Glutaminolysis is required in maintaining immune regulatory functions in B cells.

IL-10-expressing regulatory B cells (B10 cells) are dysfunctional in patients with many immune disorders. The underlying mechanism remains to be further elucidated. Glutamine is an essential nutrient for cell metabolism. This study aims to elucidate the role of glutaminolysis in maintaining the immune regulatory capacity in B10 cells. Peripheral blood samples were collected from 50 patients with allergic rhinitis and 50 healthy control subjects. B cells were isolated from blood samples by cell sorting with flow cytometry. The role of glutaminolysis in regulating B10 cell activities was assessed by immunological and biochemical approaches. The results showed that B cells from patients with allergic rhinitis expressed low levels of the transporter of glutamine and neutral amino acid. Glutaminolysis was required in the IL-10 expression in B cells. The glutamine catabolism was required in B10 cell generation. The mTOR activation mediated the glutaminolysis-associated B10 cell induction, and the suppression of the B cell glycogen synthase kinase-3 (GSK3) activation. GSK3 activation suppressed IL-10 expression in B cells. Inhibition of GSK3 enhanced IL-10 expression in B cells and alleviated experimental allergic rhinitis by generating immune competent type 1 regulatory T cells.

Interaction between Ras and Bcl2L12 in B cells suppresses IL-10 expression.

The pathogenesis of recurrent tonsillitis is to be further investigated. B cell-derived interleukin (IL)-10 plays a critical role in immune regulation. Ras activation plays an important role in cancer and many immune disorders. This study aims to investigate the role of Ras activation in down regulating IL-10 expression in tonsillar B cells. Surgically removed tonsil tissues were collected from patients with recurrent acute tonsillar inflammation; B cells were isolated from the tonsillar tissues by flow cytometry sorting to be analyzed by the Ras-specific enzyme-linked immunosorbent assay and pertinent immunological approaches. We found that, compared to peripheral B cells (pBC), B cells isolated from the tonsillar tissues with recurrent inflammation (tBC) showed higher Ras activation, lower IL-10 expression and higher Bcl2L12 expression. Bcl2L12 formed a complex with GAP (GTPase activating protein) to prevent Ras from deactivating. The Ras activation triggered the MAPK/Sp1 pathway to promote the Bcl2L12 expression in B cells. Bcl2L12 prevented the IL-10 expression in tBCs, that was counteracted by inhibition of Ras or the Ras signal transduction pathway. In conclusion, Bcl2L12 interacts with Ras activation to compromise immune tolerance in the tonsils by inhibiting the IL-10 expression in tBCs. Inhibition of Bcl2L12 can restore the IL-10 expression in tBCs.

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model.

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.

Feasibility of a remote monitoring system for home-based non-invasive positive pressure ventilation of children and infants.

OBJECTIVE: We examined the safety, efficacy, and caregiver satisfaction of a remote monitoring system for home-based non-invasive positive pressure ventilation of children and infants with upper airway obstruction. METHODS: Fourteen pediatric patients (age 50 days to 12 years) treated in our ENT unit from March 2009 to July 2011 and requiring home-based non-invasive positive pressure ventilation were enrolled in this feasibility study; one patient underwent CPAP and the other 13 patients underwent Bi-PAP. User satisfaction with the monitoring system was assessed by questionnaires given at regular intervals to parents and attending physicians. Compliance was determined by the number of days that parents uploaded data to the central server. In addition, the feasibility of the system was analyzed by comparing costs and time expenditures with traditional clinic visits. RESULTS: The patients' parents (primary caregivers) uploaded data via the system on 93.3% of trial days, indicating good compliance. No system or device failures occurred. Both parents and physicians considered the system convenient and ease to use according to >80% of the returned questionnaires, indicating high user satisfaction. The mean distance between the patients' homes and the hospital was 113 ± 71 km, and parents required 371 ± 182 min to reach the hospital for a follow-up visit. In contrast, it took only 5.7 ± 3.1 min per day to transmit data (P<0.05 compared to hospital travel time). As of August 2011, average cost per patient was 632 Chinese yuan (¥), which was ¥924 (59.4%) lower than the cost of clinic visits (¥1556). CONCLUSIONS: The remote monitoring system was safe, reliable, easy to use, cost effective, and widely acceptable to both parents and physicians. This system may allow for safe and effective home-based non-invasive positive pressure ventilation for children with upper airway obstructions in developing countries with limited health care budgets or for patients from remote regions.

