Clinical Characteristics of Chinese Pediatric Obstructive Sleep Apnea Hypopnea Syndrome

We aim to analyze the clinical characteristics of obstructive sleep apnea hypopnea syndrome (OSAHS) in children. Polysomnography (PSG) and nasopharynx lateral lm were performed, and clinical data were collected in 469 children who came to the outpatient department due to "snoring during sleep with mouth opening breathing, hard breathing or suffocation". Among the enrolled children, 123 (22.6%) were diagnosed with OSAHS, with 70 were mild and 53 were moderate-severe. Percentage of adenoid hypertrophy was higher in OSAHS patients (p <0.01), instead of tonsil enlargement. The OSAHS children were agged 5 (4, 7). Compared with PS, the percentage of snoring, apnea, dyspnea, increased nocturia, and daytime sleepness were signicsntly higher in moderate-severe patients (p <0.01). In OSAHS groups, AHI, ODI, Longest time of apnea were increased, while minimum SpO2 and mean SpO2 during sleep were decreased signicantly (p <0.01) than PS. Time ratio of NREM1 was elevated in moderate-severe OSAHS patients (p <0.01). Time ratio of REM was elevated in mild patients(p <0.01). Compared with the preschoolers, the percentage of leg movement and sleepness were signicsntly higher in school-agers (p <0.05). The youngers had higher time ratio of NREM3 and better sleep ecieny (p<0.01). However, AHI(p<0.05) and ODI(p<0.01) were higher in elder OSAHS signicantly. Snoring (OR =5.745, p < 0.01), adenoid hypertrophy (OR =4.381, p < 0.01), apnea (OR =2.670, p < 0.001), dyspnea (OR =1.975, p < 0.01), and CRP (OR =1.172, p < 0.001) were independent risk factors for OSAHS. of apnea, minimum SpO2 and mean SpO2 should be considered and analyzed simultaneously in diagnosis. The school-age OSAHS patients seems to more serious than the preschoolers. Snoring, apnea, dyspnea, adenoid hypertrophy, and CRP are risk factors for OSAHS.


Introduction
Obstructive sleep apnea hypopnea syndrome (OSAHS) is a frenquent health problem in children with sleep disordered breathing. As reported, the incidence of OSAHS in children is as high as 1.2-5.7%, and the peak age is 2-8 years old [1][2][3]. OSAHS is a common disease characterized by the presence of recurrent episodes of increased upper airway resistance during sleep, leading to spells of apnea/hypopnea, hypercapnia, nocturnal sleep fragmentation, etc. It can also cause multiple problems, such as hypertension, glucose and lipid metabolism disorder, cognitive function damage, and growth and development delay. OSAHS in children is very much defferent from that in adult, and OSAHS in children is also variable in different age group. It is still complex to diagnose and manage in childhood, and AHI is considered insu cient to assess OSAHS. Pediatricians should attach more importance to the clinical manifestations and signs. In this study, we analyzed the clinical characteristics of OSAHS diagnosed in our sleep centre, and excepted to be heipful for better diagnosis.

Patient
All 469 cases were consecutively recruited between December 2016 and November 2019, who met the following inclusion criteria: (1) aged older than 3 and younger than 15 ; (2) compllaining about snoring, mouth breathing, dyspnea or apnea, labored or paradoxical breathing and gasping during sleep; (3) Patients with recent infectious diseases, known sleep apnea on regular therapy, maxillofacial dysplasia, autoimmune diseases, congenital pulmonary and heart disease, neuromuscular diseases, and other serious disease were excluded.

