Original Article
Poor sleep quality measured by polysomnography in non-obese asthmatic children with or without moderate to severe obstructive sleep apnea
Yu-Kuei Teng a,b, Li-Chi Chiang c, Ko-Huang Lue d,e, Shen-Wen Chang f, LeeWang g, Shu-Ping Lee h, Hua Ting f,i,1, Shin-Da Lee a,j,k,1,*
a Graduate Institute of clinical medical science, China Medical University, Taichung, Taiwan
b School of Nursing, China Medical University, Taichung, Taiwan c School of Nursing, National Defense Medical Center, Taiwan
d Department of Pediatrics, Chung Shan Medical University Hospital Taichung, Taiwan
e School of Medicine, Chung Shan Medical University Taichung, Taiwan
f Center of Sleep Medicine, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung, Taiwan
g Department of Public Health, Chung-Shan Medical University, Taichung, Taiwan h Department of Foreign Languages and Literature, Asia University, Taichung, Taiwan i Department of Physical Medicine and Rehabilitation, Chung-Shan Medical
University Hospital, Chung-Shan Medical University, Taichung, Taiwan
j Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan
k Department of Healthcare Administration, Asia University, Taichung, Taiwan A B S T R A C T
Background: The co-effect of asthma and obstructive sleep apnea (OSA) on sleep quality among children remained unclear.
Objective: To compare sleep quality and emotional/behavioral problems among asthmatic and nonasthmatic children with or without moderate to severe obstructive sleep apnea.
Method: An AHI-range-matched BMI-range-matched cross-sectional design was used to examine polysomnographic evaluation and emotional/behavioral problems in 102 non-obese children aged between 6 and 12 years old, categorized as with or without asthma and sleep disordered breathing.
Results: Asthmatic children in AHI ≤ 5/h group revealed a significantly longer sleep latency, a greater leg movement index (LMI), and a lower ratio of slow wave sleep compared with non-asthmatic AHI ≤ 5/h group. Compared with non-asthmatic AHI > 5/h group, asthmatic children displayed a higher ratio of REM sleep, sleep stage 1 and 2, a lower ratio of slow wave sleep, as well as a greater respiratory arousal index and LMI. There was no significant difference in emotional/behavior problems among
groups.
Conclusion: Sleep disturbance exists in asthmatic children with or without moderate to severe obstructive sleep apnea. Non-obese asthmatic children had less slow wave sleep compared with nonasthmatic children.We might recommend that sleep quality could be noticed and evaluated in children with asthma.
1. Introduction
Asthma, which is an inflammatory and hyper-responsive condition of the airways, is one of the most common chronic illnesses
in children. The under-reporting of nocturnal asthma symptoms was found in previous studies [1,2]. Children with nocturnal symptoms had poor forced expiratory volume in first second, lower
daytime activities, and worse health perceptions than those without nocturnal symptoms [2].
Obstructive sleep apnea (OSA) is a disorder of breathing during sleep characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction [3]. Children with OSA have more arousals from sleep than normal children [4], but the proportion of the different stages of sleep have not been investigated compared to adults [5,6]. Obesity is a risk factor and a confounding factor of pediatric sleep apnea and asthma [7].
Nocturnal asthma symptoms might contribute to disrupted sleep, daytime tiredness, daytime sleepiness, and reduced alertness [8]. In a study by Fitzpatrick et al., over 80% of the asthmatic subjects woke at night with wheezing, and subjects with asthma had a lower
sleep time than subjects without asthma [9]. The polysomnography, gold standard for evaluation of sleep [10], data in asthmatic
children were found to include longer sleep latency, greater respiratory arousal index, and longer total sleep time than those in nonasthmatic children [11]. AHI was significantly higher in subjects with
poorly controlled asthma and poor sleep efficiency [12]. Until now the iso-effect, or co-effect, of asthma and OSA on sleep quality evaluated by PSG among non-obese children remains unclear.