[Application of minimally invasive technique of coblation in 30 infants with epiglottic cyst].

OBJECTIVE: To present the efficacy of minimally invasive technology of coblation in the treatment of infant epiglottic cyst. METHODS: The clinical data of 30 infants with epiglottic cyst treated between January 2008 and January 2011 were reviewed retrospectively. All infants with epiglottic cyst were treated with the ArthroCare ENT Coblator II Surgery System after being checked completely. RESULTS: All 30 patients were successfully operated. The blood loss was less than 2 ml during the surgery. The infants recovered without any complications and were discharged from hospital in 10 days after surgery. The clinical symptoms improved significantly or disappeared. No patients showed recurrence during followed-up over 6 months. CONCLUSION: The advantage of the minimally invasive technology of coblation in infant epiglottic cyst was less bleeding, little injury and postoperative organization reaction.

[Study of arousal index in children with sleep-disordered breathing].

OBJECTIVE: To explore which index is more suitable to show the degree of sleep fragment in children with sleep-disordered breathing (SDB). METHODS: Between October 2009 and August 2011, Forty-five children (4 - 8 years) who were diagnosed as obstructive sleep apnea hypopnea syndrome (OSAHS) were enrolled in OSAHS group[obstructive apnea index (OAI) > 1 times/h or apnea hypopnea index (AHI) > 5 times/h, lowest oxygen saturation (LSaO2) < 0.92] and 54 children were enrolled in SDB group (1 ≤ AHI ≤ 5 times/h and OAI ≤ 1 times/h), 18 children with chorditis nodules made up control group (AHI < 1 times/h and LSaO2 ≥ 0.92, without SDB-related history). The difference of respiratory arousal index (RAI), spontaneous arousal index (SAI), total arousal index (ARtotI) and sleep pressure score (SPS) were compared among three groups. The correlation between RAI, SAI, ARtotI, SPS and AHI were also analyzed. Furthermore, RAI, SAI, ARtotI and SPS were compared before and after operation in 14 OSAHS children with detailed pre- and after polysomnography data. RESULTS: The difference of SAI and ARtotI between SDB group and OSAHS group and ARtotI between OSAHS group and control group were not significant (P > 0.017), except this, the difference of other index between any two groups or SAI and ARtotI between otherwise two groups were significant (P < 0.017). RAI and SPS was correlated with AHI (coefficient correlation: 0.751, 0.829, P was 0.000). RAI and SPS decreased after operation and the difference was significant (Z were -3.045 and -2.982, P were 0.002 and 0.003). The difference of sleep structure was not significant. CONCLUSIONS: RAI and SPS were more suitable to show the degree of sleep fragment than other arousal index.

[Reasons of multiple operations in children with airway foreign body].

OBJECTIVE: To explore the reasons of multiple operations in children with airway foreign body through analyzing the clinical data of children who received two or more operations. METHODS: From 2003 to 2009, all children with airway foreign body who received two or more operations in hospital were enrolled. The clinical manifestations, image before and after operation and intraoperative conditions were retrospectively analyzed, in order to find the reasons of multiple operations. RESULTS: All children fully recovered, no serious complications or death. The reasons of two or more operations were multiple: 21 cases (42.8%) were related to the factor of apparatus, 20 (40.8%) cases were related to the quality, surrounding conditions and location of the foreign body and experience and surgical skills of operator, 4 (8.2%) cases were due to incarceration of foreign body, another 4 (8.2%) cases were due to unstable intraoperative oxygen saturation. CONCLUSIONS: Both subjective and objective factors (quality, surrounding conditions or location of foreign body, et al) were related to multiple operations. To reduce the chance of multiple operations, careful preoperative assessment and preparation are necessary.

[Correlation between serum uric acid levels and obstructive sleep apnea/hypopnea syndrome in children].

