Comorbid asthma is associated with rhinitis severity in children exposed to air pollutants.

BACKGROUND: The impact of asthma on the severity of rhinitis when children with allergic rhinitis (AR) are exposed to air pollutants has not been studied. METHODS: Children with AR (65 with asthma, 208 without asthma), aged 6-13 years, were recruited from a hospital in Taichung, Taiwan, between 2007 and 2011. Correlations between Pediatric-Rhinoconjunctivitis-Quality-of-Life score, nasal peak expiratory flow, and air pollutants were compared. With the same age, research time, and form the same city, children with AR (660 with asthma, 3174 without asthma) were selected from a database. Correlations between clinical visit times for AR and air pollutants were compared. RESULTS: In male children with AR and asthma, both clinical and database studies revealed a correlation between higher rhinitis discomfort (quality-of-life score), higher visit times for AR, and higher PM10, PM2.5, NO2, NMHC concentrations. Correlations between higher nasal inflammation/obstruction (lower expiratory flow) and higher air pollutant concentrations were observed in male children with AR and asthma. CONCLUSION: In children with AR, comorbid asthma was associated with increased rhinitis severity when they were exposed to air pollutants, and the association was only noted in males. Increased nasal obstruction/inflammation from exposure to air pollutants may be the mechanisms underlying this association. IMPACT STATEMENT: The influence of asthma on the severity of rhinitis when children with allergic rhinitis (AR) are exposed to air pollutants has not been studied. In children with AR, the correlation between higher rhinitis discomfort, higher number of clinical visits for AR, and higher PM10, PM2.5, NO2, NMHC concentrations were only noted in those who also had asthma. The correlation was only noted in male. Comorbid asthma was associated with higher rhinitis severity when children with AR are exposed to air pollutants The association was only noted in male.

Allergic rhinitis children with obesity are more vulnerable to air pollution: a cross sectional study.

The association between air pollution, allergic rhinitis (AR), and obesity has not been studied. From 2007 to 2011, 52 obese and 152 non-obese children (7-17 years old) with AR were recruited. Pediatric-Rhinoconjunctivitis-Quality-of-Life Questionnaire (PRQLQ) and nasal peak expiratory flow (NPEF) were tested. Association between the scores and rates of the two tests and mean air pollutant concentrations within 7 days before the tests were compared. When exposed to higher concentrations of CO, PM10, and PM2.5, the rates of worse nasal discomfort were 39.4%, 44.4% and 39.3% in obese children; and 18.0%, 21.9% and 19.7% in non-obese children, respectively. Compare to non-obese children, the rates in obese children were higher for CO (odds ratio (OR) 3.54, 95% confidence interval (CI) 1.15 ~ 10.92); PM10 (OR 3.26, 95% CI 1.01 ~ 10.57) and PM2.5 (OR 3.30; 95% CI 1.03 ~ 10.54). In obese children, correlations between higher concentrations of CO, PM10, PM2.5 and higher nasal discomfort (higher PRQLQ); and correlations between higher concentrations of CO, PM10, PM2.5, NMHC (non-methane hydrocarbon) and higher nasal mucosa inflammation (lower NPEF) were noted. Obesity negatively affected AR severity when AR children experienced higher concentrations of CO, PM10, and PM2.5. Increased nasal inflammation induced by air pollutants might be the underlying mechanism.

Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences. STUDY DESIGN: Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated. RESULTS: Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and methane (CH4) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH4. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO, NO2, nonmethane hydrocarbon, and CH4 exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH4. A positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO2, nonmethane hydrocarbon, CH4 exposure, and serum hemoglobin levels was noted in male newborns. CONCLUSION: Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.