Behavioral problems and asthma symptoms demonstrate a statistically significant association [13]. Research has been reported in
which children’s internalizing symptoms ranked by parents, such as depression, somatic complaints, and social withdrawal were related to the severity of their asthma [14]. A recent study has shown that behavioral problems are associated with poor sleep in children with asthma [15]. Asthma severity may be considered as a possible risk factor for behavioral problems. However, behavior problems have not been demonstrated among non-obese children with mild asthma and with OSA.
report sleep quality among children with asthma [11,16,17]. The relationship of OSA and asthma on sleep quality among non-obese
children has not been investigated in studies. Therefore, the purposes of the present study were to compare sleep quality and quantity as measured by PSG, and to compare behavioral problems in non-obese asthmatic children, with or without moderate to severe obstructive sleep apnea. We hypothesized that asthmatic children, with or without moderate to severe obstructive sleep apnea, will exhibit poorer sleep quality and a poorer grade in behavioral problems than non-obese non-asthmatic children, with or without moderate to severe obstructive sleep apnea.
2. Methods 2.1. Subjects
A total of 102 non-obese children aged between 6 and 12 years old were recruited from several elementary schools in this study. The study was announced by the school nurse. Subjects were recruited by purposive sampling, and all visited pediatric clinics to
check their asthma status and evaluate sleep disturbance. Asthmatic children met the standard criteria for a diagnosis of asthma,
which included a physician’s diagnosis based on the criteria of asthma symptoms and medical history such as coughing, episodic breathlessness, wheezing and chest tightness as well as a methacholine bronchoprovocation test PC20 of 8 mg/ml or less [18]. The
cutoff point for the apnea–hypopnea index was based on children criteria [19]. Exclusion criteria included respiratory diseases other than asthma, pain or discomfort conditions, obesity (body mass index above 95th percentile) [20], acute asthma exacerbations, serious physical or psychiatric disorders, and condition of AHI range cannot
be matched. For evaluating asthma effect during sleep, AHI-rangematched weight-range-matched non-asthmatic children whose
AHI ≤ 5/h and AHI > 5/h were recruited and analyzed as control
groups. Children were categorized into four groups, which were nonasthmatic children with AHI ≤ 5/h, asthmatic children with AHI ≤ 5/
h, non-asthmatic children with AHI > 5/h, and asthmatic children with AHI > 5/h by diagnosis of asthma and sleep disordered breathing.
2.2. Polysomnography (PSG)
parameters included four electroencephalogram channels,
two electrooculogram channels, one chin and two leg electromyogram channels, nasal flow cannula, oronasal airflow thermistor, endtidal CO2 cannula, chest and abdominal respiratory Piezo crystal belts, electrocardiogram, and oxygen saturation. Sleep stages and obstructive apnoeic episodes were scored according to standard criteria [10].
An obstructive apnoeic episode was defined by cessation of
airflow for more than two respiratory cycles in the presence of respiratory effort. Hypopnea was defined by a 50% reduction in respiratory
airflow accompanied by a decrease of >4% in
oxyhemoglobin saturation and/or an arousal. AHI was defined by the number of obstructive apnea and hypopnea episodes per sleeping hour. In addition, physiologic parameterswere recorded: the total sleep time in minutes (TST), the sleep efficiency, the sleep latency, rapid eye movement (REM) latency, the percentage of time in REM sleep, the percentage of time in non-rapid eye movement (NREM) sleep (divided into NREM stage 1 and 2 combined and NREM stage 3 and 4 combined), the lowest oxygen saturation over 10 s (Nadir SpO2 over 10 s), and the duration of saturation below 90% (Time SpO2 < 90%). An arousal index, with or without a respiratory event, was defined by the number of arousals or shifts in the sleep stage to a “wake” pattern lasting more than 3 s but less than 15 s divided by the total sleep. Leg movements were defined as events of tibialis anterior muscle activity with a duration between 0.5–5 s and
with an amplitude of at least 25% of the events recorded that corresponded to no activity at background level, with each movement
being separated from another by at least 1 s. Periodic leg
movements were defined as events of tibialis anterior muscle movement occurring in a series of four or more events, with intermovement
intervals between 5 and 90 s. Leg movements related
to respiratory events were defined as a respiratory event which must follow a leg movement with a delay of less than 3 seconds [21]. The leg movement index (LMI), periodic leg movement index (PLMI), and leg movement index related respiratory event (RRLMI) were derived by dividing the number of LM, PLM and RRLM by the sleep time (in hours).
