Phenotypic and functional translation of IL33 genetics in asthma.

BACKGROUND: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevated in sputum and bronchial biopsies of patients with asthma. The functional consequences of IL33 asthma SNPs remain unknown. OBJECTIVE: This study sought to determine whether IL33 SNPs associate with asthma-related phenotypes and with IL33 expression in lung or bronchial epithelium. This study investigated the effect of increased IL33 expression on human bronchial epithelial cell (HBEC) function. METHODS: Association between IL33 SNPs (Chr9: 5,815,786-6,657,983) and asthma phenotypes (Lifelines/DAG [Dutch Asthma GWAS]/GASP [Genetics of Asthma Severity & Phenotypes] cohorts) and between SNPs and expression (lung tissue, bronchial brushes, HBECs) was done using regression modeling. Lentiviral overexpression was used to study IL33 effects on HBECs. RESULTS: We found that 161 SNPs spanning the IL33 region associated with 1 or more asthma phenotypes after correction for multiple testing. We report a main independent signal tagged by rs992969 associating with blood eosinophil levels, asthma, and eosinophilic asthma. A second, independent signal tagged by rs4008366 presented modest association with eosinophilic asthma. Neither signal associated with FEV1, FEV1/forced vital capacity, atopy, and age of asthma onset. The 2 IL33 signals are expression quantitative loci in bronchial brushes and cultured HBECs, but not in lung tissue. IL33 overexpression in vitro resulted in reduced viability and reactive oxygen species-capturing of HBECs, without influencing epithelial cell count, metabolic activity, or barrier function. CONCLUSIONS: We identify IL33 as an epithelial susceptibility gene for eosinophilia and asthma, provide mechanistic insight, and implicate targeting of the IL33 pathway specifically in eosinophilic asthma.

[The Personal Antipsychotic Choice Index]. / De Persoonlijke Antipsychotica Keuzewijzer.

BACKGROUND: More than half of the patients suffering from a first psychotic episode withdraw from antipsychotic medication within the first year of treatment. Shared decision making could enhance the therapeutic relationship and thus adherence. AIM: To describe an online decision aid for the selection of antipsychotic medication: the Personal Antipsychotic Choice Index (www.pakwijzer.nl). METHOD: Per effect and side effect, the 15 most commonly prescribed antipsychotics in the Netherlands have been ranked on the basis of data on the magnitude of a desired effect and the chance of a side effect, based on a systematic literature study. We assigned scores to antipsychotics for each desired and undesired effect and processed these scores in an algorithm. A personal ranking of antipsychotics is calculated based on the value that patients attach to these effects. RESULTS: These desired and undesired criteria used are rated in the PACindex: effectiveness concerning psychotic, depressive and cognitive symptoms, weight gain, sexual dysfunction, drowsiness, hypersomnia, extrapyramidal symptoms, anticholinergic adverse effects, hypersalivation, nausea, dizziness, energy loss, blunted affect/less need for companionship. High level evidence was available for ranking weight gain, sexual dysfunction, menstrual disorders, extrapyramidal symptoms and effectiveness on psychotic symptoms. We used lower level evidence ranking the remaining criteria. CONCLUSION: A ready applicable online choixe index for the use of an antipsychotic agent has been developed and put into use. The PACindex could be updated when new evidence of new antipsychotics became available..

Correction: Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation.

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

Electron microscopy in the diagnosis of Ehlers-Danlos syndromes: correlation with clinical and genetic investigations.

