,
p2 the statistical difference between the primary snorers and the control children and
p3 the statistical difference between the OSAS children and the contols. Total apnea index includes obstructive
apneas, hypopneas and central apneas. The saturation distribution refers to the width of the saturation range of
the night when the time spent with the highest and lowest values (10 % each) have been cut off.
5.1.1.1 Comments
Less than half of the children, 41%, suspected of having OSAS proved to have the
condition according to the criteria used in this study. This finding is well in line with
other reports, where half or less of the children suspected of having OSAS actually
proved to have the state (31, 85-88). Despite the resemblance of obstructive symptoms
between the OSAS children and primary snorers, they had distinctly different nighttime
sleep characteristics based on the PSG findings, when an AHIO of one or more was
considered abnormal. This criterion is supported by the findings of others (16) and own
findings in the control group of 30 children, where there were found only two single
periods of obstructive hypopneas and no apneas in all of the children. The respiratory
frequency of children is much faster than that of adults, so the length of apneas and
hypopneas considered abnormal should probably be shorter than in adults (56). In the
present study the 10-seconds criterion used. The separately counted apneas lasting 5 –10
seconds should correlate fairly well with the criterion of missed 2-3 breaths proposed by
57
many (16, 31), but the use of the shorter apneas as criterion of abnormality would not
have affected the results of this study. Limitations of the sleep monitoring were the lack
of EEG, EOG and chin EMG-tracing, which did not allow sleep staging or detection of
cortical arousals. The role of arousals in terminating respiratory events in children is
unclear though, as EEG arousals are probably not an important mechanism in the
termination of respiratory events (31, 35, 46, 53, 56), and even if the microstructure of
sleep might be changed the macrostructure is not (57). Partial obstructive episodes were
scored quantitatively as hypopneas, as no end-tidal CO2 tracing was performed.
The OSAS children showed the typical obstructive pattern described in the literature
(39, 40), as the vast majority of the obstructive episodes were found to be partial. The
OSAS children had significantly more desaturations than the primary snorers, but some
OSAS children never had over 4% drops in the oxygen saturation despite complete over
ten-second apneas.
There are some indications that the children considered as primary snorers had other
abnormalities in nighttime respiration in addition to plain snoring, as they had a significantly higher mean 4% desaturation index than the control children. It is possible that
some of the children classified as primary snorers could have been classified differently
based upon the hypoventilation criterion (16), despite the lack of significant apneas and
hypopneas. The primary snorers had also more tachycardic episodes connected with the
termination of partial obstructive hypoventilation than the control children did. These
tachycardic episodes are thought to indicate subcortical arousals (144) and could be
assumed to be a reaction to increased respiratory resistance.
5.1.2 Symptoms and signs
Statistically there could be found significant differences between the OSAS children and
primary snorers for many of the symptoms and signs inquired and examined (Table 6).
Both groups differed statistically from the controls for all the symptoms and signs except
for excessive daytime somnolence (Table 6). There was no significant gender difference
between any of the groups.
58
Table 6. General information about the OSAS children, primary snorers and the controls
and of their symptoms and signs. Linear- by linear association test has been applied for
the symptoms with more than two answering alternatives. p1 indicates the statistical difference between the OSAS children and the primary snorers, p2 the difference between
the primary snorers and the controls and p3 the difference between the OSAS children
and the controls.
OSAS
(n = 32)
p1
Snorers
(n = 46)
p2
Controls
(n = 30)
p3
5.5 (1.8)
(2.4–10.5)
.55
5.8 (1.7)
(3.1–10.0)
.002
7.1 (1.8)
(4.3–10.9)
.001
15/17
.25
28/18
ns
17/13
ns
Earlier adenoidectomy %
(number)
63 (20)
.04
37 (17)
1.0
37 (11)
.07
Grade 3–4 tonsils,
% (number)
91 (29)
.02
65 (30)
.00
3 (1)
.00
23
8
1
.03
24
12
10
.00
0
1
7
.00
17
2
12
1
.001
7
9
12
15
.00
0
0
2
28
.00
9
7
11
2
.78
14
12
16
4
.00
0
1
14
15
.00
27
2
2
1
.82
39
3
3
1
.00
3
2
10
15
.00
69 (22)
.48
59 (27)
.00
10 (3)
.00
14
8
6
3
.057
11
9
24
2
.00
6
21
4
.05
4
28
14
.056
Age
Sex, boys/girls
Snoring
Every night
Every other night
Once a week
Detected apneas
Every night
Every other night
Once a week
Less or never
Daytime mouthbreathing
Most part of the day
Daily
Occasionally
Never
Nighttime mouthbreathing
Every night
Every other night
Once a week
Less or never
Odd sleeping positions
% (number)
Restless sleep
Every night
Every other night
Once a week
Less or never
.00
1
17
12
Excessive daytime somnolence
Every day
Some days
Never
.00
13
17
59
While the OSAS children and the primary snorers had more often excessive daytime
somnolence than the control children, in this respect they did not differ significantly from
each other. For other symptoms reported as typical of OSAS children, such as morning
headache, bed-wetting, abnormal nighttime sweating, sleep walking or concentration difficulties the OSAS children and the primary snorers were not statistically different.
