Childhood Asthma Research Articles

GSDMB/ORMDL3 Rare/Common Variants Are Associated with Inhaled Corticosteroid Response among Children with Asthma.

Inhaled corticosteroids (ICS) are efficacious in the treatment of asthma, which affects more than 300 million people in the world. While genome-wide association studies have identified genes involved in differential treatment responses to ICS in asthma, few studies have evaluated the effects of combined rare and common variants on ICS response among children with asthma. Among children with asthma treated with ICS with whole exome sequencing (WES) data in the PrecisionLink Biobank (91 White and 20 Black children), we examined the effect and contribution of rare and common variants with hospitalizations or emergency department visits. For 12 regions previously associated with asthma and ICS response (DPP10, FBXL7, NDFIP1, TBXT, GLCCI1, HDAC9, TBXAS1, STAT6, GSDMB/ORMDL3, CRHR1, GNGT2, FCER2), we used the combined sum test for the sequence kernel association test (SKAT) adjusting for age, sex, and BMI and stratified by race. Validation was conducted in the Biorepository and Integrative Genomics (BIG) Initiative (83 White and 134 Black children). Using a Bonferroni threshold for the 12 regions tested (i.e., 0.05/12 = 0.004), GSDMB/ORMDL3 was significantly associated with ICS response for the combined effect of rare and common variants (p-value = 0.003) among White children in the PrecisionLink Biobank and replicated in the BIG Initiative (p-value = 0.02). Using WES data, the combined effect of rare and common variants for GSDMB/ORMDL3 was associated with ICS response among asthmatic children in the PrecisionLink Biobank and replicated in the BIG Initiative. This proof-of-concept study demonstrates the power of biobanks of pediatric real-life populations in asthma genomic investigations.

Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres: expert practical experience and advice

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition.This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines.Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient’s journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working.Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.

Metabolomic profiles during early childhood and risk of food allergies and asthma in multiethnic children from a prospective birth cohort

BackgroundThere are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations. ObjectiveTo identify metabolites which are unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort (the Boston Birth Cohort). MethodsMass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (N=811). FA was diagnosed based on clinical symptoms consistent with an acute hypersensitivity reaction upon food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined based on physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders. ResultsDuring a median follow-up of 11.8±5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (OR=0.65, 95%CI=0.48-0.87) and 1-Oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR=0.77, 95%CI=0.66-0.90) were inversely associated with FA risk. Orotidine (OR=4.73, 95%CI=2.2-10.2) and 4-cholesten-3-one (OR=0.52, 95%CI=0.35-0.77) were the top two metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids. ConclusionIn this U.S. multi-ethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA, asthma, or both. These findings await further validation.

Asthma-chronic obstructive pulmonary disease overlap: Results from a national-multicenter study.

Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have a greater disease burden than those with COPD or asthma alone. In this study, it was aimed to determine the prevalence, risk factors, and clinical features of ACO because there are limited national data in Türkiye. The study was conducted in a cross-sectional design in nine tertiary-care hospitals. The patients followed with a diagnosis of asthma or COPD for at least one year were enrolled in the study. The frequency of ACO and the characteristics of the patients were evaluated in the asthma and COPD groups. The study included 408 subjects (F/M= 205/203, mean age= 56.24 ± 11.85 years). The overall prevalence of ACO in both groups was 20.8% (n= 85). The frequency was higher in the COPD group than in the asthma group (n= 55; 33.3% vs. n= 22; 9.8%), respectively (p= 0.001). Patients with ACO had similarities to patients with COPD in terms of advanced age, sex, smoking, exposure to biomass during childhood, being born in rural areas, and radiologic features. Characteristics such as a history of childhood asthma and allergic rhinitis, presence of chronic sinusitis, NSAID hypersensitivity, atopy, and high eosinophil counts were similar to those of patients with asthma (p<0.001). The annual decline in FEV1 was more prominent in the ACO group (mean= -250 mL) than in the asthma (mean change= -60 mL) and COPD (mean change= -230 mL) groups (p= 0.003). This study showed that ACO was common among patients with asthma and COPD in tertiary care clinics in our country. ACO should be considered in patients with asthma and COPD who exhibit the abovementioned symptoms.

Potential Impact of SOD2 (rs4880; p.Val16Ala) Variant with the Susceptibility for Childhood Bronchial Asthma.

