An association between heart rate variability and pediatric obstructive sleep apnea.

BACKGROUND: There are different findings on heart rate variability (HRV) and pediatric obstructive sleep apnea (pOSA) by an overnight HRV or a 1-hr HRV. However, there is limited data of HRV and pOSA diagnosis by using a 24-h HRV test. This study aimed to evaluate if HRV had potential for OSA diagnosis by using a 24-h HRV test. METHODS: This was a prospective study included children age between 5 and 15 years old, presenting with snoring, underwent polysomnography and a 24-h Holter monitoring. Predictors for pOSA diagnosis were analyzed using logistic regression analysis. RESULTS: During the study period, there were 81 pediatric patients met the study criteria. Of those, 65 patients (80.25%) were diagnosed as OSA. There were three factors were independently associated with OSA: standard deviation of all normal interval (SDNN), high frequency (HF), and low frequency (LF). The adjusted odds ratios of these factors were 0.949 (95% confidence interval 0.913, 0.985), 0.786 (95% confidence interval 0.624, 0.989), and 1.356 (95% confidence interval 1.075, 1.709). CONCLUSIONS: HRV parameters including SDNN, HF, and LF were associated with pOSA diagnosis in children by using the 24-h Holter monitoring.

Functional roles of orexin in obstructive sleep apnea: From clinical observation to mechanistic insights.

Obstructive sleep apnea is the most common sleep-related breathing disorder. Repetitive episodes of the obstructive respiratory events lead to arousal, sleep fragmentation, and excessive daytime sleepiness. Orexin, also known as hypocretin, is one of the most important neurotransmitters responsible for sleep and arousal regulation. Deficiency of orexin has been shown to be involved in the pathogenesis of narcolepsy, which shares cardinal symptoms of sleep apnea and excessive daytime sleep with obstructive sleep apnea. However, the relationship between orexin and obstructive sleep apnea is not well defined. In this review, we summarize the current evidence, from in vitro, in vivo, and clinical data, regarding the association between orexin and obstructive sleep apnea. The effects of orexin on sleep apnea, as well as how the consequences of obstructive sleep apnea affect the orexin system function are also discussed. Additionally, the contrary findings are also included and discussed.

Clinical and Genetic Studies of the First Monozygotic Twins with Pfeiffer Syndrome.

Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on two monozygotic twins with Pfeiffer syndrome. Results: An acceptor splice site mutation in FGFR2 (c.940-2A>G) was detected in both twins. The father and both twins shared the same haplotype, indicating that the mutant allele was from their father's chromosome who suffered severe upper airway obstruction and subsequent obstructive sleep apnea. Hypertrophy of nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Increased intracranial pressure in both twins were corrected early by fronto-orbital advancement with skull expansion and open osteotomy, in order to prevent the more severe consequences of increased intracranial pressure, including hydrocephalus, the bulging of the anterior fontanelle, and the diastasis of suture. Conclusions: Both twins carried a FGFR2 mutation and were discordant for lambdoid synostosis. Midface hypoplasia, narrow nasal cavities, and hypertrophic nasal turbinates resulted in severe upper airway obstruction and subsequent obstructive sleep apnea in both twins. Hypertrophy of the nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Fronto-orbital advancement with skull expansion and open osteotomy was performed to treat increased intracranial pressure in both twins. This is the first report of monozygotic twins with Pfeiffer syndrome.

Obstructive Sleep Apnea Effects on Pulmonary and Respiratory Muscle Function of Obese Children and Adolescents: A Preliminary Study.

OBJECTIVE: Obstructive sleep apnea causes a marked decrease in lung volume and increases lung elasticity in obese adults. However, pulmonary and respiratory muscle function of obese children with obstructive sleep apnea who are more prone to develop airway obstruction than adults is less understood. This study aimed to determine the effects of obstructive sleep apnea on pulmonary and respiratory muscle function in obese children and adolescents compared to those without obstructive sleep apnea. MATERIAL AND METHODS: This cross-sectional study enrolled 12 obese children and adolescents with a known polysomnographic diagnosis of obstructive sleep apnea and 12 controls that were matched for age, gender, and body mass index. Pulmonary function, maximal inspiratory pressure, maximum voluntary ventilation, and anthropometric variables were measured. RESULTS Obese children and adolescents with obstructive sleep apnea exhibited significantly lower maximal mid-expiratory flow and displayed a forced expiratory flow at 50% and 75% of vital capacity (all P < .05) compared to the control group. However, there were no changes in other pulmonary function variables (all P > .05). Their maximal inspiratory pressure and maximum voluntary ventilation were lower than those of the controls, but this was not statistically significant (all P > .05). CONCLUSION: Obstructive sleep apnea did not change pulmonary and respiratory muscle function in obese children and adolescents. The special assessment should be warranted to identify a reduction in maximal mid-expiratory flow and forced expiratory flow at 50% and 75% of vital capacity observed in this population.