Early Gut Microbiota Changes in Preterm Infants with Bronchopulmonary Dysplasia: A Pilot Case-Control Study.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is a complex chronic lung disease that primarily affects premature or critically ill infants. This pilot study investigated early changes in gut microbiota composition in BPD patients and explored the potential risk factors associated with these changes. STUDY DESIGN: Preterm infants admitted to our neonatal intensive care unit with a gestational age of 26 to 32 weeks were prospectively surveyed and eligible for stool collection on days 7 and 28 of postnatal age between February 2016 and June 2017. A 16S rRNA sequencing approach was applied to compare the gut microbiota composition between the BPD group and controls. Multiple linear regression analysis was used to identify the predictor variables. RESULTS: Eight subjects in the BPD group and 10 subjects in the preterm group were analyzed during the observation period. Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes were the four dominant bacteria phyla of intestinal microflora. A significantly lower diversity of gut microbiota was observed in the BPD group compared with the preterm group on day 28 (number of observed operational taxonomic units, p = 0.034; abundance-based coverage estimator, p = 0.022; Shannon index, p = 0.028). Multiple linear regression analysis revealed that high Neonatal Therapeutic Intervention Scoring System score (≧19) at 24 hours was statistically significant in predicting the proportion of aerobic with facultative anaerobic bacteria on day 28 (p = 0.002). CONCLUSION: Infants with BPD are prone to develop gut dysbiosis in early life. A higher severity of illness and treatment intensity may indicate a higher risk of disrupting an anaerobic environment in the gut during the first month of life. KEY POINTS: · BPD patients are prone to develop gut dysbiosis.. · Lower diversity of gut microbiota.. · Higher risk of disrupting anaerobic environment..

Lactobacillus Attenuate the Progression of Pancreatic Cancer Promoted by Porphyromonas Gingivalis in K-rasG12D Transgenic Mice.

Accumulating evidence suggests that there is a link between the host microbiome and pancreatic carcinogenesis, and that Porphyromonas gingivalis (P. gingivalis) increases the risk of developing pancreatic cancer. The aim of the current study was to clarify the role of P. gingivalis in the pathogenesis of pancreatic cancer and the potential immune modulatory effects of probiotics. The six-week-old LSL-K-rasG12D; Pdx-1-cre (KC) mice smeared P. gingivalis on the gums, causing pancreatic intraepithelial neoplasia (PanIN) after four weeks to be similar to the extent of lesions in untreated KC mice at 24 weeks. The oral inoculation of P. gingivalis of six-week-old LSL-K-rasG12D; Pdx-1-cre (KC) mice caused significantly pancreatic intraepithelial neoplasia (PanIN) after treatment four weeks is similar to the extent of lesions in untreated KC mice at 24 weeks. The pancreas weights of P. gingivalis plus probiotic-treated mice were significantly lower than the mice treated with P. gingivalis alone (P = 0.0028). The histological expressions of Snail-1, ZEB-1, collagen fibers, Galectin-3, and PD-L1 staining in the pancreas were also notably lower. In addition, probiotic administration reduced the histological expression of Smad3 and phosphorylated Smad3 in P. gingivalis treated KC mice. We demonstrated that oral exposure to P. gingivalis can accelerate the development of PanIN lesions. Probiotics are likely to have a beneficial effect by reducing cancer cell proliferation and viability, inhibiting PanIN progression, and cancer cell metastasis (Epithelial-mesenchymal transition, EMT). The transforming growth factor-ß signaling pathway may be involved in the tumor suppressive effects of probiotics.

The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine.

Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an adjuvant during chemotherapy for pancreatic cancer. An LSL-KrasG12D/--Pdx-1-Cre mouse model of pancreatic ductal adenocarcinoma (PDAC) was created to study the effects of using four-week multi-strain probiotics (Lactobacillus paracasei GMNL-133 and Lactobacillus reuteri GMNL-89) as an adjuvant therapy for controlling cancer progression. At 12 weeks of age, pancreatitis was induced in the mice by two intraperitoneal injection with caerulein (25 µg/kg 2 days apart). Over the next 4 weeks the mice were treated with intraperitoneal injections of gemcitabine in combination with the oral administration of probiotics. The pancreas was then harvested for analysis. Following caerulein treatment, the pancreases of the LSL-KrasG12D/--Pdx-1-Cre transgenic mice exhibited more extensive pancreatic intraepithelial neoplasia (PanIN) formation. Combined treatment with gemcitabine and probiotics revealed a lower grade of PanIN formation and a decrease in the expression of vimentin and Ki-67. Mice that received gemcitabine in combination with probiotics had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Notably, the use of high-dose probiotics alone without gemcitabine also had an inhibitory effect on PanIN changes and serum liver enzyme elevation. These findings suggest that probiotics are able to make standard chemotherapy more effective and could help improve the patient's tolerance of chemotherapy.

The Risk of Developing Constipation After Neonatal Necrotizing Enterocolitis.

