Childhood Asthma Research Articles

Recurrent wheezing and asthma-Epidemiology and environmental determinants.

Wheeze is the musical continuous sound produced by oscillations in any critically narrowed airways, and heard mostly on expiration. It is common in preschool age, about half of all children will experience an episode of wheezing by their sixth birthday. Asthma is usually characterized by cough, wheeze, chest tightness and fast breathing. It is a significant global health issue and affects both children and adults. The prevalence is on the increase, especially in LMIC. Studies from different populations have revealed the key role influencing the progression from preschool wheezing to childhood asthma. Recurrent wheezing is four or more episodes in the preceding year and has a spectrum of phenotypes and with heterogeneous features. Phenotypes of wheezing were proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. The epidemiology and environmental determinants of recurrent wheezing and asthma are discussed.

C-CBL/LCK/c-JUN/ETS1/CD28 axis restrains childhood asthma by suppressing Th2 differentiation

BackgroundAsthma is a common immune disease with high morbidity in children. Type 2 inflammation is the center of asthma development, and mainly mediated by a subset of CD4 + T cells, T helper 2 (Th2) cells. Excess Th2 differentiation was generally associated with asthmatic attack. Casitas B-lineage lymphoma (c-CBL) was reported to involved in T cell development and databank showed its decreased expression in CD4 + T cells from peripheral blood of asthmatic children. This study aims to investigate the role of c-CBL in childhood asthma and Th2 differentiation, and explore the underlying mechanism.MethodsWe collected peripheral blood samples from clinical childhood asthma cases and healthy controls, and determined c-CBL expression in CD4 + T cells. Asthma was induced in neonatal mice by ovalbumin (OVA) intraperitoneal injection and aerosol inhalation, and c-CBL expression in CD4 + T cells from peripheral blood and spleen was measured. Gain-of-function experiments was performed to confirm the effects of c-CBL on Th2 differentiation in vitro. Finally, c-CBL was delivered into asthmatic mice via lentivirus infection to verify its effects on experimental asthma.Resultsc-CBL was lowly expressed in CD4 + T cells from asthmatic children than those of healthy controls. Similarly, it was downregulated in CD4 + T cells from peripheral blood and spleen of asthma mice. Overexpression of c-CBL restrained lung pathological injury and type 2 inflammation in experimental asthmatic mice. Gain-of-function experiments demonstrated that c-CBL inhibited Th2 differentiation of CD4 + T cells from healthy children, and mediated the ubiquitination of lymphocyte cell-specific protein-tyrosine kinase (LCK). LCK acted as a kinase to phosphorylate and activate c-JUN, which was predicted to bind promoter sequence of CD28 by bioinformatic analysis. Dual-luciferase reporter assay verified that c-JUN and ETS1 synergically enhanced transcription of CD28, and this transcription activation was aggravated by LCK overexpression.Conclusionc-CBL alleviated asthma and suppressed Th2 differentiation by facilitating LCK ubiquitination, interrupting c-JUN activation and CD28 expression in vivo and in vitro. c-CBL/LCK/c-JUN/ETS1/CD28 axis was partially involved in childhood asthma, and may provide novel insights for clinical treatment for asthma.

Prevalence, symptomatology and factors associated with asthma in adolescents aged 13–14 years from rural Sri Lanka: an analytical cross-sectional study

BackgroundAsthma is the most common chronic disease affecting children. However, the epidemiology of asthma in adolescents from rural geographies is lacking.MethodsAn analytical cross-sectional study was conducted in secondary schools located...

