Pathogenesis Of Childhood Asthma Research Articles

Identification of Hub Genes and Potential Biomarkers for Childhood Asthma by Utilizing an Established Bioinformatic Analysis Approach.

Childhood asthma represents a heterogeneous disease resulting from the interaction between genetic factors and environmental exposures. Currently, finding reliable biomarkers is necessary for the clinical management of childhood asthma. However, only a few biomarkers are being used in clinical practice in the pediatric population. In the long run, new biomarkers for asthma in children are required and would help direct therapy approaches. This study aims to identify potential childhood asthma biomarkers using a genetic-driven biomarkers approach. Herein, childhood asthma-associated Single Nucleotide Polymorphisms (SNPs) were utilized from the GWAS database to drive and facilitate the biomarker of childhood asthma. We uncovered 466 childhood asthma-associated loci by extending to proximal SNPs based on r2 > 0.8 in Asian populations and utilizing HaploReg version 4.1 to determine 393 childhood asthma risk genes. Next, the functional roles of these genes were subsequently investigated using Gene Ontology (GO) term enrichment analysis, a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and a protein–protein interaction (PPI) network. MCODE and CytoHubba are two Cytoscape plugins utilized to find biomarker genes from functional networks created using childhood asthma risk genes. Intriguingly, 10 hub genes (IL6, IL4, IL2, IL13, PTPRC, IL5, IL33, TBX21, IL2RA, and STAT6) were successfully identified and may have been identified to play a potential role in the pathogenesis of childhood asthma. Among 10 hub genes, we strongly suggest IL6 and IL4 as prospective childhood asthma biomarkers since both of these biomarkers achieved a high systemic score in Cytohubba’s MCC algorithm. In summary, this study offers a valuable genetic-driven biomarker approach to facilitate the potential biomarkers for asthma in children.

The Association of Prenatal C-Reactive Protein Levels With Childhood Asthma and Atopy

The pathogenesis of childhood asthma is complex, and determinants of risk may begin in utero. To describe the association of systemic prenatal inflammation, measured by plasma C-reactive protein (CRP), with childhood asthma, eczema, and allergic rhinitis. A total of 522 maternal-offspring pairs from the Vitamin D Antenatal Asthma Reduction Trial were included. Prenatal plasma CRP level was measured between 10 and 18 weeks of gestation and between 32 and 38 weeks of gestation. Offspring asthma, eczema, and allergic rhinitis were assessed quarterly between birth and age 6 years. We performed mediation analyses of prenatal CRP on the association between several maternal characteristics and offspring asthma. Elevated early and late prenatal CRP and an increase in CRP from early to late pregnancy were associated with asthma by age 6 years (early: adjusted odds ratio [aOR], 1.76, 95% CI, 1.12-2.82, P= .02; late: aOR, 2.45, 95% CI, 1.47-4.18, P < .001; CRP increase: aOR, 2.06, 95% CI, 1.26-3.39, P < .004). Prenatal CRP and childhood asthma associations were strengthened among offspring with atopic asthma (early: aOR, 3.78, 95% CI, 1.49-10.64, P= .008; late: aOR, 4.84, 95% CI, 1.68-15.50, P= .005; CRP increase: aOR, 3.01, 95% CI, 1.06-9.16, P=.04). Early and late prenatal CRP mediated 96% and 86% of the association between maternal prepregnancy body mass index and offspring asthma, respectively. Higher prenatal CRP and an increase in CRP from early to late pregnancy are associated with childhood asthma. Systemic inflammation during pregnancy associated with modifiable maternal characteristics may be an important determinant of childhood asthma risk.

Identification of potential key genes for immune infiltration in childhood asthma by data mining and biological validation.

Asthma is the most common chronic condition among children; however, the underlying molecular mechanism remains unclear. Dysregulated immune response and different infiltration states of immune cells are critical for asthma pathogenesis. Here, three childhood asthma gene expression datasets were used to detect key genes, immune cells, and pathways involved in childhood asthma. From these datasets, 33 common differentially expressed genes (DEGs) were identified, which showed enrichment in the T helper 1 (Th1) and T helper 2 (Th2) cell differentiation pathway and the T helper 17 (Th17) cell differentiation pathway. Using the weighted gene co-expression network analysis (WGCNA), CD3D and CD3G were identified as key genes closely correlated with childhood asthma. Upregulation of CD3D and CD3G was further validated in bronchoalveolar lavage cells from childhood asthmatics with control individuals by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The immune cell infiltration analysis indicated that CD3D and CD3G were negatively correlated with increased resting mast cells and eosinophils, and highly correlated with several cell markers of Th1, Th2, and Th17 cells. In addition, we found that CD3D and CD3G were closely related to the Th1 and Th2 cell differentiation pathway and the Th17 cell differentiation pathway. Our results reveal the important roles of two key genes and immune infiltration in the pathogenesis of childhood asthma. Thus, this study provides a new perspective for exploring potential molecular targets for childhood asthma treatment.

