Assessment of pediatric asthma drug use in three European countries; a TEDDY study.

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0-18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. ß2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, ß2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for ß2-mimetics (the UK highest). Off-label use was low, and most pronounced for ß2-mimetics in children <18 months (IT) and combined ß2-mimetics + anticholinergics in children <6 years (NL). CONCLUSION: This study shows that among all asthma drugs, ß2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety

Genome-wide association study of asthma exacerbations despite inhaled corticosteroids use

Rationale Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies. Methods A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 European-descent children treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed. Results Ten independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at the CACNA2D3-WNT5A locus was nominally replicated in Europeans (rs67026078, p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found. Conclusions The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response

COPD in the general population: prevalence, incidence and survival

SummaryWorldwide, COPD is a leading cause of chronic morbidity and mortality. Although its prevalence is already well documented, very few studies have measured its incidence. We therefore investigated the prevalence, incidence and lifetime risk of COPD in the general population.In a population-based study including subjects ≥ 40, with 12 months of history available in the Dutch IPCI database, we identified COPD cases by a two-step validation algorithm.Among 185,325 participants with 601,283 years of follow-up, 7308 subjects with COPD were identified, and 1713 had incident COPD. The overall IR of physician-diagnosed COPD was 2.92/1000PY (95%CI 2.78–3.06). The incidence of COPD was higher in men (3.54; 95%CI 3.33–3.77) than in women (2.34; 95%CI 2.17–2.52), and the overall baseline prevalence of COPD was 3.02% (95%CI 2.94–3.10). For people who had entered the study free of COPD at the age of 40, the risk of developing COPD within the next 40 years was 12.7% for men and 8.3% for women. In patients with very severe COPD, 26% died after 1 year of follow-up, whereas 2.8% died among the non-COPD subjects.In the general population in the Netherlands, three on 1000 subjects were diagnosed with COPD per year. The incidence increased rapidly with age and was higher in men than in women. One in eight men and one in 12 women, being COPD free at the age of 40, will develop COPD during their further life. Mortality rates differed substantially between COPD patients and non-COPD subjects of the same age, underlining the burden of this disease

Messages from the Aalst Allergy Study

Background: The prevalence of sensitization and allergic disease has increased significantly worldwide. The aim of the "Aalst Allergy Study" was to document prevalences of sensitization and allergic symptoms, and to evaluate the effect of personal and environmental influences on these prevalences in an unbiased Belgian pediatric population. Methods: A cross-sectional study was performed in an unbiased population of 2021 Belgian schoolchildren (3.4-14.8 years). Skin prick testing with the most common aeroallergens was performed. Allergic symptoms as well as potential risk factors for sensitization and allergic disease were documented by a parental questionnaire. Results: The prevalence of sensitization to the most common aeroallergens and the prevalence of allergic diseases (eczema, asthma and rhinoconjunctivitis) were in line with the data in the literature. The association of current allergic symptoms with sensitization was only significant in the children aged >= 6 years. Age, gender, body mass index, bedroom environment and exposure to pets were the factors significantly associated with sensitization and allergic symptoms. Conclusions: Our study corroborates the reported prevalences of sensitization and allergic diseases. Moreover the study illustrates the complexity of the search for factors involved in the process of sensitization and allergic disease. The impact of different potential causative factors is not only influenced by mutual interactions of these factors, but also by the existence of distinct subtypes of disease

Inhaled anticholinergic drugs and risk of acute urinary retention

What's known on the subject? and What does the study add? Inhaled anticholinergic drugs have been associated with the risk of acute urinary retention (AUR), but this association was never studied under real life circumstances nor was this risk ever quantified. Use of inhaled anticholinergic drugs increases the risk of AUR by 40%. The risk of AUR is highest in recent starters, in patients with benign prostatic hyperplasia (BPH), and in patients receiving their anticholinergic drugs via nebulizer. It might be advisable to consider alternatives for inhaled anticholinergic drugs in COPD patients with BPH. OBJECTIVE : To investigate the association between the use of inhaled anticholinergic drugs and the risk of acute urinary retention (AUR) under real-life circumstances. PATIENTS AND METHODS : We conducted a nested case-control study within a cohort of patients with chronic obstructive pulmonary disease (COPD; as AUR has been associated with the use of inhaled anticholinergic drugs, which are used as first-line treatment for COPD) from the Integrated Primary Care Information (IPCI) database. The cohort consisted of all patients with COPD aged >= 45 years, registered between 1996 and 2006, with >= 12 months of valid history. Cases were patients with a first diagnosis of AUR. To each case, controls were selected matched for age, gender and index date. Multivariate conditional logistic regression analysis was used to calculate adjusted odds ratios (OR(adj)) with 95% confidence intervals (95% CI). RESULTS : Within the cohort of 22 579 patients with COPD, 209 cases were identified. Current use of inhaled anticholinergic drugs was associated with a 40% increase in risk for AUR (OR(adj) 1.40; 95% CI 0.99-1.98) compared with non-users. Among current users, the risk was highest for the recent starters (OR(adj) 3.11; 95% CI 1.21-7.98). The risk of long-acting anticholinergic drug tiotropium was not substantially different from that of the short-acting anticholinergic ipratropium. The association was not dose-dependent, but changed by mode of administration, with nebulizers having the highest risk (OR(adj) 2.92; 95% CI 1.17-7.31). In men with COPD and benign prostatic hyperplasia (BPH) the association was strongest (OR(adj) 4.67; 95% CI 1.56-14.0). CONCLUSION : Current use of inhaled anticholinergic drugs increases the risk of AUR, especially in patients with BPH or if administered via a nebulizer

