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Importance: Recurrent respiratory tract infection (RRTI) is common in children. Inappropriate RRTI treatment will lead to asthma and other diseases, thereby seriously affecting the growth and physical health of children. Immune function modulation can prevent and alleviate childhood RRTI. Yupingfeng (YPF), a patented traditional Chinese medicine (TCM), has immunomodulatory effects and is widely used in China to treat children with RRTI. Objective: To evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI. Methods: This multicenter, randomized, double‐blind, double‐simulation, noninferiority clinical trial was conducted from January 2015 to August 2017, with an 8‐week treatment period and 52‐week follow‐up after the drug withdrawal. Children aged 2–6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups (2:2:1 ratio) to receive YPF, pidotimod, or placebo. The primary outcome was the proportion of RRTI returning to normal standard level during the follow‐up. The secondary outcomes were reduction in the number of RRTI recurrences, effect on clinical symptoms (in accord with TCM practice), effect per symptom, and safety. The trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn) under the unique identifier ChiCTR‐IPR‐15006847. Results: Three hundred and fifty‐one children were enrolled and randomly assigned to 3 groups; 124, 125, and 61 children in the YPF, pidotimod, and placebo groups, respectively, had completed the trial. During the follow‐up, the proportion of RRTI returning to normal standard level was 73.13%, 67.15%, and 38.81% with YPF, pidotimod, and placebo, respectively (P < 0.0001). The proportion of cases who returned to normal standard level in the YPF group was 34.32% higher than that in the placebo group. The safety profile did not significantly differ among the groups. Interpretation: YPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children, and were superior to placebo, with a high safety profile. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HAdVs) are important pathogens causing respiratory infections; 3.5–11% of childhood community-acquired pneumonia is associated with HAdV infection. Human adenovirus type 3 (HAdV-3), leading to severe morbidity and mortality, is one of the most prevalent genotype among adenoviruses responsible for acute respiratory infections (ARIs) in children in China. To identify the genetic variation of HAdV-3 in children with ARIs in China, a molecular epidemiological study was conducted. A total of 54 HAdV-3 isolated strains were obtained from children with ARIs in Beijing, Wenzhou, Shanghai, Shijiazhuang, Hangzhou, Guangzhou, and Changchun from 2014 to 2018. Thirty-two strains of which were selected for whole-genome sequencing, while the hexon, penton base, and fiber genes were sequenced for remaining strains. Bioinformatics analysis was performed on the obtained sequences. The phylogenetic analyses based on whole-genome sequences, major capsid protein genes (hexon, penton base, and fiber), and early genes (E1, E2, E3, and E4) showed that the HAdV-3 strains obtained in this study always clustered together with the reference strains from Chinese mainland, while the HAdV-3 prototype strain formed a cluster independently. Compared with the prototype strain, all strains possessed nine amino acid (AA) substitutions at neutralization antigenic epitopes of hexon. The homology models of the hexon protein of the HAdV-3 prototype and strain BJ20160214 showed that there was no evident structural change at the AA mutation sites. Two AA substitutions were found at the Arg-Gly-Asp (RGD) loop and hypervariable region 1 (HVR1) region of the penton base. A distinct AA insertion (20P) in the highly conserved PPPSY motif of the penton base that had never been reported before was observed. Recombination analysis indicated that partial regions of protein IIIa precursor, penton base, and protein VII precursor genes among all HAdV-3 strains in this study were from HAdV-7. This study showed that the genomes of the HAdV-3 strains in China were highly homologous. Some AA mutations were found at antigenic sites; however, the significance needs further study. Our data demonstrated the molecular characteristics of HAdV-3 circulating in China and was highly beneficial for further epidemiological exploration and the development of vaccines and drugs against HAdV-3. [ABSTRACT FROM AUTHOR]