Altered Pattern of Macrophage Polarization as a Biomarker for Severity of Childhood Asthma.

PurposeAsthma causes a substantial morbidity and mortality burden in children and the pathogenesis of childhood asthma is not completely understood. Macrophages are heterogeneous with divergent M1/M2 polarization phenotypes in response to various stimulations during the inflammatory process. We aimed to investigate the pattern of macrophage polarization and its association with severity and exacerbation in asthmatic children.Patients and MethodsNormal and asthmatic children aged 4–18 years were enrolled for 12 months. Children with asthma were further subgrouped according to their severity and the requirement for hospitalization during exacerbations. Clinical data were obtained from medical records. Peripheral blood samples were collected to analyze macrophage polarization, including M1, M2, and subsets, by flow cytometry.ResultsFifty-one asthmatic cases and 27 normal controls were included in this study. The level of PM-2K+CD14+ but not PM-2K+CD14− was decreased in asthmatic children. The levels of M2a (CCR7−CXCR1+), M2b (CCR7−CD86+), and M2c (CCR7−CCR2+) subsets, but not M1 (CCR7+CD86+), were increased in asthmatic children. The levels of M1 were decreased, but the levels of M2c were increased, in children with moderate asthma compared to those with mild asthma. The levels of PM-2K+CD14+ cells and M1 subsets were decreased, but the M2c subset cells were increased in asthmatic children requiring hospitalization during exacerbations.ConclusionMacrophage polarization may be involved in the pathogenesis of childhood asthma and is a potential biomarker of childhood asthma disease severity.

Childhood asthma: pathogenesis and phenotypes.

In the pathogenesis of asthma in children there is a pivotal role for a type 2 inflammatory response to early life exposures or events. Interactions between infections, atopy, genetic susceptibility and environmental exposures (such as farmyard environment, air pollution and tobacco smoke exposure) influence the development of wheezing illness and the risk of progression to asthma. The immune system, lung function and the microbiome in gut and airways develop in parallel, and dysbiosis of the microbiome may be a critical factor in asthma development. Increased infant weight gain and preterm birth are other risk factors for development of asthma and reduced lung function. The complex interplay between these factors explains the heterogeneity of asthma in children. Subgroups of patients can be identified as phenotypes, based on clinical parameters, or endotypes, based on a specific pathophysiological mechanism. Paediatric asthma phenotypes and endotypes may ultimately help to improve diagnosis of asthma, prediction of asthma development and treatment of individual children, based on clinical, temporal, developmental or inflammatory characteristics. Unbiased, data-driven clustering, using a multidimensional or systems biology approach may be needed to better define phenotypes. The present knowledge on inflammatory phenotypes of childhood asthma has now been successfully applied in the treatment with biologicals of children with severe therapy-resistant asthma, and it is to be expected that more personalised treatment options may become available.

MiRNA-21 Regulates Bronchial Epithelial Cell Proliferation by Activating Tgfβ1/Smad Signaling Pathway and Its Correlation with Asthma Severity in Children

Background:This research was designed to probe into the role of miRNA-21 in the pathogenesis of childhood asthma and its correlation with the severity.Methods:Fifty-four children with bronchial asthma admitted to the Third Affiliated Hospital of Qiqihar Medical University from Jun 2018 to Dec 2019 were included. Forty nine healthy children underwent physical examination at this time period were also enrolled. The miR-21 expression in peripheral blood serum was analyzed by qRT-PCR. The relationship between the expression and severity of asthma in children was explored by Spearman correlation analysis and ROC curve. Bronchial epithelial cell lines were cultured in vitro and divided into blank control group, negative control group and miR-21 inhibition and activation group. The changes of cell proliferation after treatment were detected by CCK-8 test in different groups. The expression of TGF-β1/Smad signaling pathway protein in cells was assessed by Western blot (WB).Results:Compared with that of healthy children, the miR-21 expression in peripheral blood serum of asthmatic children was higher (P<0.001). MiR-21 expression was positively correlated with the severity of illness (r=0.853, P<0.001). The results of cell experiments in vitro signified that miR-21 can promote the proliferation of bronchial epithelial cells, and may be involved in regulating the expression of TGF-β1/Smad3 signaling pathway, thus affecting cell proliferation.Conclusion:miRNA-21 regulates the proliferation of bronchial epithelial cells by activating TGFβ1/Smad signaling pathway. And it is positively correlated with the severity of asthma in children.