OBJECTIVE: To explore the level of serum uric acid (UA) in children with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHOD: Between Sep. 2008 and Mar. 2010, 138 children with OSAHS were enrolled in study group. Sixty-five children with accessory auricle or ptosis of upper lid were enrolled into the control group. Furthermore, according to apnea/hypopnea index (AHI) or obstructive apnea index (OAI) the study group was further divided into three subgroups (mild, moderate and severe group). At last, the study group and control group were divided into two groups according to the body mass index (BMI), separately. The fasting serum UA level was compared among the different groups. Then the correlation between the serum UA level and AHI, BMI, oxygen desaturation index, least arterial oxygen saturation (LSaO(2)) and the percentage of total sleep time with arterial oxygen saturation < 0.92 was also analyzed in OSAHS children with or without overweight and obesity respectively. RESULT: The difference of serum UA level between the study group and control group (z = -0.443), and the difference among the three groups (χ(2) = 1.241) was not significant(P > 0.05). The serum UA level in overweight and obese children [study group, 273.0 (238.3 - 357.3); control group, 298.0 (253.0 - 336.0)] was significantly higher than that in children with normal BMI [study group, 246.5(215.8 - 300.0); control group, 266.0 (224.0 - 303.3)] (z = -2.084, -2.214, P < 0.05). That serum UA level did not correlate with the above index of OSAHS was observed in children with or without overweight and obesity in study group (P > 0.05). CONCLUSION: Findings of higher serum UA level were not observed in children with OSAHS. There was no correlation between serum UA level and the above indices of OSAHS. The serum UA level in overweight and obese children was significantly higher than that in children with normal BMI.

[Diagnostic role of pulse transit time in children with sleep disordered breathing].

OBJECTIVE: To explore the diagnostic value of pulse transit time (PTT) in children with sleep disordered breathing(SDB). METHODS: Forty eight randomly selected snorers (2 - 13 years) with SDB were examined by PSG and PTT in the same time. Data obtained were analyzed by different technicians respectively. Statistics and analysis of the data were performed. RESULTS: Apnea hypopnea index (AHI), obstructive apnea index (OAI), the lowest oxygen and micro-arousal index were obtained by PSG and PTT. The results was described as M [25 percentile; 75 percentile]: 4.9[1.3;10.1], 4.6[1.5;11.8]; 1.2[0.7;4.9], 1.3[0.6;5.0]; 0.93[0.85;0.95], 0.93[0.84;0.95]; 14.5[12.6;16.4], 26.0[17.4;30.6]. The difference of AHI, OAI, and the lowest oxygen were not significant (P > 0.05), while the PTT arousal index detection rate was higher than PSG (Z = -5.19, P < 0.01). There was no significant difference in the diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS) and determination of degree of patient's condition (P > 0.05). PTT could identify upper airway resistance syndrome in children without OASHS. CONCLUSIONS: Both methods can be used to diagnose SDB. However, PTT is easy to use and suitable for the diagnosis of SDB in children, especially for UARS.

[A preliminary study of the secondary postoperative haemorrhage in pediatric coblation adenotonsillectomy].

OBJECTIVE: To compare secondary postoperative haemorrhage rate of coblation with the conventional pediatric adenotonsillectomy. And to analyze possible reasons which cause the secondary bleeding after coblation adenotonsillectomy. METHODS: A retrospective study was applied to compare the secondary postoperative haemorrhage rate and the bleeding moment between two groups in which 1-14 years old children from April 2005 to September 2009 in Guangzhou Children's Hospital were included. Group A was pediatric patients who had conventional adenoidectomy and/or tonsillectomy (dissection, without heat damage to the tissue) from April 2005 to July 2006 in Department of Otorhinolaryngology. Group B was pediatric patients who had coblation adenoidectomy and/or tonsillectomy from April 2008 to September 2009 in Department of Otorhinolaryngology. RESULTS: Two of 484 cases in group A had secondary postoperative bleeding, the rate was 0.4%. One happened 2 days after operation, another after 3 days. Eleven of 502 cases in group B had secondary postoperative bleeding, the rate was 2.2%. Secondary bleeding happened 2 to 12 days after surgery, median 6.0 days. The secondary postoperative haemorrhage rate of operating by the freshman was 2.6%(10/385), and it was 0.9%(1/117) by the senior. The rate of secondary bleeding was higher in group B than group A (chi(2) = 5.987, P < 0.05). There was no significant difference of secondary bleeding time in both groups (Mann-Whitney U score was 2.500, P > 0.05). Six of 13 cases who had secondary bleeding suffered wound or upper respiratory tract infection. Three of 13 ate inappropriately after the operation. CONCLUSIONS: Pediatric coblation adenotonsillectomy is a new method. The most possible reasons of secondary bleeding are poor surgery skills and ill experience. And, infection, inappropriate eating after the operation may be the other reasons of secondary bleeding.

[Study on periodic limb movement during sleep in children with sleep-disordered breathing].