BACKGROUND: The Ehlers-Danlos syndromes (EDS) consist of 13 subtypes with overlapping features including joint hypermobility, skin and vascular fragility and generalized connective tissue friability. As DNA analysis has become the gold standard for investigation of EDS, transmission electron microscopy (TEM) in clinical practice is decreasing. However, owing to the use of next-generation sequencing, the frequency of variants of uncertain significance (VUS) identified using DNA analysis is increasing. We hypothesized that TEM can provide evidence for or against pathogenicity of VUS. OBJECTIVES: The aim of this study was to evaluate the role of TEM in the diagnosis of EDS subtypes. METHODS: Data were collected from patients who underwent a skin biopsy between October 2012 and March 2017 at the London EDS National Diagnostic Service. TEM biopsies were categorized as 'normal' or 'abnormal' according to the description and conclusion in the TEM reports. Definitive diagnoses were reached via a combination of clinical features, structural and functional studies and DNA investigations. RESULTS: The analysis included 177 patients, comprising 30 abnormal and 147 normal TEM reports. A definitive diagnosis of monogenic EDS subtypes was made in 24 patients. Overall, 17 of these 24 patients (71%) had an abnormal biopsy report and seven (29%) had a normal biopsy report. No TEM findings were specifically associated with any EDS subtype, although collagen flowers were present in most patients with a genetically confirmed diagnosis of classical EDS. CONCLUSIONS: TEM analysis of collagen structure may have the potential to provide evidence for or against the pathogenicity of a VUS, but more work is needed to establish a clear role for TEM in this process. What's already known about this topic? Collagen fibril abnormalities can be seen in several Ehlers-Danlos syndrome (EDS) subtypes. What does this study add? This study provides clinical data, transmission electron microscopy (TEM) data and molecular data of one of the largest groups of patients suspected to have a monogenetic EDS subtype. No TEM findings were specifically associated with an EDS subtype. There was a higher percentage (71%) of abnormal biopsy findings in patients with a definitive diagnosis of a monogenetic EDS subtype and where a class 4/5 genetic variant was present.

Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis.

BACKGROUND: The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. METHODS: PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed. RESULTS: A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n=10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15-3.22, p=0.01). CONCLUSION: The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.

[Monitoring with four recovery phases. First experiences in FACT]. / Monitoren met vier herstelfasen; eerste ervaringen binnen FACT.

BACKGROUND: Following an audit, the flexible assertive community treatment-teams (FACT-teams), in Winterswijk, the Netherlands, set out to discover a more recovery-oriented approach to treatment and monitoring. Their findings support researching four recovery phases described previously.
AIM: A pilot-study to investigate the possibilities to create a more recovery-oriented working method by applying the four recovery phases - ranging from being overwhelmed by the condition to living past the condition - in FACT-teams.
METHOD: The FACT-teams started to monitor patients during the recovery phases and developed a semi-structured interview that can be used to determine the current recovery phase. After the phase has been determined, a plan is written on how to progress to the next phase.
RESULTS: Monitoring during the recovery phases proved to be useful in showing both succesfull and stagnating treatments. The recovery phases also became part of the standard treatment plans in the electronic patient dossier. An important result of this project was the recovery-oriented interview we developed.
CONCLUSION: Monitoring and interviewing based on the four recovery phases subjectively leads to more in-depth and more recovery-oriented evaluations of treatment. More empirical research into this method is necessary.

Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma.

Interleukin-1 receptor-like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101).IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10-16) and serum IL1RL1-a levels (p=2.8×10-56). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.

Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission.

BACKGROUND: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVE: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. RESULTS: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 × 10-7 ) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13. CONCLUSIONS AND CLINICAL RELEVANCE: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.

Predictive value of serum sST2 in preschool wheezers for development of asthma with high FeNO.

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 (IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.

TRPA1 gene polymorphisms and childhood asthma.

BACKGROUND: Animal data have suggested that the transient receptor potential ankyrin-1 (TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. METHODS: We analysed associations between 31 TRPA1 single nucleotide polymorphisms (SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We sought to confirm the most significant associations with comparable outcomes in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) and Generation R birth cohorts. In ALSPAC, we explored interactions with prenatal paracetamol exposure. RESULTS: In ALSPAC, there was strong evidence for association between six SNPs and asthma: rs959974 and rs1384001 (per-allele odds ratio for both: 1.30 (95% CI: 1.15-1.47), p = 0.00001), rs7010969 (OR 1.28 (1.13-1.46), p = 0.00004), rs3735945 (OR 1.30 (1.09-1.55), p = 0.003), rs920829 (OR 1.30 (1.09-1.54), p = 0.004) and rs4738202 (OR 1.22 (1.07-1.39), p = 0.004). In a meta-analysis across the three cohorts, the pooled effect estimates confirmed that all six SNPs were significantly associated with asthma. In ALSPAC, TRPA1 associations with asthma were not modified by prenatal paracetamol, although associations with IgE concentration were. CONCLUSION: This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words).