The role of macroelements in the pathogenesis of bronchial asthma in children

Objective: to study the role of macroelements in the pathogenesis of bronchial asthma in children. Materials and methods: A total of 131 patients with different degrees of bronchial asthma severity were examined instantaneously. The reference group consisted of 31 children of the respective gender and age groups 1 and 2A. The average age of children was 11.83 ± 3.38 years old. All children in the cohort were given a comprehensive clinical-laboratory examination, peakflowmetry, pulsoxymetry, and spirometry. The study of mineral homeostasis in blood serum was carried out by X-ray fluorescence analysis. Statistical processing of the results was performed using the Statistica 10 and Microsoft Office Excel 2010, calculations were carried out in the program R. Results: It was found that the levels of potassium, phosphorus, and sulfur in children with bronchial asthma were elevated, while the levels of calcium, magnesium, and chlorine were reduced compared to the control group patients. The content of these macronutrients in patients with varying degrees of disease severity did not have significant differences. Conclusions: The data obtained on the changes in macro-element homeostasis indicate the important role of diselementosis in the pathogenesis of BA. It is a significant factor that contributes to the progression of chronic inflammation in bronchial organs that requires correction of therapy in children.

Neonatal airway immune profiles and asthma and allergy endpoints in childhood.

The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood. We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6years. Principal component analyses were used to describe the airway cytokine and chemokine composition. A neonatal airway immune profile particularly characterized by enhanced IL-1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1β and CXCL8, showed trend of association with development of early asthma endpoints. Development of early asthma endpoints and inhalant allergy during the first 6years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.

Relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma

BackgroundThe pathogenetic mechanisms of neutrophilic asthma are not well understood now. Whether T helper (Th)17-mediated immunity contributes to the pathogenesis of neutrophilic asthma in human is still under investigation. The aim of this study was to explore the relationship between Th17-mediated immunity and airway inflammation in childhood neutrophilic asthma.MethodsTwenty-eight children with exacerbated asthma and without using any glucocorticoids were divided into three groups: eosinophilic asthma (EA, n = 12) group, neutrophilic asthma (NA, n = 10) group and paucigranulocytic asthma (PGA, n = 6) group according to the induced sputum cytology. Ten healthy children were recruited as healthy control (HC, n = 10) group. Peripheral Th17 and Th2 cells, and the expression of Ki-67 in peripheral Th17 cells were detected by flow cytometry. The mRNA expression of retinoic acid-related orphan receptor γt (RORγt) in peripheral blood mononuclear cells (PBMCs) was detected by qRT-PCR. The concentrations of IL-17, IL-8 and IL-5 in sputum, as well as IL-17 in plasma and culture supernatant of activated PBMCs were measured by ELISA.ResultsThe percentage of Th17 cells in peripheral Th cells, and the concentrations of IL-17, IL-8 in sputum, as well as IL-17 in culture supernatant of activated PBMCs were all increased in NA group, and positively correlated with neutrophil level in sputum and with each other. Also, the mRNA expression of RORγt in PBMCs and Ki-67 positivity in peripheral Th17 cells were both increased in NA group. The percentage of Th2 cells in peripheral Th cells, and the concentration of IL-5 in sputum were both increased in EA group, and positively correlated with eosinophil level in sputum and with each other.ConclusionsBoth Th17- and Th2-mediated immunity are involved in the pathogenesis of childhood asthma. There is predominance of Th17-mediated immunity and Th17 cells proliferation in childhood neutrophilic asthma.