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

A comprehensive environmental exposure indicator and respiratory health in asthmatic children: a case study

The primary goal of asthma management is to achieve and maintain asthma control, which can be influenced by environmental factors. This longitudinal study aimed to construct a comprehensive environmental indicator to predict asthma control in children with asthma in Palermo, Italy. The study included 179 asthmatic children aged 5–16 years. The Normalized Difference Vegetation Index (NDVI) was used to measure green cover, and the Coordination of Information on the Environment (CORINE) framework was used to assess land use based on each home address. A land use regression (LUR) model centered on the home address estimated NO2 exposure for each child using GIS. An environmental indicator, including environmental and personal exposure, was formulated using an additive value model approach. A logistic regression mixed model assessed the association between the environmental indicator and uncontrolled asthma. A probability map of uncontrolled asthma was constructed. In conclusion, a comprehensive environmental indicator proved effective in identifying areas at higher and lower risk of uncontrolled asthma.

Association of factors with childhood asthma and allergic diseases using latent class analysis

We hypothesize that children characterized by deprived factors have poorer health outcomes. We aim to identify clustering of determinants and estimate risk of early childhood diseases. This 1993–2019 longitudinal cohort study combines three Canadian pediatric cohorts and their families. Mothers and children are clustered using latent class analysis (LCA) by 16 indicators in three domains (maternal and newborn; socioeconomic status [SES] and neighbourhood; environmental exposures). Hazard ratios (HR) of childhood asthma, allergic rhinitis (AR), and eczema are quantified with Cox proportional hazard (PH) regression. Rate ratios (RR) of children’s health services use (HSU) are estimated with Poisson regression. Here we report the inclusion of 15,724 mother–child pairs; our LCA identifies four mother-clusters. Classes 1 and 2 mothers are older (30–40 s), non-immigrants with university education, living in high SES neighbourhoods; Class 2 mothers have poorer air quality and less greenspace. Classes 3 and 4 mothers are younger (20–30 s), likely an immigrant/refugee, with high school-to-college education, living in lower SES neighborhoods with poorer air quality and less greenspace. Children’s outcomes differ by Class, in comparison to Class 1. Classes 3 and 4 children have higher risks of asthma (HR 1.24, 95% CI 1.11–1.37 and HR 1.39, 95% CI 1.22–1.59, respectively), and similar higher risks of AR and eczema. Children with AR in Class 3 have 20% higher all-cause physician visits (RR = 1.20, 95% CI 1.10–1.30) and those with eczema have 18% higher all-cause emergency department visits (RR = 1.18, 95% CI 1.09–1.28) and 14% higher all-cause physician visits (RR = 1.14, 95% CI 1.09–1.19). Multifactorial-LCA mother-clusters may characterize associations of children’s health outcomes and care, adjusting for interrelationships.

Volatile sulfur compounds in asthmatic children and adolescents: A cross-sectional study in breath and saliva.

Halitosis in children implies psychosocial repercussions. Risk factors associated with this condition are unclear, and detection methods are inaccurate. To quantify the levels of sulfur-like compounds in children with asthma and healthy children from a novel validated assay, and to establish the risk factors related to halitosis. One hundred and twenty-eight individuals (63 healthy and 65 asthmatic) from 3 to 17 years of age were tested using a passive colorimetric sensor to measure the levels of sulfur-like compounds in breath and saliva. Information was collected on oral hygiene habits, gingival and dental health, breathing type, and dental malocclusion. The mean values of hydrogen sulfide were 4.0 ± 6.8 and 19.7 ± 12.2 ppbv (parts per billion in volume) in the control and asthmatic groups, respectively (p < .001). The presence of higher concentrations of sulfur compounds was significantly associated (p < .05) with the presence of gingival inflammation, tongue coating, dental plaque, mouth breathing, hypomineralization, age, tongue brushing, and the use of dental floss. The level of sulfur in breath and saliva was significantly higher in patients with asthma. These results can serve as a precedent to raise awareness among paediatricians and parents about oral hygiene care in children and adolescents.

Prevalence of asthma triggers and control status among pediatric asthmatic patients in Saudi Arabia

Aim This study aims to assess the prevalence of asthma triggers and control status among pediatric asthmatic patients in Saudi Arabia. Methods From October 2015 to March 2016, an Arabic version of the Asthma Trigger Inventory questionnaire and asthma control test (ACT) were distributed to 200 parents of children diagnosed with asthma at the pulmonary clinic of King Fahad Medical City in Riyadh, Saudi Arabia. Data were collected and analyzed using the Statistical Package for Social Sciences (SPSS) software version 29. Descriptive statistics of the participants were presented in frequencies, percentages, means, and standard deviations for categorical variables. Results The survey data revealed that the most prevalent asthma triggers among pediatric asthmatic children in Saudi Arabia were Arabic incense (Bakhour) with a mean score of 3.76 (±1.3), followed by being excited 3.70 (±1.5), and stress at home 3.58 (±1.4). Furthermore, the degree of asthma control among children with asthma in Saudi Arabia was 72.0% with a mean score of 17.7 (±4.7) for the ACT, indicating partial degree of asthma. Conclusions Arabic incense (Bakhour) and psychological stimuli emerged as significant determinants of asthma triggers in Saudi Arabian children diagnosed with asthma. Further studies are warranted to elucidate the physiological mechanisms underpinning the response to Arabic incense (Bakhour).

