Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Osteonecrosis of the jaw among cancer patients in Denmark: risk and prognosis.

Osteonecrosis of the jaw (ONJ) is a serious complication of anti-resorptive therapy used in the treatment of multiple myeloma and cancerous bone metastases. In this study, patients with either multiple myeloma or solid tumours with a simultaneous or subsequent record of anti-resorptive treatment or bone metastases were identified using population-based medical registries. These patients were followed for the outcome of ONJ. Considering death as a competing risk, the cumulative incidence of ONJ was estimated, overall and by cancer site. Patients who developed ONJ were followed for the outcome of death overall and by several risk factors for ONJ. A total of 33,975 cancer patients fulfilling the inclusion criteria were identified; 233 incidents of ONJ and a cumulative incidence of 1.9% (95% confidence interval 1.6-2.3%) over a maximum follow-up time of 7.5 years were observed. The 5-year cumulative incidence was 1.3% (95% confidence interval 1.2-1.6%) and varied by cancer site. There were 126 deaths among cancer patients with ONJ over a maximum follow-up time of 6.4 years, resulting in a 5-year mortality of 91% (95% confidence interval 81-97%). Mortality among patients with ONJ varied by cancer site, osteonecrosis stage, and by history of trauma to the mucosa.

Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study.

OBJECTIVE: Studies restricted to live births may underestimate severe teratogenic effects. We address the limitation by including data from both prenatal and postnatal diagnoses of cardiac malformations. DESIGN: Register-based study. SETTING: Denmark. POPULATION: 364 012 singleton pregnancies from 2007 to 2014. METHODS: We used data from five nationwide registries. Exposure to antidepressants was measured using redeemed prescriptions. MAIN OUTCOME MEASURES: Pregnancies with cardiac malformations that end in miscarriage, termination, stillbirth, postnatal death or cardiac surgery <1 year of birth were classified as severe cardiac malformations (SCM). Propensity scores with adjusted prevalence ratios (PRs) were calculated. RESULTS: SCM were reported in 972 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval [CI] 0.89-5.13), 1.73 (95% CI 1.08-2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 [95% CI 6.41-47.2]), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52-2.30) and 1.38 (95% CI 1.00-1.92) for SCM and other cardiac malformations, respectively. CONCLUSIONS: Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations but with a low absolute risk. Potential mechanisms include direct effects or confounding by indication. Venlafaxine exposure is a marker for risk pregnancies for which fetal echocardiography may be considered. TWEETABLE ABSTRACT: Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.

Use of anti-osteoporosis medication dispensing by patients with hip fracture: could we do better?

Although Scandinavian countries have the highest incidence of hip fracture in the world, trends in anti-osteoporosis medication use have not been studied. We found less than one-third of Danish hip fracture patients had dispensing of anti-osteoporosis medication over a 10-year period using routinely collected data from population-based registries. INTRODUCTION: To examine trend in dispensing of anti-osteoporosis medication before and after hip fracture surgery in Denmark over a 10-year period using routinely collected data from population-based registries. METHODS: From the Danish Multidisciplinary Hip Fracture Registry, we included 65,011 patients aged 65 years or older with an incident hip fracture in 2005-2015. We calculated, for each calendar year of hip fracture diagnosis, the prevalence of use of anti-osteoporosis medication (at least one dispensing of bisphosphonates, strontium ranelate, denosumab, selective estrogen receptor modulators, or teriparatide) in the year before and in the year following hip fracture diagnosis. Among those without a dispensing in the year before hip fracture, we computed 1-year cumulative incidence of use following hip fracture. We treated death as a competing risk and stratified the analysis on sex, age, and comorbidity. RESULTS: The prevalence of use before hip fracture varied between 7 and 12%, increasing slightly from 2005 to 2015. The cumulative incidence of use following hip fracture decreased from 16% in 2005 to 13% in 2010, whereupon it increased to 20%. A similar pattern was seen with each stratum of sex, age groups, and comorbidity. The overall prevalence of use after hip fracture was below 22% in all calendar years. CONCLUSIONS: Less than one-third of hip fracture patients had dispensing of anti-osteoporosis medication up to 1 year after hip fracture. We observed only a slight increase in dispensing after hip fracture over the study period, irrespective of patient sex, age, and comorbidity at the time of hip fracture.

Excess risk of venous thromboembolism in hip fracture patients and the prognostic impact of comorbidity.

