Methylation of IL-2 promoter at birth alters the risk of asthma exacerbations during childhood.
ABSTRACT: BACKGROUND:Epigenetic modifications may have a role in asthma susceptibility. OBJECTIVE:To investigate whether epigenetic modification at birth of a CpG site necessary for the regulation of IL-2 transcription (IL-2 Site1) is associated with the development of asthma during childhood. METHODS:Methylation of IL-2 Site1 was assessed in cord blood from 303 children (225 with atopic mothers); as controls, we measured methylation of a site not important in the transcription of IL-2 (IL-2 Site7) and methylation of the LINE-1 repetitive element. Children were followed to the age of 8 years. Information on severe asthma exacerbations and hospital admissions was collected from child's primary care medical record. To account for potential confounding by bronchiolitis, we used exacerbations/hospitalizations after age 1 year as primary outcomes. RESULTS:There were 49 severe exacerbations amongst 33 children, and 22 hospital admissions amongst 11 children. The risk of asthma exacerbation increased 1.07-fold (95% CI 1.01-1.14, P = 0.03) and the risk of hospital admission increased 1.12-fold (95% CI 1.04-1.20, P = 0.002) for each one per cent increase in IL-2 Site1 methylation. Children who were admitted to hospital at any time-point had significantly higher IL-2 Site1 methylation than children not admitted to hospital (P = 0.007). There was a significant interaction between age at exacerbation (P = 0.03) or hospital admission (P = 0.02) and methylation, with the effect of methylation increasing with increasing age. Methylation of the control IL-2 Site7 or LINE-1 was not a significant predictor of asthma exacerbations/hospital admission, and we found no association between IL-2 Site1 methylation and hospital admissions for other reasons (0.99 [0.92-1.06]). Cord blood mononuclear cell phytohemagglutinin-stimulated lymphoproliferative responses decreased significantly with increasing IL-2 Site1 methylation (P < 0.001). CONCLUSIONS:Increasing methylation in cord blood of a functional CpG site in the IL-2 promoter is associated with increased likelihood of severe asthma exacerbations and hospital admissions for asthma/wheeze between ages of 2 and 8 years.
Project description:BACKGROUND: Population-based data on hospital admissions for children aged 0-17 years concerning all respiratory diseases are scarce. This study examined hospital admissions in relation to the preceding consultations in general practice in this age group. METHODS: Data on children aged 0-17 years with respiratory diseases included in the Second Dutch National Survey of General Practice (DNSGP-2) were linked to all hospital admissions in the Dutch National Medical Registration. Admission rates for respiratory diseases were calculated. Data were analysed using multivariate logistic regression. RESULTS: Of all 79,272 children within the DNSGP-2, 1.8% were admitted to hospital for any respiratory diagnosis. The highest admission rates per 1000 children were for chronic disease of tonsils and adenoids (12.9); pneumonia and influenza (0.97); and asthma (0.92). Children aged 0-4 years and boys were admitted more frequently. Of children with asthma, 2.3% were admitted for respiratory diseases. For asthma, admission rates varied by urbanisation level: 0.47/1000 children/year in cities with ? 30,000 inhabitants, 1.12 for cities with ? 50,000 inhabitants, and 1.73 for the three largest cities (p = 0.002). Multivariate logistic regression showed that within two weeks after a GP consultation, younger age (OR 0.81, 95% CI 0.76-0.88) and more severe respiratory diseases (5.55, 95% CI 2.99-8.11) predicted hospital admission. CONCLUSIONS: Children in the general population with respiratory diseases (especially asthma) had very low hospital admission rates. In urban regions children were more frequently admitted due to respiratory morbidity. For effectiveness studies in a primary care setting, hospital admission rates should not be used as quality end-point.