Trade blocs and currency blocs : a package deal?

Digitised version produced by the EUI Library and made available online in 2020

Association between Use of Asthma Drugs in Children and Hepatotoxicity

Background: Hepatotoxicity in relation to asthma drugs is rare. Some cases of hepatotoxicity have been described with use of Leukotriene receptor antagonists (LTRA). Our research on signal detection in children showed a new association between flunisolide, an inhaled corticosteroid, and liver injury. Objectives: To investigate the association between oral and inhaled use of asthma drugs and hepatotoxicity in children and adolescents. Methods: A population-based case-control study was performed over 2000-2008 combining three European electronic primary care databases: The Integrated Primary Care Information database in the Netherlands, plus the PEDIANET and the Health Search/CSD Longitudinal Patient Database in Italy. Cases of hepatotoxicity in the pediatric population (<18 years old) were identified and validated in each database, retaining only idiopathic cases. Up to 100 controls were matched to each case based on age, gender and the date of case diagnosis (index date). Use of antiasthmatics was classified as current if a prescription for the drug of interest lasted until index date or ended within 60 days prior to the index date. Results: We identified 938 pediatric cases of hepatotoxicity and these were matched to 93,665 controls. Significant unadjusted associations were found for current inhaled use of β2-adrenergic agonists [OR 2.3 (95% CI, 1.6 to 3.4), corticosteroids (2.3, 1.7 to 3.2), cromoglicic acid/nedocromil (3.3, 1.1 to 10.6) and oral use of LTRA (2.6, 1.1 to 5.8), compared to non-use. When adjusting for concurrent use of antibiotics, the association remained significant only for the use of β2-agonists and corticosteroids. Use of LTRA was associated with an increased risk estimate of hepatotoxicity (adj. OR 1.8, 0.8 to 4.0), but no longer significant. Conclusions: This study provides some evidence on the hepatic safety of anti-asthmatics in children. Use of β2- agonists and corticosteroids was associated with an increased risk of hepatotoxicity, but additional studies will be needed to verify that this is not due to residual confoundin

Mendelian randomization study of interleukin-6 in chronic obstructive pulmonary disease

Background: Cross-sectional studies have demonstrated that increased levels of interleukin-6 (IL6) are present in the airways and blood samples of patients with chronic obstructive pulmonary disease (COPD). Objectives: To investigate the association between IL6 and the risk of COPD using a Mendelian randomization approach. Methods: Eight common single-nucleotide polymorphisms (SNPs) in the region of the IL6 gene were genotyped using both TaqMan and Illumina in the Rotterdam Study, a prospective population-based cohort study consisting of 7,983 participants aged 55 years or older, including 928 COPD patients. At baseline, blood was drawn in a random sample of 714 subjects to measure the IL6 plasma level. Analysis of variance, logistic regression, and Cox proportional hazard models - adjusted for age, gender, pack years, and BMI - were used for analyses. Results: High levels of IL6 (>2.4 pg/ml, the highest tertile) were associated with a three-fold increased risk of developing COPD, in comparison to low levels (<1.4 pg/ml, the lowest tertile). The rs2056576 SNP was associated with a 10% increase in the risk of COPD per additional T allele. However, the association was no longer significant after adjustment. No association was found with other common SNPs in the IL6 gene and COPD. Conclusions: Although increased IL6 plasma levels at baseline are associated with the risk of developing COPD during follow-up, there was no strong evidence for an association between common variation in the IL6 gene and the risk of COPD. Copyright (C) 2011 S. Karger AG, Base