Trends in worldwide asthma prevalence Asher, M Innes; García-Marcos, Luis; Pearce, Neil E ...
The European respiratory journal,
12/2020, Letnik:
56, Številka:
6
Journal Article
Recenzirano
Odprti dostop
This review of trends in worldwide asthma prevalence starts with defining how asthma prevalence is measured in populations and how it is analysed. Four population studies of asthma across at least ...two regions are described: European Community Respiratory Health Survey (ECRHS), the International Study of Wheezing in Infants (EISL), the International Study of Asthma and Allergies in Childhood (ISAAC) and the World Health Survey (WHS). Two of these (ISAAC and WHS) covered all the regions of the world; each using its own standardised questionnaire-based methodology with cross-sectional study design, suitable for large populations. EISL (2005 and 2012) and ISAAC (1996-1997 and 2002-2003) have undertaken a second cross-sectional population survey from which trends are available: EISL in three centres in two countries; ISAAC 106 centres in 56 countries (13-14 year olds) and 66 centres in 37 countries (6-7 year olds). Key results from these studies are presented. Unfortunately, there is no new worldwide data outside of EISL since 2003. Global Burden of Disease estimates of asthma prevalence have varied greatly. Recent reliable worldwide data on asthma prevalence and trends is needed; the Global Asthma Network Phase I will provide this in 2021.
BackgroundThe UK-wide National Review of Asthma Deaths sought to identify avoidable factors from the high numbers of deaths, but did not examine variation by socioeconomic status (SES) or ...region.MethodsWe used asthma deaths in England over the period 2002–2015 obtained from national deaths registers, summarised by quintiles of Index of Multiple Deprivation (IMD) and Government Office Region. Emergency asthma admissions were obtained from Hospital Episode Statistics for England 2001–2011. The prevalence of asthma was derived from the Health Survey for England 2010. Associations of mortality, admissions and prevalence with IMD quintile and region were estimated cross-sectionally using incidence rate ratios (IRRs) adjusted for age and sex and, where possible, smoking.ResultsAsthma mortality decreased among more deprived groups at younger ages. Among 5–44 year olds, those in the most deprived quintile, mortality was 19% lower than those in the least deprived quintile (IRR 0.81 (95% CI 0.69 to 0.96). In older adults, this pattern was reversed (45–74 years: IRR 1.37 (1.24–1.52), ≥75 years: IRR 1.30 (1.22–1.39)). In 5–44 year olds the inverse trend with asthma mortality contrasted with large positive associations for admissions (IRR 3.34 (3.30–3.38)) and prevalence of severe symptoms (IRR 2.38 (1.70–3.33)). Prevalence trends remained after adjustment for smoking. IRRs for asthma mortality, admissions and prevalence showed significant heterogeneity between English regions.ConclusionsDespite asthma mortality, emergency admissions and prevalence decreasing over recent decades, England still experiences significant SES and regional variations. The previously undocumented inverse relation between deprivation and mortality in the young requires further investigation.
Data for trends in prevalence of asthma, allergic rhinoconjunctivitis, and eczema over time are scarce. We repeated the International Study of Asthma and Allergies in Childhood (ISAAC) at least 5 ...years after Phase One, to examine changes in the prevalence of symptoms of these disorders.
For the ISAAC Phase Three study, between 2002 and 2003, we did a cross-sectional questionnaire survey of 193 404 children aged 6–7 years from 66 centres in 37 countries, and 304 679 children aged 13–14 years from 106 centres in 56 countries, chosen from a random sample of schools in a defined geographical area.
Phase Three was completed a mean of 7 years after Phase One. Most centres showed a change in prevalence of 1 or more SE for at least one disorder, with increases being twice as common as decreases, and increases being more common in the 6–7 year age-group than in the 13–14 year age-group, and at most levels of mean prevalence. An exception was asthma symptoms in the older age-group, in which decreases were more common at high prevalence. For both age-groups, more centres showed increases in all three disorders more often than showing decreases, but most centres had mixed changes.
The rise in prevalence of symptoms in many centres is concerning, but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring. The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders.
The COVID-19 pandemic's first wave in England during spring 2020 resulted in an approximate 50% increase in all-cause mortality. Previously, risk factors such as age and ethnicity, were identified by ...studying COVID-related deaths only, but these were under-recorded during this period.
To use a large electronic primary care database to estimate the impact of risk factors (RFs) on excess mortality in England during the first wave, compared with the impact on total mortality during 2015-19.
Medical history, ethnicity, area-based deprivation and vital status data were extracted for an average of 4.8 million patients aged 30-104 years, for each year between 18-March and 19-May over a 6-year period (2015-2020). We used Poisson regression to model total mortality adjusting for age and sex, with interactions between each RF and period (pandemic vs. 2015-19). Total mortality during the pandemic was partitioned into "usual" and "excess" components, assuming 2015-19 rates represented "usual" mortality. The association of each RF with the 2020 "excess" component was derived as the excess mortality ratio (EMR), and compared with the usual mortality ratio (UMR).