The children with OSAS had undergone significantly more often adenoidectomy than
the primary snorers prior to entering the study. The causes of adenoidectomy were retrospectively difficult to compile, but in most cases the procedure had been performed for
infectious reasons, though the majority seemed also to have snored. The mean AHIO
among the OSAS children with previous adenoidectomy was significantly higher compared with those with intact adenoid (6.4 vs. 3.1, p = 016).
The OSA score was assessed for 58 children (Study IV). Twenty-seven children had an
AHIO of one or more, while 31 were primary snorers. The mean OSA-score for the
OSAS-children was 3.1 (SD1.7) (range –0.3 to 4.0), for the PS-children 2.1(1.4)(-3.1 to
4.0), (p = .03) and for the control-group 3.7(1.3)(-3.8 to 0.4), (p < 0.01), compared with
the OSAS children. The difference in OSA-scores was also significant between the primary snorers and control children (p < .01). Sixteen OSAS children had an OSA score
over 3.5, which value is according to Brouilette et al.. (89) highly suggestive of OSAS. All
other OSAS children belonged to the intermediate range between –1 and 3.5, when polygraphic monitoring is recommended. Of the primary snorers five had an OSA score over
3.5, while 23 had an intermediate score, and three children had a score under –1, which
would indicate absence of OSAS.
5.1.2.1 Comments
Substantial overlap of symptoms could be noticed between the OSAS children and
primary snorers, as has been noticed earlier (46, 65). Mouth breathing was equally
common in both groups. For many symptoms a clear difference could be observed
between the groups. The children in both groups had clearly more symptoms than the
control children. Many symptoms that have been found typical of OSAS in children (14,
31, 65, 85-87, 89, 96, 175) were frequently encountered also in the present study. None of
the symptoms were, however, only present in the OSAS children. Excessive daytime
somnolence was not found to be common, as pointed out by others (15, 36, 126).
Tonsillar hypertrophy, present in most of the studied children, is the principal etiology
of airway obstruction in sleeping children (14, 33, 36, 93, 101, 151). OSAS is not
explained by tonsillar hypertrophy alone, since all children did not have significant tonsillar enlargement, as has been found by others (139, 174, 202). Many of the primary snorers
had also very large tonsils, as had a few of the control children. The relative size and structure are more important than absolute size (56), as a small distance between the lateral
pharyngeal walls (151) may lead to protrusion of tonsils with lesser volume (243). The
shape of the tonsils is also important (211), as is their mobility and rotability (137).
60
The importance of the adenoid in causing nighttime airway obstruction in children is
unsettled. In the present study the majority of the OSAS children had been subjected to
adenoidectomy before entering the study, and they had in general higher AHIO:s than the
children with intact adenoids. The adenoidectomy had been performed at a young age, at a
mean age of 2.7 years. It is possible that these children had an overall strong tendency to
lymphoid tissue hypertrophy and were therefore more affected when they reached an older
age when tonsillar hypertrophy is most prominent.
The overlap of symptoms between OSAS children and primary snorers was also obvious in the light of the OSA score. Despite the significant differences in the scores between
the groups, five primary snorers were misclassified, as they had an OSA score highly predictive of OSAS. Only three primary snorers had strong evidence of absence of OSAS
(89). Though being an interesting method of trying to clinically screen children with
obstructive symptoms, OSA score seems not to be reliable enough to reduce the need for
sleep monitoring (31, 96).
5.1.3 Risk factors (Study I)
For symptoms and signs with a statistically significant difference between the OSAS
children and the primary snorers, relative risk (RR) ratios for predicting OSAS with 95%
confidence intervals (CI) were calculated (Table 7). Apneas detected by the parents were
found to be the most important risk factor, the more regularly detected the higher the risk.
If apneas were detected every night, the RR was 3.3 (CI 1.5 to 6.9). Restless sleep and
regular snoring were also found to be significant risk factors for OSAS in this study
(Table 7).
61
Table 7. Relative risk ratios for symptoms and signs predicting OSAS in snoring children
are expressed at various levels with cumulative number of cases.
Symptoms and signs
AI ≥ 1 (n = 32)
AI < 1
(n = 46)
Relative risk
95 % confidence
interval
17
7
3.3
1.5 to 6.9
Detected apneas
every night
most nights
2
9
1.6
1.0 to 2.6
occasionally
12
12
1.4
1.2 to 1.8
never
1
15
Snoring
every night
23
24
1.4
1.0 to 2.0
most nights
8
12
1.2
1.1 to 1.5
irregularly
1
10
every night
14
11
1.9
1.0 to 3.6
most nights
8
9
1.6
1.1 to 2.4
seldom or never
9
26
yes
22
27
1.2
0.8 to 1.6
no
10
19
daily
6
4
2.2
0.7 to 7.2
occasionally
20
30
1.2
1.0 to 1.6
never
3
15
0.4
0.1 to 1.2
Yes
20
17
1.7
1.1 to 2.7
No
12
29
1.4
1.1 to 1.8
Restless sleep
Odd sleeping positions
Excessive daytime sleepiness
Previous adenoidectomy
Size of tonsils
enlarged (gr 3 - 4)
29
30
normal (gr 1-2)
3
16
Regular excessive daytime sleepiness was not found to be a risk factor for having OSAS.
A history of previous adenoidectomy in snoring children was found to increase the risk
factor for having OSAS, RR 1.7 (CI 1.1 to 2.7). Also, snoring children with enlarged (Gr.