Background: Neonatal necrotizing enterocolitis (NEC) is a complex and lethal inflammatory bowel necrosis that primarily affects premature infants. Gut dysbiosis has been implicated in the pathogenesis of NEC. We aim to assess the association between NEC and two other diseases in children, including allergic diseases and constipation, considered to be associated with the alterations in gut microbiota composition. Methods: This retrospective population-based cohort study was conducted using the Taiwan Birth Registration Database, Birth Certificate Application, and National Health Insurance Research Database to inter-link the medical claims of neonates and their mothers. A total of 2,650,634 delivery events were retrieved from 2005 to 2015. We identified a NEC cohort and selected a comparison cohort according to propensity score matching (1:1). Cox proportional hazard regression models were used to determine possible associations of predictors and to obtain adjusted hazard ratios (aHRs). Results: A total of 1,145 subjects in the NEC cohort and 1,145 subjects in the matched cohort were analyzed during the observation period. No significant difference was observed in the incidence of allergic diseases between the two groups. NEC patients had a significant 30.7% increased risk of developing constipation (aHR = 1.307; 95% CI 1.089-1.568). The cumulative incidence of constipation was significantly higher in the NEC cohort than in the matched cohort by the end of follow-up (log-rank test P = 0.003). Conclusion: Infants with NEC have a significantly higher incidence rate of developing constipation and FTT but no increased risk of allergic diseases.

Minimally invasive surfactant therapy versus intubation for surfactant administration in very low birth weight infants with respiratory distress syndrome.

BACKGROUND: Minimally invasive surfactant therapy (MIST) is a new mode of surfactant administration without intubation to spontaneously breathing preterm infants with respiratory distress syndrome (RDS). The aims of this study were to assess the feasibility, efficacy and safety of using MIST to give surfactant for very low birth weight (VLBW) infants with RDS. METHODS: In total, 53 VLBW infants who were born before 32 gestational weeks with spontaneous breathing, respiratory distress, and requiring surfactant therapy were divided into two groups. The infants in group A (n = 29) were intubated and received surfactant replacement therapy via endotracheal tube, followed by mechanical ventilation (MV). The infants in group B (n = 24) received tracheal instillation of surfactant via a semirigid vascular catheter during spontaneous breathing under nasal continuous positive airway pressure (nCPAP). After surfactant instillation, the infants in group B were still placed on nCPAP. RESULTS: Our data showed that infants in group B (MIST group) had significantly lower rate (P < 0.05) of composite outcome of death or bronchopulmonary dysplasia (BPD), duration of intermittent positive airway pressure ventilation (IPPV) or MV, drug treatment of patent ductus arteriosus (PDA), and surgical ligation of PDA than group A. CONCLUSION: MIST is feasible, safe and it may reduce the composite outcome of death or BPD for VLBW infants with RDS requiring surfactant replacement therapy.

Impact of Sjogren's syndrome on Parkinson's disease: A nationwide case-control study.

OBJECTIVE: To investigate whether Sjogren's syndrome would have an influence on the development of Parkinson's disease. METHODS: A population-based case-control study was conducted. Participants consisted of 7716 subjects with newly diagnosed Parkinson's disease and a population of 75129 matched control subjects between 2000 and 2010. We measured the risk of Parkinson's disease in association with Sjogren's syndrome by using adjusted odds ratios. RESULTS: A total of 143 Parkinson's disease subjects (1.9%) and 893 control subjects (1.2%) suffered from Sjogren's syndrome (p < 0.001). The crude odds ratio for Parkinson's disease among subjects with Sjogren's syndrome was 1.56 (95% CI 1.30-1.86; p < 0.01). After adjustment for potential confounders which have been proposed that would increase the risk of development of Parkinson's disease, Sjogren's syndrome was found to be significantly associated with the risk of Parkinson's disease with an odds ratio of 1.37 (95% CI 1.15-1.65; p < 0.01). CONCLUSION: This study preliminarily proposed that Sjogren's syndrome was significant associated with an increased risk of Parkinson's disease.

Association between allergic disease, sleep-disordered breathing, and childhood nocturnal enuresis: a population-based case-control study.

BACKGROUND: Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. METHODS: Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. RESULTS: A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. CONCLUSIONS: Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present.