Bronchiolitis recovery and the use of High Efficiency Particulate Air (HEPA) Filters (The BREATHE Study): study protocol for a multi-center, parallel, double-blind, randomized controlled clinical trial

BackgroundAcute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM2.5), a common component of household air pollution that is strongly linked to health effects.MethodsBREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child’s sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM2.5 levels in the home.DiscussionWe propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization.Trial registrationNCT05615870. Registered on November 14, 2022.

Clinical efficacy of montelukast sodium combination therapy for cough variant asthma in children: A meta-analysis.

This meta-analysis aims to assess the clinical effectiveness of combination therapy with montelukast sodium for the treatment of cough variant asthma (CVA) in children, intending to provide clinical evidence and data to guide the selection of clinical therapy. A literature review was conducted using numerous databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science, from inception to December 2023. Trials meeting the criteria for the combined treatment of montelukast sodium for CVA in children were included. Stata 16.0 software was utilized for meta-analysis. The combined treatment group received montelukast sodium in addition to the control group, while the control group received budesonide, fluticasone propionate, salmeterol-fluticasone, or ketotifen alone. This investigation included 18 papers. All subjects were from the Chinese population. Compared to the control group, the combined treatment group demonstrated a higher effective rate (relative ratio [RR] = 1.23, 95% confidence interval [CI]: 1.18-1.29, p < .001), but no difference in the incidence of adverse reactions (RR = 0.65, 95%CI: 0.42-1.02, p = .060) after treatment. Moreover, the peak expiratory flow (PEF) (SMD = 1.69, 95%CI: 1.09-2.30, p < .001), forced vital capacity (FVC) (SMD = 1.67, 95%CI: 0.94-2.39, p < .001), forced expiratory volume in 1 s (FEV1) (SMD = 1.74, 95%CI: 1.09-2.40, p < .001), and FEV1/FVC (SMD = 1.84, 95%CI: 0.41-3.28, p = .012) were significantly higher in the combined treatment group than in the control group after treatment. Compared with the control group, the levels of tumor necrosis factor-α (SMD = -2.38, 95%CI: -3.22to -1.55, p < .001), IL-4 (SMD = -2.65, 95%CI: -3.26 to-2.04, p < .001), and IgE (SMD = -2.98, 95%CI: -3.24 to -2.72, p < .001) were significantly lower in the combined treatment group after treatment. The combined use of montelukast sodium in the treatment of pediatric CVA in China is associated with a significant clinical effect, making it a reasonable therapeutic approach.

Recent Insights into the Environmental Determinants of Childhood Asthma.

Ubiquitous environmental exposures, including ambient air pollutants, are linked to the development and severity of childhood asthma. Advances in our understanding of these links have increasingly led to clinical interventions to reduce asthma morbidity. We review recent work untangling the complex relationship between air pollutants, including particulate matter, nitrogen dioxide, and ozone and asthma, such as vulnerable windows of pediatric exposure and their interaction with other factors influencing asthma development and severity. These have led to interventions to reduce air pollutant levels in children's homes and schools. We also highlight emerging environmental exposures increasingly associated with childhood asthma. Growing evidence supports the present threat of climate change to children with asthma. Environmental factors play a large role in the pathogenesis and persistence of pediatric asthma; in turn, this poses an opportunity to intervene to change the course of disease early in life.

Association between Second-Hand Exposure to E-Cigarettes at Home and Exacerbations in Children with Asthma.

Several studies have shown the effects of e-cigarettes in adults. Nowadays, few data are available in the pediatric population. This study aims to assess the relationship between asthma exacerbations and home exposure to e-cigarettes. We conducted a pilot, retrospective, monocenter, observational study. Demographic and clinical data were collected, including number of asthma exacerbations, need for rescue therapy and/or therapeutic step-up, and Asthma Control Test (ACT) and children-Asthma Control Test (c-ACT) scores. The cohort consisted of 54 patients (5-17 years old), divided into two groups: A, including patients exposed to e-cigarette aerosols; B, including unexposed patients. The statistical analysis showed no relevant variation in the number of asthma symptomatic days and need for rescue therapy in group A versus group B (p = 0.27 and 0.19, respectively). There were no statistically significant variations when also considering the number of patients who needed a therapeutic step-up (p = 0.3). The mean values of ACT and c-ACT were, respectively, 17.2 ± 7.6 and 18.3 ± 5.6 in group A and 19.6 ± 3.8 and 14.6 ± 5.8 in group B (p = 0.3 and 0.4, respectively). Although we did not find a statistically significant correlation between second-hand e-cigarette exposure and asthma exacerbations, our findings suggest that asthmatic children exposed second-hand to e-cigarettes may have increased risk of asthma symptomatic days. Future research is warranted.