The CBCL was designed to assess emotional and behavioral problems in children of 4–18 years of age, by parent or care-giver ratings. The CBCL is derived from the 113 emotional and behavioral items and includes nine behavioral aspects: withdrawal, anxiety/
depression, somatic complaints, social problems, thought problems, attention problems, delinquent behaviors, aggressive behaviors and one other. Parents were asked to rate their children’s problems on a 3-point scale (0: not true; 1: sometimes true; 2: very true/ often true) during the previous 6 months. The three scales of this
questionnaire are expressed in scores for: anxiety/depression, withdrawal, and somatic complaints for internalization; aggressive and
delinquent behavior for externalization; and global score. Scoreswere transformed into age- and gender-standardized T-scores. Higher T-scores depict expanded behavioral problems. The reliability and validity of the CBCL were determined to be satisfactory for Taiwanese adolescents [22].
2.4. Procedure
A cross-sectional studywas used to investigate sleep quality based on asthma disease and respiratory disturbance in children aged 6–12 years old. The effective size of the pilot study was estimated by a mean difference of 9 min and standard deviation of 15. The sample size calculation was performed to detect a 0.5 standardized mean difference in sleep latency between the asthmatic group and non-asthmatic group with a power of 80% and a type one error of 5%.We enrolled 51 subjects in both the asthmatic children group and non-asthmatic children group. The study was approved by the Institutional Review Board prior to commencement. After being provided with a description of the procedures and purposes of the study,
informed consent was obtained from all parents or guardians of the participating children. After enrollment, children received an asthma
diagnostic evaluation and overnight sleep evaluation. As the children were undergoing their asthma evaluation, the parents were
asked to complete a questionnaire which included questions concerned with emotional and behavioral problems. The overnight sleep
evaluation occurred within 2 weeks at the sleep laboratory at Chung Shing Hospital. The aim of this study was to compare sleep quality in children who were either asthmatic or non-asthmatic, with or without moderate to severe obstructive sleep apnea [apnea–
hypopnea index (AHI) > 5 events/h during sleep or not]. The outcome measures included sleep quality and parent-reported emotional and behavioral problems.
2.5. Data analysis
SPSS forWindows (version 17.0) was used to calculate descriptive and inferential statistics. Results were presented as numbers and percentages for categorical data and were expressed as mean and standard deviation for continuous data. Demographic data, polysomnographic data and behavioral problems were using ANOVA with preplanned contrast comparison analysis to compare with AHIrange-matched BMI-range-AHIrange-matched non-asthmatic non-obese group.
In addition, we also compare asthmatic children with AHI > 5/h to non-asthmatic children with AHI ≤ 5/h to clarify asthma plus OSA effect. Chi-square was performed to analyze asthma symptoms among asthmatic children. Statistical significance was set as α < 0.05.
3. Results
3.1. Demographic and pulmonary function data
Of the total subjects, 56 boys and 46 girls completed the PSG
in this study. Children were categorized into four groups by diagnosis of asthma and sleep disordered breathing. Forty-six children
were in AHI ≤ 5 group, i.e., 23 children with asthma and 23 children without asthma. Fifty-six children were in AH I> 5 group, i.e., 28 children with asthma and 28 children without asthma. The
homogeneity test showed that the demographic data were homogeneous between the asthmatic children and non-asthmatic children
within the two respiratory disturbance groups, except the items of pulmonary function data, AHI and snore index (Table 1). Age, neck circumference, waist circumference, hip circumference, BMI, BMI z-score, and gender distribution were similar among comparison groups. The percentage of allergic rhinitis in asthmatic children is greater than in non-asthmatic children by parental reporting (3.9% vs. 66.7%). The pulmonary function data of asthmatic children were poorer than those of non-asthmatic children. No significant differences were showed on asthma symptoms between
asthmatic children with AHI ≤ 5/h and asthmatic children with AHI ≤ 5/h (Table 2).
As seen in Table 3, comparison between asthmatic children and non-asthmatic children with AHI > 5/h showed no significant
(p > 0.05) changes in CBCL scores. Mean parent-reported emotional and behavioral symptoms scores were not statistically significant
(p > 0.05) between asthmatic children and non-asthmatic children with AHI ≤ 5/h. The emotional and behavioral symptoms
scores were not statistically significant (p > 0.05) between nonasthmatic children with AHI ≤ 5/h and asthmatic children with
AHI > 5/h.
