Koen Simons

Short-Term Effect of Pollen and Spore Exposure on Allergy Morbidity in the Brussels-Capital Region

Belgium is among the European countries that are the most affected by allergic rhinitis. Pollen grains and fungal spores represent important triggers of symptoms. However, few studies have investigated their real link with disease morbidity over several years. Based on aeroallergen counts and health insurance datasets, the relationship between daily changes in pollen, fungal spore concentrations and daily changes in reimbursable systemic antihistamine sales has been investigated between 2005 and 2011 in the Brussels-Capital Region. A Generalized Linear Model was used and adjusted for air pollution, meteorological conditions, flu, seasonal component and day of the week. We observed an augmentation in drug sales despite no significant increase in allergen levels in the long term. The relative risk of buying allergy medications associated with an interquartile augmentation in pollen distributions increased significantly for Poaceae, Betula, Carpinus, Fraxinus and Quercus. Poaceae affected the widest age group and led to the highest increase of risk which reached 1.13 (95% CI [1.11–1.14]) among the 19- to 39-year-old men. Betula showed the second most consistent relationship across age groups. Clear identification of the provoking agents may improve disease management by customizing prevention programmes. This work also opens several research perspectives related to impact of climate modification or subpopulation sensitivity.

Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study

Objective For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC. Design We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4–10 weeks after surgery. Somatic mutations in individual patient’s tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results. Results We analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001). Conclusion Postoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

The Cytome Assay as a Tool to Investigate the Possible Association Between Exposure to Extremely Low Frequency Magnetic Fields and an Increased Risk for Alzheimer’s Disease

Exposure to extremely low frequency magnetic fields (ELF-MF) has been identified as one of the potential environmental risk factors for Alzheimers disease (AD). However, this is far from being established. So far there is no experimental evidence supporting this alleged association. We have performed an in vitro cytogenetic laboratory investigation to explore the plausibility of such association. Our investigation was based on possible similarities found in cells from AD patients and in cells exposed to ELF-MF. We especially found that 50  Hz ELF-MF increase the frequency of cells with (large) micronuclei and nuclear buds indicating that fields above 50 μT may induce chromosome instabilities as those found in AD patients. It should be stressed yet that results from the few published experimental studies on ELF-MF and AD are rather reassuring. Thus, our findings certainly do not prove anything. They only suggest that further investigations might be necessary.

Direct cost saving potential in medication costs due to a reduction in outdoor air pollution for the Brussels Capital Region.

INTRODUCTION The adverse health effects of exposure to air pollution have been well-established and include mortality, hospital admissions, emergency department visits, etc, but also less severe outcomes such as medication use and purchase. The economic impact, an additional motivator for policy, has been studied primarily for the more severe outcomes. METHODS Purchase data of reimbursed medications typically prescribed for asthma and chronic obstructive pulmonary disease, were obtained through the mandatory Belgian health insurance system. A time series analyses approach was used to model daily sales on daily air pollution concentrations (NO2, PM10 and PM2.5) for residents of the Brussels Capital Region as a whole. In addition, a higher geographical resolution of both sales and pollutant concentrations allowed for a multi-sector approach. Annual savings were estimated for the scenario of a 10% reduction in each of the pollutants. RESULTS Medication purchase was significantly associated with NO2 concentrations, leading to an annual cost saving potential of € 107,845 [95%CI: € 71,483-€ 143,823] in R03 sales (WHO classification for drugs of obstructive airway diseases). Saving potentials of PM10 and PM2.5 were not significant. Estimates were not sensitive to the geographical resolution, however, higher precision can be obtained with higher resolution data, subject to the condition that the number of sales is sufficiently large.

Thyroid cancer incidence around the Belgian nuclear sites: Surrogate exposure modelling

BACKGROUND In a recent ecological study among residents living around Belgian nuclear sites (the NUCABEL study), significant increased incidences of thyroid cancer were observed around the two nuclear facilities with industrial and research activities (Mol-Dessel and Fleurus), prompting further research. METHODS The data from the NUCABEL study were reanalysed to test the hypothesis of a gradient in cancer incidence with increasing levels of exposure from these sites using three measures of surrogate exposure, being (i) residential proximity, (ii) prevailing wind directions and (iii) simulated dispersion of radioactive discharges. Single-site focussed hypothesis tests were complemented with Generalized Additive Models to estimate the exposure-response relationships. RESULTS For Mol-Dessel, the results of the focussed hypothesis tests were far from significant. For Fleurus, the p-values were much closer to significance with p=0.05 for Bithells Linear Risk Score using radioactive discharge estimates as surrogate. CONCLUSIONS The re-analyses refute an association with the nuclear facilities for the site of Mol-Dessel. For the site of Fleurus, one of Europes major production sites of radio-iodines, the results were less conclusive and further research suggests itself.