The significance of the distribution of the indicators of humoral and cell immunity and their role in the pathogenesis of bronchial asthma in children with the position of system analysis

Bronchial asthma is one of the common diseases in children of different ages. In recent years, around the world, including in Ukraine, there is a trend towards its sustainable growth. To date, there are no methods of systemic immunodiagnostics that would allow with high diagnostic accuracy to identify clinical forms and severity of asthma, which would allow more fully reveal the pathogenetic mechanisms and individualize approaches to the treatment of asthma in children. The aim of this work was to study the hierarchy of immunological parameters in the pathogenetic matrix, which will determine the features of clinical forms and severity of asthma in children on the basis of systematic analysis. A comprehensive clinical and immunological examination of 176 children with asthma aged 6 to 15 years. To detect the autoimmune component used lipopolysaccharide antigens obtained from homologous cell-tissue structures of the trachea, bronchi and lung tissue from sectional samples of the bronchopulmonary system from accidentally killed children with group I (0) blood 2–4 hours after death. The level of autoantibodies to lipopolysaccharide antigens of the bronchopulmonary system was determined by quantifying the autoantibody index – Qφ. As a result of the study for the first time to improve the diagnosis and differentiation of clinical forms and severity of asthma from the standpoint of system analysis was developed immunodiagnostic complex, which took into account the degree of deviation from the norm values (Student's t-test, t = 1.96) and their distribution in pathogenetic matrix. This approach to ranking the positions of immunological parameters allowed to determine the features of humoral and cellular immunity, the process of apoptosis of cell-tissue structures of the bronchopulmonary system and the autoimmune component in the pathogenesis of asthma in children, which opens approaches to individualization of pathogenetic therapy.

Correlation of vitamin D and asymmetric dimethylarginine in children with bronchial asthma

ABSTRACT Bronchial Asthma is outlined as a chronic irritation of the airways in children. Vitamin D is a real immune system regulator which has a potential part in allergy. Asymmetric Dimethyl Arginine (ADMA) is an endogenic Nitric Oxide Synthase (NOS) inhibitor. This study is to determine if there is a role of vitamin D deficiency, ADMA in the pathogenesis of asthma in children, And whether the decreased arginine bioavailability and NOS suppression by ADMA contribute to respiratory tract blockage or not. We measured serum vitamin D, ADMA, nitric oxide and plasma L-arginine in 30 asthmatic and 10 healthy children. Serum 25-hydroxy vitamin D, plasma L-Arginine and serum Nitric Oxide were decreased significantly in asthmatic patients compared to healthy children. On the other hand, ADMA serum levels were increased significantly in asthmatic patients. In asthmatic children, there were positive correlations between serum vitamin D concentration and forced expiratory volume in the first, second FEV1 (%predicted). Furthermore, there were negative correlations between serum ADMA concentration and FEV1 (%predicted). In conclusion, marked reduction of vitamin D and elevated ADMA serum levels in asthmatic children has contributed to NOS-related pathophysiology, therefore ADMA and vitamin D could be considered reliable in managing oxidative stress in asthma.

Differentially expressed serum proteins in children with or without asthma as determined using isobaric tags for relative and absolute quantitation proteomics.

BackgroundAlthough asthma is one of the most common chronic, noncommunicable diseases worldwide, the pathogenesis of childhood asthma is not yet clear. Genetic factors and environmental factors may lead to airway immune-inflammation responses and an imbalance of airway nerve regulation. The aim of the present study was to determine which serum proteins are differentially expressed between children with or without asthma and to ascertain the potential roles that these differentially expressed proteins (DEPs) may play in the pathogenesis of childhood asthma.MethodsSerum samples derived from four children with asthma and four children without asthma were collected. The DEPs were identified by using isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Using biological information technology, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Cluster of Orthologous Groups of Proteins (COG) databases and analyses, we determined the biological processes associated with these DEPs. Key protein glucose-6-phosphate dehydrogenase (G6PD) was verified by enzyme linked immunosorbent assay (ELISA).ResultsWe found 46 DEPs in serum samples of children with asthma vs. children without asthma. Among these DEPs, 12 proteins were significantly (>1.5 fold change) upregulated and 34 proteins were downregulated. The results of GO analyses showed that the DEPs were mainly involved in binding, the immune system, or responding to stimuli or were part of a cellular anatomical entity. In the KEGG signaling pathway analysis, most of the downregulated DEPs were associated with cardiomyopathy, phagosomes, viral infections, and regulation of the actin cytoskeleton. The results of a COG analysis showed that the DEPs were primarily involved in signal transduction mechanisms and posttranslational modifications. These DEPs were associated with and may play important roles in the immune response, the inflammatory response, extracellular matrix degradation, and the nervous system. The downregulated of G6PD in the asthma group was confirmed using ELISA experiment.ConclusionAfter bioinformatics analyses, we found numerous DEPs that may play important roles in the pathogenesis of childhood asthma. Those proteins may be novel biomarkers of childhood asthma and may provide new clues for the early clinical diagnosis and treatment of childhood asthma.