Workers' health surveillance: implementation of the Directive 89/391/EEC in Europe.

BACKGROUND: European Union (EU) Directive 89/391 addressed occupational health surveillance, which recommends to provide workers with 'access to health surveillance at regular intervals', aiming to prevent work-related and occupational diseases. AIMS: To investigate how EU countries adopted this Directive. METHODS: We invited one selected representative per member state to complete a questionnaire. RESULTS: All 28 EU countries implemented the Directive in some form. Workers' health surveillance (WHS) is available to all workers in 15 countries, while in 12, only specific subgroups have access. In 21 countries, workers' participation is mandatory, and in 22, the employer covers the cost. In 13 countries, access to WHS is not available to all workers but depends on exposure to specific risk factors, size of the enterprise or belonging to vulnerable groups. In 26 countries, the employer appoints and revokes the physician in charge of WHS. Twelve countries have no recent figures, reports or cost-benefit analyses of their WHS programmes. In 15 countries where reports exist, they are often in the native language. CONCLUSIONS: Coverage and quality of occupational health surveillance should be evaluated to facilitate learning from good practice and from scientific studies. We propose a serious debate in the EU with the aim of protecting workers more effectively, including the use of evidence-based WHS programmes.

Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood.

BACKGROUND: Genome-wide association studies identified IL33 and IL-1 receptor-like 1 (IL1RL1)/IL18R1 as asthma susceptibility loci. IL33 and IL1RL1 constitute a single ligand-receptor pathway. OBJECTIVE: In 2 birth cohorts, the Prevalence and Incidence of Asthma and Mite Allergy (PIAMA) study and Avon Longitudinal Study of Parents and Children (ALSPAC), we analyzed associations of longitudinal wheezing phenotypes and asthma with single nucleotide polymorphisms (SNPs) of 8 genes encoding IL-33, IL1RL1, its coreceptor IL1RAcP, its adaptors myeloid differentiation primary response gene 88 (MyD88) and Toll-IL-11 receptor domain containing adaptor protein (TIRAP), and the downstream IL-1 receptor-associated kinase 1, IL-1 receptor-associated kinase 4, and TNF receptor-associated factor 6 (TRAF6). Furthermore, we investigated whether SNPs in this pathway show replicable evidence of gene-gene interaction. METHODS: Ninety-four SNPs were investigated in 2007 children in the PIAMA study and 7247 children in ALSPAC. Associations with wheezing phenotypes and asthma at 8 years of age were analyzed in each cohort and subsequently meta-analyzed. Gene-gene interactions were assessed through model-based multifactor dimensionality reduction in the PIAMA study, and gene-gene interactions of 10 SNP pairs were further evaluated. RESULTS: Intermediate-onset wheeze was associated with SNPs in several genes in the IL33-IL1RL1 pathway after applying multiple testing correction in the meta-analysis: 2 IL33 SNPs (rs4742170 and rs7037276), 1 IL-1 receptor accessory protein (IL1RAP) SNP (rs10513854), and 1 TRAF6 SNP (rs5030411). Late-onset wheeze was associated with 2 IL1RL1 SNPs (rs10208293 and rs13424006), and persistent wheeze was associated with 1 IL33 SNP (rs1342326) and 1 IL1RAP SNP (rs9290936). IL33 and IL1RL1 SNPs were nominally associated with asthma. Three SNP pairs showed interaction for asthma in the PIAMA study but not in ALSPAC. CONCLUSIONS: IL33-IL1RL1 pathway polymorphisms are associated with asthma and specific wheezing phenotypes; that is, most SNPs are associated with intermediate-onset wheeze, a phenotype closely associated with sensitization. We speculate that IL33-IL1RL1 pathway polymorphisms affect development of wheeze and subsequent asthma through sensitization in early childhood.

Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment.

Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Undergraduate teaching of occupational medicine in European schools of medicine.

