Integrative traditional Chinese medicine treatment for children with obstructive sleep apnea.

Purpose: Obstructive sleep apnea (OSA) is a chronic disease that affects 1%-6% of children. Our study aims to explore the effectiveness and clinical characteristics of integrative Traditional Chinese Medicine (ITCM) for pediatric OSA. Materials and methods: In this retrospective cohort study, we assessed differences of polysomnography (PSG) parameters and clinical characteristics between 2009 and 2020. Children <12 years old diagnosed with OSA (n = 508) were included and were categorized into ITCM cohort, western medicine (WM) cohort ,and surgery cohort. Outcomes were apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and body mass index (BMI). Results: There were 56 (11%), 324 (63.8%), and 128 (25.2%) patients in the ITCM, WM, and surgery cohorts. Among 17, 26, and 33 patients in the ITCM, WM, and surgery cohorts underwent follow-up PSG studies, respectively. In the ITCM follow-up cohort, AHI were significantly reduced (9.59 to 5.71, p < 0.05). BMI significantly increased in the WM follow-up cohort (19.46 to 20.50, p < 0.05) and the surgery follow-up cohort (18.04 to 18.85, p < 0.01). Comparing ITCM to WM cohort, a significant difference was found between the changes in RDI (ITCM: -6.78, WM: 0.51, p < 0.05) after treatment. Among ITCM follow-up cohort, the most prescribed TCM formula was Forsythia and Laminaria Combination. The most prescribed TCM herb was Ephedrae Herba. Conclusions: ITCM therapy can significantly reduce RDI and control BMI. We identified potential TCM treatments for pediatric OSA. Further study of the pharmacological mechanisms and clinical efficacy is warranted.

Correlation between impulse oscillometry parameters and test for respiratory and asthma control in kids (TRACK) in asthma control of preschoolers with asthma.

BACKGROUND: Little research has been conducted to evaluate the correlation between impulse oscillometry (IOS), Childhood Asthma Control Test (C-ACT), and Test for Respiratory and Asthma Control in Kids (TRACK). METHODS: This study was conducted at China Medical University Hospital between September 1, 2019, and March 31, 2021. Children aged 2-6 years who had been diagnosed with asthma with acute exacerbation were enrolled and followed-up until the end of the study. Correlations between the parameters of IOS, C-ACT and TRACK were assessed. The validity and reliability of TRACK were verified. RESULTS: A total of 114 children with asthma and acute exacerbations were recruited. Their mean age was 4.1 ± 1.1 years, and 60.5% were males. After a year of treatment, the change of R5-R20 from baseline 0.64 ± 0.38 kPa/L/s to 12th month 0.48 ± 0.2 kPa/L/s (p = 0.022). TRACK and C-ACT scores were significantly correlated during the observation period. R5-R20 in IOS at baseline and at the 12th month of follow-up as well as the change in IOS parameters were significantly associated with C-ACT (p = 0.003, 0.015, and 0.001, respectively). R5% and R5-R20 changes in IOS were associated with TRACK (p = 0.04 and 0.025, respectively). Sensitivity and specificity of TRACK were 80.8% (67.5-90.4) and 100% (94.1-100), respectively, with cut-off points >95 and AUC 93.8%. CONCLUSION: TRACK score appears to have a stronger association with the IOS parameter than C-ACT score. Our findings indicate that TRACK is a valid tool for assessing asthma control in preschool children.

Acute Bronchitis and Bronchiolitis Infection in Children with Asthma and Allergic Rhinitis: A Retrospective Cohort Study Based on 5,027,486 Children in Taiwan.

