Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke: results from the NOR-FIB Study.

BACKGROUND: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study. METHOD: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. RESULTS: In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7. CONCLUSION: Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.

Atrial fibrillation in cryptogenic stroke and TIA patients in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results.

Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA2DS2-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.

Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation.

BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Increased risk of atrial fibrillation among elderly Norwegian men with a history of long-term endurance sport practice.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence increases with increasing age. In middle-aged men, endurance sport practice is associated with increased risk of AF but there are few studies among elderly people. The aim of this study was to investigate the role of long-term endurance sport practice as a risk factor for AF in elderly men. A cross-sectional study compared 509 men aged 65-90 years who participated in a long-distance cross-country ski race with 1768 men aged 65-87 years from the general population. Long-term endurance sport practice was the main exposure. Self-reported AF and covariates were assessed by questionnaires. Risk differences (RDs) for AF were estimated by using a linear regression model. After multivariable adjustment, a history of endurance sport practice gave an added risk for AF of 6.0 percent points (pp) (95% confidence interval 0.8-11.1). Light and moderate leisure-time physical activity during the last 12 months reduced the risk with 3.7 and 4.3 pp, respectively, but the RDs were not statistically significant. This study suggests that elderly men with a history of long-term endurance sport practice have an increased risk of AF compared with elderly men in the general population.

Genetic association between human chitinases and lung function in COPD.

Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

Candidate genes for COPD in two large data sets.

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies.

BACKGROUND: The identification of gene-by-environment interactions is important for understanding the genetic basis of chronic obstructive pulmonary disease (COPD). Many COPD genetic association analyses assume a linear relationship between pack-years of smoking exposure and forced expiratory volume in 1 s (FEV(1)); however, this assumption has not been evaluated empirically in cohorts with a wide spectrum of COPD severity. METHODS: The relationship between FEV(1) and pack-years of smoking exposure was examined in four large cohorts assembled for the purpose of identifying genetic associations with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects. RESULTS: Non-linear relationships between smoking and FEV(1) were identified in the four cohorts. It was found that, in most situations where the relationship between pack-years and FEV(1) is non-linear, a piecewise linear approach to model smoking and gene-by-smoking interactions is preferable to the commonly used total pack-years approach. The piecewise linear approach was applied to a genetic association analysis of the PI*Z allele in the Norway Case-Control cohort and a potential PI*Z-by-smoking interaction was identified (p=0.03 for FEV(1) analysis, p=0.01 for COPD susceptibility analysis). CONCLUSION: In study samples of subjects with a wide range of COPD severity, a non-linear relationship between pack-years of smoking and FEV(1) is likely. In this setting, approaches that account for this non-linearity can be more powerful and less biased than the more common approach of using total pack-years to model the smoking effect.

Socioeconomic risk factors for lung function decline in a general population.

The aim of our study was to examine sex-specific associations between different aspects of socioeconomic status (SES) (educational level, occupational status, income) and lung function in a general adult population. In the Hordaland County Cohort Study, 1,644 subjects aged 26-82 yrs at baseline answered questionnaires and performed post-bronchodilator spirometry both in 1996-1997 and in 2003-2006. We performed adjusted linear regression analysis on the effect of SES on decline in forced experimental volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC. Mean annual decline in FEV(1) from baseline to follow-up was 57 mL (se 1.3) and 48 mL (se 1.0) for males and females, respectively. Males had a larger decline in FVC than females, while females had a larger decline in FEV(1)/FVC. Lower education and low occupational status were associated with larger male lung function decline. SES did not affect female lung function decline. However, marital status was a significant predictor; unmarried females had less decline than both married and widowed females in both FEV(1) (adjusted mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8 mL and 18 mL). Low SES was associated with increased lung function decline in males. For females, marital status was more important.

Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study.

Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study. 14 sites recruited population-based samples of adults aged > or =40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data. Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV(1)/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV(1) either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV(1)/FEV(6) ratio in place of the FEV(1)/FVC yielded similar prevalence estimates. Use of the FEV(1)/FVC

Present and future costs of COPD in Iceland and Norway: results from the BOLD study.