Background: Our previous study has developed a four‐gene model involving IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 associated with asthma and atopy in Chinese Han children. However, whether the gene model is associated with allergies in early life has yet to be determined. This study aimed to apply the gene model in a birth cohort to investigate its associations with the development of allergic diseases in Chinese Han toddlers. Methods: Five hundred and ninety‐seven children from a birth cohort completing 2‐year follow‐up were included. Epidemiologic information and cord blood were collected. Children were genotyped for the above polymorphisms and divided into high or low genetic risk groups based on the genotypes. Subjects were followed at 6, 12, and 24 months, with information on allergic diseases collected via standard questionnaires and assessed by specialists. Results: Two hundred and eighty‐four children were divided into a high‐risk group and 313 into a low‐risk group. Between the two groups, a significant difference was only found in delivery mode among all the subject characteristics (p =.025). After stratification for delivery mode, children at high risk were more likely to develop eczema (relative risk [RR] = 1.46, p =.040) over 2 years of follow‐up compared with those at low risk. No significant associations were found between genetic risk and food allergy, wheezing and allergic rhinitis (p >.05). Conclusion: The gene model was significantly associated with the development of eczema in Chinese Han toddlers. Long‐term follow‐up along with functional and replication studies on the gene model are still needed in future. [ABSTRACT FROM AUTHOR]

Objective: With increased industrialization and urbanization in China, pediatric asthma is becoming more prevalent. Despite a growing body of evidence, there remains a significant unmet need for adequate management of childhood asthma. The Subspecialty Group of Respiratory Diseases of the Society of Pediatrics, the Chinese Medical Association, and the editorial board of the Chinese Journal of Pediatrics have recently updated the "Guidelines for diagnosis and optimal management of asthma in children," first published in 2008. Methods: This article reviews the major updates to the guidelines and covers the main recommendations for diagnosis, assessment, and treatment of pediatric asthma in China. Key regional data on epidemiology, clinical features, disease burden, knowledge among children and parents, and risk factors including pollution are provided to contextualize the recommendations. Results: The major updates to the guidelines include: (1) A more practical definition of asthma; (2) assessment of asthma control that takes into account both current symptom control and future risk; (3) classification based on disease severity that corresponds with treatment step; (4) differentiation between difficult-to-treat and poorly controlled asthma; (5) an open-ended approach to pharmacological management; and (6) allergen immunotherapy (AIT) in mild- to moderate-persistent asthma. Conclusions: The updated "Guidelines for the diagnosis and optimal management of asthma in children (2016)" combine the latest national and international clinical evidence and experience to provide practical and reliable recommendations to Chinese clinicians. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a chronic inflammatory airway disease that can be aggravated by cold air. However, its mechanism remains largely unknown. As a thermo-sensing cation channel, transient receptor potential melastatin 8 (TRPM8) can be activated by cold stimuli (8-22 °C) and cooling agents. Whereas TRPM8 activation leads to enhanced expression of inflammatory cytokines and mucus hypersecretion in human bronchial epithelial cell lines, no previous study has examined its role in regulating the cold-induced inflammatory responses and its mechanism in asthmatic airway epithelium. Airway epithelial cells were isolated from asthma model mice and exposed to low temperature (18 °C). The TRPM8 overexpression plasmid and siRNA lentivirus were transfected to up- or downregulate the TRPM8 level. The expression of mRNAs of inflammatory cytokines was tested using real-time reverse transcription-polymerase chain reaction (RT-PCR). The activities of phosphorylated protein kinase C (PKC) and phosphorylated inhibitor of nuclear factor kappa B (IκB) were measured using the immunofluorescence assay. The expression of mRNAs of inflammatory cytokines [interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-13, granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-α] increased significantly under cold conditions, which was boosted after TRPM8 overexpression and augmented further in the presence of PKC inhibitor, calphostin C. However, the downregulation of TRPM8 and nuclear factor kappa B (NF-κB) impaired the transcription of these cytokine genes. In addition, the phosphorylated PKC and phosphorylated IκB were activated by cold stimuli. Moreover, the expression of phosphorylated IκB protein improved in the presence of TRPM8, while disruption with the TRPM8 gene or TRPM8 antagonist prohibited the activation of IκB. Cold air could induce inflammatory responses through the TRPM8-mediated PKC/NF-κB signal pathway in primary airway epithelial cells of asthmatic mice. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that caesarean section (CS) may increase the risk of asthma in children, but none of them could preclude potential confounding effects of underlying medical indications for CS. We aim to assess the association between CS itself (without medical indications) and risk of childhood asthma. Methods: We conducted a hospital-based case-control study on childhood asthma with 573 cases and 812 controls in Shanghai. Unconditional logistic regression models in SAS were employed to control for potential confounders. Results: Our study found that CS without medical indication was significantly associated with elevated asthma risk (adjusted OR = 1.58 [95% CI 1.17–2.13]). However, this risk was attenuated in children fed by exclusive breastfeeding in the first six months after birth (adjusted OR = 1.39 [95% CI 0.92–2.10]). In contrast, the risk was more prominent in children with non-exclusive breastfeeding or bottle feeding (adjusted OR = 1.91 [95% CI 1.22–2.99]). Conclusions: CS without medical indication was associated with an increased risk of childhood asthma. Exclusive breastfeeding in infancy may attenuate this risk. [ABSTRACT FROM AUTHOR]