This study evaluated the risks of childhood acute bronchitis and bronchiolitis (CABs) for children with asthma or allergic rhinitis (AR). Using insurance claims data of Taiwan, we identified, from children of ≤12 years old in 2000-2016, cohorts with and without asthma (N = 192,126, each) and cohorts with and without AR (N = 1,062,903, each) matched by sex and age. By the end of 2016, the asthma cohort had the highest bronchitis incidence, AR and non-asthma cohorts followed, and the lowest in the non-AR cohort (525.1, 322.4, 236.0 and 169.9 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratios (aHRs) of bronchitis were 1.82 (95% confidence interval (CI), 1.80-1.83) for the asthma cohort and 1.68 (95% CI, 1.68-1.69) for the AR cohort, relative to the respective comparisons. The bronchiolitis incidence rates for these cohorts were 42.7, 29.5, 28.5 and 20.1 per 1000 person-years, respectively. The aHRs of bronchiolitis were 1.50 (95% CI, 1.48-1.52) for the asthma cohort and 1.46 (95% CI, 1.45-1.47) for the AR cohort relative to their comparisons. The CABs incidence rates decreased substantially with increasing age, but were relatively similar for boys and girls. In conclusion, children with asthma are more likely to develop CABs than are children with AR.

Roles of Ambient Temperature and PM2.5 on Childhood Acute Bronchitis and Bronchiolitis from Viral Infection.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006−2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June−August). The highest incidence was 698 cases/day at <20 °C with PM2.5 > 37.0 µg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97−1.04) compared to 568 cases/day at <20 °C with PM2.5 < 15.0 µg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85−1.06) with PM2.5 > 37.0 µg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58−0.65) when PM2.5 was <15.0 µg/m3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

Association between gaseous air pollutants and idiopathic nephrotic syndrome in children: a 12-year population-based cohort study.

BACKGROUND: To date, there is insufficient knowledge about the association of air pollution and childhood nephrotic syndrome in the real world. This study aimed to evaluate the effects of the three common gaseous air pollutants, including sulfur dioxide, total hydrocarbon, and methane, on the risk of idiopathic nephrotic syndrome (INS) in children. METHODS: We collected data from the Taiwan National Health Insurance Research Database and Taiwan Air Quality-Monitoring Database. Children younger than 18 years old, identified from January 1, 2000, were followed up until the first diagnosis of INS was established or until December 31, 2012. We measured the incidence rates and hazard ratios for INS stratified based on the quartiles (Q1-Q4) of air pollutant concentration. Multivariate Cox proportional hazards models were also applied by adjusting age, sex, monthly income, and urbanization. RESULTS: Compared with participants exposed to Q1 concentrations, the adjusted hazard ratios (aHRs) for INS increased progressively along the four quartiles of sulfur dioxide, total hydrocarbon, and methane, from 1 (Q1) to 1.78 (Q4), 1 (Q1) to 3.49 (Q4), 1 (Q1) to 7.83 (Q4), respectively. CONCLUSIONS: Our study revealed that children with exposure to higher concentrations of sulfur dioxide, total hydrocarbon, and methane was associated with an increased risk of INS.

Validation of the traditional Chinese version of the Sinus and Nasal Quality of Life Survey (SN-5) for children.

BACKGROUND: Persistent sinonasal symptoms are common in children with chronic rhinosinusitis. The Sinus and Nasal Quality of Life (QoL) Survey (SN-5) was the first validated questionnaire measuring sinonasal-related QoL in populations aged 2-12 years. No norm has been established for Chinese-speaking countries. We translated the SN-5 into traditional Chinese and evaluated validity and reliability. METHODS: From December 2016 to December 2017, healthy volunteers and children with persistent sinonasal symptoms were enrolled. Guardians of the participants completed the SN-5, a visual analog scale (VAS) of nasal symptoms, and the Obstructive Sleep Apnea-18 (OSA-18); the responses were used to assess internal consistency, discriminant validity, and treatment responsiveness. A nontreatment group was administered the SN-5 1 week later to assess test-retest reliability. RESULTS: We recruited 31 healthy volunteers and 85 children with rhinosinusitis, 50 and 35 in the treatment and nontreatment groups, respectively. The SN-5 demonstrated good internal consistency (Cronbach's α = 0.86) and test-retest reliability (0.74, p < 0.01). It exhibited good discriminant validity between the healthy and rhinosinusitis groups (p < 0.001). The SN-5 scores were correlated with the VAS scores (0.63, p < 0.001). The effect size of the SN-5 scores was 0.51. The total SN-5 and OSA-18 scores changed significantly after 4-week treatment (p < 0.05) and demonstrated good responsiveness. The SN-5 and OSA-18 scores were significantly and positively correlated (r2 = 0.53, p < 0.001). CONCLUSION: Our traditional Chinese version of the SN-5 is reliable and valid for measuring sinonasal-related QoL in children in Chinese-speaking countries. TRIAL REGISTRATION NUMBER: NCT04836403.

