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Project description:Maternal asthma (MA) is among the most consistent risk factors for asthma in children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 nonasthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene coexpression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA and MA cases, respectively, compared with controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five comethylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared with NMA cases (P = 7.1 × 10−3), a finding that replicated in nasal epithelial cells from an independent cohort (P = 0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum immunoglobulin E, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that MA alters diverse epigenetically mediated pathways that lead to distinct subtypes of severe asthma in adults, including hard-to-treat T2-low asthma.
| S-EPMC9214527 | biostudies-literature
Project description:Maternal asthma (MA) is among the most consistent risk factors for asthma in her children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 non-asthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene co-expression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA or MA cases, respectively, compared to controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five co-methylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared to NMA cases (P=7.1x10-3), a finding that replicated in nasal epithelial cells from an independent cohort (P=0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum IgE, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that maternal asthma alters diverse epigenetically-mediated pathways that lead to distinct subtypes of severe asthma in adults including hard-to-treat T2-low asthma.
2022-05-04 | GSE201955 | GEO
Project description:Maternal asthma (MA) is among the most consistent risk factors for asthma in her children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 non-asthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene co-expression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA or MA cases, respectively, compared to controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five co-methylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared to NMA cases (P=7.1x10-3), a finding that replicated in nasal epithelial cells from an independent cohort (P=0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum IgE, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that maternal asthma alters diverse epigenetically-mediated pathways that lead to distinct subtypes of severe asthma in adults including hard-to-treat T2-low asthma.
2022-05-02 | GSE201872 | GEO
Project description:DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma
| PRJNA867702 | ENA
Project description:DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma (RNA sequencing)
| PRJNA833856 | ENA
Project description:DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma (DNA methylation)
| PRJNA833397 | ENA
Project description:Mothers' knowledge about childhood asthma influences management practices and disease control, but validating knowledge/practice questionnaires is difficult due to the lack of a gold standard. We hypothesized that Latent Class Analysis (LCA) could help identify underlying mother profiles with similar knowledge/practices. A total of 438 mothers of asthmatic children answered a knowledge/practice questionnaire. Using answers to the knowledge/practice questionnaire as manifest variables, LCA identified two classes: Class 1, "poor knowledge" (33%); Class 2, "good knowledge" (67%). Classification accuracy was 0.96. Mothers in Class 2 were more likely to be aware of asthma-worsening factors and indicators of attacks. Mothers in Class 1 were more likely to prevent exposure to tobacco smoke (91.1% vs. 78.8%, p = 0.005). For attacks, mothers in Class 2 were more likely to go to the emergency department and follow the asthma action plan. Mothers in Class 2 more frequently had a high education level (79.5% vs. 65.2%, p = 0.004). Children in Class 2 more frequently had fully controlled asthma (36.7% vs. 25.9%, p = 0.015) and hospitalizations for attacks in the previous 12 months (24.2% vs. 10.7%, p = 0.003). LCA can help discover underlying mother profiles and plan targeted educational interventions.
| S-EPMC8909612 | biostudies-literature
Project description:BackgroundThe timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception.ObjectiveWe sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception.MethodsWe used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell-derived IL-1β levels were measured by means of ELISA.ResultsNeonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma-associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1β, an innate inflammatory mediator.ConclusionsThe trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory.
| S-EPMC5479765 | biostudies-literature
Project description:It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O₃) and nitrogen dioxide (NO₂) were estimated at the child's residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO₂ (4.95 ppb), O₃ (3.85 ppb), and PM2.5 (1.82 μg/m³) of 1.095 (95% CI 1.058-1.131), 1.052 (95% CI 1.037-1.066) and 1.025 (95% CI 1.017-1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO₂ or O₃. Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth.
| S-EPMC4997457 | biostudies-literature
Project description: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.
| S-EPMC11406832 | biostudies-literature