The Burden of Obstructive Lung Disease (BOLD) initiative provides standardised estimates of the burden of chronic obstructive pulmonary disease (COPD) worldwide. We estimate the current and future economic burden of COPD in Reykjavik, Iceland and Bergen, Norway using data from the BOLD initiative. Data on utilisation of healthcare resources were gathered from the BOLD survey, existing literature and unit costs from national sources. Economic data were applied to a Markov model using transition probabilities derived from Framingham data. Sensitivity analyses were conducted varying unit costs, utilisation and prevalence of disease. The cost of COPD was 478 euro per patient per yr in Iceland and 284 euro per patient per yr in Norway. The estimated cumulative costs of COPD for the population aged > or = 40 yrs, were 130 million euro and 1,539 million euro for the following 10 yrs in Iceland and Norway, respectively. Costs of COPD accounted for 1.2 and 0.7% of healthcare budgets in Iceland and Norway, respectively. Sensitivity analyses showed estimates were most sensitive to changes in exacerbation frequency. COPD has a significant economic burden in both Iceland and Norway and will grow in the future. Interventions aimed at avoiding exacerbations will have the most impact on costs of COPD over the next 20 yrs.

CTLA4 gene polymorphisms are associated with chronic bronchitis.

Chronic obstructive pulmonary disease (COPD) is characterised by chronic and progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell activation. Genetic association between nine CTLA4 single nucleotide polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896 individuals) from the International COPD Genetics Network (ICGN) population. We then replicated the associations in 342 COPD subjects with chronic bronchitis and 511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based association tests were used to analyse the ICGN cohort, and a logistic regression model was used for the Bergen cohort. Six CTLA4 SNPs were significantly associated with chronic bronchitis in the ICGN cohort (0.0079< or = p < or =0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325< or = p < or =0.0408). One of these replicated SNPs (rs231775) encodes the Thr to Ala substitution at amino acid position 17. Haplotype analyses supported the results of single SNP analyses. Thus, CTLA4 is likely to be a genetic determinant of chronic bronchitis among COPD cases.

Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking.

We investigated how quantitative high-resolution computed tomography (HRCT) measures of emphysema and airway wall thickness (AWT) vary with sex, age and smoking history. We included 463 chronic obstructive pulmonary disease (COPD) cases and 431 controls. All included subjects were current or ex-smokers aged > or = 40 yrs, and all underwent spirometry and HRCT examination. The HRCT images were quantitatively assessed, providing indices on lung density and airway dimensions. The median (25-75th percentile) %LAA950 (% low-attenuation area < -950 HU) was 8.9 (3-19) and 4.7 (1-16) in male and female COPD cases, respectively, and 0.71 (0.3-1.6) and 0.32 (0.1-0.8) in male and female controls, respectively. %LAA950 was higher in ex-smokers and increased with increasing age and with increasing number of pack-years. The mean+/-SD standardised AWT was 0.504+/-0.030 and 0.474+/-0.031 in male and female COPD cases, respectively, and 0.488+/-0.028 and 0.463+/-0.025 in male and female controls, respectively. AWT decreased with increasing age in cases, and increased with the degree of current smoking in all subjects. We found significant differences in quantitative HRCT measures of emphysema and AWT between varying sex, age and smoking groups of both control and COPD subjects.

Quality-of-life and asthma-severity in general population asthmatics: results of the ECRHS II study.