III- IV) palatine tonsils have a greater risk of having OSAS than children with Gr. I–II
tonsils, RR 1.4 (CI 1.1 to 1.8).
62
5.1.3.1 Comments
Significant risk factors for OSAS in snoring children were found from the symptoms and
signs in the present study. Clearly the most important risk factor was witnessed apneas.
The symptoms associated with the highest risk, witnessed apneas, restless sleep and
chronic snoring, are in the literature reported as the most common symptoms of pediatric
OSAS (14, 31, 65, 85-89, 139, 175). Still, none of the symptoms are patognomonous for
OSAS, and the presence of symptoms with a high relative risk ratio can only have a
predictive value. The knowledge of these risk factors is on the other hand valuable in the
diagnostic work-up of children with obstructive nighttime symptoms.
Profound daytime somnolence in OSAS children is obviously not common. The finding
that snoring children with regular or occasional EDS had slightly increased risk of having
OSAS results from the lack of EDS in many of the primary snorers. This finding should be
interpreted with caution, although it may be indicative.
Visually assessed tonsillar hypertrophy as a risk factor for OSAS seems logical, as the
airway is potentially narrowed. Tonsillar volume alone is not the only important measurement though (137, 151, 211, 243).
Previous adenoidectomy in children with obstructive symptoms was found to be a risk
factor for OSAS. This finding most probably indicates that the children who either had
developed or had persistent OSAS after adenoidectomy had either an underlying tendency
to OSAS or to significant lymphoid tissue hypertrophy.
The number of OSAS children vs. primary snorers is different in the results section
than in the original article (Study I). A manual re-check of all the PSGs was performed
after Study I, and two children considered as primary snorers were found to have an AHIO
of over one. Also, one girl assessed in Study I was not participating in further studies
whereas a boy who proved to have OSAS entered the study after Study I. Hence, the RRs
and CIs presented in Table 7 are slightly different from those in Study I.
5.1.4 Dental arch dimensions (Study II)
Differences in dental arch dimensions were found among the studied 27 children (15
boys, 12 girls, mean age 5.8 years, range 3.6 to 9.9 years) depending on degree of
obstruction and sleeping posture. In the multiple regression analysis when calculating the
effect of age, AHIO and sleeping position, the AHIO was found to be significantly
associated with increased overjet (p = .007). The AHIO was not significantly associated
with intercanine width, whereas the time spent in supine position was (p = .04). When
calculating the effects of age, AHIO and extended head posture, prolonged head extension
and low AHIO were found to be correlated with reduced overjet (p = .005 & .03).
63
5.1.4.1 Comments
Children with obstructive sleep disorders have been recognized to have more
malocclusion and craniofacial modifications than other children, such as open bite and
lateral cross bite, deeper palatal height and retroposition and rotation of the mandible
(169, 202, 244, 245). Children with OSAS have also been shown to have narrower width
of maxilla than non-obstructed children (169), which according to the present results
could be correlated with sleeping position rather than airway obstruction per se,
presumably due to reduced moulding effect of the tongue. That the AHIO was found to be
significantly associated with increased overjet confirms earlier results, that children with
obstructed breathing tend to have longer maxillary dental arches and shorter lower dental
arches than non-obstructed children (169). The unanswered question is whether these
changes are genetically determined or results of abnormal breathing and altered head
position, which could result in changes of the moulding effects of the soft tissues on the
dental arches. Prolonged head extension, which has in the present study been found to be
common (Table 6) was found to be correlated with reduced overjet. Again, the
explanation might be reduced lingual moulding effect on the maxillary dental arches.
5.1.5 Nasalance scores (Study III)
Fifty-three children (31 boys), mean age 6.1, range 3.2 to 10.5 years, had successful
nasalence measurements at the first visit. Nineteen children had OSAS, the mean AI for
the OSAS group being 4.2 (1.1–11.6). Thirty-four children were primary snorers.
Twenty-two children had had a previous adenoid operation, 10 of them in the OSAS
group.
For all the studied children the mean score for the nasal sentence M, which contains
only nasal consonants, was significantly higher than for normal Finnish children (76.3 +
10(SD) vs. 69.9 + 8.2(SD) (232). This means that more acoustic energy was omitted
through the nasal passage than would have been expected. For the oral sentences the children in the present study did not differ from the normative data (232). The children with
and without an earlier adenoid operation showed no significant differences in nasalence
scores for either oralized or nasalized sentences. When comparing the OSAS children and
the primary snorers, they did not differ statistically for any of the measured sentences.
5.1.5.1 Comments
Most children with nighttime obstructed breathing have enlarged palatine tonsils or
adenoid or both. This could be assumed to alter the ratio of nasal/nasal+orally emitted
acoustic energy. Indeed, this was found to be the case in the present study, but, perhaps
unexpectedly, the children had higher values for the nasal sentences than normal Finnish
children. This finding may be explained by hypertrophic tonsils with posterior placement
64
of the upper poles of the tonsils into the oropharyngeal and nasopharyngeal airway (246),
prohibiting the consonants from constricting the posterior oral cavity normally (247).
That no significant differences in nasalance scores were found between children with
OSAS and primary snorers is probably explained by the relatively similar tonsillar status,
with functional differences causing airway obstruction in some children but not in others.