Antimicrobial Resistance and Diagnostic Imaging in Infants Younger Than 2 Months Old Hospitalized With a First Febrile Urinary Tract Infection: A Population-based Comparative Study.

BACKGROUND: Data on urinary tract infection (UTI) in infants ≤2 months of age are limited. We examined clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes in infants ≤2 months of age and children 2-24 months of age hospitalized with the first febrile UTI. METHODS: Children ≤24 months of age hospitalized with their first-diagnosed febrile UTI were prospectively studied. Renal ultrasonography, Tc-dimercaptosuccinic acid scanning and voiding cystourethrography were performed in all children. RESULTS: Of the 388 children analyzed (255 boys and 133 girls), 61 patients were ≤2 months of age, representing 15.7% of the whole population, whereas 327 patients were 2-24 months of age. Escherichia coli was the predominant bacterium, with similar antimicrobial resistance in the 2 groups, and associated E. coli bacteremia occurred in 9 patients (2.3%). Renal ultrasonography showed abnormal findings in 130 patients (33.5%), but there was no difference in the rate of abnormal findings between the groups. Vesicoureteral reflux (VUR) was present in 130 children (33.5%), including 93 (24%) with grades III-V VUR. VUR was more prevalent in the infants ≤2 months of age (P = 0.007), but there was no difference in the prevalence of grades III-V VUR between the groups. The incidence of renal scarring was 28.6% (111/388), and it did not differ between the groups. CONCLUSIONS: There are similarities in clinical characteristics, antimicrobial resistance, imaging findings and clinical outcomes after a first UTI between the young infants ≤2 months and children 2-24 months of age. The same guidelines for the diagnosis and management after the first febrile UTI can be applied to children who are ≤24 months of age.

Faecal calprotectin as a novel biomarker for differentiating between inflammatory bowel disease and irritable bowel syndrome.

The present study aimed to investigate faecal calprotectin as a diagnostic marker to differentiate between patients with inflammatory bowel disease (IBD) and those with irritable bowel syndrome (IBS). A total of 20 healthy control subjects, 26 patients with IBS and 58 patients with IBD, including 22 with ulcerative colitis (UC) and 36 with Crohn's disease (CD), were recruited for the present study. Calprotectin was analysed in stool samples, and C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were assessed in blood samples. CRP and calprotectin levels, and the ESR were observed to be significantly higher in patients with CD and UC compared with those of the healthy control subjects (P<0.0001). Furthermore, in patients with IBD and IBS, significant increases in faecal calprotectin and CRP levels were observed (694.8±685.0 µg/g in IBD vs. 85.8±136.1 µg/g in IBS and 0.851±1.200 mg/dl in IBD vs. 0.16±0.23 mg/dl in IBS, respectively; P<0.0001). Area under the receiver operating characteristic curve analysis revealed that, in patients with IBD, the levels of faecal calprotectin [0.931±0.029; 95% confidence interval (CI), 0.874­0.987] were significantly higher than that of CRP (0.865±0.041; 95% CI, 0.785­0.946) and the ESR (0.869±0.042; 95% CI, 0.786­0.952). These findings indicate that faecal calprotectin may represent a novel biomarker for diagnosing IBD and may be effective in distinguishing between IBD and IBS.

Association between the growth rate of renal cysts/angiomyolipomas and age in the patients with tuberous sclerosis complex.

PURPOSE: Renal manifestations of tuberous sclerosis complex (TSC) occur with a high frequency and a wide range of severity. The onset and complications of each affected organ depend on the age. This study aimed to investigate the associations between comorbidities, frequency, and size of cysts/angiomyolipomas of TSC and the patients in the different ages. METHODS: We performed a systematic evaluation of patients with TSC at integrated clinics for TSC. The patients were diagnosed with TSC according to Roach's clinical diagnostic criteria. All the patients underwent a systematic evaluation with a medical history review, recording of cutaneous manifestations, magnetic resonance imaging of the brain, chest computed tomography scan, and cardiac echography. Each patient was routinely evaluated with renal magnetic resonance imaging. RESULTS: Of the 57 patients with TSC, renal lesions or manifestations were observed in 38.5 % at preschool-age group (<6 years) that increased to 75.0, 85.7, and 100 % in school-age group (6-18 years), young adulthood group (18-30 years), and middle-aged group >30 years, respectively. Renal complications or interventions were found in 72.7 % of patients >30 years. There was a strongly positive association between the size of renal lesions and age (p < 0.001). Comorbidities of TSC were significantly correlated with pulmonary lymphangiomyomatosis (p < 0.001) and seizure remission (p = 0.018). CONCLUSIONS: The results indicate a positive association of progressively growing renal lesions in patients with TSC with increasing age. It is mandatory for clinicians that monitor the high-risk patients to minimize and prevent renal complications in the future.