Hip fracture patients were at increased excess risk of venous thromboembolism (VTE) up to 1 year following hip fracture. During the first year, interaction between hip fracture and comorbidity was observed among patients with severe and very severe comorbidity. INTRODUCTION: We compared the risk of VTE in hip fracture patients with that in the general population. We also examined whether and to what extent the association between hip fracture and VTE varied by comorbidity level. METHODS: Nationwide cohort study based on Danish health registries, 1995-2015. We identified hip fracture patients (n = 110,563) and sampled a comparison cohort without hip fracture from the general population (n = 552,774). Comorbidity was assessed using the Charlson comorbidity index. We calculated attributable fraction, as the proportion of the VTE rate, among persons exposed to both hip fracture and comorbidity, attributed to exposure interaction. RESULTS: The cumulative incidences of VTE were 0.73% within 30 days and 0.83% within 31-365 days among hip fracture patients, and 0.05 and 0.43% in the general population. Adjusted hazard ratios (HRs) of VTE among hip fracture patients were 17.29 [95% confidence interval (CI) 14.74-20.28] during the first 30 days and 2.13 (95% CI 1.95-2.32) during 31-365 days following hip fracture. The relative risks of VTE were 1.03 (95% CI 0.96-1.11) and 1.11 (95% CI 1.00-1.23) after 1-5 years and 6-10 years. During the first 30 days and 31-365 days, 14%/28% of VTE rates and 5%/4% of VTE rates were attributable to the interaction between hip fracture and severe/very severe comorbidity, respectively. Mortality risks within 30 days of VTE were 29.4% in hip fracture and 11.0% in general population cohorts. CONCLUSIONS: Hip fracture patients were at increased excess risk of VTE up to 1 year following their fracture. During the first year, interaction between hip fracture and comorbidity was observed among patients with severe and very severe comorbidity.

Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK.

AIMS: To assess risk of lactic acidosis among metformin users compared with other glucose-lowering agent users, according to renal function. METHODS: Using routine registries and databases, we conducted a cohort study. Of 43 580 metformin and 37 788 other glucose-lowering agent users in northern Denmark and 102 688 metformin and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we identified lactic acidosis using diagnostic codes. We calculated the incidence rates of lactic acidosis in metformin and other glucose-lowering agent users overall and according to baseline estimated GFR (eGFR) levels. RESULTS: In Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and 1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other glucose-lowering agent use, respectively. In the UK, the corresponding lactic acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per 100 000 person-years of metformin use and of other glucose-lowering agent use. The incidence rates increased with decreasing baseline eGFR in both countries. Of the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the UK experienced a decline in renal function in the year before the diagnosis. CONCLUSIONS: Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function.

Perceived stress and risk of any osteoporotic fracture.

UNLABELLED: Perceived stress is associated with several adverse health outcomes; however, little is known about the impact of stress on fracture risk. In this population-based cohort study, persons with high perceived stress have an increased 5-year risk of any osteoporotic fracture, in particular hip fracture. INTRODUCTION: We conducted a population-based cohort study in Denmark to examine the association between perceived stress and risk of subsequent osteoporotic fracture. METHODS: A 2006 population-based health survey in the Central Danish Region (with 1.25 million inhabitants) was used to identify 7943 persons who were 55 years or older on the survey date and completed the Perceived Stress Scale. Individuals were categorized into two groups: high level of stress and low level of stress (including no stress). We obtained information on all osteoporotic fractures through linkage to the Danish National Registry of Patients. We used Cox regression to compute hazard ratios (HRs) with 95 % confidence interval (CI) adjusted for a number of lifestyle factors, socioeconomic data, perceived general health, and prescription history, comparing high- and low-stress persons. RESULTS: A total of 1799 persons (22.6 %) reported high level of perceived stress, whereas 6144 (77.4 %) reported low level or no stress. The 5-year risk of any osteoporotic fracture was 7.4 and 5.4 % in persons with high and low perceived stress, respectively, corresponding to adjusted HR of 1.37 (CI 1.00-1.89). The adjusted HR for hip fracture within 5 years associated with high perceived stress was 1.68 (CI 1.04-2.72). The associations weakened with increasing follow-up time. CONCLUSIONS: Persons with high perceived stress have an increased risk of any osteoporotic fracture, in particular risk of hip fracture within 5 years of stress assessment even after adjusting for differences in lifestyle, comorbidities, osteoporosis presence, medication use, and socioeconomic status at the time of stress level evaluation. The association attenuated after longer follow-up time.

Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study.