Measurement of nasalance has been suggested as an aid in selection of children for adenoidectomy, since words containing nasal consonants have been found to show large
reductions in the Nasalance scores when the nostrils have been occluded (248). Different
results have however been reported (249), as in the present study, where no differences
were found between the children with preserved adenoids and those without.
5.1.6 Growth characteristics (Study V)
Seventy children (40 boys), mean age 5.8 years, range 2.4–10.5 years, completed the
anthropometrical measurements at the first visit and comprised accordingly the initial
study group (Table 8). Thirty of the studied children had OSAS, while 40 were
considered as primary snorers. For anthropometric measurements and endocrinological
studies 35 children (16 boys), mean age 6.45, range 1.5–10.2 years, recruited from child
welfare clinics and schools, were used as control subjects (Table 8) (235, 250).
65
Table 8. Anthropometric measurements on the first visit in the children with OSAS, the
children with primary snoring and the control group presented as mean values and their
95% confidence intervals.
OSAS
Snorers
Controls
(n = 30)
p1
(n = 40)
p2
(n = 35)
p3
Age (years)
5.67
(4.93–6.30)
.40
6.04
(5.50–6.58)
.37
6.45
(5.63–7.27)
.15
Relative height
(SDS)
0.23
(-0.15–0.61)
.72
0.13
(-0.25–0.51)
.39
0.36
(0.03–0.69)
.60
Target height
(SDS)
0.35
(0.15–0.55)
.46
0.25
(0.07 - 0.43)
.12
0.07
(-0.08 - 0.21)
.02
Target height deficit (SDS)
-0.09
(-0.40–0.23)
.92
-0.13
(-0.44–0.17)
.05
0.29
(-0.01- 0.58)
.07
Weight for height
(%)
101.9
(97.2–106.7)
.96
101.2
(98.2–104.2)
.74
100.3
(97.2–103.3)
.50
BMI
15.9
(15.2–16.7)
.92
15.7
(15.2–16.3)
.51
16.0
(15.5–16.5)
.86
IGF-1 (nmol/l)
11.02
(9.79–12.23)
.15
12.15
(11.14–13.16)
.19
11.11
(9.81–12.41)
.92
IGFBP-3 (µg/l)
2.65
(2.46–2.85)
.95
2.66
(2.49–2.83)
.001
3.47
(3.17–3.78)
.001
(kg/m2)
p1 indicates the statistical difference between the OSAS children and primary snorers,
p2 the difference between the primary snorers and normal controls and
p3 the difference between the OSAS children and controls.
At the first visit the relative height and weight for height did not differ between the
groups. The OSAS and PS children showed a similar trend towards a target height deficit
compared with the controls. Mean relative height was lower in both groups than mean
target height (Table 8).
The BMI´s were quite similar in the three groups, while the body fat mass was somewhat but not significantly higher in the OSAS children than in the two other groups (Table
8). All the children studied were prepubertal, and therefore the anthropometric data were
not presented according to sex.
The bone age was available only from 27 children in the control group. Children with
OSAS and the primary snorers had a retarded relative bone age, while the controls had an
advanced bone age (Study V). As a consequence, the OSAS children and snorers had a
significantly younger relative bone age than the control subjects.
The circulating concentrations of IGF-1 were of the same magnitude in all the three
groups (Table 8). Both the OSAS and PS children had lower IGFBP-3 concentrations than
the control subjects (p = .001) (Table 8). This was true also after adjustment for age.
66
5.1.6.1 Comments
OSAS in children is often associated with growth failure (14, 33, 43, 102, 183-186, 188,
251). In the present study no obvious growth retardation could be observed in OSAS
children or primary snorers, when comparing the relative height and weight for height to
the control children, but the children in both groups showed a target height deficit, which
possibly indicates reduced growth potential compared with the control children. This
interpretation is also supported by the finding that the children in the two groups had
younger relative bone age than the controls, though individual growth patterns may
explain some of the difference. The fact that no significant differences could be observed
in the anthropometric data between the children with OSAS and those with primary
snoring might be explained by sleep abnormalities, which may have been present in the
children considered primary snorers as commented in chapter 5.1.1.
Obesity is not common in children with OSAS according to the present results, as has
been stated by others (31). Only one OSAS child (AHIO 11.8) had a BMI slightly over 20.
The grounds of impaired growth in OSAS children are poorly understood, though many
causes have been suggested (43, 102, 183, 186). Recent results (188) and earlier case
reports (1, 187) indicate changes of the somatotrophic axis in children with OSAS. In the
present study circulating concentrations of IGF-1 and IGFBP-3 were studied. IGF-1 is
considered as the main mediator of the growth-promoting actions of GH (189), reflecting
the daily mean GH levels, and it has been reported to correlate well with the physiological
changes in GH secretion (190). GH stimulates the production of IGF-1 in the liver and
other target tissues (252). IGFBP-3, the GH-dependent major carrier protein of IGF-1, has
also been shown to correlate significantly with nocturnal GH secretion, but not as strongly
as in the case of IGF-1 (241). Although IGFBP-3 probably exerts some functions of its
own on cells, its major role is to prolong the half-life of IGF-1 (253). The major advantage
of IGFBP-3 determinations in diagnostics is its relative stability over time (241), and it
may therefore be a more reliable indicator of GH secretion over a longer time span than
IGF-1. It is also less dependent on age than IGF-1 (253). This is perhaps the cause of the
finding that the circulating concentrations of IGFBP-3 were in the present study found to
be significantly lower both in the OSAS children and the primary snorers than in the controls, whereas there were no significant differences in the circulating concentration of
IGF-1. That the concentrations of neither IGF-1 nor IGFBP-3 differed between the OSAS
children and primary snorers may be explained by sleep disturbances in the primary snorers group not recognized by the present monitoring device.