Epidemiological evidence suggests that formaldehyde (FA) exposure may influence the prevalence and severity of allergic asthma. However, the role of genetic background in FA-induced asthma-like responses is poorly understood. In the present study, we investigated the nature and severity of asthma-like responses triggered by exposure to different doses of FA together with or without ovalbumin (OVA) in two genetically different mouse strains—BALB/c and C57BL/6. Both mouse strains were divided into two main groups: the non-sensitized group and the OVA-sensitized group. All the groups were exposed to 0, 0.5 or 3.0 mg/m3 FA for 6 h/day over 25 consecutive days. At 24 h after the final FA exposure, the pulmonary parameters were evaluated. We found that FA exposure induced Th2-type allergic responses in non-sensitized BALB/c and C57BL/6 mice. In addition, FA-induced allergic responses were significantly more prominent in BALB/c mice than in C57BL/6 mice. In sensitized BALB/c mice, however, FA exposure suppressed the development of OVA-induced allergic responses. Exposure to 3.0 mg/m3 FA in sensitized C57BL/6 mice also led to suppressed allergic responses, whereas exposure to 0.5 mg/m3 FA resulted in exacerbated allergic responses to OVA. Our findings suggest that FA exposure can induce differential airway inflammation and bronchial hyperresponsiveness in BALB/c and C57BL/6 mice. [ABSTRACT FROM AUTHOR]

Background: Aspirin is widely used in general population and low-dose aspirin is commonly prescribed to prevent recurrent pregnancy loss associated with antiphospholipid syndrome and preeclampsia, often used throughout pregnancy. But aspirin is associated with asthma pathogenesis. We aim to examine whether in utero exposure to aspirin at different fetal stages is associated with asthma in childhood.Methods: We used data from the Collaborative Perinatal Project. Maternal exposure to aspirin before and during pregnancy was recorded at each prenatal visit. Children were followed up to 7 years of age. A total of 19,928 singleton children without maternal history of asthma were included. We used multilevel multiple logistic regression models to control for potential confounders.Results: In utero exposure to aspirin was associated with an increased risk of childhood asthma (adjusted odds ratio [aORs] = 1.3, 95% confidence interval [CI] = 1.1, 1.6). aORs for exposure in first, second, and third trimesters were 1.1 (95% CI = 0.87, 1.3), 1.2 (95% CI = 1.0, 1.4), and 1.4 (95% CI = 1.1, 1.6), respectively. Furthermore, aORs of asthma were 1.3 (95% CI = 1.0, 1.7) and 1.3 (95% CI = 1.0, 1.7) for aspirin use for 2 to 7 days or more than 7 days in third trimester, respectively.Conclusion: In utero exposure to therapeutic dose of aspirin even just briefly in late pregnancy is associated with childhood asthma by 7 years of age. More research is needed to carefully examine the association between low-dose aspirin with extended exposure period and long-term child outcomes. [ABSTRACT FROM AUTHOR]