Project description:<h4>Background</h4>Outdoor aeroallergens are one of a number of environmental factors thought to precipitate asthma exacerbations.<h4>Aims</h4>To investigate the short term associations between daily fungal spore concentrations and indicators of daily asthma exacerbations in a large urban population.<h4>Methods</h4>Daily counts of visits for asthma to family physicians and hospital accident and emergency (A&E) departments and emergency hospital admissions in London 1992-93 were compiled. Daily concentrations of fungal spores (30 species), daily average temperature, humidity, and concentrations of pollen and outdoor air pollution were also compiled. The analysis was restricted to the period when fungal spores were most prevalent (June to mid October). Non-parametric regression time series methods were used to assess associations controlling for seasonality, day of week, and meteorological factors. The sensitivity of the findings to the inclusion of pollen and air pollution into the models was also assessed.<h4>Results</h4>In children aged 0-14 years the relative risks for increases in the number of A&E visits and hospital admissions associated with changes in fungal spore concentrations from the lower to upper quartiles were 1.06 (95% CI 0.94 to 1.18) and 1.07 (0.97 to 1.19) respectively. The addition of pollen or air pollutants had little impact on the observed associations. A number of individual spore taxa, in particular Alternaria, Epicoccum, Agrocybe, Mildews, and both coloured and colourless Basidiospores and Ascospores, were associated with increases in the number of emergency visits and hospital admissions for asthma, although the precision of these estimates were low. No evidence was found for associations in adults.<h4>Conclusions</h4>Fungal spore concentrations may provoke or exacerbate asthma attacks in children resulting in visits to A&E departments and emergency hospital admissions. These findings were unlikely to be due to confounding by other environmental factors. The associations were comparable to those observed for ambient air pollution from similarly designed studies.
Project description:To compare risk factors for severe disease as measured by admission to hospital and intensive care unit (ICU) and other clinical outcomes in children with pandemic H1N1 (pH1N1) versus those with seasonal influenza.Retrospective analysis of children admitted to hospital with pH1N1 versus seasonal influenza A.Canadian tertiary referral children's hospital.All laboratory-identified cases of pH1N1 in children younger than 18 years admitted to hospital in 2009 (n=176) and all seasonal influenza A cases admitted to hospital from influenza seasons 2004-2005 to 2008-2009 (n=200). Children with onset of symptoms more than 3 days after admission were excluded.Primary outcomes include admission to hospital and ICU and need for mechanical ventilation. Secondary outcomes include length of stay in hospital and duration of supplemental oxygen requirement.Children admitted with pH1N1 were older than seasonal influenza A admissions (hospital admission: 6.5 vs 3.3 years, p<0.01; ICU admission: 7.3 vs 3.6 years, p=0.02). Children hospitalised with pH1N1 were more likely to have a pre-existing diagnosis of asthma (15% vs 5%, p<0.01); however, there was no difference in the severity of pre-existing asthma between the two groups. After controlling for obesity, asthma (OR 4.59, 95% CI 1.42 to 14.81) and age ?5 years (OR 2.87, 95% CI 1.60 to 5.16) were more common risk factors in admitted children with pH1N1. Asthma was a significant predictor of the need for intensive care in patients with pH1N1 (OR 4.56, 95% CI 1.16 to 17.89) but not in patients with seasonal influenza A.While most pH1N1 cases presented with classic influenza-like symptoms, risk factors for severe pH1N1 disease differed from seasonal influenza A. Older age and asthma were associated with increased admission to hospital and ICU for children with pH1N1.