67
5.2 Follow-up study
5.2.1 Polysomnography results
Fifty-eight children (31 boys) had a successful second sleep study and clinical appraisal.
Twenty-one children with an AHIO of greater than two had been treated surgically shortly
after the first visit. The other 37 children were subjected to follow-up without
intervention. In this group were included two children with AHIO initially slightly above
2 (2.3 and 2.6) due to phoniatric contraindications to surgery at the time, as well as four
children with an AHIO of over one but less than two at the first visit.
Of the surgically treated children 73 % (16/21) had undergone adenoidectomy prior to
entering the study, which operation had not resolved the obstructive symptoms, or the
symptoms had begun after the adenoidectomy. By the time of tonsillectomy the epipharynx was controlled, and none of the children had any significant regrowth of the adenoidal
tissue.
After tonsillectomy, or adenotonsillectomy in five cases, the mean AHIO had decreased
significantly (Table 9). The AHIO was zero in 16 children, while three children had an
AHIO of 1 or less. The other monitored parameters had all improved significantly as well,
except for the central apnea index and the saturation distribution, which last was however
narrower than prior to surgery, but not significantly (Table 9). One child’s AHIO was one,
whereas one boy, who had an initial AHIO of 8.9, had still a clearly abnormal AHIO of 5.1.
This boy had undergone adenoidectomy prior to entering the study, and he had got enormously enlarged tonsils removed, without showing any morphological abnormalities on
clinical evaluation.
68
Table 9. Polysomnography results of the 21 children operated on. Unless otherwise indicated, data are mean (SD) (range). p1 indicates the statistical difference between the
results from the first and second measurements.
Visit 1
Age
Earlier adenoidectomy %
(number)
p
5.6 (2.1)
(2.4–10.5)
Visit 2
6.3 (2.0)
(2.9–11.1)
76 % (16/21)
Total apnea index
7.5 (4.4)
(2.1–16.8)
< .01
0.7 (1.2)
(0–5.3)
Obstructive apnea-hypopneaindex
6.9 (4.1)
(2.0–14.6)
< .01
0.3 (1.1)
(0–5.1)
Obstructive apnea index
1.4 (1.2)
(0.1–4.2)
< .01
0.0 (0.03)
(0–0.1)
Obstructive hypopnea index
5.5 (3.9)
(0.4–14.5)
< .01
0.3 (1.1)
(0–5.0)
Central apnea index
0.7 (1.3)
(0–5.8)
.08
0.3 (0.4)
(0–1.4)
Short obstructive apnea index
(5–10 sec)
1.6 (1.6)
(0–5.7)
.001
0.1 (0.1)
(0–0.6)
4% desaturation index per hour
5.0 (7.4)
(0–29.6)
.04
0.2 (0.6)
(0–2.6)
10% desaturation index per hour
0.2 (0.4)
(0–1.4)
.02
0 (0)
(0–0.2)
Saturation distribution %
(90–10)
3.4 (1.9)
(0.8–10.2)
.19
2.7 (0.5)
(1.7–3.9)
Periods with tachycadia associated with partial hypopnea (min/
hour)
1.4 (1.3)
(0.2–4.6)
.001
0.4 (0.4)
(0.0 –1.3)
In the non-treated group the mean AHIO had decreased insignificantly from 0.4 to 0.2.
The AHIO had been normalized for all the four children with an AHIO of less than two
but more than one, as well as for the one with an AHIO of initially 2.3, while for one the
AHIO had remained the same at 2.6. None of the primary snorers had developed OSAS.
The group mean values had changed insignificantly for all the monitored parameters
(Study IV).
5.2.1.1 Comments
The present study confirmed the previously reported results (14, 33, 39, 56, 86, 88, 93,
139, 170, 174, 201) that adenotonsillectomy is efficient treatment of OSAS in children in
most cases. Only one child had clearly abnormal AHIO even after surgery. The finding
that most of the operated OSAS children were already free of adenoid tissue strongly
69
indicates that at least in many OSAS children the site of airway obstruction is at the
oropharyngeal level, whereas nasopharyngeal obstruction is not so important (154).
Further, based on this finding, adenoidectomy alone is not the perfect treatment of OSAS.
The course of obstructive sleep disorders in children is unpredictable (36). Habitual
snoring often ceases by itself (114, 115) and has no obvious tendency to progress to OSAS
(32), as was noticed in the present study, too. None of the primary snorers had a clearly
abnormal second sleep study.
5.2.2 Symptoms (Study IV)
All the children were re-evaluated for the symptoms. Clinically, all the children operated
on had benefited from the operation. All the symptoms disappeared completely from 16
children. Five children continued to have minor problems, mainly occasional snoring.
None of these children had however any need for additional treatment. The mean OSA
score had changed significantly from 3.4 (median 3.9) to –3.1 (median –3.8) (p < .01).
The boy with the postoperative AHIO 5.1 was snoring lighter, and he was more alert in
daytime. Four children continued to snore irregularly, while one of them had at times
laborious breathing.
