Association of perfluoroalkyl substances with pulmonary function in adolescents (NHANES 2007-2012).

Perfluoroalkyl substances (PFASs) constitute an environmentally persistent and widespread class of anthropogenic chemicals that have been used in industrial and commercial applications in the USA and around the world. Animal studies suggested its toxic impact on lung development, but the adverse effect of PFAS exposure on childhood pulmonary function has not been clearly determined. We investigated the potential cross-sectional association of environmental PFAS exposures with pulmonary function in 765 adolescents aged 12-19 years from the US National Health and Nutrition Examination Survey (NHANES) 2007-2012. Exposure to PFASs was estimated by measuring serum concentrations, and pulmonary function was assessed by spirometry. Linear regression and weighted quantile sum (WQS) regression were performed to estimate the associations of individual chemicals and chemical mixtures with pulmonary function. Median concentrations of PFOA, PFOS, PFNA, and PFHxS (detection frequencies > 90%) were 2.70, 6.40, 0.98, and 1.51 ng/mL, respectively. No associations were found between the four individual congeners and Σ4PFASs and the pulmonary function measures in total adolescents. Sensitive analyses were further conducted stratified by age (12-15 and 16-19 years) and sex (boys and girls). In adolescents aged 12-15 years, PFNA was negatively associated with FEV1:FVC (p-trend = 0.007) and FEF25-75% (p-trend = 0.03) among girls, while PFNA was positively associated with FEV1: FVC (p-trend = 0.018) among boys. No associations were found among adolescents aged 16-19 years, either boys or girls. The aforementioned associations were confirmed when further applying WQS models, and PFNA was identified to be the most heavily weighing chemical. Our results suggested that environmental exposure to PFNA may affect pulmonary function among adolescents aged 12-15 years. Given the cross-sectional analysis and less consistent results, further replications of the association in large prospective cohort studies are warranted.

circEXOC5 promotes acute lung injury through the PTBP1/Skp2/Runx2 axis to activate autophagy.

To understand the pathogenesis of acute lung injury (ALI), we focused on circEXOC5, a significantly up-regulated circular RNA in ALI. Using the in vivo cecal ligation and puncture (CLP)-induced ALI mouse model and in vitro LPS-challenged mouse pulmonary microvascular endothelial cell (MPVEC) model, we examined the impacts of knockdown circEXOC5 on lung injury, inflammation, and autophagy. The regulation between circEXOC5, polypyrimidine tract-binding protein 1 (PTBP1), S-phase kinase-associated protein 2 (Skp2), and Runt-related transcription factor 2 (Runx2) was investigated by combining RNA immunoprecipitation, qRT-PCR, mRNA stability, and ubiquitination assays. The significance of PTBP1 in circEXOC5-induced ALI phenotypes was examined both in vitro and in vivo. circEXOC5 was up-regulated and associated with increased inflammation and activated autophagy in cecal ligation and puncture-induced ALI lung tissues and LPS-challenged MPVECs. Through the interaction with PTBP1, circEXOC5 accelerated Skp2 mRNA decay, an E3 ubiquitin ligase for Runx2, and therefore increased Runx2 expression. Functionally, overexpressing PTBP1 reversed shcircEXOC5-inhibited ALI, inflammation, or autophagy. The signaling cascade circEXOC5/PTBP1/Skp2/Runx2, by essentially regulating inflammation and autophagy in MPVECs, aggravates sepsis-induced ALI.

Validation of the accuracy of the childhood asthma model for clinical decision support: a study protocol.

BACKGROUND: In China, the average prevalence of asthma in children aged 0-14 years increased by approximately 50% every 10 years. Hence, a specific decision support system that fits China's situation is needed for childhood asthma. This prospective, multicenter, observational study aims to assess the accuracy of the Childhood Asthma Model for Clinical Decision Support (CAMCDS) in clinical practice in four hospitals in Shanghai in China. METHODS: The study will be conducted in two phases. Phase I of the study aims to evaluate the accuracy of the CAMCDS for diagnosis, while phase II of the study aims to examine the treatment predicting accuracy of the CAMCDS model. In total, 817 children diagnosed with stable asthma and 545 suspected asthma will be enrolled. The accuracy of the CAMCDS model will be calculated using the receiver operating characteristic (ROC) curve compared with the results of pediatrician's diagnosis. Besides, the treatment patterns from CAMCDS and real-world environment for Chinese children with stable asthma will be assessed, and the factors that affect the CAMCDS implementation in routine clinical practice will be explored. CONCLUSIONS: This will be the first study to examine the diagnostic accuracy and treatment predicting accuracy of a clinical decision support system in children with asthma in China. We hope that the CAMCDS will be help pediatricians in basic-level hospitals to improve the diagnosis and treatment strategy of asthma. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100045283.