3.3. Comparison of sleep quality
Table 4 summarizes the polysomnographic variables in sleep architecture among asthmatic children and non-asthmatic children
without and with sleep apnea. Compared with non-asthmatic children in the AHI ≤ 5/h group, asthmatic children in the AHI ≤ 5/h group had significantly longer sleep latency (25.59 ± 20.73 vs. 10.63 ± 9.59 min, p = 0.004), a greater rate of LMI (5.12 ± 2.69 vs. 3.40 ± 2.93 n/h, p = 0.04), and a lower ratio of slow wave sleep (43.35 ± 13.16 vs. 52.59 ± 14.11%, p = 0.03) as well as asthmatic children in the in AHI > 5/h group had significantly higher ratio of sleep stage 1 and
2 (41.23 ± 12.57 vs. 32.78 ± 13.15%, p = 0.02), a greater rate of respiratory arousal index (5.14 ± 4.00 vs. 1.67 ± 2.25 n/h, p < 0.001), a
greater rate of RRLMI (0.36 ± 0.48 vs. 0.03 ± 0.09 n/h, p = 0.001), and a lower ratio of slow wave sleep (41.38 ± 11.73 vs. 52.59 ± 14.11%, p < 0.001).
Compared with the non-asthmatic children in AHI > 5/h, asthmatic children exhibited a higher ratio of REM sleep (17.39 ± 5.22
vs. 13.43 ± 5.41 %, p = 0.007), sleep stage 1 and 2 (41.23 ± 12.57 vs. 29.18 ± 12.8 %, p = 0.001), and lower ratio of slow-wave sleep
(41.38 ± 11.73 vs. 57.48 ± 11.41%, p < 0.001). Asthmatic children had a greater respiratory arousal index (5.14 ± 4.00 vs. 3.22 ± 2.94 n/h,
p = 0.04), and LMI (4.84 ± 2.44 vs. 2.77 ± 3.40 n/h, p = 0.01) in comparison with non-asthmatic children in the AHI > 5/h group.
4. Discussion
Three major findings were found in this study. First, asthmatic children without moderate to severe obstructive sleep apnea had significantly longer sleep latency than AHI-range-matched BMIrange-matched non-asthmatic children. Second, asthmatic children
AHI-range-matched BMI-range-matched non-asthmatic children. Third, asthmatic children both with or without moderate to severe
obstructive sleep apnea had significantly more leg movement than
AHI-range-matched BMI-range-matched non-asthmatic children. According to the findings of this study, PSG supports the hypothesis
that non-obese asthmatic children, with or without moderate to severe obstructive sleep apnea, will exhibit poor sleep quality as compared with non-obese non-asthmatic children.
Obstructive sleep apnea might suffer from increasing nasal resistance such as nasal mucosa edema among asthmatic subjects [23].
Furthermore, obesity and sleep apnea have been confounding factors in the objective sleep study of asthmatic children and non-asthmatic children in the past [7]. To clarify the confounding effects of asthma and obstructive sleep apnea, this study was designed to exclude obesity and stratify the results forwith or without moderate to severe obstructive sleep apnea and with or without asthma into four groups. The cutoff point for the apnea–hypopnea index over 5 events per hour during sleepwas considered as a pathological breathing problem [24]. In previous research, Kaditis et al. founded that children with
history of wheezing had significantly more frequently tonsillar hypertrophy than those without wheezing [25]. In our study, the snore
index in asthmatic children with AHI > 5/h was showed significant higher than those in non-asthmatic children with AHI ≤ 5/h. Tonsillar hypertrophymaybe mediates the association between asthma and obstructive sleep-disordered breathing among children.
In this study, asthmatic children without moderate to severe obstructive sleep apnea took a longer time to fall asleep compared with
non-asthmatic children without moderate to severe obstructive sleep apnea. Previous study found that the sleep latency in asthmatic children was significantly longer compared with non-asthmatic children
[17]. Further research is therefore required to clarify whether longer sleep latency among asthmatic children will debilitate health conditions.