In the non-treated group (n = 31) six children had developed more symptoms, while 15
children had unchanged symptoms and 16 had reportedly decreased symptoms. One child
had become totally symptomless. The mean OSA score had on the other hand decreased
from 2.1 (median 2.5) to 0.5 (median 1.1), (p = .001).
5.2.2.1 Comments
In line with results from many other studies (14, 33, 39, 56, 86, 88, 93, 139, 170, 174,
201), (adeno)tonsillectomy of OSAS children was found to definitely improve the dayand nighttime symptoms. Five children were not totally free from symptoms though.
As noted earlier, primary snoring seems to have a favourable prognosis in children (32).
In the present study the vast majority of the untreated children had unchanged or
decreased symptoms, and the children with subjective worsening of symptoms had still
PSG results within the normal range.
5.2.3 Impact on nasalence (study II)
Altogether 36 children were successfully measured at both the first and the second visit.
The mean age of these children was 6.5 years, range 3.3 to 10.5 years of age, at the first
visit. Twelve children had OSAS, of whom nine had an AHIO of over 2 and had
subsequently undergone (adeno) tonsillectomy. Twenty-four children were primary
70
snorers. Adenotonsillectomy had no statistically significant influence on the nasalence
scores. Neither had the nasalence scores changed among the 27 non-treated children. No
single parameter seems to have statistically significantly affected the nasalence scores
between the measurements.
5.2.3.1 Comments
Adenotonsillectomy does not produce permanent changes in nasality in normal children
(254), as seems be the case with OSAS children, too. The higher mean nasalance values
than in normal Finnish children for the nasal sentence (232) were repeated in the
surgically treated OSAS children. The lack of change in the nasalence scores of the nontreated children indicates diagnostic reliability of the measurements.
5.2.4 Effects on growth
Of the original 70 children, six did not participate in the follow-up study. In four cases
there was a protocol violation, and in one case a technical problem. In six cases the
laboratory or x-ray examinations could not be repeated. The result was that 53 children
(27 boys), mean age 6.5 years, range 2.9–11.1 years, successfully completed the whole of
this part of the study protocol. Nineteen of these children had had an AHIO of over two,
and had been treated surgically shortly after the first visit. Among the 34 children not
subjected to intervention two children were included with an AHIO of over two (2.3 and
2.6) due to contraindications to surgery.
Weight for height and BMI had increased significantly in the group which had undergone an operation (p = .001 and p = .01, respectively). The increase in the weight for
height in this group seemed to be largely due to an increase of body fat (p = .02), since
though the mean fat-free mass increased more in this group, the difference was not significant according to the linear regression model with age and intervention status as independent variables (B = 0.59, r2 = 0.21, p = .08). Relative height increased significantly only
in the non-surgery group (p = .02). There were no significant changes in bone age
between the two visits in either group.
The peripheral concentrations of IGF-1 and IGFBP-3 were significantly higher on the
second occasion in the surgically treated children (p = .002 and p < .001) (Fig. 4 and 5).
In the non-treated group the changes in the circulating IGF-1 and IGFBP-3 levels were
insignificant. The initially significant difference in IGFBP-3 levels between the children
operated on and the controls (p = .001) had disappeared at the second visit (Fig. 4). Only
in two cases out of 19 (10%) were the IGF-1 and IGFBP-3 concentrations lower at the second visit in the operated group, while in the non-operated group the IGF-1 and IGFBP-3
levels were lower at the second visit in 44% (15/34) and 29% (10/34) of the cases, respectively.
71
Fig. 4. Plasma IGF-1 levels in children treated surgically for OSAS and in primary snorers
(non-operated) at the first and second visits 6 months apart and in the control subjects. Each
box-plot represents the median (thick black band) and the 25th and 75th centiles. The error bars
represent the smallest and largest observed values except the outliers.
Fig. 5. Serum IGFBP-3 levels in children treated surgically for OSAS and in primary snorers
(non-operated) at the first and second visits 6 months apart and in the control subjects. Each
box-plot represents the median (thick black band) and the 25th and 75th centiles. The error bars
represent the smallest and largest observed values except the outliers.
72
5.2.4.1 Comments
That the normal growth pattern of children with night time airway obstruction is
potentially affected was confirmed by the results of the follow-up study. A “catch-up
growth phenomenon” after treatment of OSAS has been well reported (43, 102, 183,
186), when growth deceleration in OSAS children turns into growth acceleration, being
especially fast for the weight. The findings of the present study support a growth pattern
of this kind, as a significant increase in the weight for height and BMI was noticed in the
surgically treated children, whereas the relative height did not increase significantly. The
analysis of the different body mass components showed that the weight increase after
treatment of OSAS was due to an increased amount of fat rather than an increase in fatfree mass. Increased energy consumption due to increased work of respiration has been
suggested as a cause for growth failure in OSAS children (186), which could be thought
to explain this finding, but a recent study showed that OSAS in children is not associated
with increased energy requirements (251).