Alterations in Serum-Free Amino Acid Profiles in Childhood Asthma.

Asthma often begins in childhood, although making an early diagnosis is difficult. Clinical manifestations, the exclusion of other causes of bronchial obstruction, and responsiveness to anti-inflammatory therapy are the main tool of diagnosis. However, novel, precise, and functional biochemical markers are needed in the differentiation of asthma phenotypes, endotypes, and creating personalized therapy. The aim of the study was to search for metabolomic-based asthma biomarkers among free amino acids (AAs). A wide panel of serum-free AAs in asthmatic children, covering both proteinogenic and non-proteinogenic AAs, were analyzed. The examination included two groups of individuals between 3 and 18 years old: asthmatic children and the control group consisted of children with neither asthma nor allergies. High-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS technique) was used for AA measurements. The data were analyzed by applying uni- and multivariate statistical tests. The obtained results indicate the decreased serum concentration of taurine, L-valine, DL-β-aminoisobutyric acid, and increased levels of ƴ-amino-n-butyric acid and L-arginine in asthmatic children when compared to controls. The altered concentration of these AAs can testify to their role in the pathogenesis of childhood asthma. The authors’ results should contribute to the future introduction of new diagnostic markers into clinical practice.

Low expression and hypermethylation of FOXP3 in regulatory T cells are associated with asthma in children.

The aim of the present study was to determine the expression and methylation levels of forkhead transcription factor P3 (FOXP3) in peripheral blood CD4+CD25+ regulatory T cells (Tregs) harvested from children with asthma, and to explore the pathogenesis of asthma. The percentages of CD4+CD25+FOXP3+ Tregs in CD4+ T lymphocytes from 15 children with asthma and 15 healthy controls were measured by flow cytometry, and FOXP3 mRNA expression in the CD4+CD25+ Tregs was measured by reverse transcriptase-quantitative PCR. In addition, the forced expiratory volume in one second (FEV1) was measured to determine lung function. The methylation statuses of 16 CpG sites in two regions of the FOXP3 gene's exon and intron were analysed with bisulfite-specific PCR and pyrophosphate sequencing. The differences in methylation levels between the asthma and control groups were compared. The percentage of CD4+CD25+FOXP3+ Tregs in CD4+ T lymphocytes and FOXP3 mRNA expression were significantly lower in children with asthma than in control children (P<0.05). The FOXP3 mRNA levels in children with asthma were positively correlated with FEV1 (P<0.001; r=0.895). The methylation levels in 12 of the 16 studied CpG loci of the FOXP3 gene, and of the 6th CpG locus in the exon regions, were significantly higher in the asthma group compared with the control group (P<0.05). In summary, low expression and hypermethylation of the FOXP3 gene in the peripheral blood were associated with the pathogenesis of asthma in children. Thus, the FOXP3 mRNA expression level can be used to predict the severity of asthma in children.

Correlations of severity of asthma in children with body mass index, adiponectin and leptin.

BackgroundThis study aims to investigate the correlations of asthma in children with body mass index (BMI), adiponectin, and leptin.MethodsA total of 122 children with asthma in our hospital from January 2017 to February 2018 were randomly selected and divided into control group (normal) and observation group (BMI > 28 kg/m2) according to BMI. BMI, adiponectin, and leptin levels between the two groups were measured and compared, and correlations of disease grade with BMI, adiponectin, or leptin were analyzed. Moreover, risk factors for asthma in children were also identified.ResultsBody mass index, leptin level, forced vital capacity (FVC), FVC%, and forced expiratory volume in 1s (FEV1)/FVC in observation group were significantly higher than those in control group (P < 0.05), while the adiponectin level, forced expiratory capacity in 1s (FEC1), and FEV1% in observation group were significantly lower than those in control group (P < 0.05). The amount of severe patients in observation group was much larger than that in control group. The severity of disease was positively correlated with BMI and leptin and negatively correlated with adiponectin. BMI, adiponectin, and leptin were identified as risk factors for asthma in children.ConclusionAdiponectin, leptin, and BMI are involved in the pathogenesis of asthma in children, suggesting they might be therapeutic targets for clinical treatment.