Data collection
The medical records of patients were reviewed retrospectively. Parental complaint was recorded which consisted of snoring, mouth breathing, salivation, labored breathing, bruxism, apnea, increased nocturia(IE), night enuresis(NE), nightmare, oppressive wake and so on. Physical examination, nasopharyngeal lateral lm, and report of polysomnography were also integrated.
IE was defned as the frequency of urinating at night reaching three or more times after falling asleep. NE was defned as bed wetting for more than twice a week for 3 consecutive months, or a child 5-6 years old should have two or more bed-wetting episodes per month, and a child older than 6 years of age should have one or more bed-wetting episodes per month [4,5].
Tonsil and adenoid size assessment Tonsil grade was determined using the Brodsky grading scale, in which the tonsils are assigned a grade from 1 to 4. This is dependent on the percentage of oropharyngeal airway occupied by the tonsils. Grade 1 = 25%, grade 2 = 26-50%, grade 3 =51-75%, and grade 4 >75%. The Clemens and McMurray adenoid grading system was used [6]. Grade 1 has adenoid tissue lling 1/3 the vertical height of the choana; Grade 2 up to 2/3; Grade 3 from 2/3 to nearly all but not complete lling of the choana and Grade 4 with complete choanal obstruction [7].
A lateral neck X-ray was used to determine the size of adenoid. Adenoid/tonsil size can be determined using adenoidal-nasopharyngeal (A/N) ratio. A: The perpendicular distance from the maximum convexity of the adenoid to the lateral surface of the occipital slope of the skull. N: The distance between the posterior end of the hard palate to the pterygoid and the intersection of the skull base is the width of the nasopharyngeal space[8]. A/N≤0.6 is normal. Between 0.61 and 0.7 is physiological hypertrophy. And A/N≥0.71 is Pathological hypertrophy [9].

Assessment of anthropometry
Height(m) and weight(kg) of the children were measured. According to the Body Mass Index Growth Carves For Chinese Children And Adolescents Aged 0 To 18 Years [10], obesity was defned as a body mass index (BMI, kg/m 2 ) >95th percentile of peers with the same age and gender.

Polysomnography
Overnight PSG (Compumedics E series and Greal series, Australia) was performed for all patients at the rst night of admission starting from 10 p.m. to 6 a.m. next morning, and at least 7 h of recording time was considered a successful monitoring. Alcohol, tea, caffeine, sedatives or hypnotics were forbidden 24h before.

Diagnosis of OSAHS and grouping
According to the Draft guidelines for diagnosis and treatment of obstructive sleep apnea hypopnea syndrome in children (urumqi). Mild OSAHS was de ngd as 5 AHI ≤10 or 1 OAI≤5, moderate was de ngd as 10 AHI≤20 or 5 OAI≤10, severe was de ngd as AHI 20 or OAI 10 [12]. Primary snoring (PS) was de ngd as AHI≤5 and OAI≤1, and other sleep related diseases were excluded.

Blood sampling and biochemical investigations
Samples of venous blood were collected after overnight fasting. C-reactive protein (CRP) was measured.

Statistical analyses
Variables exhibiting a normal distribution are represented as mean ± standard deviation (SD) , whereas those with a non-normal distribution are represented by the corresponding nonparametric statistics. Statistical testings between the two groups (OSAHS vs. PS) were carried out by Student's t-test, nonparametric test (Mann-Whitney) or Chi-square test when appropriate. When the three groups (mild OSAHS, moderate-severe OSAHS and PS) were compared, variance analysis or non-parametric test (Mann-Whitney) were used appropriately. In addition, binary logistic regression analyses were performed to investigate the relationships between OSAHS against the clinical and PSG parameters. All statistical analyses were conducted using SPSS 22.0 software for Windows. All probabilities were 2-tailed, and values of p <0.05 were considered statistically signi cant.
The OSAHS patients were aging from 3 to 12 years old, with a median age of 5 (4, 7) (seen in picture 1). There were 86 boys and 37 girls. There was no signi cant difference between boy and girl with OSAHS.  Table 3).
The moderate-severe patients were much more sleepness than PS (p<0.01). However, there is no difference between the groups in common daytime symptoms, including di culty in concentration, behavioral and emotional problems, and morning headaches.  Data are presented as mean ± SD and/or median (minimum, maximum).

Comparison of OSAHS children in preschool and school age
Children with OSAHS were divided into two group: Preschoolers: 3~6 year old (N=87) , and School-agers: 7~12 year old (N=36). Compared with preschoolers, the percentage of leg movement and sleepness were signi csntly higher in school-agers (p <0.05) ( Table 4). The younger ones had higher time ratio of NREM3 and better sleep e cieny (p<0.01). time ratio of REM was also elevated in younger children. However, AHI(p<0.05) and ODI(p<0.01) were higher in elder OSAHS (Table 5).
Among the patients over 5 years old, increased nocturia in moderate-severe OSAHS occured more often (p<0.05). Pearson correlation analysis had shown that nocturnal urination was positively correlated with OAI (p<0.01) , and negatively correlated with average SpO 2 (p<0.01) .