Project description:Universal health coverage (UHC) aims to improve child health through preventive primary care and vaccine coverage. Yet, in many developed countries with UHC, unplanned and ambulatory care sensitive (ACS) hospital admissions in childhood continue to rise. We investigated the relation between preventive primary care and risk of unplanned and ACS admission in children in a high-income country with UHC.We followed 319,780 children registered from birth with 363 English practices in Clinical Practice Research Datalink linked to Hospital Episodes Statistics, born between January 2000 and March 2013. We used Cox regression estimating adjusted hazard ratios (HR) to examine subsequent risk of unplanned and ACS hospital admissions in children who received preventive primary care (development checks and vaccinations), compared with those who did not.Overall, 98% of children had complete vaccinations and 87% had development checks. Unplanned admission rates were 259, 105 and 42 per 1000 child-years in infants (aged <?1 year), preschool (1-4 years) and primary school (5-9 years) children, respectively. Lack of preventive care was associated with more unplanned admissions. Infants with incomplete vaccination had increased risk for all unplanned admissions (HR 1.89, 1.79-2.00) and vaccine-preventable admissions (HR 4.41, 2.59-7.49). Infants lacking development checks had higher risk for unplanned admission (HR 4.63, 4.55-4.71). These associations persisted across childhood. Children who had higher consulting rates with primary care providers also had higher risk of unplanned admission (preschool children: HR 1.17, 1.17-1.17). One third of all unplanned admissions (62,154/183,530) were for ACS infectious illness. Children with chronic ACS conditions, asthma, diabetes or epilepsy had increased risk of unplanned admission (HR 1.90, 1.77-2.04, HR 11.43, 8.48-15.39, and HR 4.82, 3.93-5.91, respectively). These associations were modified in children who consulted more in primary care.A high uptake of preventive primary care from birth is associated with fewer unplanned and ACS admissions in children. However, the clustering of poor health, a lack of preventive care uptake, and social deprivation puts some children with comorbid conditions at very high risk of admission. Strengthening immunisation coverage and preventive primary care in countries with poor UHC could potentially significantly reduce the health burden from hospital admission in children.
Project description:There are limited data on reasons for hospital admission among patients dependent on substances other than alcohol. We compared primary discharge diagnoses for heroin- or cocaine-dependent patients to non-dependent patients.We evaluated a cohort of patients admitted to a general medicine service at a public teaching hospital during July 2005-June 2008. Through bedside interviews, we identified patients who had substance-use disorders. We categorized patients by substance used, route of administration, and dependent or non-dependent use. We grouped diagnostic codes (i.e., ICD-9) using Healthcare Utilization Project categories. We excluded HIV-infected patients.Of 11,397 patients, 341 (3.0%) were dependent on inhalational heroin, 260 (2.3%) on non-injection cocaine, and 106 (0.9%) on injection heroin. Compared to non-dependent patients, inhalational heroin-dependent patients were over three-fold more likely to have been admitted for respiratory diseases (28% vs. 8%, p<0.01); this association was strongest for asthma exacerbation (OR=7.0; 95% CI, 4.7 to 70.4, p<0.01). Of the 225 admissions for an asthma exacerbation, 44 (19.6%) had co-occurrent heroin-dependence. The most frequent diagnostic category among cocaine-dependent patients was circulatory, which was similar to non-dependent patients (22% vs. 21%, p=0.92).There is a strong association between heroin dependence and hospital admission for an asthma exacerbation. Provision of specialized substance-use treatment for inhalational heroin users will be necessary to reduce the frequency of exacerbations and repeat hospital admissions.
Project description:BACKGROUND:Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap. METHODS:We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors. RESULTS:Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]). CONCLUSION:Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.
Project description:BACKGROUND:Significant numbers of chronic obstructive respiratory disease patients are readmitted for Acute Exacerbation (AE) within 30 days of discharge. And these early readmissions have serious clinical and socioeconomic consequences. The objective of our study was to determine the rate of readmission within 30 days of discharge and it's predictors among patients treated for acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). METHODS:A prospective cohort study involving 130 patients (asthma = 59, COPD = 71) was conducted from April-September, 2019, in Jimma Medical Center (JMC), South-West Ethiopia. Socio-demographic, clinical, laboratory, and drug-related data were recorded at admission and during hospital stay. Cox regression analysis was performed to identify risk factors for readmissions following an AE of asthma and COPD. RESULTS:During the study period, 130 (male, 78(60%)) patients were admitted with AE of asthma and COPD. The median age was 59(IQR, 50-70) years. Of 130 patients, 21(18.10%) had a new AE of asthma and COPD that required hospitalization in the 30 days after discharge. The overall median survival time to 30-day readmission was 20 days (IQR, 16-29). Multivariate analysis revealed prolonged use of oxygen therapy (AHR = 4.972, 95% CI [1.041-23.736] and frequent hospital admissions (AHR = 11.482 [1.308-100.793]) to be independent risk factors for early readmissions. CONCLUSION:Early hospital readmission rates for AE of asthma and COPD were alarmingly high. Frequent hospital admission and long-term oxygen therapy during hospital stay were independent predictors of 30-day readmission.