BACKGROUND/OBJECTIVE: Prenatal exposure to antibacterials may permanently dysregulate fetal metabolic patterns via epigenetic pathways or by altering maternal microbiota. We examined the association of prenatal exposure to systemic antibacterials with overweight and obesity in schoolchildren. SUBJECTS/METHODS: We conducted a prevalence study among Danish schoolchildren aged 7-16 years using data from routine school anthropometric evaluations conducted during 2002-2013. Prenatal exposure to antibacterials was ascertained by using maternal prescription dispensations and infection-related hospital admissions during pregnancy. We defined overweight and obesity among the children using standard age- and sex-specific cutoffs. We computed sex-specific adjusted prevalence ratios (aPRs) of overweight and obesity associated with exposure to prenatal antibacterials, adjusting for maternal age at delivery, marital status, smoking in pregnancy and multiple gestation; we also stratified the analyses by birth weight. RESULTS: Among 9886 schoolchildren, 3280 (33%) had prenatal exposure to antibacterials. aPRs associated with the exposure were 1.26 (95% confidence interval (CI): 1.10-1.45) for overweight and 1.29 (95% CI: 1.03-1.62) for obesity. Among girls, aPRs were 1.16 (95% CI: 0.95-1.42) for overweight and 1.27 (95% CI: 0.89 to 1.82) for obesity. Among boys, aPRs were 1.37 (95% CI: 1.13-1.66) for overweight and 1.29 (95% CI: 0.96-1.73) for obesity. The aPR for overweight was higher among schoolchildren with birth weight <3500 g (aPR: 1.30, 95% CI: 1.05-1.61) than in schoolchildren with birth weight ⩾3500 g (aPR: 1.18, 95% CI: 0.95-1.46). Inversely, the association for obesity was higher among schoolchildren with birth weight ⩾3500 g (aPR: 1.35, 95% CI: 1.00-1.81) than among those who were <3500 g at birth (aPR: 1.16, 95% CI: 0.82-1.65). CONCLUSIONS: Prenatal exposure to systemic antibacterials is associated with an increased risk of overweight and obesity at school age, and this association varies by birth weight.

Breast cancer risk in hyperprolactinemia: a population-based cohort study and meta-analysis of the literature.

OBJECTIVE: To enhance the precision of the risk estimate for breast cancer in hyperprolactinemia patients by collecting more data and pooling our results with available data from former studies in a meta-analysis. DESIGN: Population-based cohort study and meta-analysis of the literature. METHODS: Using nationwide registries, we identified all patients with a first-time diagnosis of hyperprolactinemia during 1994-2012 including those with a new breast cancer diagnoses after the start of follow-up. We calculated standardised incidence ratios (SIRs) as a measure of relative risk (RR) using national cancer incidence rates. We performed a meta-analysis, combining data from our study with data in the existing literature. RESULTS: We identified 2457 patients with hyperprolactinemia and 20 breast cancer cases during 19,411 person-years of follow-up, yielding a SIR of 0.99 (95% CI 0.60-1.52). Data from two additional cohort studies were retrieved and analyzed. When the three risk estimates were pooled, the combined RR was 1.04 (95% CI 0.75-1.43). CONCLUSIONS: We found no increased risk of breast cancer among patients with hyperprolactinemia.

A prospective cohort study of a woman's own gestational age and her fecundability.

STUDY QUESTION: What is the magnitude of the association between a woman's gestational age at her own birth and her fecundability (cycle-specific probability of conception)? SUMMARY ANSWER: We found a 62% decrease in fecundability among women born <34 weeks of gestation relative to women born at 37-41 weeks of gestation, whereas there were few differences in fecundability among women born at later gestational ages. WHAT IS KNOWN ALREADY: One study, using retrospectively collected data on time-to-pregnancy (TTP), and self-reported data on gestational age, found a prolonged TTP among women born <37 gestational weeks (preterm) and with a birthweight ≤1500 g. Other studies of women's gestational age at birth and subsequent fertility, based on data from national birth registries, have reported a reduced probability of giving birth among women born <32 weeks of gestation. STUDY DESIGN, SIZE, DURATION: We used data from a prospective cohort study of Danish pregnancy planners ('Snart-Gravid'), enrolled during 2007-2011 and followed until 2012. In all, 2814 women were enrolled in our study, of which 2569 had complete follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women eligible to participate were 18-40 years old at study entry, in a relationship with a male partner, and attempting to conceive. Participants completed a baseline questionnaire and up to six follow-up questionnaires until the report of pregnancy, discontinuation of pregnancy attempts, beginning of fertility treatment, loss to follow-up or end of study observation after 12 months. MAIN RESULTS AND THE ROLE OF CHANCE: Among women born <34 gestational weeks, the cumulative probability of conception was 12, 28 and 48% within 3, 6 and 12 cycles, respectively. Among women born at 37-41 weeks of gestation, cumulative probability of conception was 47, 67 and 84% within 3, 6 and 12 cycles, respectively. Relative to women born at 37-41 weeks' gestation, women born <34 weeks had decreased fecundability (fecundability ratio (FR) 0.38, 95% confidence interval (CI): 0.17-0.82). Our data did not suggest reduced fecundability among women born at 34-36 weeks of gestation or at ≥42 weeks of gestation (FR 1.03, 95% CI: 0.80-1.34, and FR 1.13, 95% CI: 0.96-1.33, respectively). LIMITATIONS, REASONS FOR CAUTION: Data on gestational age, obtained from the Danish Medical Birth Registry, were more likely to be based on date of last menstrual period than early ultrasound examination, possibly leading to an overestimation of gestational age at birth. Such overestimation, however, would not explain the decrease in fecundability observed among women born <34 gestational weeks. Another limitation is that the proportion of women born before 34 weeks of gestation was low in our study population, which reduced the precision of the estimates. WIDER IMPLICATIONS OF THE FINDINGS: By using prospective data on TTP, our study elaborates on previous reports of impaired fertility among women born preterm, suggesting that women born <34 weeks of gestation have reduced fecundability. STUDY FUNDING/COMPETING INTERESTS: The study was supported by the National Institute of Child Health and Human Development (R21-050264), the Danish Medical Research Council (271-07-0338), and the Health Research Fund of Central Denmark Region (1-01-72-84-10). The authors have no competing interests to declare.