Clinical Predictors of Wheezing Among Children Infected With Mycoplasma Pneumoniae.

Background: Mycoplasma pneumoniae (MP) not only was a common pathogen of respiratory tract infections, but also could trigger the exacerbation of asthmatic symptoms in children with or without asthma. Objective: This study aimed to identify possible risk factors associated with wheezing among children diagnosed with MP infection. Methods: A retrospective analysis of medical records of children aged 28 days to 18 years old who visited the Shanghai Children's Hospital between January 2019 and January 2020 was carried out, and all children were then classified into three groups: two wheezing groups (with or without MP infection) and a non-wheezing group with MP infection. Information including patient's demographics, clinical features, laboratory data, and radiography findings was extracted from the electronic medical record system. Chest radiographs were reviewed independently by two board-certified, blinded pediatric radiologists. Results: A total of 1,512 patients were included in our study, and 21.9% of them belonged to the wheezing group without MP infection. Among 1,181 patients with MP infection, 295 people (25.0%) suffered from wheezing, and males accounted for 61%. Through the multivariable logistic regression analyses, we found that six variables were positively associated with wheezing attacks in children with MP infection: male gender (likelihood ratio [LR] = 2.124, 95% confidence interval [CI]: 1.478-3.053), history of allergy (LR= 3.301, 95% CI: 2.206-4.941), history of wheezing (LR = 7.808, 95% CI: 5.276-11.557), autumn in reference to summer (LR = 2.414, 95% CI: 1.500-3.885), non-end-point infiltration in reference to consolidation or pleural effusion (LR = 1.982, 95% CI: 1.348-2.914), and infiltration scope (LR = 1.773, 95% CI: 1.293-2.432). However, the model showed that the probability of wheezing after MP infection decreased as age increased (LR = 0.257, 95% CI: 0.196-0.337). Moreover, the area under the curve (AUC) of the regression model was as high as 0.901 (0.847-0.955). Conclusion: The model integrated with factors including gender, age, season, radiological patterns, infiltration scope, and history of allergy performed well in predicting wheezing attack after MP infection in children.

Inhaled Budesonide vis-à-vis Inhaled Mometasone in Chinese Children with Mild Persistent Asthma: A Single-Center, Retrospective Study.

INTRODUCTION: A very limited option of inhaled corticosteroids (ICSs) is approved for pediatric use in China because in children the use of ICSs for long periods is associated with dose-dependent growth reduction. Due to the lack of consensus on which is the best ICS-based treatment option to manage mild persistent asthma in children, the present study was performed to evaluate the efficacy and safety of budesonide (BUD)-based therapy vis-à-vis mometasone-based therapy in children with mild persistent asthma. METHODS: A single-center, retrospective study was conducted in asthmatic children aged between 6 and 11 years. BUD and mometasone furoate (MF) were administered as per the approved dosing regimen using pressurized metered-dose inhalers via oral inhalation route for a period of 12 weeks. The study outcome was assessed in terms of the forced expiratory volume in 1 s (FEV1), symptom scores, and nonoccurrence of side effects. RESULTS: Among the 77 asthmatic children, 71 completed the study treatment and were used in carrying out the analysis. The improvement of spirometric parameters like FEV1, Tiffeneau-Pinelli index (FEV1/forced vital capacity [FVC]), and peak expiratory flow (PEF) values observed in the MF cohort was significantly greater than those of the BUD cohort (p < 0.05 for all). An increase of approximately 12%/child was observed for FEV1/FVC ratios for the BUD cohort and MF cohorts. After the 12-week study, the PEFm and PEFe values increased to about 50 L/min/child for the BUD cohort and about 98 L/min/child for the MF cohort. During the study, no asthma exacerbation event was observed in the MF cohort, whereas 1 child in the BUD cohort had asthma exacerbation in week 4. The use of rescue medication during the study was required for 16.2 and 6% of children, respectively, for BUD and MF cohorts. Owing to low dosing frequency, MF could provide a better treatment approach than BUD due to improved patient compliance. CONCLUSIONS: Although both drugs showed improvement in the quality of life of asthmatic children with manageable treatment-emergent adverse effects, the improvement was augmented in MF-treated children. LEVEL OF EVIDENCE: The level of evidence was III. Technical Efficacy Stage: The technical efficacy stage was 4.