Dental Anomalies in Ciliopathies: Lessons from Patients with BBS2, BBS7, and EVC2 Mutations.

Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis−van Creveld syndrome and two patients with Bardet−Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis−van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. Patient 2 had Bardet−Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. Patient 3 had Bardet−Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.

Treacher Collins syndrome: A novel TCOF1 mutation and monopodial stapes.

Treacher Collins syndrome (TCS: OMIM 154500) is an autosomal dominant craniofacial disorder belonging to the heterogeneous group of mandibulofacial dysostoses. OBJECTIVE: To investigate four Treacher Collins syndrome patients of the Sgaw Karen family living in Thailand. METHOD: Clinical examination, hearing tests, lateral cephalometric analyses, Computed tomography, whole exome sequencing and Sanger direct sequencing were performed. RESULTS: All of the patients affected with Treacher Collins syndrome carried a novel TCOF1 mutation (c.4138_4142del; p.Lys1380GlufsTer12), but clinically they did not have the typical facial gestalt of Treacher Collins syndrome, which includes downward-slanting palpebral fissures, colobomas of the lower eyelids, absence of eyelashes medial to the colobomas, malformed pinnae, hypoplastic zygomatic bones and mandibular hypoplasia. Lateral cephalometric analyses identified short anterior and posterior cranial bases, and hypoplastic maxilla and mandible. Computed tomography showed fusion of malleus and incus, sclerotic mastoid, hypoplastic middle ear space with a soft tissue remnant, dehiscence of facial nerve and monopodial stapes. CONCLUSION: Treacher Collins syndrome in Sgaw Karen patients has not been previously documented. This is the first report of monopodial stapes in a TCS patient who had a TCOF1 mutation. The absence of a common facial phenotype and/or the presence of monopodial stapes may be the effects of this novel TCOF1 mutation.

High-intensity interval training combined with resistance training improved apnea-hypopnea index but did not modify oxygen desaturation index and oxygen saturation nadir in obese children with obstructive sleep apnea.

PURPOSE: To investigate the effect of high-intensity interval training (HIIT) combined with resistance training (RT) on sleep indices and vascular functions in obese children with obstructive sleep apnea (OSA). METHODS: A quasi-experimental study. Forty-four obese children with OSA were allocated into either an exercise intervention (n = 22) or a usual care control group (n = 22). The exercise group received 24 min of HIIT (> 60% heart rate reserved) and 20 min of RT (50-80% one-repetition maximum), three times per week for 8 weeks. Primary outcomes included the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation (SaO2) nadir. Secondary outcomes included the Sleep-Related Breathing Disorder-Pediatric Sleep Questionnaire (SRBD-PSQ) scores, vascular functions (flow-mediated dilation and mean blood flow velocity), and anthropometric variables. Outcomes were measured at baseline, at week 8, and at week 16. RESULTS: No baseline differences were observed between groups. The compliance rate of exercise training was 99.47%. The AHI significantly decreased in the exercise group compared with the control group at week 16 (median AHI 1.30 to 0.60 and 1.00 to 1.60 episode/h, p = 0.01), but not at week 8. There were no differences between the groups in regard to the ODI and SaO2 nadir and any secondary outcomes at weeks 8 and 16 (all p > 0.05). CONCLUSIONS: The eight-week HIIT combined with RT decreased AHI in obese children with OSA at week 16 follow-up. No changes in the ODI, SaO2 nadir, SRBD-PSQ, vascular function, and anthropometric outcomes were revealed at any time point. Further research is warranted.