BACKGROUND: Health-related quality-of-life (HRQL) has been poorly studied in large samples of asthmatics from the general population. HRQL and its relationship to asthma-severity were assessed among 900 asthmatics enrolled in the European Community Respiratory Health Survey. METHODS: Among asthmatics, 864 completed the short form-36 (SF-36) questionnaire and 477 also completed the Asthma Quality-of-life Questionnaire (AQLQ). A 4-class asthma-severity scale, combining clinical items, forced expiratory volume in 1 s and the level of treatment and the different asthma-severity components (each of the clinical items and hospitalization) were studied in relation to HRQL. RESULTS: Mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (45.5 and 48.8 respectively) were lower than expected in a general population. The mean total AQLQ score was 5.8. The AQLQ score and to a lesser extent the PCS score were significantly related to the 4-class asthma-severity scale, although the risk of having a lower HRQL score did not vary proportionally across the levels of severity. Asthma-severity had no impact on the MCS score. Asthma attack frequency and hospitalization were associated with both total AQLQ and PCS scores, whereas nocturnal symptoms and lung function were more strongly related to the AQLQ and PCS score respectively. CONCLUSION: In population-based asthmatics, the specific AQLQ questionnaire, and also to a lesser extent the generic SF-36 questionnaire, were sensitive to asthma-severity. Frequencies of asthma attacks, of nocturnal symptoms and hospitalization for asthma have independent impact on HRQL.

Clinical data discriminating between adults with positive and negative results on bronchodilator testing.

OBJECTIVE: To evaluate how spirometry, symptoms and smoking discriminate between subjects who are responsive to bronchodilator testing and those who are non-responsive, and to examine how cut-off points of positive tests are related to symptoms of chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Subjects aged 47-48 and 71-73 years living in Bergen, Norway, were recruited. The 3506 participants (69%) filled in questionnaires and performed a bronchodilator test using salbutamol. RESULTS: Tests were positive (forced expiratory volume in 1 s [Delta FEV1] >or=200 ml and >or=12%) in 107 subjects (3%). In logistic regression, spirometry (FEV1 < 80%, OR 6.0, 95%CI 3.6-10.2, and FEV1/FVC < 0.70, OR 3.1, 95%CI 1.9-5.2) and pack-years >or= 20 (OR 0.3, 95%CI 0.2-0.7), but not symptoms, predicted the test outcome. FEV1% and FEV1/forced volume capacity (FVC) discriminated equally well between positive and negative tests (area under the receiver operating characteristic [ROC] curve 0.81, 95%CI 0.77-0.85 vs. 0.77, 95%CI 0.72-0.82). The largest likelihood ratio for positive tests was 5.4 (95%CI 3.8-7.8) using FEV1 < 80% and FEV1/FVC < 0.70. CONCLUSIONS: Spirometry and to a lesser extent smoking, but not symptoms, are useful in discriminating between middle-aged and elderly patients with positive and negative bronchodilator tests. Acute responses to salbutamol, expressed by commonly used Delta FEV1 cut-off points, are poorly related to COPD- and asthma-like symptoms.

Norwegian population surveys on respiratory health in adults: objectives, design, methods, quality controls and response rates.

BACKGROUND AND AIMS: Quantifying the prevalence of asthma, chronic obstructive pulmonary disease (COPD) and restrictive pulmonary diseases in Norway is needed to document the burden of chronic respiratory inflammatory diseases on disability, health care costs and impaired quality of life. To introduce effective interventions for prevention, cure and care, there is a prerequisite to know the environmental causes. Furthermore, using relevant and precise phenotypes from community-based studies are important for detecting molecular-genetic causes for diseases. METHODS: The Norwegian Population Survey Initiative on Respiratory Health in Adults has, for four decades, applied international standardised methods for the recording of respiratory symptoms, health status, exposure to risk factors, socio-economic factors and the use of health services. Measurements of spirometry, metacholine bronchial responsiveness, transfer factor for carbon monoxide, atopy as well as chest X-ray examinations have been used advocating the internationally accepted methods. All surveys had similar quality controls, supervision and training of the field-worker team. RESULTS: From 1965 to 1999, random population samples, altogether including 178 690 individuals, have been invited by random sampling to seven surveys on respiratory health in the counties of Oslo (39 998 people) and Hordaland (138 692 people). The surveys were initiated in 1964, 1972, 1985, 1988, 1991 and two in 1998. The age span of those invited persons varied from 15 to 74 years at baseline. It included 43 330 women and 135 537 men. Altogether 130 075 (73%) persons participated by returning an answered questionnaire. Spirometry results are available from 41 335 persons at baseline. A biobank for DNA and blood markers has been established. Data from longitudinally clinical-epidemiological studies were available by 2007, for three surveys after 20 years, 10 years and 6-7 years, and also for parts of three other surveys, while one survey has been examined for cause-specific mortality after 30 years. The response rates of the baseline studies varied from 90% to 68% of those invited and, in general, it has declined over 35 years. The response rate of the longitudinal studies with follow-ups also declined with time after the baseline study. CONCLUSIONS: Great challenges for future population-based studies are (i) to keep the participation rates high in community studies; (ii) to standardise the basic clinical-epidemiological methods over decades of follow-up and to systematically transfer these methods into new populations with different languages and cultures and (iii) to focus on important research questions on respiratory health for the community.