Long noncoding RNA LINC-PINT retards the abnormal growth of airway smooth muscle cells via regulating the microRNA-26a-5p/PTEN axis in asthma.

BACKGROUND: Asthma is a chronic respiratory disease worldwide. This study aimed to explore the functions of the long noncoding RNA LINC-PINT (LINC-PINT) in asthma and to determine its underlying molecular mechanisms. METHODS: Rat asthma model was established with ovalbumin sensitization and challenge. The serum level of IgE, airway hyperresponsiveness (AHR), airway inflammation, and pathological changes of lung were evaluated. Airway smooth muscle cells (ASMCs) were stimulated with platelet-derived growth factor-BB (PDGF-BB) to mimic the asthma-like condition at cellular level. QRT-PCR was performed to detect the expression of LINC-PINT, microRNA-26a-5p (miR-26a-5p), and PTEN. MTT and transwell assays were performed to measure the viability and migration of ASMCs. The protein expression of airway remodelling marker MMP-1 and MMP-9 was measured by western blot. The interactions among LINC-PINT, miR-26a-5p, and PTEN were determined by dual-luciferase reporter assay. RESULTS: The expression of LINC-PINT and PTEN was decreased, while miR-26a-5p expression was increased in PDGF-BB-stimulated ASMCs. In vivo, overexpression of LINC-PINT decreased the serum level of IgE, AHR, airway inflammation, and pathological changes of lung in asthma rat model. In vitro, up-regulation of LINC-PINT decreased the viability, migration, and MMP-1 and MMP-9 protein expression in PDGF-BB-stimulated ASMCs. Dual-luciferase reporter assay determined that LINC-PINT targeted miR-26a-5p, and miR-26a-5p targeted PTEN in ASMCs. Feedback approaches confirmed that miR-26a-5p up-regulation or PTEN down-regulation reversed the suppressive effect of LINC-PINT overexpression on the abnormal growth of ASMCs. CONCLUSIONS: LINC-PINT overexpression retarded the abnormal growth of ASMCs by regulating the miR-26a-5p/PTEN axis, offering a potential therapeutic target for asthma.

Urinary 3-phenoxybenzoic acid (3-PBA) concentration and pulmonary function in children: A National Health and Nutrition Examination Survey (NHANES) 2007-2012 analysis.

Epidemiological studies have reported association of urinary 3-phenoxybenzoic acid (3-PBA), a major metabolite of pyrethroid insecticides (PYRs), with respiratory disease. However, knowledge regarding its effect on pulmonary function in susceptible children is limited. This study aimed to assess the associations between environmental 3-PBA concentrations and pulmonary function in children aged 6-17 years. Using data on 1174 children aged 6-17 years from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007-2012, the exposure to PYRs was assessed by measuring urinary 3-PBA concentrations and pulmonary function was assessed by spirometry. Multivariable linear regression and generalized linear models (GLMs) were used to examine the associations between 3-PBA concentrations and pulmonary function in children, controlling for confounders. We found that 3-PBA concentrations were inversely associated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) in the pediatric population (p-trends < 0.05). When stratified by age (6-10 and 11-17 years) and gender (boys and girls), the adverse effects of PYR exposures on pulmonary function were more pronounced among boys aged 11-17 years. Among this age group, 3-PBA concentrations were negatively associated with FEV1, FVC, forced expiratory flow between 25% and 75% of FVC (FEF25-75%), and PEF. However, among children aged 6-10 years, no associations were found between 3-PBA concentrations and any of the pulmonary function measures, in either boys or girls. Our findings suggest that environmental PYR exposures may adversely affect children's pulmonary function, with the strongest associations among 11-17 years old boys.

Thyroid hormone concentrations in second trimester of gestation and birth outcomes in Shanghai, China.

