Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 cases, 118,538 controls) from ethnically-diverse populations. We identified five new asthma loci, uncovered two additional novel associations at two known asthma loci, established asthma associations at two loci implicated previously in comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. Enrichment of asthma risk loci in enhancer marks, especially in immune cells, suggests a major role of these loci in the regulation of immune-related mechanisms.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large‐scale ‘omics’ and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

BackgroundOveruse of short-acting β2-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme.MethodsBy linking data from Swedish national registries, asthma patients aged 12–45 years with two or more collections of drugs for obstructive lung disease during 2006–2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3–5, 6–10 and ≥11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality.ResultsThe analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3–5 canisters per year, 7% collecting 6–10 canisters per year and 2% collecting ≥11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3–5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24–1.28); 6–10 canisters: 1.44 (1.41–1.46); and ≥11 canisters: 1.77 (1.72–1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3–5 canisters: HR 1.26 (95% CI 1.14–1.39); 6–10 canisters 1.67 (1.49–1.87); and ≥11 canisters: 2.35 (2.02–2.72) compared to two or fewer canisters per year.ConclusionOne-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management.

The European Community Respiratory Heath Survey (ECRHS) was the first study to assess the geographical variation in asthma and allergy in adults using the same instruments and definitions. The database of the ECRHS includes information fromy140,000 individuals from 22 countries. The aim of this review is to summarize the results of the ECRHS to date.The ECRHS has shown that there are large geographical differences in the prevalence of asthma, atopy and bronchial responsiveness, with high prevalence rates in English speaking countries and low prevalence rates in the Mediterranean region and Eastern Europe. Analyses of risk factors have highlighted the importance of occupational exposure for asthma in adulthood. The association between sensitization to individual allergens and bronchial responsiveness was strongest for indoor allergens (mite and cat). Analysis of treatment practices has confirmed that the treatment of asthma varies widely between countries and that asthma is often undertreated.In conclusion, the European Community Respiratory Health Survey has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and most likely due to environmental factors. Eur Respir J 2001; 18: 598-611. During the first half of the 1990s, information on the variation in asthma prevalence, known or suspected risk factors for atopy and asthma, and information on the management of asthma in young adults was collected in the European Community Respiratory Health Survey (ECRHS).The reason for undertaking the ECRHS was a rapid increase in the prevalence of asthma that had been reported from many different countries [1][2][3][4]. This increase was over too short a time period to be explained by genetic factors and must therefore have been related to nongenetic or environmental changes. Further evidence of the importance of environmental factors in asthma was that studies comparing prevalence in urban and rural areas in developing countries had shown large differences in asthma prevalence [5][6][7]. Treatment patterns of asthma [8] and asthma mortality [9] had been found to vary considerably in Europe which raised the question of whether the variation in mortality was due to geographical differences in the prevalence of asthma or differences in asthma fatality. Research directed towards identifying the environmental factors that explain this geographical variation in asthma was required to identify potential strategies to counter the global increase in the prevalence of asthma.The information available on the variation in the prevalence of asthma and allergy at the beginning of the 1990s had been collected through several studies using different protocols. The ECRHS was, therefore, the first study that assessed the prevalence of asthma and allergic disease in a large number of countries