Risk factors of vesicoureteral reflux and urinary tract infections in children with imperforate anus: A population-based case-control study in Taiwan.

ABSTRACT: Imperforate anus (IA) is associated with several urological anomalies, including vesicoureteral reflux (VUR), a major contributor to high morbidity in patients with anorectal malformations. This retrospective study was performed to elucidate the risk factors of vesicoureteral reflux (VUR) and UTI in children with IA.We used the National Health Insurance Research Database (NHIRD) to estimate the frequency of congenital anomalies of the kidney and urinary tract (CAKUT) in children with IA. We also investigated the frequencies of VUR, UTI, and CAKUT in children with IA along with the risk factors of VUR.We enrolled 613 children between 2000 and 2008 (367 males and 246 females; 489 low-position IA and 124 high-position IA). High-position IA was associated with a significantly increased risk of VUR compared with low-position IA (OR: 2.68, 95% CI: 1.61, 4.45). In addition, children with IA along with CAKUT, hydronephrosis, or UTI had a higher risk of VUR (OR: 8.57, 95% CI: 3.75, 19.6; OR: 7.65, 95% CI: 4.48, 13.1; and OR: 31.8, 95% CI: 11.5, 88.3, respectively). UTI, as well as chromosomal anomalies, were more frequent in children with high-position IA.Patients with a high-position IA had a greater risk of VUR, particularly those with CAKUT, hydronephrosis, or UTI. Such patients must periodically undergo urinalysis to screen for UTI and early voiding cystourethrogram to rule out VUR and prevent consequent renal damage. Chromosomal analysis is suggested to rule out Down syndrome.

Association of exposure to hydrocarbon air pollution with the incidence of atopic dermatitis in children.

BACKGROUND: There is growing evidence suggesting that air pollution may act as an important environmental risk factor in the development and aggravation of childhood atopic dermatitis (AD). METHODS: We collected data from the Taiwan National Health Insurance (NHI) research database and linked the data to the Taiwan Air Quality-Monitoring Database. From January 1, 2000 to December 31, 2012; children aged below 18 years were selected from the database and followed longitudinally until the diagnosis of AD, withdrawal from the NHI, or December 31, 2012. Children with missing data or those diagnosed with AD before enrolment in this study were excluded. We measured the incidence rate and hazard ratios (HRs) for AD and stratified them by quartiles (Q1-Q4) of air pollutant concentration. Multivariable Cox proportional hazards models were also applied by adjusting for age, sex, monthly income, and level of urbanization. RESULTS: When compared with the concentrations of pollutants in the Q1 quartile, the adjusted HR for AD increased with an increase in the exposure concentrations of total hydrocarbons (THCs), non-methane hydrocarbons (NMHCs), and methane (CH4) from 1.65 (95% confidence interval [CI]: 1.47-1.84) to 10.6 (95% CI: 5.85-7.07), from 1.14 (95% CI: 1.06-1.24) to 2.47 (95% CI: 2.29-2.66), and from 1.70 (95% CI: 1.52-1.89) to 11.9 (95% CI: 10.8-13.1), respectively. Patients exposed to higher levels of THCs, NMHCs, and CH4 exhibited greater incidence rates of childhood AD. CONCLUSIONS: The present study demonstrated that exposure to higher concentrations of THCs, NMHCs, and CH4 were associated with an increased risk of childhood AD.