RFs where excess mortality was greatest and notably higher than usual were age >80, non-white ethnicity (e.g., black vs. white EMR = 2.50, 95%CI 1.97-3.18; compared to UMR = 0.92, 95%CI 0.85-1.00), BMI>40, dementia, learning disability, severe mental illness, place of residence (London, care-home, most deprived). By contrast, EMRs were comparable to UMRs for sex. Although some co-morbidities such as cancer produced EMRs significantly below their UMRs, the EMRs were still >1. In contrast current smoking has an EMR below 1 (EMR = 0.80, 95%CI 0.65-0.98) compared to its UMR = 1.64.
Studying risk factors for excess mortality during the pandemic highlighted differences from studying cause-specific mortality. Our approach illustrates a novel methodology for evaluating a pandemic's impact by individual risk factor without requiring cause-specific mortality data.
Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public ...health importance, since vitamin D insufficiency is common and correctable.
We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval CI 0.90-1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69-1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92-1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia.
In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.
Imputation using external reference panels (e.g. 1000 Genomes) is a widely used approach for increasing power in genome-wide association studies and meta-analysis. Existing hidden Markov models ...(HMM)-based imputation approaches require individual-level genotypes. Here, we develop a new method for Gaussian imputation from summary association statistics, a type of data that is becoming widely available.
In simulations using 1000 Genomes (1000G) data, this method recovers 84% (54%) of the effective sample size for common (>5%) and low-frequency (1-5%) variants increasing to 87% (60%) when summary linkage disequilibrium information is available from target samples versus the gold standard of 89% (67%) for HMM-based imputation, which cannot be applied to summary statistics. Our approach accounts for the limited sample size of the reference panel, a crucial step to eliminate false-positive associations, and it is computationally very fast. As an empirical demonstration, we apply our method to seven case-control phenotypes from the Wellcome Trust Case Control Consortium (WTCCC) data and a study of height in the British 1958 birth cohort (1958BC). Gaussian imputation from summary statistics recovers 95% (105%) of the effective sample size (as quantified by the ratio of Formula: see text association statistics) compared with HMM-based imputation from individual-level genotypes at the 227 (176) published single nucleotide polymorphisms (SNPs) in the WTCCC (1958BC height) data. In addition, for publicly available summary statistics from large meta-analyses of four lipid traits, we publicly release imputed summary statistics at 1000G SNPs, which could not have been obtained using previously published methods, and demonstrate their accuracy by masking subsets of the data. We show that 1000G imputation using our approach increases the magnitude and statistical evidence of enrichment at genic versus non-genic loci for these traits, as compared with an analysis without 1000G imputation. Thus, imputation of summary statistics will be a valuable tool in future functional enrichment analyses.
Publicly available software package available at http://bogdan.bioinformatics.ucla.edu/software/.
bpasaniuc@mednet.ucla.edu or aprice@hsph.harvard.edu
Supplementary materials are available at Bioinformatics online.
Background Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active ...investigation. Objective We sought to ascertain the genetic risk factors that lead to IgE dysregulation. Methods A genome-wide association study (GWAS) was performed in 6819 participants from the Framingham Heart Study (FHS). Seventy of the top single nucleotide polymorphisms (SNPs) were selected based on P values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with 5 independent populations from the Cooperative Health Research in the Region of Augsburg cohort, the British 1958 Birth Cohort, and the Childhood Asthma Management Program cohort. Results Thirteen SNPs located in the region of 3 genes, FCER1A , signal transducer and activator of transcription 6 (STAT6) , and IL13 , were found to have genome-wide significance in the FHS cohort GWAS. The most significant SNPs from the 3 regions were rs2251746 ( FCER1A , P = 2.11 × 10−12 ), rs1059513 ( STAT6 , P = 2.87 × 10−8 ), and rs1295686 ( IL13 , P = 3.55 × 10−8 ). Four additional gene regions, HLA-G , HLA-DQA2 , HLA-A , and Duffy blood group, chemokine receptor (DARC) , reached genome-wide statistical significance in a meta-analysis combining the FHS and replication cohorts, although the DARC association did not appear independent of SNPs in the nearby FCER1A gene. Conclusion This GWAS of the FHS cohort has identified genetic loci in HLA genes that might have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of the known susceptibility loci FCER1A , STAT6 , and IL13 for the dysregulation of total IgE.
The Global Asthma Network (GAN), established in 2012, followed the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Phase One involved over 700 000 adolescents and children ...from 156 centres in 56 countries; it found marked worldwide variation in symptom prevalence of asthma, rhinitis and eczema that was not explained by the current understanding of these diseases; ISAAC Phase Three involved over 1 187 496 adolescents and children (237 centres in 98 countries). It found that asthma symptom prevalence was increasing in many locations especially in low- and middle-income countries where severity was also high, and identified several environmental factors that required further investigation.GAN Phase I, described in this article, builds on the ISAAC findings by collecting further information on asthma, rhinitis and eczema prevalence, severity, diagnoses, asthma emergency room visits, hospital admissions, management and use of asthma essential medicines. The subjects will be the same age groups as ISAAC, and their parents. In this first global monitoring of asthma in children and adults since 2003, further evidence will be obtained to understand asthma, management practices and risk factors, leading to further recognition that asthma is an important non-communicable disease and to reduce its global burden.
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is ...a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
ObjectiveTo investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.DesignRetrospective cohort study using primary care data.Setting75 ...Greater London practices.Participants130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.Primary and secondary outcome measuresA first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.Results2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2 concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from primary traffic sources only and Lnight, but only NO2 and PM2.5 remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.ConclusionsWe have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.
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