Translation, cross-cultural adaptation and psychometric properties of the Sleep-Related Breathing Disordered-Pediatric Sleep Questionnaire for obese Thai children with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a comorbid condition with obesity that can produce deleterious effects on children's health and well-being. Unfortunately, valid instruments for screening OSA in obese Thai children are limited. This study aimed to translate and cross-culturally adapt, from English to Thai, the Sleep-Related Breathing Disordered-Pediatric Sleep Questionnaire (SRBD-PSQ) and to determine its psychometric properties. METHODS: The SRBD-PSQ was translated into Thai and cross-culturally adapted. It was administered to 62 parents of obese children and adolescents 7-18 years of age who had polysomnographically confirmed OSA. The psychometric properties including validity, reliability, and diagnostic accuracy were examined. RESULTS: The Thai SRBD-PSQ possessed excellent content validity index for scale (S-CVI = 0.95). An acceptable internal consistency (cronbach's α ≥ 0.7) and good to excellent test-retest reliability (intraclass correlation coefficients [ICCs] = 0.82-0.90) of the Thai SRBD-PSQ and subdomain were observed. There was a significant correlation between the SRBD scale and polysomnography (PSG) indices: apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) (r = 0.35, p < 0.01, and r = 0.27, p < 0.05, respectively). The Thai SRBD-PSQ had an area under the curve of 0.71 (p < 0.05) with a sensitivity of 72% and a specificity of 54%. CONCLUSION: The Thai SRBD-PSQ is a reliable and valid instrument for use in obese children with OSA. However, the Thai SRBD-PSQ should be used in combination with other investigations.

Etiology of Acute Otitis Media in Children Less Than 5 Years of Age: A Pooled Analysis of 10 Similarly Designed Observational Studies.

BACKGROUND: Acute otitis media (AOM) is an important cause of childhood morbidity and antibiotic prescriptions. However, the relative importance of the well-known otopathogens, Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hflu), remains unclear because of a limited number of tympanocentesis-based studies that vary significantly in populations sampled, case definitions and heptavalent pneumococcal conjugate vaccine use. METHODS: We conducted a pooled analysis of results from 10 AOM etiology studies of similar design, the protocols of which were derived from a common protocol and conducted in children 3 months to 5 years of age in different countries. Generalized estimating equations were used to account for within-study correlations. RESULTS: The majority, 55.5% (95% confidence interval: 47.0%-65.7%) of 1124 AOM episodes, were bacterial pathogen positive: 29.1% (24.8%-34.1%) yielded Hflu and 23.6% (19.0%-29.2%) Spn. Proportions of Hflu and Spn were higher and lower, respectively, in heptavalent pneumococcal conjugate vaccine-vaccinated children. Hflu and Spn were each isolated from 20% to 35% of children in every 1-year age range. Hflu was less likely to be isolated from first (vs. subsequent) episodes [relative risk (RR): 0.71 (0.60-0.84)]. Spn was more often isolated from sporadic (vs. recurrent) cases [RR: 0.76 (0.61-0.97)]; the opposite was true for Hflu [RR: 1.4 (1.00-1.96)]. Spn cases were more likely to present with severe (vs. mild) symptoms [RR: 1.42 (1.01-2.01)] and Hflu cases with severe tympanic membrane inflammation [RR: 1.35 (1.06-1.71)]. CONCLUSIONS: Spn and Hflu remain the leading otopathogens in all populations examined. While associated with overlapping symptoms and severity, they exhibit some differences in their likelihood to cause disease in specific subpopulations.

What are the leading causative pathogens in acute otitis media with tympanic membrane perforation?

OBJECTIVES: Acute otitis media (AOM) is a common infectious disease in children. Data regarding the distribution of causative pathogens are not universal. Tympanic perforation due to AOM may occur in 5-30% of AOM patients. The causative pathogens for AOM with tympanic perforation are limited. METHODS: This was a prospective study conducted at the Department of Otolaryngology, Faculty of Medicine, Chiang Mai University, Thailand. All consecutive children diagnosed as having AOM with tympanic perforation were enrolled. The age of the eligible patients was between 3 months and 5 years. Pus from the middle ear of each patient was swabbed and tested for culture/sensitivity. RESULTS: There were 40 eligible patients diagnosed with AOM with tympanic perforation in this study. The mean age of all patients was 24.3 months and the patients were predominantly male (26 male; 65.0%). None of these patients received S. pneumoniae or H. influenzae vaccination. All specimens were culture positive (100%) and 13 organisms were identified. There were 53 identified pathogens; the most common pathogen was H. influenzae (19 times or 35.8%), followed by Staphylococcus aureus (14 times or 26.4%). H. influenzae was 100% sensitive to chloramphenicol, amoxicilllin/clavulanic acid, cefotaxime, and ciprofloxacin, while S. aureus was also 100% sensitive to oxacillin, vancomycin, and fusidic acid. CONCLUSIONS: The two most common pathogens for AOM with tympanic perforation were H. influenzae and Staphylococcus aureus. Both pathogens were mostly sensitive to antibiotics.

Factors Associated with Successful Treatment by Radiofrequency Treatment of the Soft Palate in Obstructive Sleep Apnea as the First-Line Treatment.