Rosiglitazone use and post-discontinuation glycaemic control in two European countries, 2000-2010.

OBJECTIVES: To evaluate the impact of risk minimisation policies on the use of rosiglitazone-containing products and on glycaemic control among patients in Denmark and the UK. DESIGN, SETTING AND PARTICIPANTS: We used population-based data from the Aarhus University Prescription Database (AUPD) in northern Denmark and from the General Practice Research Database (GPRD) in the UK. MAIN OUTCOME MEASURES: We examined the use of rosiglitazone during its entire period of availability on the European market (2000-2010) and evaluated changes in the glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels among patients discontinuing this drug. RESULTS: During 2000-2010, 2321 patients with records in AUPD used rosiglitazone in northern Denmark and 25 428 patients with records in GPRD used it in the UK. The proportion of rosiglitazone users among all users of oral hypoglycaemic agents peaked at 4% in AUPD and at 15% in GPRD in May 2007, the month of publication of a meta-analysis showing increased cardiovascular morbidity associated with rosiglitazone use. 12 months after discontinuation of rosiglitazone-containing products, the mean change in HbA1c was -0.16% (95% CI -3.4% to 3.1%) in northern Denmark and -0.17% (95% CI -0.21% to 0.13%) in the UK. The corresponding mean changes in FPG were 0.01 mmol/L (95% CI -7.3 to 7.3 mmol/L) and 0.03 mmol/L (95% CI -0.22 to 0.28 mmol/L). CONCLUSIONS: Publication of evidence concerning the potential cardiovascular risks of rosiglitazone was associated with an irreversible decline in the use of rosiglitazone-containing products in Denmark and the UK. The mean changes in HbA1c and FPG after drug discontinuation were slight.

Prenatal exposure to acid-suppressive drugs and the risk of childhood asthma: a population-based Danish cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) may activate the immune system and cause asthma. AIM: To investigate the association of prenatal exposure to PPIs and histamine 2-receptor antagonists (H2RAs) with risk of asthma. METHODS: In this cohort study, 197,060 singletons born between 1996 and 2008 in northern Denmark were followed until the end of 2009. Data were obtained through Danish medical registries. Asthma in offspring was defined as at least two prescriptions of both a ß-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during the follow-up. Cox proportional-hazard regression was used to compute incidence rate ratios, adjusting for covariates. RESULTS: A total of 2238 (1.1%) children were prenatally exposed to PPIs and 24,506 (12.4%) children developed asthma during follow-up (median follow-up = 6.8 years). The adjusted IRR (aIRR) of asthma associated with prenatal exposure to PPIs was 1.41 (95% confidence interval (CI): 1.27-1.56), compared with those unexposed. The association did not vary by trimester of exposure, and prenatal exposure to H2RAs was associated with similar increase in risk. The aIRR for maternal PPI and H2RA use in the year after, but not during pregnancy was 1.32 (95% CI: 1.20-1.46) and 1.13 (0.93-1.36), respectively, compared with non-use during and in the year after pregnancy. CONCLUSIONS: Prenatal exposure to both PPIs and H2RAs was associated with an increased risk of asthma in our study. Because the observed association is not drug specific and also observed for maternal postnatal use it may be explained by a 'class effect' or maternal underlying condition.