The findings of the present study indicate that changes in the somatotrophic axis can
take place in OSAS children. The significant increase in the circulating IGF-1 and
IGFBP-3 concentrations in the surgically treated OSAS children indicates an initially
decreased nocturnal growth hormone secretion, followed by a significant increase after
treatment. In line with the present findings, Bar et al. (188) have lately demonstrated, that
IGF-1 concentrations increased significantly in surgically treated OSAS children. In
contrast to their findings, in the present study there was observed a significant increase
also in the IGFBP-3 concentrations along with the IGF-1 levels in the surgically treated
children, implicating a decreased GH secretion in OSAS children over a longer time span
prior to treatment. That the significant difference in the concentrations of IGFBP-3
between the OSAS children and controls had disappeared at the second measurement,
indicates a normalisation of GH secretion after treatment of OSAS.
In this study, the children remained in prepuberty, when the peripheral IGF-1 levels
increase fairly slowly (255), and since the time interval between the first and second
measurements was relatively short in our study, the increase in age must have very
modestly affected the circulating IGF-1 concentrations, as shown by the small increase
observed in the children not operated on. Accordingly, the significant increase in
peripheral IGF-1 levels observed in the surgically treated children suggests that the
alleviated airway obstruction resulted in an increased GH secretion.
How the somatotrophic axis of OSAS children may be disturbed is unknown. As the
main burst of growth hormone secretion takes place at the beginning of the night (252,
256), when apneas and hypopneas in children are rare (35), it seems likely that the
somatotrophic axis is not necessarily disturbed by cortical arousals associated with
obstructive apneas or hypopneas as in adults (257, 258), but rather by subcortical
reactions or autonomic arousals linked to obstructed periods (51, 63, 259), as the
macrostructure of sleep is little affected (57).
6 General discussion
In the light of current knowledge, some of the snoring children may be seriously affected,
if the nature of their nighttime breathing obstruction passes the limit of harmless acoustic
phenomena. As snoring is so common in children (114-117, 119), it is a big task to
recognize the children with more serious sleep disorders among the snorers. There is a
great deal of overlap between the different levels of seriousness of the sleep-related
breathing disorders (46, 64), also as regards the symptoms. This is obvious from the
results of many studies, where half or less of the children suspected of having OSAS
actually proved to have it (31, 85-88), as was the case also in the present study.
Polysomnography is recommended to differentiate benign snoring from snoring associated with either partial or complete airway obstruction, hypoxemia and sleep disruption,
i.e. pediatric OSAS (70). The nature of OSAS in children is different from that in adults,
which necessitates its own diagnostic criteria (16, 31, 40). There exists however no consensus statement on PSG criteria for OSAS in children. Different approaches for measuring respiratory events may contribute to substantial variability to identification and
classification of OSAS (71). Obstructive events are nevertheless rare in asymptomatic
children, so the apnea-hypopnea index of one or more (16) was found to be statistically
abnormal also in this study.
There is often a big discrepancy between PSG results and the clinical diagnosis score in
children with strongly suspected OSAS (49). In the present study substantial overlap of
symptoms could be noticed between the OSAS children and the primary snorers, which is
obviously explained by the continuum of the sleep-related breathing disorders in children
and the unsettled role of UARS in children (46, 64, 65). Some of the primary snorers were
probably beyond the stage of a plain acoustic phenomenon, judged from the cardiac reactions to partial airway obstruction, which probably indicate subcortical arousals (62). The
diagnosis of OSAS in children should therefore perhaps be based on a combination of factors gathered from PSG and clinical symptomatology (49). It has also been suggested that
PSG is not necessary in all children with strong clinical evidence of OSAS, since PSG is
rather expensive and the availability may be poor (80, 81). If one has to rely on clinical
symptoms and signs in an attempt to make the diagnosis of OSAS, or has to screen candidates for limitedly available PSGs, the knowledge of symptoms and signs associated with
74
increased risk of having OSAS is important. Many symptoms have been found typical of
OSAS in children (14, 31, 65, 85-87, 89, 96, 175), but none of the symptoms is pathognomonic for OSAS. The significant risk factors for predicting OSAS found in the present
study can contribute to the diagnostic work-up of snoring children.
Anatomical abnormalities, often associated with different syndromes, may predispose
to OSAS in children (14, 33, 121, 155-157). More subtle anatomic differences have been
recognized to be correlated with increased incidence of OSAS in adults (260, 261). Adenotonsillar hypertrophy is the main etiology of OSAS in children (14, 33, 36, 93, 101,
151). The airway closure is a dynamic process though, and other underlying factors must
be involved in the process, as tonsillar hypertrophy is not necessarily present in all children with OSAS (152, 202), and many children with tonsillar enlargement do not have
OSAS, as was also the case in the present study. Children with obstructive disorders have
been recognized to have more malocclusion and craniofacial modifications than other children (169, 202, 244, 245, 262). The unanswered question is whether these changes are
genetically determined or the results of abnormal breathing and altered head position.
Snoring and OSAS have been found to have a tendency to familial aggregation when studied in adults (162-164, 263), which can be a result of hereditary abnormal facial morphology, and to some extent increased obesity in the families (120). Obvious morphological
differences between obstructed and non-obstructed children have been advocated to be
results of altered breathing function (152, 167, 168), and many of the changes have been
found to reverse after treatment (202, 244, 264, 265), which supports the idea that not all
the differences are genetically determined. It is unknown whether the observed differences
will stay permanent if they remain untreated or are treated late, and whether this can predispose to development of OSAS later in life (204), especially since the morphological
modifications mentioned above may develop also in mouthbreathing children without
OSAS (166, 171).