Slow-wave sleep has been demonstrated to play an important role in strengthening memory [26], which might have an impact on learning during childhood. Peigneux et al. [27] found that humans process memory traces during slow wave sleep. Slow wave sleep was found to be reduced in insomniac subjects compared with
healthy subjects, and a reduction in slow wave sleep was significantly associated with reduced memory [28]. In our study,
asthmatic children had significantly less slow wave sleep than nonasthmatic children in either the sleep apnea group or the nonsleep
apnea group. In addition, asthmatic children with moderate to severe obstructive sleep apnea had longer NREM stage 1 and 2 and REM sleep compared with non-asthmatic children with moderate to severe obstructive sleep apnea. Reduction in slowwave sleep has been reported in children with asthma in a previous study [29]. Because childhood is an important period for brain maturity, the impact of slow wave sleep might have a more severe outcome than in older children. The association of a decrease in slow wave sleep and memory among asthmatic children will need further investigation.
Restless leg syndrome during sleep in children is associated with pathologic conditions such as asthma [30]. Leg jerking and kicking were observed during sleep in some children [31]. In this study, there were more movement events of the anterior tibialis muscles in asthmatic children with or without moderate to severe obstructive sleep apnea. Children with wheezing (a symptom of asthma)
had a higher risk of restless sleep compared to children without wheezing [32,33]. The observed symptomof leg jerking and kicking needs to be evaluated for clinical presentations during sleep in children. In addition, asthmatic children with AHI > 5 had significant
higher snore index, respiratory arousal index, and RRLMI to nonasthmatic children with AHI ≤ 5/h. It is still unknown whether
restless leg movements may cause poor sleep quality. Therefore, the impact of leg movement on sleep also needs further
investigation.
The CBCL has been found to be a good instrument for assessing the emotional and behavioral problems of children and adolescents [34]. Our result shows that asthmatic children had no greater level of behavioral problems than non-asthmatic children with and without moderate to severe obstructive sleep apnea. In previous studies, asthmatic children with average severity in moderate level
(range from mild to severe) had significantly higher scores on internalizing, externalizing, and total problem scores compared with
was associated with the severity and the duration of illness [35]. Our findings are not in accordance with these previous studies. The reason for this may be that the severity of asthma in our subjects is at a relatively mild level. These emotional and behavioral findings did not support our hypothesis that asthmatic children will
exhibit a poorer grade in behavioral problems, compared with non-obese AHI-range-matched BMI-range-matched non-asthmatic children.
There are some limitations in this study. First, the severity of the disease was diagnosed as mild asthma by pediatricians, and two subjects were regularly taking asthma medicine (Singulair,
montelukast sodium) while others did not take any medication. Asthmatic conditions might get worse with increasing severity of sleep
quality [37]. Secondly, we did not execute the diagnosis of allergic rhinitis for children by clinical test. The probability of allergic rhinitis in asthmatic children is higher than non-asthmatic children
according to parent reports. It might have unknown co-effects on sleep between asthma and allergic rhinitis. Third, because we excluded the confounding factor obesity, the current findings were
only suitable for non-obese asthma and SDB cases [7]. Fourth, children without any apnea or hypopnea (AHI < 1) were difficult to be
recruited in the current study.
In summary, non-obese asthmatic children had sleep disturbances with less slow wave sleep relative to AHI-range-matched
group. Besides, the effect of asthma plus sleep apnea appeared to have sleep disturbance in slowwave sleep, snore, respiratory arousal, and leg movement due to respiratory event. The findings of this study suggest that sleep conditions could be noticed and examined in children with asthma.
Conflict of interest
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the
following link: http://dx.doi.org/10.1016/j.sleep.2014.04.017. Acknowledgements
Thisworkwas supported by the grants fromAsia University [102-asia-18] granted by Shu-Ping Lee, National Science Council Taiwan [NSC 100-2314-B-039 -016 -MY] granted by Hua Ting and by Taiwan Department of Health Clinical Trial and Research Center of Excellence
[DOH102-TD-B-111-004].We thank Dr. Tim Williams for his
support throughout the editing process. Finally, we also gratefully acknowledge and thank the children and parents who participated in the study.
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