Neonatal and early infancy antibiotic exposure is associated with childhood atopic dermatitis, wheeze and asthma

Antibiotics are frequently administered in the neonatal period and early infancy. Little is known about the long-term health consequences of early life antibiotic exposure. The objective is to investigate the association between neonatal and early life (0–6 months) antibiotic treatment and the development of atopic dermatitis, asthma and the use of inhaled corticosteroid medication later in childhood. We analyzed data obtained from hospital records and national registers in a cohort of 11,255 children. The association between early antibiotic exposure and the outcomes were analyzed using logistic regression. Confounding factors were included in the model. Neonatal antibiotic therapy for confirmed infection was associated with childhood atopic dermatitis (adjusted odds ratio 1.49; 95% confidence interval 1.15–1.94). Antibiotic therapy by six months of age was more common in children developing atopic dermatitis (adjusted odds ratio 1.38; 95% confidence interval 1.15–1.64), asthma (adjusted odds ratio 1.56; 95% confidence interval 1.32- 1.85) and inhaled corticosteroid medication use (adjusted odds ratio 1.88; 95% confidence interval 1.66–2.13). Conclusions: Neonatal antibiotic therapy for confirmed or clinically diagnosed infection is associated with increased risk of atopic dermatitis later in childhood. Antibiotic treatment before six months of age is associated with atopic dermatitis, asthma and inhaled corticosteroid use.What is known:• The use of antibiotics early in life has been associated with an increased risk of developing atopic dermatitis or asthma.• Confounding by indication or reverse causation may underlie the observed associations.What is new:• Our results demonstrate that neonatal antibiotic therapy for confirmed or clinically diagnosed infection was associated with increased risk of atopic dermatitis and antibiotic treatment before six months of age was associated with atopic dermatitis, asthma and inhaled corticosteroid use in analyses adjusted for confounding factors.

The Telehealth Education for Asthma Connecting Hospital and Home (TEACHH) pilot study

Objective To evaluate the feasibility of a novel intervention of health literacy-informed, telemedicine-enhanced asthma education and home management support for hospitalized children and caregivers, and assess caregiver perspectives of the intervention. Methods We conducted a pilot randomized trial of the Telehealth Education for Asthma Connecting Hospital and Home (TEACHH) intervention vs. standardized care (SC) for children (5–13 yrs) hospitalized with asthma. Participants in TEACHH received health literacy-informed teaching prior to discharge, including pictorial materials (e.g. flipchart, action plan), color- and shape-coded medication labels, and medication demonstration. Two Zoom-based follow-up teaching visits were completed within 1-month of discharge. Feasibility was assessed by tracking visit completion, and we measured preliminary outcomes using health records (i.e. total asthma-related acute healthcare visits) and blinded surveys of caregivers 2-, 4-, and 6-months post-discharge (i.e. symptom-free days, quality of life). We interviewed caregivers about their perceptions of TEACHH. Transcripts were coded inductively. Results We enrolled 26 children and interviewed 14 caregivers (9 TEACHH, 5 SC). All inpatient sessions were completed, as were 77% of virtual visits. Both groups experienced improved symptoms and quality of life over time. Caregivers valued the teaching, involvement of children, visual tools, and color-coded information of TEACHH. They described child-specific benefits, greater support after discharge, and improved asthma-related communication, and indicated that other families would benefit from similar teaching. Conclusions A novel program of patient-centered asthma education was feasible in both hospital and home settings and well received by caregivers. A larger study is needed to assess the impact of TEACHH on childhood asthma morbidity. Clinicaltrials.gov identifier NCT04995692 (Registration date 8/9/2021)

Variability in forced expiratory volume in 1 s in children with symptomatically well-controlled asthma

AimsSpirometry is used by many clinicians to monitor asthma in children but relatively little is understood about its variability over time. The aim of this study was to determine the...

Development and validation of asthma diagnostic scale for children.