Association between polymorphisms on chromosome 17q12-q21 and rhinovirus-induced interferon responses

BackgroundSingle nucleotide polymorphisms (SNPs) in genes on chromosome 17q12-q21 are associated with childhood-onset asthma and rhinovirus-induced wheezing. There is little mechanistic data linking chromosome 17q12-q21 to wheezing illness. ObjectiveTo investigate whether 17q12-q21 risk alleles may be associated with impaired interferon (IFN) responses to rhinovirus. MethodsIn a population-based birth cohort of European ancestry, we stimulated peripheral blood mononuclear cells (PBMCs) with rhinovirus-A1 (RV-A1) and rhinovirus-A16 (RV-A16) and measured IFN and IFN-induced chemokine CXCL10/IP10 responses in supernatants. We investigated associations between virus-induced cytokines and six SNPs in 17q12-q21. Bayesian profile regression was applied to identify clusters of individuals with different immune response profiles and genetic variants. ResultsFive SNPs (in high linkage disequilibrium, r2≥0.8) were significantly associated with RV-A1-induced IFN-β (rs9303277: P=0.010; rs11557467: P=0.012; rs2290400: P=0.006; rs7216389: P=0.008; rs8079416: P=0.005). A reduction in RV-A1-induced IFN-β was observed among individuals carrying asthma risk alleles. There were no significant associations for RV-A1-induced IFN-α or CXCL10, or for any RV-A16-induced IFN/CXCL10. Bayesian profile regression analysis identified three clusters which differed in IFN-β induction to RV-A1 (low, medium and high). The typical genetic profile of the cluster associated with low RV-A1-induced IFN-β responses was characterised by a very high probability of being homozygous for the asthma risk allele for all SNPs. Children with persistent wheeze were almost 3-times more likely to be in clusters with reduced/average RV-A1-induced IFN- β responses than in the high immune response cluster. ConclusionsPolymorphisms on chromosome 17q12-q21 are associated with rhinovirus-induced IFN-β, suggesting a novel mechanism (impaired IFN-β induction) linking 17q12-q21 risk alleles with asthma/wheeze.

Associations between cord blood acetaminophen biomarkers and childhood asthma with and without allergic comorbidities

BackgroundPrevious studies have linked prenatal acetaminophen use to increased asthma risk in children. However, none have explored this association while differentiating between asthma cases with and without other allergic conditions or by employing objective biomarkers to assess acetaminophen exposure. ObjectiveTo evaluate whether the detection of acetaminophen biomarkers in cord blood is associated with the subgroups of asthma both with and without allergic comorbidities in children. MethodsAcetaminophen biomarkers, including unchanged acetaminophen and acetaminophen glucuronide, were measured in neonatal cord blood samples from the Boston Birth Cohort. Asthma subgroups were defined on the basis of physician diagnoses of asthma and other allergic conditions (atopic dermatitis and allergic rhinitis). Multinomial regressions were used to evaluate the associations between acetaminophen biomarkers and asthma subgroups, adjusting for multiple confounders, including potential indications for maternal acetaminophen use such as maternal fever. ResultsThe study included 142 children with asthma and at least 1 other allergic condition, 55 children with asthma but no other allergic condition, and 613 children free of asthma. Detection of acetaminophen in cord blood, reflecting maternal exposure to acetaminophen shortly before delivery, was associated with 3.73 times the odds of developing asthma without allergic comorbidities (95% CI: 1.79-7.80, P = .0004). In contrast, the detection of acetaminophen in cord blood was not associated with an elevated risk of asthma with allergic comorbidities. Analysis of acetaminophen glucuronide yielded consistent results. ConclusionIn a prospective birth cohort, cord blood acetaminophen biomarkers were associated with an increased risk of childhood asthma without allergic comorbidities, but were not associated with childhood asthma with allergic comorbidities.