Clinical characteristics and outcome in norovirus gastroenteritis.

OBJECTIVE: To examine differences in clinical characteristics among children with norovirus, rotavirus, and bacterial gastroenteritis and investigate the outcomes in children with sporadic norovirus gastroenteritis. METHODS: The study included patients aged 4 mo to 14 y who had acute gastroenteritis and were admitted to a tertiary care center between April 2008 and July 2009. The clinical features and laboratory findings of acute gastroenteritis were recorded. Fecal specimens were collected and tested for viruses, bacteria, and parasites. RESULTS: A total of 198 children (median age, 2.1 y) with acute gastroenteritis were studied. The pathogens identified included norovirus (n = 38), rotavirus (n = 47), adenovirus (n = 5), astrovirus (n = 1), bacteria (n = 43), and mixed infections (n = 7). No causative organisms were identified in 57 patients. The norovirus-infected group had a significantly higher proportion of those still vomiting 1 d after the onset of vomiting (p < 0.001, OR 5.0, 95 % CI 1.9-12.8), cessation of diarrhea 4 d after the onset of diarrhea (p < 0.001, OR 15.5, 95 % CI 5.1-47.0) and no fever 3 d after the onset of fever (p < 0.001, OR 27.5, 95 % CI 5.8-129.7) compared with the bacteria-infected group. The length of hospital stay of the norovirus-infected patients was positively correlated with the number of diarrhea episodes, duration of diarrhea, and severity score. CONCLUSIONS: The clinical manifestations on the day after onset of diarrhea, vomiting and fever reflected the occurrence of norovirus infection in children with sporadic gastroenteritis.

Neurological images and the predictors for neurological sequelae of epidemic herpangina/hand-foot-mouth disease with encephalomyelitis.

Since 1998 in Taiwan, enterovirus (EV) 71 epidemics have caused encephalomyelitis and placed a significant burden on parents and physicians. In this study, we present clinical manifestations, magnetic resonance (MR) imaging findings, and neurological sequelae on epidemic EV-infected patients with encephalomyelitis. Of the 46 patients, 14 patients presented with neurological sequelae; of them, 3 patients suffered from complications of mental regression. Predictors of unfavorable neurological sequelae were myoclonic jerks (> 4 times/night) and pleocytosis (167/µL) of the cerebrospinal fluid (CSF). Results from viral culture and MR imaging indicated that positive identification of EV71 infection was associated significantly with lesions on MR imaging. Our results show that hand-foot-mouth disease carries a higher risk of encephalomyelitis and that frequent myoclonic jerks and pleocytosis of the CSF are risk factors for subsequent neurological sequelae. Positive identification of EV71 might be useful as a predictor of lesions in MR imaging.

Normal uricemia in Lesch-Nyhan syndrome and the association with pulmonary embolism in a young child-a case report and literature review.

Deficiency of hypoxanthine phosphoribosyltransferase activity is a rare inborn error of purine metabolism with subsequent uric acid overproduction and neurologic presentations. The diagnosis of Lesch-Nyhan syndrome (LNS) is frequently delayed until self-mutilation becomes evident. We report the case of a boy aged 1 year and 10 months who was diagnosed with profound global developmental delay, persistent chorea, and compulsive self-mutilation since the age of 1 year. Serial serum uric acid levels showed normal uric acid level, and the spot urine uric acid/creatinine ratio was >2. The hypoxanthine phosphoribosyltransferase cDNA showed the deletion of exon 6, and the boy was subsequently diagnosed to have LNS. He also had respiratory distress due to pulmonary embolism documented by chest computed tomography scan. This report highlights the need to determine the uric acid/creatinine ratio caused by increased renal clearance in LNS in young children. The presence of pulmonary embolism is unusual and may be the consequence of prolonged immobilization.