To construct an asthma diagnostic scale for children under 6 years old. An electronic medical record database was used to develop the scale. Item pool was established through literature survey and expert opinion. Items were screened and optimized by using the Delphi method, t-test, reactivity analysis, Pearson correlation coefficient, factor analysis, reliability and validity test. The predictive probability of asthma was calculated using logistic regression, and receiver operating characteristic curve. Another childhood asthma database was used to validated the scale. The asthma diagnostic scale for children under 6 years old included five dimensions: dimension 1 (shortness of breath, three concave sign, cyanosis, moist rale, heart rhythm, heart sound and dyspnea), dimension 2 (respiratory sound, cough, sputum), dimension 3 (frequency of wheezing, allergic rhinitis, history of allergy in one or both parents), dimension 4 (sex, wheezing, atopic dermatitis), and dimension 5 (reversible airflow, positive in vitro or in vivo allergy test). The Cronbach's α coefficients for the five dimensions were 0.846, 0.459, 0.019, 0.202, and 0.024. The area under the ROC curve (AUC), sensitivity, and specificity were 0.737, 59.1%, and 81.2%. AUC, sensitivity, and specificity in the validation database were 0.614, 76.2%, and 46.7%. The scale has significant diagnostic value for asthma in children under 6 years old. 1. The aim of the study was to establish an asthma diagnosis scale for children younger than 6 years old. 2. Our study not only addresses the lack of diagnostic criteria of young children asthma, but also indicates the accuracy of the diagnostic scale. 3. The data may help to reduce the missed diagnosis and misdiagnosis rate of asthma, and improve the diagnostic accuracy of the disease, and thus reduces the harm of asthma to children's physical and mental health.

Integrated nasopharyngeal airway metagenome and asthma genetic risk endotyping of severe bronchiolitis in infancy and risk of childhood asthma.

Infants with bronchiolitis are at increased risk for developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition. However, little is known about its biologically distinct subgroups based on the integrated metagenome and asthma genetic risk signature and their longitudinal relationships with asthma development. In a multi-center prospective cohort study of infants with severe bronchiolitis (i.e., bronchiolitis requiring hospitalization), we profiled nasopharyngeal airway metagenome and virus at hospitalization, and calculated the polygenic risk score of asthma. Using similarity network fusion clustering approach, we identified integrated metagenome-asthma genetic risk endotypes. We also examined their longitudinal association with the risk of developing asthma by age six years. Of 450 infants with bronchiolitis (median age, 3 months), we identified five distinct endotypes-characterized by their nasopharyngeal metagenome, virus, and asthma genetic risk profiles. Compared with endotype A infants (who clinically resembled "classic" bronchiolitis), endotype E infants (characterized by a high abundance of H. influenzae, high proportion of RV-A and RV-C infections, and high asthma genetic risk) had a significantly higher risk for developing asthma (35.9% versus 16.7%; ORadj, 2.24; 95%CI, 1.02-4.97; p=0.046). The pathway analysis showed that endotype E had enriched microbial pathways (e.g., glycolysis, L-lysine, arginine metabolism) and host pathways (e.g., IFNs, IL-6/JAK/STAT3, fatty acids, MHC, and immunoglobin-related) (FDR<0.05). Additionally, endotype E had a significantly higher proportion of neutrophils (FDR<0.05). In this multi-center prospective cohort study of infant bronchiolitis, the clustering analysis of integrated-omics data identified biologically distinct endotypes with differential risks for developing asthma.

Clinical and immunological efficacy of complex therapy for bronchial asthma in children with the inclusion of components of far eastern brown algae

Classical basic therapy for asthma is aimed at stopping inflammation, primarily atopic, and has achieved significant positive results in the treatment of the disease, which has led to a decrease in the severity of asthma. The proportion of patients in whom asthma control is achieved does not exceed 30%; complete control is achieved in 5%, that is associated with the influence non-atopic factors on the pathogenesis of BA, leading to the search for additional methods of correction. Despite the identified biological, immunomodulatory properties of the components of brown algae, the mechanisms of their action, in asthma, are not sufficiently illuminated, which became the purpose of this study: to determine the possible immunomodulatory effect of a functional food product in children with asthma based on brown algae (Far Eastern kelp) and its use in addition to standard therapy to improve control of the course of this disease. Children with asthma (n = 56) aged from 5 to 17 years were comprehensively examined and divided into 2 groups: those who received a functional food product in addition to standard therapy (n = 20) and those who received only standard therapy (n = 36). Laboratory tests included CBC, immunogram, cytokines (IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL- 10, IL-18, TNFá), blood ICC MPM, and herpesvirus DNA. Against the background of complex treatment, changes in the interleukin profile (IL-6, IL-10, IL-18) were noted, characteristic of a decrease in the intensity of inflammatory processes, including nonspecific ones, expressed in a tendency towards a decrease in the total number of lymphocytes, an increase in the immunoregulatory index both due to an increase in the number of T helper cells and and reduction of killer T cells. This was confirmed by a decrease in monocytes and ESR. Improved energy supply of immunocompetent blood cells (granulocytes and monocytes), a decrease in the number of patients with active replication of EBV and herpes virus type 6 indicate its immunomodulatory effect. The result of these changes was the positive clinical dynamics of asthma control indicators, which allows us to recommend the inclusion of a functional food product based on Far Eastern brown algae in addition to standard therapy for children with asthma aged 5-17 years.