PURPOSE: General practitioners play or should play a role in occupational medicine (OM), either in diagnosing occupational diseases or in counseling on return to work. Nevertheless, their training has been reported to be insufficient in most single country studies. AIMS: The objectives of this study were to analyze the content and extent of undergraduate teaching of OM in European medical schools. METHODS: An e-mail questionnaire survey of the teaching of OM to undergraduates was undertaken from December 2010 to April 2011 in all medical schools and medical faculties listed in 27 European countries (n = 305). RESULTS: Among the 305 universities identified, 135 answered to the questionnaire, giving a response rate of 44%. The mean number of hours given to formal instruction in occupational medicine to medical undergraduates was 25.5 h. Nevertheless, this number of hours varied widely between countries, but also within countries. Overall, 27% of medical schools gave their students 10 h of teaching or less, 52% 20 h or less and 69% 30 h or less. Whereas occupational diseases and principles of prevention were covered in most schools, disability and return to work were very poorly represented among the topics that were taught to students. CONCLUSION: Dedicated undergraduate teaching on occupational health or OM in European medical schools is present in most medical schools, usually at a low level, but is very variable between and within countries. Medical schools across Europe are very unequal to provide qualifying doctors education on the topics they will frequently come across in their working lives.

Expression signature in peripheral blood cells for molecular diagnosis of head and neck squamous cell carcinoma.

Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis due to the development of locoregional recurrences, distant metastases, and second primary tumors. There is an urgent need for biomarkers that enable detection and monitoring of the disease to provide adequate therapeutic strategies. In this study, we have investigated markers in peripheral blood cells (PBC) of 28 HNSCC patients who underwent surgery by means of expression profiling. Our hypothesis is that nucleated blood cells circulate continuously, also pass the tumor, and change their expression profile in response to tumor cell factors. For comparison, we enrolled a control group of 11 patients who underwent surgery in the head and neck region for non-HNSCC reasons. A set of 2949 genes was found to be statistically different between the groups (P < 0.05, false discovery rate-corrected) and the most prominently different pathways were EIF2, EIF4, and mTOR signaling. These preliminary results are promising and warrant further studies on the definitive role of PBC gene expression as a biomarker for HNSCC detection and monitoring.

Ethical issues of genetic susceptibility testing for occupational diseases: opinions of trainees in a high-risk job.

PURPOSE: Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are scarce. We investigated whether opinions of an intended stakeholder group, that is, student nurses, are sufficiently addressed by existing recommendations. METHODS: Attitudes and opinions of Dutch student nurses toward a genetic test for susceptibility to occupational contact eczema were studied in a qualitative setup using focus groups, interviews and electronic questionnaires. The results were compared with guidelines and recommendations extracted from the literature. RESULTS: Sixty-nine percent of the student nurses said they would partake in a genetic test for susceptibility to occupational contact eczema when available. Concerns were expressed regarding the difficulty of interpreting test results, the utility of the test result in practice and the necessity of genetic tests for non-severe diseases. For the issue of privacy and confidentiality, the students expressed few worries and much confidence. The existing guidelines largely covered the students' opinions. Still, the data emphasized the need for good individual risk communication both before and after testing, taking into account that the test concerns susceptibility. CONCLUSIONS: Comparing the students' statements with the issues addressed by the guidelines, we conclude that the guidelines should pay more attention to risk communication and practical advice accompanying the test results.

Effect evaluation of a self-management program for dutch workers with a chronic somatic disease: a randomized controlled trial.

PURPOSE: The objective of this study is to investigate the effect of a Self-Management Program for workers with a chronic disease. This program is based on the Chronic Disease Self-Management Program of Stanford University, modified for workers with a chronic somatic disease. METHODS: In a randomized controlled trial, the effectiveness of a Self-Management Program was evaluated. Participants were randomly assigned to the experimental group (n = 57) and the control group (n = 47). The experimental group received an intervention, the control group received care as usual. Primary outcome measures were self-efficacy at work and the attitude towards self-management at work. Secondary outcomes were the SF-12 health survey questionnaire, job satisfaction and intention to change job. The results were measured at baseline, after the intervention and 8 months after the intervention. RESULTS: The attitude towards self-management at work (enjoyment) improved after 8 months for the intervention group (p = 0.030). No other outcome variable differed significantly. As an interaction effect, it was found that low educated workers developed a better physical health quality (SF-12) in the intervention group compared with the control group. The attitude towards self-management at work (importance) improved in the intervention group for older and female workers and the attitude toward enjoying self-management at work improved for female workers only. CONCLUSION: The results show that low educated workers, older workers and women benefit significantly more from the training than higher educated workers, younger workers and men.