Association between vesicoureteral reflux, urinary tract infection and antibiotics exposure in infancy and risk of childhood asthma.

BACKGROUND: The use of antibiotics for treating infection in childhood and their association with increased risk of asthma remain controversial. Infants diagnosed with vesicoureteral reflux (VUR) belong to a unique population who are administered antibiotics for a long time and are susceptible to recurrent UTI. It is interesting to study the risk of asthma in these infants with or without VUR. METHODS: Taiwanese children born between 2000 and 2007 were enrolled in population-based birth cohort study. Participants diagnosed with VUR and UTI within first year were classified into four groups (VUR, UTI, VUR and UTI, and control). We calculated follow-up person-years for each participant from the index date until the asthma diagnosis, their withdrawal from the insurance system (because of death or loss to follow-up), or till the end of 2008. The risk of asthma was compared between the 4 cohorts by using Cox proportional hazards model analysis, adjusted hazard ratio (aHR), and 95% confidence interval (95% CI). RESULTS: Children diagnosed with VUR (n = 350), UTI (n = 15542), VUR and UTI (n = 1696), and randomly selected controls (n = 17588) were enrolled. The overall rate of incidence of asthma was found to be 1.64-fold, 1.45-fold, and 1.17-fold higher in the UTI, VUR/UTI, and VUR cohorts than in the controls (5.60, 5.07, and 4.10 vs. 3.17 per 100 person-years), respectively. After adjusting the potential factors, the overall risk of asthma remained the highest in UTI (aHR: 1.74, 95% CI : 1.65 to 1.80) followed by VUR/UTI (aHR: 1.56, 95% CI : 1.40 to 1.75) and VUR cohorts (aHR: 1.25, 95% CI: 0.96 to 1.62). The incidence of asthma was higher in boys than in girls. CONCLUSION: The nationwide retrospective cohort study demonstrated that short-term therapeutic dose of antibiotics for UTI in infants with or without VUR has a positive correlation with the prevalence of childhood asthma. Significant risk of childhood asthma was not observed when VUR cohort was exposed to long-term low-dose of prophylactic antibiotics.

Allergic rhinitis and dental-supporting tissue diseases in children.

ABSTRACT: The etiology of dental-supporting tissue diseases in children is multi factorial and not merely related to oral hygiene. Therefore, in the present study, we investigated the relationship between children <18 years old with allergic rhinitis (AR) and the risk of dental-supporting tissue diseases.Data from the National Health Insurance Research Database (NHIRD) of Taiwan were used to conduct a retrospective longitudinal cohort study. The study cohort comprised 378,160 patients with AR (AR group) and 378,160 patients without AR (non-AR group), who were selected through frequency matching based on age, sex, and the index year. The study patients were followed until dental-supporting tissue diseases occurrence, withdrawal from the National Health Insurance program, or December 31, 2013. Cox proportional hazards regression analysis was conducted to calculate the risk of dental-supporting tissue diseases in the AR group after adjustment for age, sex, and relative comorbidities.The adjusted HRs of periodontal, pulp, and periapical diseases in AR children were higher than those in the non-AR controls (1.51, 95% CI: 1.50 to 1.53; 1.06, 95% CI: 1.05 to 1.07, respectively). The AR to non-AR HRs of these inflammatory dental diseases were particularly higher in children <6 years old and in boys. The HRs of periodontal, pulp, and periapical diseases were greatest in those with >5 AR-related medical visits/year (5.57, 95% CI: 5.50 to 5.56; 4.06, 95% CI: 4.00 to 4.12, respectively).Children with AR had a greater risk of inflammatory dental-supporting tissue diseases, particularly those <6 years old with primary teeth, boys, and those with severe persistent AR.

Galectins in allergic inflammatory diseases.

Allergic inflammatory diseases are a global public health concern affecting millions of people. Although there are several potential hypotheses, details regarding their molecular mechanisms are still ambiguous. Recently, a group of ß-galactoside-binding proteins, galectins, have been revealed as important factors in altering allergic chronic inflammatory diseases. In this review, we describe the molecular and cellular basis of how galectins modulate inflammatory reactions. We also provide an overview of clinical features related to galectins. Finally, we discuss the potential issues that might lead to misrepresentation of the exact biological functions of galectins.