Caregivers of children with asthma alarmed by climate change: a cross-sectional study.

Climate change poses significant health risks, with children being particularly vulnerable to its adverse health effects. Children with asthma are expected to have worsening disease due to increased exposure to heat, air pollution, mold from flooding, and pollen. Understanding caregiver perspectives on these health harms is crucial for informing public health policy and education. Therefore, we aimed to explore caregiver perceptions of climate change-related health risks to children with asthma. In this cross-sectional study, a survey instrument was created and distributed to caregivers of children with asthma during their visits to pulmonology clinics located in an urban northeastern US setting and via email. Among 198 completed surveys, 78% of participants reported high levels of concern about climate change, with most respondents agreeing that climate change has already impacted their child's health. Examples provided by respondents included worsening asthma control due to air pollution, wildfire events, pollen exposure, and rapid changes in weather. Respondents who self-identified as female had greater concern. Most respondents agreed that these topics should be further discussed with their child's doctor. Although, barriers to such discussions were noted by the respondents. Caregivers of children with asthma have high levels of concern regarding climate change and report adverse impacts on their child's asthma. Clinicians caring for children with asthma should consider discussing the respiratory health impacts of climate change with caregivers. However, barriers to these discussions need further examination.

The main etiological factors of bronchial asthma in young children today

The main etiological factors of bronchial asthma in young children today

Peak expiratory flow rate monitoring can predict asthma exacerbation better as compared to monitoring by symptoms, prospective cohort study

Background: Global initiative for asthma (GINA) guidelines suggest to use peak expiratory flow rate (PEFR) monitoring to assess response to treatment, to identify triggers for exacerbation and to have a baseline value for action plan (especially for the poor perceivers). In comparison to adults, there are less evidence in support of the routine use of PEFR recording for the diagnosis and monitoring level of control of asthma in children. This study was conducted with objective to assess the effect of PEFR monitoring on numbers of exacerbations in comparison to monitoring by symptoms in asthma. Methods: This was a prospective cohort study done for a in department of pediatrics and respiratory medicine, of a tertiary care hospital, North India. Prior to recruitment ethical approval and informed consent/assent was taken. Study subjects were children with partial and uncontrolled asthma aged 5-12 years of age. Patients were divided into two groups on their first visit by using random allocation number. In group “A” monitoring was done with symptoms only, while in group “B” monitoring was done by symptoms and PEFR. Number of exacerbations during study period was noted. At baseline and follow up, CACT score was calculated. Spirometry was done at the end of 3 months. Results: Group B had statistically significant lesser exacerbation during study period as compared to group A (OR=0.23; 95% CI=0.06-0.81; p=0.020). Conclusions: PEFR based monitoring can be used as a potential tool for aborting or decreasing the severity of episodes of exacerbations of asthma especially in resource limited areas.

Educational Intervention to Promote Parent/Caregiver Self-Efficacy in the Management and Control of Childhood Asthma: A Randomized Clinical Trial.