Background. Radiofrequency ablation (RFA) is recommended as the second-line treatment for obstructive sleep apnea (OSA). This study aims to study the factors associated with successful treatment by RFA in OSA patients as the first-line treatment. Methods. All patients diagnosed as mild to moderate OSA were enrolled prospectively and treated with RFA. Three points of soft palate were ablated: midline, left, and right paramedian sites. Baseline characteristics and clinical factors including snoring score (SS), Epworth Sleepiness Scale (ESS), and apnea-hypopnea index (AHI), with minimal oxygen saturation, were recorded at baseline and three months after treatment. Results. During the study period, there were 51 patients who met the study criteria and received RFA treatment. At three months, the SS, ESS, and AHI were significantly lower than baseline values, while the minimal oxygenation was significantly increased from the baseline values. There were 16 patients (31.37%) who had an AHI of < 5 times/h. Only baseline AHI was significantly associated with an AHI of < 5 times/h at three months after RFA treatment. The adjusted odds ratio was 0.804 (95% CI: 0.699, 0.924). Conclusion. Transoral RFA treatment may be effective in mild to moderate OSA as the first-line treatment. Baseline AHI is associated with preferable outcome by RFA treatment.

Human papillomatosis genotyping and severity in patients with recurrent respiratory papillomatosis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) and is the most common benign laryngeal neoplasm in children. Although RRP is rarely fatal, the disease requires prolonged, extensive medical and surgical treatment, leading to physical and emotional suffering in affected children and their families. Previous studies show HPV type 11 and type 6 in the lesion of Thai subjects with RRP. There is currently no published data available from Thailand that compares staging and severity with RRP genotypes. OBJECTIVE: To identify the genotypes of human papilloma virus (HPV) isolated from patients with RRP and compare the staging and severity with human papilloma virus genotype. MATERIAL AND METHOD: This prospective study was designed to assess population characteristics and follow the clinical course of RRP from January 2011 to January 2013. At each endoscopic evaluation or debridement, all surgeons to stage each patient's disease severity used a consistent scoring system. The samples were analyzed for HPV genotype. RESULTS: Fifteen Thai children (7 female, 8 male) with respiratory papillomatosis were enrolled. Results showed that HPV type 6 and HPV type 11 caused RRP in 6 (40%) and 9 (60%) of the children, respectively. No co-infection between HPV type 6 and type 11 was found. Overall mean age at diagnosis of patients with RRP was 2.65 ± 0.82 years. The age at diagnosis was significantly different between both HPV genotypes (p = 0.008). The mean disease severity score for HPV type 6 infection was 13.83 ± 9.94, and that of HPV type 11 infection was 27.44 ± 8.24. The mean disease severity score of HPV type 11 infection was significantly higher than that of HPV type 6 infection (p = 0.013). CONCLUSION: HPV type 6 and type 11 caused RRP in Thai children. RRP attributable to infection with HPV type 11 is more aggressive in disease severity and has a shorter life time than HPV type 6 at time of first diagnosis. RRP is an incurable disease that requires long-term medical management. Improved awareness and understanding amongst the Thai population should be promoted to limit the spread of the disease. In addition, further research on the treatment of RRP would benefit patients.

Haemophilus influenzae type b as an important cause of culture-positive acute otitis media in young children in Thailand: a tympanocentesis-based, multi-center, cross-sectional study.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) are considered major causes of bacterial acute otitis media (AOM) worldwide, but data from Asia on primary causes of AOM are limited. This tympanocentesis-based, multi-center, cross-sectional study assessed bacterial etiology and antimicrobial susceptibility of AOM in Thailand. METHODS: Children 3 to 59 months presenting with AOM (< 72 hours of onset) who had not received prescribed antibiotics, or subjects who received prescribed antibiotics but remained symptomatic after 48-72 hours (treatment failures), were eligible. Study visits were conducted from April 2008 to August 2009. Bacteria were identified from middle ear fluid collected by tympanocentesis or spontaneous otorrhea swab sampling (< 20% of cases). S. pneumoniae and H. influenzae serotypes were determined and antimicrobial resistance was also assessed. RESULTS: Of the 123 enrolled children, 112 were included in analysis and 48% of the 118 samples were positive for S. pneumoniae (23% (27/118)), H. influenzae (18% (21/118)), Moraxella catarrhalis (6% (7/118)) or Streptococcus pyogenes (3% (4/118)). The most common pneumococcal serotypes were 19F (26%) and 14 (22%). The majority of H. influenzae isolates were encapsulated (18/21), with 13 type b (Hib) representing 62% of all H. influenzae isolate or 11% of all samples (13/118), and there were only 3 non-typeable isolates. Despite high antibiotic resistance, amoxicillin/clavulanate susceptibility was high. No pneumococcal vaccine use was reported. CONCLUSIONS: S. pneumoniae and H. influenzae, both frequently antibiotic resistant, were leading causes of bacterial AOM and there was an unexpectedly high burden of Hib in this population unvaccinated by any Hib conjugate vaccine. Conjugate vaccines effective against pneumococcus and H. influenzae could potentially reduce the burden of AOM in this population.