TET1 contributes to allergic airway inflammation and regulates interferon and aryl hydrocarbon receptor signaling pathways in bronchial epithelial cells

Previous studies have suggested a role for Tet1 in the pathogenesis of childhood asthma. However, how Tet1 contributes to asthma remains unknown. Here we used mice deficient for Tet1 in a well-established model of allergic airway inflammation and demonstrated that loss of Tet1 increased disease severity including airway hyperresponsiveness and lung eosinophilia. Increased expression of Muc5ac, Il13, Il33, Il17a, Egfr, and Tff2 were observed in HDM-challenged Tet1-deficient mice compared to Tet1+/+ littermates. Further, transcriptomic analysis of lung RNA followed by pathway and protein network analysis showed that the IFN signaling pathway was significantly upregulated and the aryl hydrocarbon receptor (AhR) pathway was significantly downregulated in HDM-challenged Tet1−/− mice. This transcriptional regulation of the IFN and AhR pathways by Tet1 was also present in human bronchial epithelial cells at base line and following HDM challenges. Genes in these pathways were further associated with changes in DNA methylation, predicted binding of transcriptional factors with relevant functions in their promoters, and the presence of histone marks generated by histone enzymes that are known to interact with Tet1. Collectively, our data suggest that Tet1 inhibits HDM-induced allergic airway inflammation by direct regulation of the IFN and AhR pathways.

Influence of environment on residence and selected demographic and clinical parameters of preschool children with IgE-dependent asthma.

An important role in the pathogenesis of asthma in children is played by individual parameters and environmental factors, in particular, those related to the place of residence. The aim of this study was to assess the impact of the living environment on the basic demographic and clinical parameters of preschool children with IgE-dependent asthma. 176 children (126 from urban and 52 from rural areas) aged 5.22±0.34 years, with newly-diagnosed IgE-dependent asthma, hospitalised at the Clinic for Lung Diseases and Paediatric Rheumatology of the Prof. Antoni Gębala Children's Hospital of Lublin, were qualified for the study. Medical documentation of the children was analysed, including the implementation of vaccinations. Due to the clinical form of the disease, patients were separated into groups with mild, moderate and severe asthma. No statistically significant differentiation was observed between age and current body weight and height of the children. Similarly, gender and the clinical form of asthma were not significantly correlated with the place of residence. Children with asthma, at the time of exacerbation symptoms of the disease, living in a city, significantly more often (p <0.05) were treated with antibiotics in the hospital during hospitalization, while the value of OR (5.08) indicated that the rural environment enforces more frequent use of OGCs during asthma exacerbation therapy. In children from the urban environment, there was a significant correlation between the current body weight and serum calcium concentration, as well as a negative statistically significant correlation between the current body weight and serum selenium concentration. Residence does not determine the clinical course of IgE-dependent asthma in preschool children.

Correlation between IL-4 and IL-13 gene polymorphisms and asthma in Uygur children in Xinjiang.

Correlation between interleukin-4 (IL-4) and interleukin-13 (IL-13) gene polymorphisms and bronchial asthma in Uygur children in Xinjiang, China, and the effects on serum total immunoglobulin E (IgE) were investigated. Thirty-seven child patients with asthma and 29 healthy children were screened. The gene polymorphisms of Arg130Gln in IL-13 and −590C/T in IL-4 gene promoter region were analyzed using the polymerase chain reaction (PCR) and direct gene sequencing; the asthma-related indexes were detected using the enzyme-linked immunosorbent assay, and the relevant indexes were analyzed; moreover, whether there was a synergistic effect between Arg130Gln in IL-13 and −590C/T in IL-4 gene promoter region in the pathogenesis of asthma in children was analyzed. The T/T homozygote genotype frequency and T allele frequency of C-590T gene in IL-4 in the asthma group were significantly higher than those in the control group (45.9 vs. 10.3%, OR=8.91; 63.5 vs. 36.2%, OR=3.07, P<0.05). The A/A genotype frequency and A allele frequency of Arg130Gln locus in IL-13 in the asthma group were obviously higher than those in the control group (54.1 vs. 17.2%, OR=6.29; 67.6 vs. 39.7%, OR=3.17, P<0.05). In the two gene loci, the level of serum IgE in the same genotype in the asthma group was higher than that in the control group (Z=−2.128, −2.050, −2.700 vs. −3.766, −3.799, −3.397; P<0.05). The risk of asthma in carriers of both IL-4 −590C/T TT and Arg130Gln locus AA genotypes was significantly increased compared with that in carriers of either IL-4 −590C/T TT genotype or Arg130Gln locus AA genotype (OR=6.00, P=0.046; OR=4.50, P=0.033; OR=22, P=0.005). The IL-4 −590C/T and Arg130Gln locus gene polymorphisms are associated with the asthma susceptibility and increased serum total IgE in Uygur children in Xinjiang. There is a synergistic effect between the T allele of IL-4 −590C/T locus and the A allele of IL-13 Arg130Gln locus.