OBJECTIVE: To explore the correlation between periodic limb movement index (PLMI) and the apnea-hypopnea index (AHI), apnea index (AI), hypopnea index (HI) and lowest oxygen saturation (LSaO2) in sixty-four children with sleep-disordered breathing (SDB). METHODS: Between March 2008 and May 2009, sixty-four children suspected of OSAHS underwent overnight polysomnogram monitoring in our medicine sleep center. OSAHS was diagnosed according to the general criterion. Sixty-four children were divided into two groups. Thirty children were diagnosed as OSAHS and 34 children were diagnosed as primary snoring (PS, 32 children) or upper airway resistance syndrome (UARS, 2 children). The difference of PLMI and periodic limb movement index during sleep associated with arousals (PLMI-arousal) were compared between the two groups. Besides this, the correlation between PLMI, periodic limb movement index during sleep associated with arousals and AHI, AI, HI and LSaO2 were also analyzed in all SDB children. Furthermore, all SDB children were divided into two groups according to PLMI (< 5 events/h vs ≥ 5 events/h). AHI, AI, HI, LSaO2 and sleep structure were compared between the two groups. RESULTS: (1) The difference of PLMI and PLMI-arousal between the children with OSAHS and children with other SDB types (PS and UARS) were not significant (z value, -1.279, -1.490; P value, 0.201, 0.136, respectively). (2) The increased sleep stage I was significant as being compared between the two groups (< 5 events/h vs ≥ 5 events/h, t = -2.16, P < 0.05). However, other sleep stages and sleep efficiency were not significantly different (P value, all > 0.05). (3) The difference of HI, AI, AHI, arousals index (ArI) and LSaO2 were not significant between the two groups (< 5 events/h vs ≥ 5 events/h, P value, all > 0.05). (4) PLMI and PLMI-arousal were not correlated with AHI, HI, AI, AHI and LSaO2 (Spearman rank correlation analysis). CONCLUSIONS: PLMS may be independent of SDB and PLMS had a little influence on sleep structure.

[Clinical analysis of upper airway resistance syndrome and obstructive sleep apnea-hypopnea syndrome in children].

OBJECTIVE: To analyze the similarities and differences of the clinical manifestations between the children with upper airway resistance syndrome (UARS) and obstructive sleep apnea-hypopnea syndrome (OSAHS), and to explore the clinical features and characteristics of sleep respiratory parameters. METHODS: Using the double-blind method, all children were diagnosed as UARS or OSAHS through the polysomnography test and the results of all children were analyzed by a sleep technician and an otolaryngologist. Another ENT doctor recorded their clinical and physical examination in detail. RESULTS: Polysomnography showed that the apnea-hypopnea index (AHI) and the lowest oxygen in 253 children with OSAHS were 3.60[2.00;7.55] times/h and 0.90[0.85;0.91], and were 0.90[0.50;1.10] times/h and 0.95[0.92;0.96] in 102 children with UARS, the difference of the two groups by rank test was statistically significant. The proportion of UARS and OSAHS was more common during preschool period than during school-age period. The chief complaint in two groups was sleep snoring, and the main symptoms were sleep restless, attention deficit/hyperactivity and breath with mouth open. The incidence rate of above symptoms were as follows, 94.1%, 72.5%, 62.7% and 37.3% in children with UARS, 92.9%, 78.7%, 57.7% and 45.5% in children with OSAHS. The difference was not significant by chi-square test (P>0.05). Tonsil and adenoid hypertrophy were also observed in the two groups, the difference was not significant (chi2 = 0.27, P= 0.87). However, the children with OSAHS were more apt to have the sleep apnea than with UARS, the difference was statistically significant (chi2 = 34.07, P<0.001). CONCLUSIONS: The clinical manifestations of two groups are similar, the difference between UARS and OSAHS can not be determined by the patient's clinical performance. Sleep apnea can be more easily observed in children with OSAHS than that in UARS, the final diagnosis is based on polysomnography.

[Diagnosis and treatment of obstructive sleep apnea hypopnea syndrome in children with risk factors].

