Aims: To investigate the association between climate and atopic diseases using worldwide data from 146 centres of the International Study of Asthma and Allergies in Childhood (ISAAC). Methods: ...Between 1992 and 1996, each centre studied random samples of children aged 13–14 and 6–7 years (approx. 3000 per age group and centre) using standardised written and video questionnaires on symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema during the past 12 months. Data on long term climatic conditions in the centres were abstracted from one standardised source, and mixed linear regression models calculated to take the clustering of centres within countries into account. Results: In Western Europe (57 centres in 12 countries), the prevalence of asthma symptoms, assessed by written questionnaire, increased by 2.7% (95% CI 1.0% to 4.5%) with an increase in the estimated annual mean of indoor relative humidity of 10%. Similar associations were seen for the video questionnaire and the younger age group. Altitude and the annual variation of temperature and relative humidity outdoors were negatively associated with asthma symptoms. The prevalence of eczema symptoms correlated with latitude (positively) and mean annual outdoor temperature (negatively). Conclusions: Results suggest that climate may affect the prevalence of asthma and atopic eczema in children.
Background: Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma. Methods: A trend ...analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality. Results: Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971–91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio-oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991. Conclusions: The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.
The morphometric characteristics of the retinal vasculature are associated with future risk of many systemic and vascular diseases. However, analysis of data from large population based studies is ...needed to help resolve uncertainties in some of these associations. This requires automated systems that extract quantitative measures of vessel morphology from large numbers of retinal images. Associations between retinal vessel morphology and disease precursors/outcomes may be similar or opposing for arterioles and venules. Therefore, the accurate detection of the vessel type is an important element in such automated systems. This paper presents a deep learning approach for the automatic classification of arterioles and venules across the entire retinal image, including vessels located at the optic disc. This comprises of a convolutional neural network whose architecture contains six learned layers: three convolutional and three fully-connected. Complex patterns are automatically learnt from the data, which avoids the use of hand crafted features. The method is developed and evaluated using 835,914 centreline pixels derived from 100 retinal images selected from the 135,867 retinal images obtained at the UK Biobank (large population-based cohort study of middle aged and older adults) baseline examination. This is a challenging dataset in respect to image quality and hence arteriole/venule classification is required to be highly robust. The method achieves a significant increase in accuracy of 8.1% when compared to the baseline method, resulting in an arteriole/venule classification accuracy of 86.97% (per pixel basis) over the entire retinal image.
•Morphology of retinal vasculature associated with risk markers of many diseases.•Large population based studies help to resolve uncertainties in these associations.•Automated system extracts morphometric data from the UK Biobank cohort study.•Detection of the vessel type is an important element in such automated systems.•Deep learning approach for the automatic classification of arterioles and venules.
Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the ...identification of environmental influences on the development of asthma and airway diseases in predisposed individuals.
Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age.
Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mumol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV(1) per mumol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes.
The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.
The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma ...remain unclear.
To identify common genetic variants affecting susceptibility to severe asthma.
A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies.
An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance.
The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
Objective: A biomedical survey of the 1958 British birth cohort at age 45 years provides a baseline for future studies of chronic disease. The extent and nature of bias in this sample was examined. ...Methods: Follow-up of all births in Great Britain in one week in March 1958. At 45 years the sample was compared with the surviving cohort on characteristics recorded at birth and seven years, and in adulthood (42 years). Results: Sample attrition to age 45 years was chiefly through avoidable (35.8%) than unavoidable loss through death or emigration (13.7%). 11 971 individuals were invited to participate at 45 years. Of 9377 participants (78.3%), most consented to, and had valid values for, physical and mental measurements, survey questionnaires, and blood and saliva sampling; 8302 (88.5%) provided a blood sample. Groups moderately underrepresented in the 45-year sample included those with externalising or internalising behaviours, poor reading or maths scores, and shorter stature. For example, 8.8% of the 45-year sample had been poor readers at age seven years compared with 11.1% of the total surviving cohort; for shorter stature the figures were 7.2% versus 8.4%, respectively. There was also underrepresentation of some minority groups (non-whites, births in households with no male head and children in social care). Most bias was present before the 45-year survey. Conclusion: The 45-year sample remains broadly representative of the surviving cohort, but specific biases may need to be taken into account in future research. Renewed efforts to re-engage all cohort members will improve the representativeness and value of the study.
Summary
Background
Although allergy represents an important source of patient morbidity and healthcare utilization, there is little reliable information on the overall disease burden posed by ...allergic conditions in the UK.
Objectives
Focusing on the following conditions: allergic rhinitis, anaphylaxis, asthma, conjunctivitis, eczema/dermatitis, food allergy and urticaria/angioedema, we sought to (i) describe the prevalence, incidence and outcomes of allergic disorders; (ii) describe the NHS healthcare burden posed by allergic disorders; (iii) estimate the costs of allergic disorders from a healthcare perspective.
Methods
Secondary analyses of data from the Health Survey for England, Scottish Health Survey, International Study of Allergies and Asthma in Childhood, European Community Respiratory Health Survey, Morbidity Statistics from General Practice 1991/1992, Royal College of General Practitioners Weekly Returns Service, Prescribing Analysis and Cost data, Hospital Episodes Statistics and national mortality data.
Results
Thirty‐nine percent of children and 30% of adults have been diagnosed with one or more atopic conditions. Six percent of general practice consultations and 0.8% of hospital admissions are for allergic diseases. Treatments for asthma and other allergic disorders currently account for 10% of primary care prescribing costs. Direct NHS costs for managing allergic problems are estimated at over one billion UK pounds per annum.
Conclusions
Allergic disorders are common throughout the UK, affecting males and females of all ages and peoples from all social classes and ethnic groups. They currently represent a substantial burden of morbidity and health service cost.
Farmers' children have a reduced prevalence of allergic disorders. The specific protective environmental factors responsible are not yet identified.
We sought to determine whether farmers' children ...in the rural county of Shropshire, England, have a reduced risk of atopy and, if so, to identify the factors responsible.
The Study of Asthma and Allergy in Shropshire was a 2-stage cross-sectional study. In stage 1 a questionnaire to elicit allergic status, diet, and farming exposure was completed by the parents of 4767 children. In stage 2 a stratified subsample of 879 children underwent skin prick testing and measurement of domestic endotoxin.
Compared with rural nonfarming children, farmers' children had significantly less current asthma symptoms (adjusted odds ratio (OR), 0.67; 95% CI, 0.49-0.91;
P = .01) and current seasonal allergic rhinitis (adjusted OR, 0.50; 95% CI, 0.33-0.77;
P = .002) but not current eczema symptoms (adjusted OR, 0.91; 95% CI, 0.68-1.21;
P = .53) or atopy (adjusted OR, 0.68; 95% CI, 0.40-1.16;
P = .15). In contrast, current unpasteurized milk consumption was associated with significantly less current eczema symptoms (adjusted OR, 0.59; 95% CI, 0.40-0.87;
P = .008) and a greater reduction in atopy (adjusted OR, 0.24; 95% CI, 0.10-0.53;
P = .001). The effect was seen in all children, independent of farming status. Unpasteurized milk consumption was associated with a 59% reduction in total IgE levels (
P < .001) and higher production of whole blood stimulated IFN-γ (
P = .02).
Unpasteurized milk consumption was the exposure mediating the protective effect on skin prick test positivity. The effect was independent of farming status and present with consumption of infrequent amounts of unpasteurized milk.
Unpasteurized milk might be a modifiable influence on allergic sensitization in children.
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