The Efficacy of Everolimus for Facial Angiofibromas in Tuberous Sclerosis Complex Patients Treated for Renal Angiomyolipoma/Subependymal Giant Cell Astrocytoma.

BACKGROUND: Facial angiofibromas may be present since early childhood in individuals with tuberous sclerosis complex (TSC), causing substantial cosmetic disfigurement. Current therapies are partially effective, but they are uncomfortable, produce scarring, and are especially expensive. OBJECTIVE: The aim of the present study was to evaluate the efficacy of oral everolimus for TSC-associated angiofibromas. METHODS: This retrospective study included TSC patients being treated with oral everolimus for subependymal giant cell astrocytomas (SEGAs) and angiomyolipomas (AMLs). We recorded the changes in facial angiofibromas. Changes in the Angiofibroma Grading Scale (AGS) indicators were recorded according to erythema, average lesion size, lesion density, and percent involvement on the forehead, nose, cheeks, and chin. The scores were recorded before and after the administration of oral everolimus. RESULTS: Twenty-one patients being treated with oral everolimus were enrolled in this study. The mean age was 20.5 years (range 11-44 years, 4 males, and 17 females). The mean dose of oral everolimus was 3.6 mg/day. Clinically meaningful and statistically significant improvement was observed in erythema (p = 0.001), average lesion size (p < 0.001), lesion density (p < 0.001), and percent involvement (p < 0.001). Changes in the AGS findings were statistically significant on the forehead (p = 0.001), nose (p < 0.001) cheeks (p < 0.001), and chin (p = 0.004). CONCLUSION: Everolimus shows evident improvement and is approved for TSC-associated SEGAs and AMLs. The current study demonstrated the efficacy of oral everolimus in reducing facial angiofibromas, showing the parallel benefits of the treatment protocol for TSC.

Long-term risk of pneumothorax in asthmatic children: A 12-year population-based cohort study.

ABSTRACT: Pneumothorax is a life-threatening complication during acute asthma attack. However, long-term risk of pneumothorax in asthmatic children remains unknown.In this retrospective cohort study, 333,657 children were defined as asthma cohort and a 1:1 matched non-asthma cohort were generated from 2000 to 2011. At the end of 2012, the incidence of pneumothorax in asthma and non-asthma cohorts and asthma to non-asthma hazard ratios (HRs) with confidence intervals (CIs) of pneumothorax were analyzed.The incidence of pneumothorax was 1.35-fold higher in the asthma cohort than that in the non-asthma cohort. The asthma to non-asthma HRs of pneumothorax were higher in children younger than 6 years (1.76, 95% CI: 1.21-2.57) and in girls (2.27; 95% CI: 1.23-4.16). The HRs of pneumothorax were higher in asthmatic children with more asthma-related out-patient clinic visits/per year (>5 visits; HR: 2.81; 95% CI: 1.79-4.42), more emergency department visits/per year (>4 visits; HR: 1.68; 95% CI: 1.02-2.78), and longer hospitalization days due to asthma (>4 days; HR: 3.42; 95% CI: 1.52-6.94) (P < .0001, the trend test).Asthmatic children had greater risk for pneumothorax, particularly in young children and in those with severe and uncontrolled asthma.

Long-Term Ambient Air Pollutant Exposure and Risk of Recurrent Headache in Children: A 12-Year Cohort Study.