Risk factors for acute pulmonary edema after adenotonsillectomy in children.

OBJECTIVE: Adenotonsillectomy is a common surgical procedure in children. Acute pulmonary edema after this procedure is a rare complication but may be fatal. The factors associated with pulmonary edema after adenotonsillectomy were studied. METHODS: All consecutive patients with an age of less than 15 years who underwent adenotonsillectomy at Chiang Mai University Hospital were enrolled. The study period was from January 2004 to December 2008. Clinical factors were retrospectively retrieved from medical records. Factors associated with acute pulmonary edema after adenotonsillectomy were computed using multiple logistic regression analysis. RESULTS: There were 216 patients who underwent adenotonsillectomy due to airway obstruction during the study period. Five patients were excluded due to incomplete data. Of those included, 129 patients (61.1%) were male with mean age of 6.6 (SD 3.2) years. Four significant factors associated with the development of post-operative pulmonary edema after the adenotonsillectomy were procedure, age, obesity, and pulmonary hypertension. CONCLUSION: Factors associated with acute pulmonary edema after adenotonsillectomy in children were adenotonsillectomy procedure, young age, obesity, or having pulmonary hypertension. Clinicians should be aware of these risk factors while performing adenotonsillectomy in children.

A novel mutation in CDKN1C in sibs with Beckwith-Wiedemann syndrome and cleft palate, sensorineural hearing loss, and supernumerary flexion creases.

We report on two daughters and a son of a Thai family who were affected with BWS. Their clinical findings consist of cleft palate, omphalocele, anterior ear creases, indented lesions on the posterior rim of the helix, macroglossia, posterior crossbite, and anterior open bite. The younger daughter and son had newly recognized findings of the BWS including sensorineural hearing loss and supernumerary flexion creases of the fingers. A novel mutation in CDKN1C (c.579delT; p.A193AfsX46) was found in all affected individuals and their mother. This mutation is located in the central highly polymorphic hexanucleotide repeat encoding a proline-alanine series of repeats (PAPA-domain). This domain is involved in MAP kinase phosphorylation. This is for the first time that sensorineural hearing loss and supernumerary flexion creases of the fingers are associated with mutation in CDKN1C.

The relationships between cephalometric parameters and severity of obstructive sleep apnea.

OBJECTIVE: To verify the relationships between cephalometric parameters and apnea hypopnea index (AHI) in snoring patients in Chiang Mai University Hospital. METHODS: Fifty patients who attend ENT snoring clinic, Faculty of Medicine, Chiang Mai University Hospital during 1 October, 2007 to 31 October, 2008 were enrolled. All subsequently underwent overnight polysomnography by SOMNOCHECK(®) V2.04 and lateral cephalometric radiographs. RESULTS: Of the 50 patients, 78% were men (n=39) and 22% were women (n=11). Ages ranged from 31 to 65 years. Average apnea hypopnea index (AHI)=18.4 ± 18.2 events/h. Body mass index (BMI)=27.2 ± 3.3 kg/m². The mean sella-nasion-subspinale (SNA)=84.1 ± 4.3°. Sella-nasion-supramental (SNB)=81.8 ± 3.4°. Posterior airway space (PAS)=14.9 ± 4.3mm. Distance between mandibular plane and hyoid (MP-H)=27.7 ± 5.6 mm. Distance between posterior nasal spine and tip of soft palate (PNS-P)=42.5 ± 5.4mm. Using Pearson's correlation analysis of BMI, the cephalometric parameters from all subjects with AHI revealed BMI, PAS and MP-H had significant correlation with AHI; p=0.009, p=0.003, and p=0.005, respectively. BMI, MP-H, and PAS were correlated with AHI. The multiple regression model for the effects of BMI, PAS, and MP-H on AHI is AHI=2.090(BMI)-1.953(PAS)+1.1333(MP-H)-40.54. CONCLUSION: The model seems to be useful as a screening tool to assess the severity of obstructive sleep apnea in snoring patients.