Discussion
Obstructive sleep apnea hypopnea syndrome is one of the common type of sleep disordered breathing in children. It may cause multiple complications in organs and systems, affecting children's growth and development negtively. However, it is still complex to diagnose and manage in the pediatric age. This study retrospectively analyzed the clinical and PSG manifestations of OSAHS in children dignosed in our centre.
In our study, the median age of OSAHS in children is 5 (4, 7) years old in this study, and 25.6% of the children recruited were diagnosisd OSAHS, which was consistent with the reports [13 ] . Adenoidal and tonsillar hypertrophy is recognized to be closely with OSAHS severity [14]. In our study, adenoidal hypertrophy were the prominent elements found in OSAHS patient, and it was independently related to OSAHS. But there was no signi cant difference in tonsillar hypertrophy between the groups. Researchers have thought that using tonsil size only in diagnosis was limited, even the clear parent-reported history of habitual snoring was more valuable [15,16].
Moderate-severe patients had higher frequency of rhinitis and/or nasosinusitis, which was obviously correlated with OSAHS. In our study, C-reaction protein was associated with OSAHS independently.
Therefore, recurrent in aming in upper airway must be treated effectively and in time and was considered to be related to OSAHS [17]. It may lead to a persistent systemic in ammatory response in the children.
In ammatory response is considered as an important pathophysiological process of OSAHS.
Daytime symptoms of OSAHS chilldren usually included di culty concentrating, behavioral and emotional problems, morning headaches, excessive daytime sleepiness, and dysplasia [18]. In our study, sleepiness was the only factor found to be different between the groups. We may need to expand the data sources through asking teachers from preschool or school.
The common nocturnal symptoms of children with OSAHS include snoring, excessive sweating, restless sleep, mouth breathing, apnea, wheezing, dyspnea or abnormality, and excessive neck extension during sleep. We found that the symptoms of snoring, dyspnea, apnea, nocturia, and oppressive wake were more discriminative. Increased nocturia was an interesting symptom of OSAHS, especially the moderate-severe ones. Nocturia has been shown to be a complication of OSAHS in children. A meta-analysis found a strong correlation between OSAHS and nocturia, and signi cant improvement in nocturia symptoms was found in treated children [19,20]. Su et al. had found that the risk of nocturia in children with OSAHS was increased markedly [21]. In our data, we found that the increased nocturia in moderate-severe OSAHS was particularly evident among the patients over 5 years old. Pearson correlation analysis had shown that nocturnal urination was positively correlated with hypoxia. This reminds us to pay special attention to the symptoms of increased nocturia in snoring children over 5 years old. Cardiopulmonary and renal refexinduced neuroendocrine disorder may play an important role in the mechanism of night enuresis in children with OSAHS [22].  [24]. However, Goh DY found that children with OSAHS have normal sleep stage distribution [25]. In our data, time ratio of NREM1 was elevated in Moderate-severe OSAHS patient, and REM was higher in mild OSAHS patients.
OSAHS in children is variable in different age groups. The school age group had signi cantly decreased proportion of NREM3 and REM, and increased AHI and ODI than the preschool one. It seems that the condition of elder children was much more serious, which is worthy of further exploring.

Limitation
Due to the limitation of sample size, no further analysis was made in different age. We will continue to collect cases.

Conclusion
We found that the median age of OSAHS in children was 5 (4, 7) years old. Compared with PS, snoring, dyspnea, apnea, oppressive wake, nocturia and daytime sleepiness were more common in OSAHS children. The school-age OSAHS patients seems to more serious than the preschoolers. Sleep structure disorder was found more often in children with OSAHS aged from 7 to 12 years old, mainly including shortening in the stage of NREM3 and REM. Chileren with snoring, apnea, dyspnea, adenoid hypertrophy and high lever of CRP were more likely to be OSAHS patients. We hope to give clinicians better diagnosis basis.  Figure 1 The age distribution of the OSAHS patients