Although studies have suggested environmental factors to be triggers of headache, the contribution of long-term air pollution exposure to recurrent headaches is poorly understood. Hence, we executed this nationwide cohort study to investigate associations between levels of ambient air pollutants and risks of recurrent headaches in children in Taiwan from 2000 to 2012. We used data from the Taiwan National Health Insurance Research Database and linked them to the Taiwan Air Quality Monitoring Database. Overall, 218,008 children aged < 18 were identified from 1 January 2000, and then followed until they were diagnosed by a physician for ≥3 times with recurrent headaches or until 31 December 2012. We categorized the annual average concentration of each air pollutant (fine particulate matter, total hydrocarbon, methane, sulfur dioxide, and nitrogen dioxide) into quartiles (Q1-Q4). We measured the incidence rate, hazard ratios (HRs), and the corresponding 95% confidence intervals for recurrent headaches. stratified by the quartiles. A total of 28,037 children (12.9%) were identified with recurrent headaches. The incidence rate and adjusted HR for recurrent headaches increased with higher-level exposure of air pollutants, except sulfur dioxide. We herein demonstrate that long-term ambient air pollutant exposure might be a risk factor for childhood recurrent headaches.

PM2.5 and NOx exposure promote myopia: clinical evidence and experimental proof.

Myopia is caused by complex genetic and environmental factors. However, information regarding the effect of long-term exposure to air pollutants on the risk of development of myopia is lacking. We collected data from two linked databases: the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Air Quality-Monitoring Database (TAQMD). A total of 15,822 children (16.3%) were diagnosed with myopia within the cohort. The incidence rate of myopia increased with exposure to increasing concentrations of particulate matter (PM2.5) and nitrogen oxides (NOx), increasing from 15.8 to 24.5 and from 13.7 to 34.4, per 1000 person-years, respectively. The adjusted hazard ratio for myopia increased with elevated PM2.5 and NOx exposure concentrations in Q4 to 1.57 and 2.60, respectively, compared to those exposed to the corresponding concentrations in Q1. In the animal experiments, PM2.5 induced myopia in hamsters by enhancing inflammation and was inhibited by resveratrol treatment compared to the control group. The change in axial length in the PM2.5 group was 0.386 ± 0.069 mm versus 0.287 ± 0.086 mm in the control group and 0.257 ± 0.059 mm in the PM2.5 + resveratrol group. We provide both clinical and experimental correlations that exposure to ambient air pollutants is associated with the pathogenesis of myopia.

Correction: Risk of Obstructive Sleep Apnea in Adult Patients with Asthma: A Population-Based Cohort Study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0128461.].

Is Long-term Ambient Air Pollutant Exposure a Risk Factor for Irritable Bowel Syndrome in Children? A 12-year Longitudinal Cohort Study.

BACKGROUND/AIMS: Recent studies suggest that air pollution may play a role in gastrointestinal disorders. However, the effect of long-term exposure to air pollution on childhood irritable bowel syndrome (IBS) is unclear. Hence, we conducted a nationwide cohort study to investigate the association between long-term air pollution exposure and the incidence and risk of IBS in Taiwanese children during 2000-2012. METHODS: We collected data from the Taiwan National Health Insurance Research Database, linked to the Taiwan Air Quality-Monitoring Database according to the insurant living area and the air quality-monitoring station locations. Children < 18 years old, identified from January 1st, 2000, were followed-up until IBS diagnosis or December 31st, 2012. The daily average air pollutant concentrations were categorized into 4 quartile-based groups (Q1-Q4). We measured the incidence rate, hazard ratios (HRs), and 95% confidence intervals for IBS stratified by the quartiles of air pollutant concentration. RESULTS: A total of 3537 children (1.39%) were diagnosed with IBS within the cohort during the follow-up period. The incidence rate for IBS increased from 0.84 to 1.76, from 0.73 to 1.68, from 0.85 to 1.98, and from 0.52 to 3.22 per 1000 person-years, with increase in the carbon monoxide, nitrogen dioxide, non-methane hydrocarbon, and methane quartile (from Q1 to Q4) exposure concentration, respectively. The adjusted HR for IBS increased with elevated carbon monoxide, nitrogen dioxide, non-methane hydrocarbon, and methane exposure in Q4 to 1.98, 2.14, 2.19, and 5.87, respectively, compared with Q1. CONCLUSION: Long-term ambient air pollutant exposure is an environmental risk factor for childhood IBS.