Project description:INTRODUCTION:Respiratory syncytial virus infection in early childhood has been linked to longer-term respiratory morbidity; however, debate persists around its impact on asthma. The objective was to assess the association between respiratory syncytial virus hospitalization and childhood asthma. METHODS:Asthma hospital admissions and medication use through 18 years were compared in children with (cases) and without (controls) respiratory syncytial virus hospitalization in the first 2 years of life. All children born in National Health Service Scotland between 1996 and 2011 were included. RESULTS:Of 740?418 children (median follow-up: 10.6 years), 15?795 (2.1%) had a respiratory syncytial virus hospitalization at ?2 years (median age: 143 days). Asthma hospitalizations were three-fold higher in cases than controls (8.4% vs 2.4%; relative risk: 3.3, 95% confidence interval [CI]: 3.1-3.5; P?<?.0001) and admission rates were four-fold higher (193.2 vs 46.0/1000). Cases had two-fold higher asthma medication usage (25.5% vs 14.7%; relative risk: 1.7, 95% CI: 1.7-1.8; P?<?.0001) and a three-fold higher rate of having both an asthma admission and medication (4.8% vs 1.5%; relative risk 3.1, 95% CI: 2.9-3.3; P?<?.0001). Admission rates and medication use remained significantly (P?<?.001) higher for cases than controls throughout childhood (admissions: ?2-fold higher; medication: ?1.5-fold higher). Respiratory syncytial virus hospitalization was the most significant risk factor for asthma hospitalizations±medication use (odds ratio: 1.9-2.8; P?<?.001). CONCLUSIONS:Respiratory syncytial virus hospitalization was associated with significantly increased rates and severity of asthma throughout childhood, which has important implications for preventive strategies.
Project description:BACKGROUND:The 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. OBJECTIVE:We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. METHODS:We 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-1? levels were measured by means of ELISA. RESULTS:Neonatal 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-1?, an innate inflammatory mediator. CONCLUSIONS:The 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.
Project description:BACKGROUND: Quality assessment in pediatric care has recently gained momentum. Although many of the approaches to indicator development are similar regardless of the population of interest, few nationwide sets of indicators specifically designed for assessment of primary care of children exist. We performed an empirical analysis of the validity of "Pediatric Asthma Hospitalization Rate" indicator under the assumption that lower admission rates are associated with better performance of primary health care. METHODS: The validity of "Pediatric Asthma Hospitalization Rate" indicator proposed by the Agency for Healthcare Research and Quality in the Italian context was investigated with a focus on selection of diagnostic codes, hospitalization type, and risk adjustment. Seasonality and regional variability of hospitalization rates for asthma were analyzed for Italian children aged 2-17 years discharged between January 1, 2009, and December 31, 2011 using the hospital discharge records database. Specific rates were computed for age classes: 2-4, 5-9, 10-14, 15-17 years. RESULTS: In the years 2009-2011 the number of pediatric hospitalizations for asthma was 14,389 (average annual rate: 0.52 per 1,000) with a large variability across regions. In children aged 2-4 years, the risk of hospitalization for asthma was 14 times higher than in adolescents, then it dropped to 4 in 5- to 9-year-olds and to 1.1 in 10- to 14-year-olds. The inclusion of diagnoses of bronchitis revealed that asthma and bronchitis are equally represented as causes of hospital admissions and have a similar seasonality in preschool children, while older age groups experience hospital admissions mainly in spring and fall, this pattern being consistent with a diagnosis of atopic asthma. Rates of day hospital admissions for asthma were up to 5 times higher than the national average in Liguria and some Southern regions, and close to zero in some Northern regions. CONCLUSIONS: The patterns of hospitalization for pediatric asthma in Italy showed that at least two different indicators are needed to measure accurately the quality of care provided to children. The candidate indicators should also include day hospital admissions to better assess accessibility. Future evaluation by a structured clinical panel review at the national level might be helpful to refine indicator definitions and risk groupings, to determine appropriate application for such measures, and to make recommendations to policy makers.