A health inequality analysis of childhood asthma prevalence in urban Australia

Long-standing health inequalities in Australian society that were exposed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were described as "fault lines" in a recent call to action by a consortium of philanthropic organizations. With asthma a major contributor to childhood disease burden, studies of its spatial epidemiology can provide valuable insights into the emergence of health inequalities early in life. The aims of this study were to characterize the spatial variation of asthma prevalence among children living within Australia's 4 largest cities and quantify the relative contributions of climatic and environmental factors, outdoor air pollution, and socioeconomic status in determining this variation. A Bayesian model with spatial smoothing was developed to regress ecologic health status data from the 2021 Australian Census against groups of explanatory covariates intended to represent mechanistic pathways. The prevalence of asthma in children aged 5 to 14 years averages 7.9%, 8.2%, 8.5%, and 7.6% in Sydney, Melbourne, Brisbane, and Perth, respectively. This small inter-city variation contrasts against marked intracity variation at the small-area level, which ranges from 6% to 12% between the least and most affected locations in each. Statistical variance decomposition on a subsample of Australian-born, nonindigenous children attributes 66% of the intracity spatial variation to the assembled covariates. Of these covariates, climatic and environmental factors contribute 30%, outdoor air pollution contributes 19%, and areal socioeconomic status contributes the remaining 51%. Geographic health inequalities in the prevalence of childhood asthma within Australia's largest cities reflect a complex interplay of factors, among which socioeconomic status is a principal determinant.

Association between Outdoor and Indoor Air Pollution Sources and Atopic Eczema among Preschool Children in South Africa.

The objective of the study was to investigate the association between outdoor and indoor air pollution sources and atopic eczema among preschool children in South Africa. A cross-sectional design, following the International Study of Asthma and Allergies in Childhood (ISAAC) Phase III protocol, was applied. The study was conducted in Mabopane and Soshanguve Townships in the City of Tshwane Metropolitan Municipality in Gauteng, South Africa. A total population of 1844 preschool children aged 7 years and below participated in the study; 1840 were included in the final data analysis. Data were analyzed using multilevel logistic regression analysis. The prevalence of eczema ever (EE) and current eczema symptoms (ESs) was 11.9% and 13.3%, respectively. The use of open fires (paraffin, wood, or coal) for cooking and heating increased the likelihood of EE (OR = 1.63; 95% CI: 0.76-3.52) and current ESs (OR = 1.94; 95% CI: 1.00-3.74). Environmental tobacco smoke (ETS) exposure at home increased the likelihood of EE (OR = 1.66; 95% CI: 1.08-2.55) and current ESs (OR = 1.61; 95% CI: 1.07-2.43). Mothers or female guardians smoking cigarettes increased the likelihood of EE (OR = 1.50; 95% CI: 0.86-2.62) and current ESs (OR = 1.23; 95% CI: 0.71-2.13). The use of combined building materials in homes increased the likelihood of EE, and corrugated iron significantly increased the likelihood of current ESs. The frequency of trucks passing near the preschool children's residences on weekdays was found to be associated with EE and current ESs, with a significant association observed when trucks passed the children's residences almost all day on weekdays. Atopic eczema was positively associated with exposure to outdoor and indoor air pollution sources.

Childhood asthma biomarkers including zinc: An exploratory cross-sectional study.

Childhood bronchial asthma (BA) is a chronic inflammatory respiratory disease. Nutritional conditions, including zinc deficiency, can affect such allergic disorders. To outline the difference in serum zinc levels between asthmatic children and healthy controls. A cross-sectional study was carried out at Children's Hospital, Cairo University, investigating serum zinc levels in children with BA (n = 40) and healthy children (n = 21). Other markers included serum ferritin, iron, hemoglobin (Hb), and immunoglobulin E (IgE) levels. Independent t-tests and Mann-Whinny tests were used for comparisons. The Kruskal-Wallis test was applied to compare serum ferritin and IgE levels with regard to asthma severity. Spearman's rank correlation was performed to explore the relationship between serum ferritin levels and both iron and Hb levels in asthmatic children. Children with BA had higher levels of zinc, yet the difference was not significant (P = 0.115). Serum ferritin and IgE levels were significantly higher in asthmatic children (P = 0.006 and 0.001, respectively), yet their levels did not differ significantly by severity (P = 0.623 and 0.126, respectively). There was a nonsignificant weak correlation between serum ferritin levels and both serum iron and Hb levels. Serum zinc levels do not seem to differ between asthmatic children and healthy children. Serum ferritin levels may be a marker of asthma control. Serum IgE levels are not markers of asthma severity.

Circulating miRNAs associate with historical childhood asthma hospitalization in different serum vitamin D groups

BackgroundVitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels.MethodsWe sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA).ResultsWe identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels.ConclusionsmiRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.