A Comparison of Activity Participation between Children with and without Asthma

Background: Asthma affects approximately 6 million children in the United States and can greatly impact quality of life and occupational engagement. Although occupational therapists are well-equipped to address participation limitations, insufficient evidence exists to support the role of occupational therapists in asthma treatment. Method: The purpose of this study was to further understand the occupational limitations experienced by children with asthma. We also explored a dual diagnosis of asthma and obesity. The participants included children with (n = 84) and without (n = 63) asthma living in New York City. The Child Behavior Checklist, Youth Self Report, Brief Respiratory Questionnaire, and accelerometer data were used to examine occupational participation. Results: Although accelerometry data demonstrated that children with asthma were equally as active as their non-asthmatic peers, the participants with asthma perceived themselves as participating more in sedentary occupations and were less likely to be members of sports teams. They also had more missed school days and nights of troubled sleep. The children with both asthma and obesity reported the highest level of activity limitations. Conclusion: This study illustrates specific limitations experienced by children with asthma and supports the need for occupational therapy intervention. Future studies are needed to design and assess interventions that will support the addition of occupational therapists to multidisciplinary asthma treatment teams

Reduced mouse allergen is associated with epigenetic changes in regulatory genes, but not mouse sensitization, in asthmatic children

Chronic exposure to mouse allergen may contribute greatly to the inner-city asthma burden. We hypothesized that reducing mouse allergen exposure may modulate the immunopathology underlying symptomatic pediatric allergic asthma, and that this occurs through epigenetic regulation. To test this hypothesis, we studied a cohort of mouse sensitized, persistent asthmatic inner-city children undergoing mouse allergen-targeted integrated pest management (IPM) vs education in a randomized controlled intervention trial. We found that decreasing mouse allergen exposure, but not cockroach, was associated with reduced FOXP3 buccal DNA promoter methylation, but this was unrelated to mouse specific IgE production. This finding suggests that the environmental epigenetic regulation of an immunomodulatory gene may occur following changing allergen exposures in some highly exposed cohorts. Given the clinical and public health importance of inner-city pediatric asthma and the potential impact of environmental interventions, further studies will be needed to corroborate changes in epigenetic regulation following changing exposures over time, and determine their impact on asthma morbidity in susceptible children

Additional file 1: Figure S1. of Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization

Conserved promoter regions. Black lines mark loci that are conserved between human and mouse in the promoter region of IL4, IFNγ, and ARG2. White areas are not conserved. Conserved regions were identified using Standard Nucleotide BLAST (blastn for more dissimilar regions; https://blast.ncbi.nlm.nih.gov/Blast.cgi.) for the 400 nucleotides upstream of the transcriptional start site (TSS) in the human sequence. The NOS2A promoter region under investigation is not conserved between mice and human. Figure S2: Schematic demonstration of collected measures. Numbers in the box represent the number of participants. N:n = number of repeat subjects: number of observations. Grey dotted box indicates two measures (both time 1 and time 2, 6 months apart) available and white box only one measure (Time 1) available. N = 10 participants dropped due to invalid personal or residential air pollution measures. N = 17 participants were further excluded from the analysis due to missing total IgE (N = 16) and invalid DNA methylation due to technical failures in the laboratory (N = 1), resulting in N = 136 of the final sample size. Figure S3: Correlations between day 1 and day 6 buccal cell DNA methylations of (a) IL4 (CpG−326,CpG−48, (b) IFNγ (CpG−186,CpG−54), and (c) NOS2A (CpG+5099, CpG+5106) and (d) ARG2 (average methylation of CpG−32, CpG−30, and CpG−26), Spearman correlation coefficient presented. (DOCX 466 kb

Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter

Abstract Background Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 (FOXP3) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC). Methods We performed a cross-sectional study of 135 children ages 9–14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter. Results In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation (p > 0.05). However, in stratified analyses, among children with higher BC exposure (≥1200 ng/m3), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs −77, −65, and −58) (β estimate = −2.37%, p  0.05). Differences across strata were statistically significant (p interaction = 0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV1/FVC (β estimate = −0.40%, p < 0.01) and reduced FEF25–75% (β estimate = −1.46%, p < 0.01). Conclusions Physical activity in urban children appeared associated with lower FOXP3 promoter methylation, a possible indicator of greater Treg function, under conditions of high BC exposure. Reduced FOXP3 promoter methylation was associated with higher lung function. These findings suggest that physical activity may induce immunologic benefits, particularly for urban children with greater risk of impaired lung function due to exposure to higher air pollution. FOXP3 promoter buccal cell methylation may function as a useful biomarker of that benefit

Additional file 1: Table S1. of Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children

Promoter region CpG locations and rationale. Table S2. Primers for PCR and pyrosequencing. Table S3. Intraclass correlation coefficients (ICC) among repeated measures of buccal cell DNA methylation. Table S4. Associations between residential PM2.5 and Day 6 DNA methylation: by asthma and overweight. Table S5. Associations between residential V and Day 6 DNA methylation: by asthma and overweight. Figure S1. Targeted CpG sites in promoter region. Figure S2. Seasonal variations in (a) PM2.5 and (b) vanadium (V). Figure S3. Repeated residential indoor measures of (a) PM2.5 and (b) vanadium (V), 6 months later. Figure S4. Distribution of percent DNA methylation of IL4, IFNγ, NOS2A, and ARG2 at Day 6. Figure S5. Correlation matrix for Day 6-buccal cell DNA methylations of IL4, IFNγ, NOS2A, and averaged ARG2 at Time 1. (DOCX 286 kb

Additional file 1: Figure S1. of Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter

Sampling scheme for accelerometer, black carbon (BC), buccal swabs for DNA and RNA analysis and spirometry. Figure S2. Schematic representation of the FOXP3 gene and the six CpG sites in the promoter region that were investigated. TSS transcription start site, TSDR Treg-specific demethylated region, CNS conserved non-coding sequence. Figure S3. Correlations of FOXP3 methylation across promoter regions and with mRNA relative expression. Figure S4. Distribution of FOXP3 promoter methylation in females vs. males stratified by physical activity (active vs. non-active). Females have lower FOXP3 promoter methylation compared to males. Figure S5. Distribution of FOXP3 promoter methylation in females vs. males stratified by BC concentration (low vs. high). Females have lower FOXP3 promoter methylation compared to males. Figure S6. Distribution of FOXP3 promoter methylation stratified by combined activity and BC concentration in females (n = 67). Figure S7. Distribution of FOXP3 promoter methylation stratified by combined activity and BC concentration in males (n = 68)

Additional file 2: Table S1. of Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter

Primers for PCR and pyrosequencing experiments. Table S2. Correlations of day 1 vs. day 6 FOXP3 methylation and mRNA expression. Table S3. Among children with high BC exposure, there is a trend towards active children (coded 1) having a greater odds of lower methylation compared to non-active children (coded 0). Table S4. Higher FOXP3 promoter 2 methylation is associated with overall lower lung function (n = 135). Table S5. The relationship between FOXP3 promoter 2 methylation and lung function does not significantly vary by high vs. low BC exposure. Table S6. Among children with high BC, the association between physical activity and FOXP3 promoter methylation is greater in females. Table S7. The relationship between FOXP3 promoter methylation and lung function is greater among females compared to that among males

Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12–1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13–1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25–1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08–1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15–1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12–1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15–1·44], p<0·0001). Interpretation: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12–21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.6 month embargo; published: 01 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]