Objective: Asthma afflicts many children in China but information about asthma management among Chinese pediatric asthma patients is limited. This study aims to evaluate asthma control among Chinese pediatric patients and identify risk factors associated with uncontrolled asthma.Methods: A total of 4223 patients with persistent asthma aged 2–16 years from 42 tertiary hospitals across all regions of mainland China except Tibet were surveyed. Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT) and Global Initiative for Asthma (GINA) criteria were used to assess asthma control for children aged 12–16 years, 4–11 years and 2–3 years, respectively. Uncontrolled asthma was defined as ACT or C-ACT score ≤19 or GINA-defined uncontrolled asthma. Risk factors associated with uncontrolled asthma were identified using multivariate logistic regression models.Results: Asthma was uncontrolled in 19.9% of the subjects. High rates of uncontrolled asthma were found in subjects with treatment non-adherence (44.1%), concomitant allergic rhinitis (AR) (23.3%), disease duration ≥ 1.5 years (22.8%), and first-degree relatives with AR (21.5%). The risk of uncontrolled asthma was much higher in the treatment non-adherence group compared to the complete adherence group (OR = 5.79,p< 0.001). Concomitant AR, disease duration ≥ 1.5 years, and first-degree relatives with AR were also confirmed as risk factors associated with uncontrolled asthma.Conclusions: About 20% of Chinese pediatric asthma patients had uncontrolled asthma. Treatment adherence and AR were the most significant risk factors. Tailored measures aimed at improving treatment adherence and diagnosis and treatment of AR should be adopted to improve the level of asthma control in Chinese children. [ABSTRACT FROM PUBLISHER]

Background: Recent meta-analyses indicate that children delivered by cesarean section have increased risk for asthma. However, the studies included in these previous meta-analyses showed significant heterogeneity. Furthermore, no previous meta-analysis has distinguished the association of elective and emergency CS, spontaneous and instrumental vaginal deliveries (VD) with the odds of asthma. Objective: To examine the association between specific mode of delivery and the prevalence of asthma. Methods: PUBMED, Google Scholar, EMBASE, and MEDLINE were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated from the prevalence of asthma in children born by elective CS, emergent CS, instrumental VD and spontaneous VD. Meta-analysis was then used to derive a combined OR. Heterogeneity between studies was also tested in the findings. Results: A total of 26 studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by CS (OR = 1.16, 95% CI 1.14, 1.29), and no evidence of heterogeneity was found ( I2 = 24.6%). Elective and emergency CS moderately increased the risk of asthma (OR = 1.21, 95% CI 1.17, 1.25; I2 = 39.9%; OR = 1.23, 95% CI 1.19-1.26). The risk of asthma was also higher in the children born by instrumental VD (OR = 1.07, 95% CI, 1.04-1.11) but with evidence of heterogeneity ( I2 = 54.9%). Conclusion: About 20% increase in the subsequent risk of asthma was both found in children delivered by elective and emergency CS. The increasing rates of CS worldwide might partly explain the concomitant rise in asthma during the same time period. [ABSTRACT FROM AUTHOR]

Abstract: China is now becoming the largest consumer of pesticides worldwide. In recent years, there has been a heightened public awareness of pesticides and children's health in North America and around the world. Human epidemiological studies have examined the relationship of pesticide exposures with children's health such as neurodevelopment and cancer, and they reported less consistent results. With regard to this topic, however, China is still in the early stages of cross-sectional or case–control design, and few data have been available. Furthermore, we have discussed several important limitations such as study design, exposure measurement, and developmental assessment from current literature, which should be interpreted with caution. We also presented the vulnerability and source of children's exposure to pesticides. [Copyright &y& Elsevier]