[Objective assessment of total noise exposure over 24 hours: a cross-sectional study in Bavaria]. / Objektive Bestimmung der 24-Stunden-Gesamtlärmbelastung: eine Querschnittsstudie in Bayern.

INTRODUCTION: Noise can affect well-being and performance of individuals and might be associated with an increased risk of cardiovascular events. To date most epidemiological studies considered exposure from a single source of noise. The EU Environmental Noise Directive (2002/49/EC) requires a summative measurement of ambient noise. This study aimed to capture the participants' exposure to environmental noise by means of personal noise dosimetry. METHODS: Children (n=628, participation=61%, age 8-12 years), adolescents (n=632, participation=58%, age 13-17 years) and adults (n=482, participation=40%, age 18-65 years) were selected randomly from the population registry of 4 Bavarian towns and were invited to participate in a 24-h measurement using noise dosimetry. Noise exposures during day and night were analyzed separately. In addition, predictors of noise exposure were assessed. RESULTS: For daytime noise exposure mean±standard deviation were in children 80.0±5.8 dB(A), in adolescents 76.0±6.2 dB(A), in adults 72.1±6.1 dB(A) (p(ANOVA)<0.001). During the day personal noise exposure was statistically significantly higher for participants from smaller towns than for those living in Munich, while nighttime noise exposure was highest for participants from Munich [44.1±7.2 dB(A)]. CONCLUSION: The summative noise exposure in urban Bavaria is high, in particular among children at daytime. Increased exposure levels in children might be caused by themselves while, e.g., playing. Whether the higher daytime exposure in towns is due to high noise levels commuting between home and work has to be assessed in future studies.

[Acute effects on the health of children after accidental exposure to epichlorohydrine]. / Akute gesundheitliche Effekte bei Kindern nach einer akzidentellen Freisetzung von Epichlorhydrin.

PURPOSE: In September 2002, two freight trains collided at Bad Muender, Germany. The inhabitants were potentially exposed to combustion products and to the human carcinogen epichlorohydrine (ECH). We aimed to describe the geographical distribution of and potential risk factors for acute symptoms among children residing in Bad Muender. METHODS: The parents of a random sample of children were invited to answer a mail-in questionnaire (response rate 63%). The main outcome measures were self-reported acute symptoms potentially associated with combustion products (e. g., irritation of the eyes, nose, or throat) and stress-related unspecific symptoms (e. g., gastrointestinal complaints, sleep problems, headaches). The main location during the first 26 hours after the train accident served as exposure proxy measure. In addition, potential predictors for the symptoms under study were assessed. RESULTS: The prevalence of symptoms associated with combustion products was 5.9%. Unspecific symptoms were reported for 6.3% of the children. Main location and prevalence of symptoms were not significantly associated. Physician-diagnosed asthma and nasal allergies were the main predictors of symptoms. CONCLUSION: The prevalence of acute symptoms was relatively high in a random sample of children living close to the incident. However, associations between exposure to the accident and symptoms could not be established conclusively.

[Prevalence of respiratory symptoms and diseases in neighbours of large-scale farming in Northern Germany]. / Atemwegsgesundheit und Allergiestatus bei jungen Erwachsenen in ländlichen Regionen Niedersachsens.

BACKGROUND: Up to now potential health effects of environmental exposure to intensive livestock production facilities have not been thoroughly studied. The aim of the Lower Saxony Lung Study (NiLS) was to assess the prevalence of respiratory symptoms and disease in an area with intensive animal production facilities taking into account environmental exposure to emissions from these large-scale farms. METHODS: All 10 864 inhabitants (age 18 to 44 years) of four towns with a large number of intensive animal production facilities in the area were invited to answer a mail-in questionnaire. Of these, 6416 subjects were randomly selected for the clinical part of the study (specific IgE, lung function measurements, bronchial provocation with methacholine). Overall, 6937 subjects answered the questionnaire (68 %), 60 % took part in the clinical tests. RESULTS: The prevalence of allergic disease in the study population was lower than in urban citizens. Subjects with more than 12 animal houses within 500 m of their home had an increased odds ratio for wheezing without a cold (odds ratio 2.7; 95 % confidence interval 1.4 - 5.4). They also showed a significantly decreased FEV (1) (mean 0.26 l; 0.04 l - 0.48 l) as well as a trend for a lower Tiffeneau-Index. CONCLUSIONS: In result, a large number of intensive animal production facilities might be associated with decreased lung function results in the immediate neighbours. Further studies are necessary to confirm our findings.