Asthma is a leading cause of pediatric hospitalization and morbidity, necessitating the development of educational interventions for its management and control. To evaluate the effectiveness of an educational intervention in promoting parent/caregiver self-efficacy in the management and control of their children's asthma. A clinical trial was conducted in Fortaleza, Ceará, Brazil, involving two randomized groups of parents/caregivers of children: the comparison group (CG) (n = 42) and the intervention group (IG) (n = 42). Data collection took place in two phases: the first included face-to-face sessions followed by the educational intervention in the IG, and the second included telephone follow-up. The educational intervention included the use of an educational booklet and a brief motivational interview. The groups were homogeneous at baseline. After the intervention, the mean self-efficacy scores of the IG were significantly higher than those of the CG (p < 0.05), and children whose parents/caregivers were in the CG were 1.43 times more likely to experience an asthma crisis than those in the IG. The educational intervention proved effective in increasing parent/caregiver self-efficacy in asthma management and control. Furthermore, children whose parents/caregivers did not receive the educational intervention were more likely to experience an asthma crisis.

Improving inhaler technique and adherence in children

Inhalers are an essential part of the management of asthma in children and young people, however, technique and adherence are often poor. It is essential to improve these through adequate education and training. This article looks at possible reasons behind errors in inhaler use and strategies health professionals can put in place to remedy these, including repeated education, using multiple training formats, and patient involvement.

Atopy and asthma in children born to mothers at risk of gestational diabetes mellitus: a follow-up study

BackgroundGestational diabetes mellitus (GDM) is the most prevalent metabolic disturbance during pregnancy and is associated with adverse outcomes in offspring, including an elevated risk for developing atopic diseases in early childhood. Research is limited regarding only women at risk of GDM among whom some develop GDM while others do not. Information about adverse health outcomes in the offspring of these women is also lacking. The main aim was to assess whether maternal GDM increases the offspring’s risk of atopic dermatitis (AD), asthma and allergic rhinitis at 1, 2 and 5 years of age. The second aim was to analyze the association of other maternal health characteristics on the development of these disorders in offspring.MethodsThe follow-up study group of the Gestational Diabetes Study (GDS), conducted at Tartu University Hospital, Estonia, between 2014 and 2020, comprised 223 mother–child dyads. All women had at least one risk factor for GDM, of whom only some developed GDM. Information about the diagnoses of interest was obtained from Electronic Health Records. Allergen-specific IgE from children’s serum was measured using ImmunoCAP™ Phadiatop™ Infant, with results ≥ 0.35 kU/l considered positive. Statistical analysis was performed using the RStudio software (version 4.3.0).ResultsAccording to our results, only the cases of GDM requiring the use of antidiabetic medications were associated with the development of asthma and/or allergic rhinitis at 2 years of age (aOR 4.68, 95%CI 1.08–20.21, p = 0.039). Maternal obesity (BMI > 30) was associated with offspring´s asthma and/or allergic rhinitis diagnosis at 2 years of age (aOR 3.15, 95%CI 1.03–9.63, p = 0.045).Maternal abnormal weight gain during pregnancy was associated with asthma and/or allergic rhinitis at 5 years of age (aOR 2.76, 95%CI 1.04–7.31, p = 0.041).ConclusionAmong pregnant women at risk for GDM, maternal weight-related factors significantly influence the development of atopic diseases in their children between 1 and 5 years of age, regardless of the GDM diagnosis. This suggests that, besides women with GDM greater attention should also be paid to women at risk but who do not develop GDM, as their children seem to be at higher risk of atopic diseases.

A Laconic Review on Potential Herbals as Antiasthmatic Agents

Asthma is a condition in which a person's airways become inflamed, narrowed, swollen, and produce excessive mucus, making it difficult to breathe due to some allergens such as pollen, dust mites, mould spores, pet dander, particles of cockroach waste etc. The word "asthma" originates from the Greek meaning short of breath, meaning that any patient with breathlessness was asthmatic. The term was refined in the latter part of the 19th Century with the publication of a treatise by Henry Hyde Salter entitled "On Asthma and its Treatment". Asthma is a common condition diagnosed in as many as 25% of Scottish children by the age of 11 years. Childhood asthma is heterogeneous in terms of severity. In traditional system of medicines, plants herbs like ginger, Echinacea, garlic etc. are used in the treatment of asthma. Medicinal plants have been known for millennia and are highly esteemed all over the world as a rich source of therapeutic agents for the prevention of diseases and ailments. The importance of herbal medicine in the treatment of asthma is indisputable. This review highlights the etiology of asthma and few plants which are known to show antiasthmatic activity which are popular in traditional system of medicine.