OBJECTIVE: To analyse the clinical features of children with obstructive sleep apnea-hypopnea syndrome (OSAHS), accompanying with risk factors. METHODS: The clinic data of 19 patients treated in the Department of Otorhinolaryngology of Guangzhou Children's Hospital between January 2005 to January 2008 were investigated retrospectively. Among them, 5 were < 2 years old, 6 with craniofacial deformity: small mandible and (or) mandibular retrusion (5 cases), transverse facial cleft (1 case), Down's syndrome (2 cases), cerebral palsy (2 cases), chronic bronchitis (3 cases) and mucopolysaccharidoses (1 case). Nineteen patients with symptoms of snoring, mouth breathing, were diagnosed as OSAHS by polysomnography (PSG) and treated by tonsillectomy and (or) adenoidectomy in hospital. All patients were closely followed-up. RESULTS: Fourteen patients underwent PSG 6 months to 1 year after operation, 11 patients recovered, the median [percentiles 25; percentiles 75] apnea-hypopnea index (AHI) decreased from the pre-operative 22.5 [16.5; 24.3] times/h to 2.0 [1.5; 4.3] times/h, and the lowest oxygen saturation (LSaO(2)) before operation was 0.63, and was higher than 0.92 after operation, 1 case accompanying with chronic bronchitis, the pulmonary hypertension was improved after operation. One case with Down's syndrome was not significantly improved, preoperative AHI and LSaO(2) was 22.4 times/h and 0.67, and after operation was 14.2 and 0.84; 2 cases accepted adenoidectomy only, snoring, mouth breathing reappeared 3 months after operation, pre-operative PSG results showed AHI 24.6 times/h and 26.6 times/h, LSaO(2) was 0.69 and 0.73, after operation the AHI was 10.6 times/h and 8.5 times/h, LSaO(2) was 0.90 and 0.88, the symptoms disappeared after adenotonsillectomy. Five cases did not have PSG because they lived far away in the other cities, their pre-operative PSG showed AHI 16.4 to 26.2 times/h, LSaO(2) was 0.65 to 0.76. One year after operation, these patients were followed-up by telephone, 4 children were significantly improved, 1 case with mandibular symptoms showed no improvement. CONCLUSIONS: For OSAHS children accompanying with risk factors, if they have adenoid and tonsil hypertrophy, adenotonsillectomy is the major treatment. Because of the existence of risk factors, perioperative risk increased, even the failure of operation. so these patients must be comprehensively assessed before operation. Satisfied results can be achieved by close observation after operation and management of complications as soon as possible.

[Arousals in children with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the difference of arousal index between the children with obstructive sleep apnea-hypopnea syndrome (OSAHS) and children with primary snoring. Furthermore, to explore the correlation between the above mentioned arousals and the apnea-hypopnea index (AHI) and lowest oxygen saturation (LSaO(2)). METHODS: Between March 2007 and February 2008, 102 children suspected of OSAHS underwent overnight polysomnogram monitoring in our medicine sleep center. OSAHS was diagnosed according to the general criterion [Draft of guidelines for the diagnosis and treatment of pediatric sleep apnea hypopnea syndrome (Urumqi) which was published in Chin J Otorhinolaryngol Head Neck Surg in February, 2007]. One-hundred and two children were divided into two groups according to the guidelines. Sixty six children [56 boys, 10 girls; aged 4 - 17 years, (7.01 +/- 2.24) years (x(-) +/- s)] who were diagnosed as OSAHS were enrolled in study group and 36 children [29 boys, 7 girls; aged 4 - 13 years, (7.44 +/- 2.68) years] who were diagnosed as primary snoring made up control group. The difference of spontaneous arousal index, total arousal index and arousal index related to respiratory stimuli and limb movement were compared between the two groups. Besides this, the correlation between spontaneous arousal index, total arousal index and arousal index related to respiratory stimuli and limb movement and AHI and LSaO(2) were also analyzed. Furthermore, the study group were divided into three subgroups according to AHI (< or = 10 times/h, 10 times/h < AHI < or = 20 times/h, > 20 times/h). Spontaneous arousal index, total arousal index and arousal index related to respiratory stimuli and limb movement were compared among the three groups. RESULTS: The increased total arousal index and arousal index related to respiratory stimuli and the decreased spontaneous arousal index of study group were significant as compared to those of control group (Mann-Whitney U, z value, -3.148, -3.866, -2.791; P value, 0.002, 0.000, 0.005, respectively). The increased arousal index related to respiratory stimuli were significant as being compared among the three groups. Arousal index related to respiratory stimuli was correlated with AHI (coefficient correlation: 0.734, P = 0.000). Other kinds of arousals and arousal index related to respiratory stimuli were not correlated with LSaO(2) (Spearman rank correlation analysis). When compared to control group, stage I increased and stage REM decreased and the difference was significant (z were -2.423, -3.519; P were 0.015, 0.000). CONCLUSIONS: The arousal index related to respiratory stimuli were increased and spontaneous arousal index were decreased in children with OSAHS. Arousal index related to respiratory stimuli is more suitable to show the degree of sleep fragment than other arousal index.