Manganese (Mn) exposure can affect brain development. Whether Selenium (Se) can protect neonates against neurotoxicity from Mn exposure remains unclear. We investigated this issue in 933 mother-newborn pairs in Shanghai, China, from 2008 through 2009. Umbilical cord serum concentrations of Mn and Se were measured and Neonatal Behavioral Neurological Assessment (NBNA) tests were conducted. The scores <37 were defined as the low NBNA. The median concentrations of cord serum Mn and Se were 4.0 µg/L and 63.1 µg/L, respectively. After adjusting for potential confounders, the interaction between Se and Mn was observed. Cord blood Mn levels had different effects on NBNA scores stratified by different cord blood Se levels. With Se

Background. Increasing research is available verifying that asthma is a familial and hereditary disorder of a complex of factors and genes. Objective. To investigate the single and combined associations of five single nucleotide polymorphism loci in three genes with the development of asthma in children of Chinese Han Nationality. Methods. A total of 192 children with asthma and an equal number of control subjects were recruited in this study. Asthma was diagnosed in accordance with American Thoracic Society criteria. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of the single nucleotide polymorphism loci. Results. No statistic differences (p > 0.05) were found between experimental and control group in genotype distribution among three loci (NOS1 C5266T, TGF-beta1 L10P, and TGF-beta1 R25P). However, a significant diversity was observed among IL4-RA Q551R (p = 0.004) and TGF-beta1 C-509T (p = 0.000). Furthermore, the frequency of IL4-RA Q551R A/G and TGF-beta1 C-509T C/T in the asthma group were significantly higher than those in the control group (OR = 1.91, P = 0.002; OR = 2.90, P = 0.000, respectively). The carriers of both IL4-RA Q551R A/G and TGF-beta1 C-509T C/T did not have a more significant risk of having asthma than those who covered either. Conclusion. The three loci (NOS1 C5266T, TGF-beta1 L10P and TGF-beta1 R25P) have little contribution to the development of childhood asthma in Chinese Han Nationality. IL4-RA Q551R and TGF-beta1 C-509T are single nucleotide polymorphism loci with significant association to childhood asthma, but they do not have synergistic effects. [ABSTRACT FROM AUTHOR]

Since late 2012, coxsackievirus A6 (CVA6) has gradually become the predominant pathogen responsible for hand-foot-mouth disease (HFMD) in several provinces of China. A total of 626 patients diagnosed with HFMD in Shanghai, China from January 2012 to September 2013 were enrolled in this study. Of these, 292 CVA6 infected cases were subjected to clinical analyses. Whole-genome sequencing, recombination and phylogenetic analyses were also performed. A recombinant CVA6 monophyletic lineage was found during an outbreak of CVA6-associated HFMDs in Shanghai, China in November 2012, and accounted for 21.9% (64/292) of the CVA6 strains during the study period. Recombination analyses showed that the 2C gene of the novel CVA6 virus was probably derived from a coxsackievirus A4 (CVA4) strain circulating in the population. Clinical observation showed that this recombinant CVA6 virus led to a more generalized rash than did the non-recombinant CVA6 virus. This newly emerged CVA6 lineage was associated with a considerable proportion of HFMD cases from 2012 to 2013 in Shanghai, and poses a potential threat to public health. [ABSTRACT FROM AUTHOR]

Asthma affects over 300 million people globally and is a cause of substantial burden of disease, including both premature death and reduced quality of life in people of all ages. Although both genetic and environmental factors play an important role in the pathogenesis of asthma, the rising trend of asthma and other allergic diseases over recent decades is thought to be largely caused by alteration in environmental conditions. Thus, a considerable amount of attention has been paid to environmental modification for the treatment and management of asthma, including household allergen reduction and/or irritant removal. More advanced environmental modification strategies (e.g., health resort medical rehabilitation, high-altitude climate therapy and multiple-hit interventions) have also been suggested. Research advances have been made over the past decades, but major challenges and opportunities coexist in this emerging field. Concerted efforts are required to tackle these formidable challenges. • Asthma is one of the most common chronic diseases in the world. • The prevalence of asthma has been rising in many countries over recent decades. • It is likely caused by alteration in environmental conditions. • Increasing attention is paid to environmental modification for asthma management. • Formidable challenges and great opportunities coexist in this emerging field. [ABSTRACT FROM AUTHOR]