Soft tissues obstructing the upper airways could be thought to affect the air escape into
the nose and nasal resonance, which can be objectively measured. Indeed, this was found
to be the case, whereas the studied children showed abnormally high nasalance values
compared with normal children. This unexpected result is most probably explained by
impaired velopharyngeal closure secondary to tonsillar hypertrophy (246, 266).
The lack of change in the nasalance scores in the surgically treated OSAS children is an
intriguing finding, since removal of large palatine tonsils might be expected to influence
the nasal/oral acoustic ratio. Whether the lack of change is due to phonetic adaptation, or
the persistent higher nasalance scores are secondary to other pharyngeal soft tissue abnormalities, such as a large velopharyngeal sphincter, which has been noted in OSAS children
(154), is unsettled.
Adenotonsillectomy has been found to be curative treatment of OSAS in children in
most cases (14, 33, 56, 86, 93, 101, 139, 170, 174, 201, 202), which finding was confirmed
by the results of the present study. All children are however not cured or only partially
cured by adenotonsillectomy, even some of those without obvious deviations in facial
morphology (86), as was the case in the present study. Underlying subtle deviations in
facial morphology or soft tissues may explain some of the residual symptoms (54) or
relapses later in adolescence (204). As was mentioned earlier, functional changes may
affect the facial morphology of OSAS children, which is mainly reversed after treatment,
but perhaps not always. The dental/facial irregularities have been found to worsen during
75
periods of fast growth and rarely reverse spontaneously (171), so modifications of the continuous interaction between airway patency during sleep and maxillo-mandibular growth
may be part of the explanation (167). In the present study none of the five children who
were not totally free of symptoms, or were found to have some obstructive events left after
surgery, had any obvious skeletal abnormalities, and they all had had removed grade-IV
palatine tonsils, and had all been subjected to adenoidectomy already before entering the
study. The children with residual symptoms were nevertheless among those with the initially highest AHIO:s, who were found to have increased overjet.
As the clinical presentation of OSAS in children differs from that in adults, so do also
the complications, due to the specific state of ongoing development (259). Cardiovascular
complications are the most serious ones, though obviously rare, with cor pulmonale and
right-sided heart failure being potentially life threatening. OSAS in children is often associated with growth failure and a “catch-up” growth after treatment (14, 33, 43, 102, 183186, 188, 251). The cause of this phenomenon has been unknown. In the present study it
was observed that growth, especially weight gain, is improved after resolved OSAS in
children. The somatotrophic axis is most likely to be affected by obstructive sleep disorders in children; resolved upper airway obstruction was seen to result in a significant
increase in the circulating IGF-1 and IGFBP-3 concentrations, both factors being mediators of the growth-promoting actions of GH.The present results indicate an impaired GH
secretion in OSAS children, which is normalized after treatment. A significant increase in
the circulating concentrations of IGF-1 after surgical treatment of OSAS has also been
verified by others (188). In the present study it was also found that the initially low IGFBP3 concentrations, indicating a reduced GH secretion over a longer time span, increased
significantly in OSAS children after treatment to the level of those of the control children.
This complication of OSAS in children seems to be reversible by successful treatment.
The prevalence of snoring seems quite stable in the pediatric population, as in many
children snoring abates on its own while other children start snoring (114, 115). As in the
study by Marcus et al. (32), the natural history of primary snoring was in the present study
found to be favourable. This is an interesting finding, raising the question which children
to treat and when. There exists no doubt about the necessity of prompt treatment of children with serious OSAS with severe symptoms and signs of complications. However, as
our understanding and the public knowledge of sleep-related breathing disorders in children have improved, we find the children earlier, usually before serious complications
have developed. In today’s clinical practice we often meet children with nocturnal symptoms of obstructive sleep disturbances, who may prove to have mild OSAS on overnight
PSG, but have no daytime complaints or signs of complications. Should they all be
treated? Surely, the treatment in these cases would not be addressed to the daytime symptoms as in adults, but rather to prevention of complications, since the natural course of
OSAS may be unpredictable (36). Complications of OSAS can develop in children without any daytime complaints of OSAS (194, 195). The problem is that no test or PSG can
predict in which of the children with mild OSAS complications will develop. Further, if
the diagnosis and treatment are delayed (3), could the complications possibly developed
be expected to be reversed by treatment? One of the main targets for future research is to
find prognostic factors suggesting negative outcome of sleep related breathing disorders.
7 Conclusions
1. Snoring children have many typical symptoms and signs associated with an increased
risk of having OSAS. However, PSG is needed to confirm the diagnosis of OSAS.
2. Dentofacial differences exist between children with OSAS and those without. These
differences may be secondary to functional changes and sleeping positions.
3. Nasalance scores in children with nighttime obstructive symptoms are higher than in
normal Finnish children. There does not seem to be differences in nasalance scores
between snoring children with and without OSAS, neither are the scores affected by
surgical treatment of OSAS. Nasometry is not useful in the prediction of OSAS.
4. Adenotonsillectomy is a curative treatment of OSAS in children in most cases, but
some children may be left with residual symptoms.
5. Primary snoring in children seems seldom to progress to OSAS, and mild OSAS
does not seem to have a tendency to progress to more serious stages during a sixmonth follow-up.
6. Growth impairment in children with OSAS is associated with reduced concentrations of insulin-like growth factors and their binding protein, suggesting decreased
nocturnal GH secretion secondary to upper airway obstruction in children.
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