What can we learn about asthma and allergy from the follow-up of the RHINE and the ECRHS studies?

OBJECT: The international population-based studies RHINE and ECRHS have provided new insight in the epidemiology and management of asthma, allergy and rhinitis in young adults. The aim of the present review is to focus on longitudinal results with regard incidence and net change of asthma and asthma-like symptoms, risk factors and management of asthma, with special reference to the Nordic-Baltic countries. RESULTS: Asthma and rhinitis are common conditions that are important in a public health perspective. There are gender differences in incidence and remission. A socio-economic gradient that non-atopic asthma is more strongly related to poverty seems to have developed in the last decade. These findings will challenge our welfare states in the future. In addition, occupational, as well as indoor and outdoor environmental exposures, influenced the onset of asthma. The population-attributable risk for adult asthma because of occupational exposures is equivalent to an incidence of new-onset asthma of 250-300 cases per million per year. Genetic factors, allergic sensitisation, gastro-oesophageal reflux, habitual snoring, diet and other factors may also contribute to the onset of asthma and rhinitis. Even though management of asthma has improved, there are still great variations throughout Europe. These findings highlight the key role doctors and nurses play in educating and reviewing management of patients.

Economics of COPD: literature review and experiences from field work.

INTRODUCTION: The burden of diseases should be described in terms of costs. The available literature gives imprecise estimates of costs of chronic obstructive pulmonary disease (COPD) in the Nordic populations. Previous studies have methodological weaknesses related to choice of disease criteria, the use of highly selected populations and insufficient specification of the cost process. There are no robust estimates concerning the economics of COPD in Norway. METHODS: We have conducted a 1 year follow-up cost of illness study in a general population, recruiting ever-smoking Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2+ COPD patients and ever-smokers without COPD. We have used diaries to recollect data, and comprehensive questionnaires to cover all costs of COPD. RESULTS: The main challenges were the participants' unwillingness to complete diaries, the large amount of information and the logistics related to following up 476 individuals on four occasions during one year. CONCLUSIONS: We doubt the effect of diaries. However, we recommend a detailed planning of logistics and to emphasize main cost drivers.

Genetics of chronic obstructive pulmonary disease: a case-control study in Bergen, Norway.

AIMS: Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by multiple genetic and environmental factors. This short communication gives a description of the preliminary genetic results from a case-control study in Bergen, Norway. METHODS: A large case-control study in Bergen in 2003-2005 with 6365 invited subjects generated 1954 cases or controls. The overall attendance of invited subjects was 60%, but causes of non-attendance varied considerably among different sources of recruitment. RESULTS: In this case-control study, the candidate gene SERPINE2 on chromosome 2q has demonstrated significant association to COPD. However, only weak or lacking associations have so far been observed for the other candidate genes examined. CONCLUSION: These findings provide support for SERPINE2 as a COPD susceptibility gene in the Norwegian population.

The socio-economic burden of asthma is substantial in Europe.

BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.