Networks of human milk microbiota are associated with host genomics, childhood asthma, and allergic sensitization

The human milk microbiota (HMM) is thought to influence the long-term health of offspring. However, its role in asthma and atopy and the impact of host genomics on HMM composition remain unclear. Through the CHILD Cohort Study, we followed 885 pregnant mothers and their offspring from birth to 5 years and determined that HMM was associated with maternal genomics and prevalence of childhood asthma and allergic sensitization (atopy) among human milk-fed infants. Network analysis identified modules of correlated microbes in human milk that were associated with subsequent asthma and atopy in preschool-aged children. Moreover, reduced alpha-diversity and increased Lawsonella abundance in HMM were associated with increased prevalence of childhood atopy. Genome-wide association studies (GWASs) identified maternal genetic loci (e.g., ADAMTS8, NPR1, and COTL1) associated with HMM implicated with asthma and atopy, notably Lawsonella and alpha-diversity. Thus, our study elucidates the role of host genomics on the HMM and its potential impact on childhood asthma and atopy.

Prenatal exposure to phthalates and childhood wheeze and asthma in the PROGRESS cohort

IntroductionPrenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America. MethodsWe assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity. ResultsIn Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54). ConclusionsPrenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease.

Correlation analysis of serum Rac1 level with asthma control, airway inflammatory response and lung function in asthmatic children

ObjectiveTo investigate the correlation between serum Rac1 enzyme (Rac1) level with asthma control, airway inflammatory response and lung function in asthmatic children.MethodsA retrospective analysis was performed on 79 children with asthma who were diagnosed and treated in our hospital from June 2020 to January 2023. According to the severity of the disease, the children were divided into mild group (25 cases), moderate group (30 cases) and severe group (24 cases). 36 healthy children who underwent physical examination at the same period in our hospital were selected as the control group. The state of an illness, control level, serum mRNA Rac1, inflammatory factors, and lung function of the children in two groups were compared between the control group and the observation group.ResultsThe Rac1 mRNA levels, forced vital capacity (FVC), forced expiratory volume in one second/FVC (FEV1/FVC), peak expiratory flow (PEF), and maximum mid-expiratory flow (MMEF) in the observation group were significantly lower than these in the control group (P < 0.05). The tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5), IL-6, and IL-33 in the observation group were markedly higher than these in the control group (P < 0.05). As the state of an illness worsened, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually reduced (P < 0.05), while the levels of TNF-α, IL-5, IL-6, and IL-33 increased (P < 0.05). As the degree of disease control improved, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually elevated (P < 0.05), and the levels of TNF- α, IL-5, IL-6, and IL-33 showed the opposite trend (P < 0.05). Rac1 was negatively related to the levels of TNF-α, IL-5, IL-6 and IL-33 (P < 0.05), and positively to the levels of FVC, FEV1/FVC, PEF and MMEF (P < 0.001). Rac1 mRNA levels, FVC, FEV1/FVC, PEF and MMEF were protective factors, while TNF-α, IL-5, IL-6 and IL-33 were risk factors for the prognosis of children with asthma (P < 0.05).ConclusionChildren with asthma have obviously lower serum Rac1 mRNA levels, higher inflammatory factor levels and lower lung function. Serum Rac1 mRNA level may be associated with better asthma control, lower airway inflammatory response, better lung function and lower disease severity. It has important reference value for the evaluation of the state of an illness, efficacy and prognosis of children with bronchial asthma.

Sequence variants influencing the regulation of serum IgG subclass levels

Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.