Non-specific factors of immunity in the pathogenesis of bronchial asthma in children

The role of nonspecific immunity factors in the pathogenesis of bronchial asthma in children with different clinical forms and degrees of severity of its course has been investigated in the work. A total of 228 children with BA who were aged from 5 to 14 years were examined. We determined the complement titer (C0) in the serum, components of complement C2 and C3a, the protein component of blood serum of properdin, and the level of total serum IgE. The data were statistically processed using Student's t-test. In patients with non-allergic form of BA, the greatest increase in deviation from the norm was noted in relation to the circulating immune complexes (CIC)(t = 16.74). The second ranking place occupies an increased content of C3a (t = 8.21), then in descending order from IgE (t = 4.55) to C0 (t = 1.89). Rating of the degree of deviation from the norm of indices of nonspecific immunity in patients with atopic BA has shown that, in contrast to patients with non-allergic form of BA, the main pathogenetic role belongs to reactive hypersensitivity (IgE; t = 17,39). The value of immunocomplex hypersensitivity in atopic form of BA is in the second ranked place. In children with mixed BA, an intermediate pathogenetic variant was identified, which consisted in approximately equal activity of both immunocomplex and reactive reactions with a certain dominant of the first: from CIC (t = 13.66) to IgE (t = 11.19). Thus, the obtained data confirm that in the pathogenesis of bronchial asthma in children is involved immunocomplex immunological mechanism (type III according to Gell-Coombs), which enhances immunospecific reactions, aggravating the severity of the course of the disease. In the blood serum of children with bronchial asthma, there is a decrease in the protein component properdin, which is consumed to activate the alternative (properdin) complement pathway through C3a, nonspecific immunological mechanisms are able to stimulate and maintain chronic allergic inflammation in the bronchopulmonary system in children with bronchial asthma.

Fibulin-5 promotes airway smooth muscle cell proliferation and migration via modulating Hippo-YAP/TAZ pathway

Asthma is a common chronic disease mainly occurs from childhood. Increased airway smooth muscle mass is involved in the pathogenesis of asthma. Fibulin-5 was upregulated in the lung tissues of patients with COPD and idiopathic pulmonary fibrosis. This study aimed to investigate Fibulin-5 expression in asthmatic patients and the effect and mechanism of Fibulin-5 on the proliferation and migration of airway smooth muscle cells (ASMCs). The expression of Fibulin-5, YAP, and TAZ in the induced sputum of 38 asthmatic children (19 mild and 19 moderate asthmatics) and 19 healthy controls was determined. The effects and mechanisms of Fibulin-5 on the proliferation and migration of ASMCs were analyzed through upregulating Fibulin-5. We found compared with healthy controls, the expression of Fibulin-5, YAP, and TAZ was increased in the induced sputum of asthmatic children and much higher in moderate asthmatics. Fibulin-5 overexpression promoted the proliferation and migration of ASMCs, upregulated the expression of YAP and TAZ, and reduced the levels of p-YAP and p-TAZ. YAP inhibitor (Peptide 17) abrogated the proliferation and migration of ASMCs induced by Fibulin-5 overexpression in a dose-dependent manner. Additionally, Fibulin-5 overexpression enhanced its binding capacity of β1 integrin, and β1 integrin blocking antibody partly reversed the effect of Fibulin-5 overexpression on the levels of YAP and TAZ. In conclusion, Fibulin-5 expression is correlated with the pathogenesis of childhood asthma. It may function at least partly through binding to β1 integrin and modulating Hippo-YAP/TAZ pathway to promote the proliferation and migration of ASMCs.