BACKGROUND: Previous studies suggested that thyroid function in the first trimester of gestation played an important role in fetal growth. However, limited clinical data are available to support this relationship in the second trimester of gestation. OBJECTIVE: We examined the relationship of maternal thyroid function parameters in early second trimester of gestation with birth outcomes in China. METHODS: Participating 5016 mother-infant pairs were recruited from the Songjiang District Maternity and Infant Hospital, Shanghai, China, between July and December 2016. Linear regression assessed the associations of thyroid hormones with birthweight. Logistic regression tested the correlations between thyroid hormones and low birthweight, macrosomia, small for gestational age , and large for gestational age infants. Maternal serum TSH, TT3, TT4, FT3, and FT4 concentrations were measured in 16-20 weeks of gestation. RESULTS: TT3 and FT3 were positively associated with birthweight, while TT4 and FT4 were negatively associated with birthweight, respectively. Furthermore, higher TT3 and FT3 were associated with increased risks of LGA infants (OR = 1.48, 95% CI: 1.15-1.9; OR = 1.22, 95% CI: 1.01-1.46), respectively. Higher TT3 was associated with an increased risk of macrosomic infants (OR = 1.35, 95% CI: 1.04-1.74). In contrast, higher FT4 was associated with decreased risks of LGA (OR = 0.87, 95% CI: 0.81-0.93) and macrosomic infants (OR = 0.90, 95% CI: 0.84-0.96), respectively. No associations were found between TSH and any of the outcomes. CONCLUSIONS: TT3 and FT3 were positively associated with fetal growth, while TT4 and FT4 were negatively associated with fetal growth. Our findings suggested that thyroid function in early second trimester of gestation is a potential risk factor for abnormal fetal growth.

Bronchiectasis with secondary pulmonary infection in a child: A case report.

RATIONALE: Although bronchiectasis is conventionally considered a chronic pulmonary disease of adulthood, knowledge of pediatric bronchiectasis not related to cystic fibrosis started to emerge. Limited information in this field is available and the management is based on expert opinion. PATIENT CONCERNS: An 8-year-old girl admitted for 7 days history of wet cough, purulent fetid sputum, shortness of breath and low-grade fever. The wet cough has presented for the past 4 years, during which she had frequent hospitalization for recurrent lower respiratory tract infections. DIAGNOSIS: Chest high-resolution computerized tomography revealed diffuse bronchial dilations accompanied by inflammation in the bilateral lung fields. Microbiologic investigation for bronchoalveolar lavage fluid was positive for Pseudomonas aeruginosa. INTERVENTIONS: With a working diagnosis of bronchiectasis with secondary pulmonary infection, sensitive cefoperazone-sulbactam was administrated for 14 days with gradual improvement of clinical symptoms. Bronchoscopy washing substantially soothed the symptoms, reducing the cough and sputum volumes. OUTCOMES: The child was discharged after 14 days, and treated on long-term prophylactic antibiotic use (amoxicillin-clavulanic acid, 20 mg/kg/d, ≥ 4 weeks). LESSONS: Although bronchiectasisis are condition in childhood, the diagnosis is suspected in children with persistent wet or productive cough, and should be confirmed by a chest high-resolution computerized tomography scan. Antibiotics and airway clearance techniques represent the milestones of bronchiectasis management although there are only a few guidelines in children.

Maternal preconception body mass index and time-to-pregnancy in Shanghai Women, China.

Previous studies suggested an association between female fertility and body size, but most of these studies were from Western countries and focused mainly on obesity. This study investigated the association between preconception body mass index (BMI) and time to pregnancy (TTP) in women planning to conceive from Shanghai, China. A total of 1,182 women aged 24-46 years were recruited from the Shanghai Birth Cohort between 2013 and 2015 and were followed up for 12 months. Preconception BMI was categorized as underweight, normal weight, and overweight/obesity according to the Chinese classification of BMI. Fecundability (FOR) and infertility (IOR) odds ratios were estimated using Cox (n = 1,092) and Logistic (n = 820) regression models, respectively. We found no differences in fecundability between underweight and overweight/obese women and normal-weight women. Furthermore, underweight and overweight/obese women did not have a higher risk of infertility compared with normal-weight women. Our findings suggest that non-optimal preconception BMI does not appear to influence female fecundability and infertility in Chinese women. These results should be interpreted with caution as they may be applicable only to women with demographic and anthropometric characteristics similar to our study population. Our findings need to be confirmed in other populations.

Tracheobronchial foreign body aspiration in children: A retrospective single-center cross-sectional study.