Comparative long-term trend analysis of daily weather conditions with daily pollen concentrations in Brussels, Belgium

A clear rise in seasonal and annual temperatures, a gradual increase of total radiation, and a relative trend of change in seasonal precipitation have been observed for the last four decades in Brussels (Belgium). These local modifications may have a direct and indirect public health impact by altering the timing and intensity of allergenic pollen seasons. In this study, we assessed the statistical correlations (Spearman’s test) between pollen concentration and meteorological conditions by using long-term daily datasets of 11 pollen types (8 trees and 3 herbaceous plants) and 10 meteorological parameters observed in Brussels between 1982 and 2015. Furthermore, we analyzed the rate of change in the annual cycle of the same selected pollen types by the Mann-Kendall test. We revealed an overall trend of increase in daily airborne tree pollen (except for the European beech tree) and an overall trend of decrease in daily airborne pollen from herbaceous plants (except for Urticaceae). These results revealed an earlier onset of the flowering period for birch, oak, ash, plane, grasses, and Urticaceae. Finally, the rates of change in pollen annual cycles were shown to be associated with the rates of change in the annual cycles of several meteorological parameters such as temperature, radiation, humidity, and rainfall.

Respiratory medication sales and urban air pollution in Brussels (2005 to 2011).

BACKGROUND We investigated the associations between daily sales of respiratory medication and air pollutants in the Brussels-Capital Region between 2005 and 2011. METHODS We used over-dispersed Poisson Generalized Linear Models to regress daily individual reimbursement data of prescribed asthma and COPD medication from the social security database against each subjects residential exposure to outdoor particulate matter (PM10) or NO2 estimated, by interpolation from monitoring stations. We calculated cumulative risk ratios (RR) and their 95% confidence intervals (CI) for interquartile ranges (IQR) of exposure for different windows of past exposure for the entire population and for seven age groups. RESULTS Median daily concentrations of PM10 and NO2 were 25μg/m(3) (IQR=17.1) and 38μg/m(3) (IQR=20.5), respectively. PM10 was associated with daily medication sales among individuals aged 13 to 64y. For NO2, significant associations were observed among all age groups except >84y. The highest RR were observed for NO2, among adolescents, including three weeks lags (RR=1.187 95%CI: 1.097-1.285). CONCLUSION The associations found between temporal changes in exposure to air pollutants and daily sales of respiratory medication in Brussels indicate that urban air pollution contributes to asthma and COPD morbidity in the general population.

Using spatial measures to test a conceptual model of social infrastructure that supports health and wellbeing

Abstract Social infrastructure requires a consistent and measurable definition and more evidence is needed to demonstrate why it is important to health, wellbeing and the liveability of a community. In this paper, social infrastructure is defined as life-long social service needs related to health, education, early childhood, community support, community development, culture, sport and recreation, parks and emergency services. These services are needed to promote health and wellbeing and underinvestment and poor planning of social infrastructure has been linked to area-based health inequities. Current methods used to plan infrastructure delivery in communities were analysed and a new conceptual framework of social infrastructure developed and empirically tested using geocoded health survey data linked to spatial social infrastructure measures. Both accessibility and mix of social infrastructure were associated with higher Subjective Wellbeing. Residents were most likely to have close access to childcare services, dentists, doctors and sport facilities and least likely to have access to services of culture and leisure including cinemas, theatres, libraries, museums and art galleries. Results provide evidence of direct associations between social infrastructure planning and public health, the need for alternative social infrastructure urban planning methods and policies, and areas for future research.

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium.

BACKGROUND Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. OBJECTIVES (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. METHODS Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). RESULTS The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. DISCUSSION AND CONCLUSION The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.

The impact of social housing on mental health: longitudinal analyses using marginal structural models and machine learning-generated weights

Background Social housing may provide an affordable and secure residential environment, but has also been associated with stigma, poor housing conditions and locational disadvantage. We examined the cumulative effect of additional years, and tenure security (number of transitions in/out), of social housing on mental health in a large cohort of lower-income Australians. Methods We analysed a longitudinal panel survey that annually collected information on tenure and health from 2001 to 2013. To address the time-varying effect of previous health on social housing occupancy, we used marginal structural models. Stabilized inverse probabilities of treatment weights were generated using ensemble learning to improve prediction. To address remaining residual imbalance across covariates, double adjustment was made by additionally including baseline covariates in models. Mental health was measured using the Mental Health Short-Form summary measure of the SF-36 (MH), and psychological distress was measured using the Kessler Psychological Distress Scale (K10). Results People who had continuous exposure to social housing had worse mental health on average than people continuously occupying other tenures. The worst mental health outcomes, however, were observed for people who made multiple transitions. Mental health deteriorated and psychological distress increased with number of transitions: MH -1.04 [95% confidence interval (CI) -2.16; 0.09) and K10 0.56 (95% CI 0.12; 1.00). Estimates are in the order of 6% (MH) and 9% (K10) of one standard deviation for each measure. Conclusions The more transitions people made in/out of social housing, the greater the impact on mental health and psychological distress, supporting the case for provision of more stable forms of social housing.