Foreign body (FB) aspiration is a common and serious problem in childhood as it requires early recognition and treatment to avoid potentially lethal consequences. This study aimed to characterize the clinical and epidemiological features of airway FBs in a pediatric Chinese population.A retrospective review of medical records of children aged 0 to 14 years who attended with a diagnosis of FB aspiration the Shanghai Children's Hospital between January 2013 and December 2017 was carried out. Descriptive analysis was used to assess patient's demographics, clinical, radiographic, bronchoscopic findings, time to presentation, and characteristics of the FBs.Among the 200 patients included in the study, 92% were under 3 years of age, with a peak incidence of FB aspiration occurring between 1 and 2 years old. The male to female ratio was about 2.6:1. Twenty-three percent of the patients were admitted within 24 hours of the event, 40% within 1 week, 30% within 1 month, and 7% more than 1 month after aspiration. The most common presenting symptoms of laryngotracheal FBs were cough, dyspnea, and wheezing; those of bronchial FBs were cough, decreased air entry, and wheezing. Chest X-ray was normal in four-fifths of the children with laryngotracheal FBs, whereas most common abnormal X-ray findings in children with bronchial FBs were mediastinal shift, obstructive emphysema, and pneumonia. There was a trend that in children younger than 2 years FBs were more frequently found in the left bronchus, whereas in older children FBs were more frequently found in the right bronchus. Ninety-three percent of the removed FBs were organic materials such as food items and the most frequently aspirated FBs were peanuts. Flexible bronchoscopy was performed in 82.5% of the patients, while rigid bronchoscopy or direct laryngoscopy in 17.5% of the patients. Four patients were subjected to thoracic surgery and 1 died during rigid bronchoscopy due to acute respiratory failure.FBs is a frequent pathology among Chinese children. Tracheobronchial FBs should be strongly suspected in young children who have sudden onset of cough and wheezing episode, even when physical and radiographic evidence is absent.

No Associations Between Serum Lipid Levels or HOMA-IR and Asthma in Children and Adolescents: A NHANES Analysis

Objective: Studies have reported inconsistent results on the associations between lipids and insulin resistance (IR) and asthma. The purpose of this study was to examine the associations between abnormal serum lipid levels and homeostatic model assessment-IR (HOMA-IR) and the presence of current asthma in children and adolescents. Methods: The United States National Health and Nutrition Examination Survey database from 1999 to 2012 was randomly searched for children (aged 3-11 years) and adolescents (aged 12-19 years) with and without asthma and with complete demographic and clinical data of interest. Logistic regression analyses were performed to examine associations between abnormal serum lipids, glucose and HOMA-IR and the current presence of asthma. Results: The data of 11,662 children (3 to 11 years of age) and 12,179 adolescents (12 to 19 years of age) were included in the analysis. The study group included 3,703 participants with asthma and 20,138 participants without asthma. The prevalence of self-reported current asthma was higher among participants aged between 3-11 years (52.9%) than among those aged between 12-19 years (50.7%). Multivariate analyses, after adjusting for sex, race, income-to-poverty ratio, low birth weight, prenatal maternal smoking, tobacco exposure, C-reactive protein level and body mass index Z-score, revealed no associations between elevated fasting plasma glucose, reduced high-density lipoprotein cholesterol, elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides and HOMA-IR and the presence of current asthma in children or adolescents. Conclusion: In this cross-sectional study, no association was found between abnormal serum lipids or HOMA-IR and the presence of current asthma in children or adolescents.

FeNO and asthma treatment in children: a systematic review and meta-analysis.

Traditional asthma treatments are typically adjusted in children with asthma using symptoms and spirometry. Treatments tailored in accordance to inflammatory markers, such as fraction of exhaled nitric oxide (FeNO) or sputum eosinophils, are increasing in use. This meta-analysis evaluated the potential benefit of incorporating the use of monitoring FeNO with guideline-based management in treating children with asthma. PubMed and Cochrane CENTRAL databases were searched until November 2013 for randomized control trials that investigated the use of FeNO compared with conventional monitoring in managing asthma in children. Included studies had at least 2 intervention groups: one that utilized FeNO and the other that utilized only conventional or standard methods (eg, spirometry, symptoms, and others) to guide treatment. Six studies were included in the meta-analysis comprising 506 subjects whose treatment was monitored using FeNO and 511 subjects who were managed using conventional methods. We found no difference between the FeNO and the conventional groups in FeNO value (95% confidence interval [CI]: -0.31, 0.1), change from baseline in FEV1 (95% CI: -0.07, 0.20), or steroid use (95% CI: -0.67, 1.80). However, the FeNO group was associated with a lower frequency of >1 asthma exacerbation (95% CI: 0.532, 0.895). This meta-analysis suggests that using FeNO to guide treatment decisions has little clinical benefit, although may result in a decrease in asthma exacerbations. Our findings support the use of guideline-based asthma management and diagnosis.