Outdoor air pollution as a risk factor for testing positive for SARS-CoV-2: A nationwide test-negative case-control study in the Netherlands.

Air pollution is a known risk factor for several diseases, but the extent to which it influences COVID-19 compared to other respiratory diseases remains unclear. We performed a test-negative case-control study among people with COVID-19-compatible symptoms who were tested for SARS-CoV-2 infection, to assess whether their long- and short-term exposure to ambient air pollution (AAP) was associated with testing positive (vs. negative) for SARS-CoV-2. We used individual-level data for all adult residents in the Netherlands who were tested for SARS-CoV-2 between June and November 2020, when only symptomatic people were tested, and modeled ambient concentrations of PM10, PM2.5, NO2 and O3 at geocoded residential addresses. In long-term exposure analysis, we selected individuals who did not change residential address in 2017-2019 (1.7 million tests) and considered the average concentrations of PM10, PM2.5 and NO2 in that period, and different sources of PM (industry, livestock, other agricultural activities, road traffic, other Dutch sources, foreign sources). In short-term exposure analysis, individuals not changing residential address in the two weeks before testing day (2.7 million tests) were included in the analyses, thus considering 1- and 2-week average concentrations of PM10, PM2.5, NO2 and O3 before testing day as exposure. Mixed-effects logistic regression analysis with adjustment for several confounders, including municipality and testing week to account for spatiotemporal variation in viral circulation, was used. Overall, there was no statistically significant effect of long-term exposure to the studied pollutants on the odds of testing positive vs. negative for SARS-CoV-2. However, significant positive associations of long-term exposure to PM10 and PM2.5 from specifically foreign and livestock sources, and to PM10 from other agricultural sources, were observed. Short-term exposure to PM10 (adjusting for NO2) and PM2.5 were also positively associated with increased odds of testing positive for SARS-CoV-2. While these exposures seemed to increase COVID-19 risk relative to other respiratory diseases, the underlying biological mechanisms remain unclear. This study reinforces the need to continue to strive for better air quality to support public health.

Effects of long-term exposure to outdoor air pollution on COVID-19 incidence: A population-based cohort study accounting for SARS-CoV-2 exposure levels in the Netherlands.

Several studies have linked air pollution to COVID-19 morbidity and severity. However, these studies do not account for exposure levels to SARS-CoV-2, nor for different sources of air pollution. We analyzed individual-level data for 8.3 million adults in the Netherlands to assess associations between long-term exposure to ambient air pollution and SARS-CoV-2 infection (i.e., positive test) and COVID-19 hospitalisation risks, accounting for spatiotemporal variation in SARS-CoV-2 exposure levels during the first two major epidemic waves (February 2020-February 2021). We estimated average annual concentrations of PM10, PM2.5 and NO2 at residential addresses, overall and by PM source (road traffic, industry, livestock, other agricultural sources, foreign sources, other Dutch sources), at 1 × 1 km resolution, and weekly SARS-CoV-2 exposure at municipal level. Using generalized additive models, we performed interval-censored survival analyses to assess associations between individuals' average exposure to PM10, PM2.5 and NO2 in the three years before the pandemic (2017-2019) and COVID-19-outcomes, adjusting for SARS-CoV-2 exposure, individual and area-specific confounders. In single-pollutant models, per interquartile (IQR) increase in exposure, PM10 was associated with 7% increased infection risk and 16% increased hospitalisation risk, PM2.5 with 8% increased infection risk and 18% increased hospitalisation risk, and NO2 with 3% increased infection risk and 11% increased hospitalisation risk. Bi-pollutant models suggested that effects were mainly driven by PM. Associations for PM were confirmed when stratifying by urbanization degree, epidemic wave and testing policy. All emission sources of PM, except industry, showed adverse effects on both outcomes. Livestock showed the most detrimental effects per unit exposure, whereas road traffic affected severity (hospitalisation) more than infection risk. This study shows that long-term exposure to air pollution increases both SARS-CoV-2 infection and COVID-19 hospitalisation risks, even after controlling for SARS-CoV-2 exposure levels, and that PM may have differential effects on these COVID-19 outcomes depending on the emission source.

Seasonality of antimicrobial use in Dutch food-producing animals.

Due to globally increasing antimicrobial resistance (AMR), it is pivotal to understand factors contributing to antimicrobial use (AMU) to enable development and implementation of AMR-reducing interventions. Therefore, we explored seasonal variations of systemic AMU in food-producing animals in the Netherlands. Dutch surveillance data from January 2013 to December 2018 from cattle, pig, and broiler farms were used. AMU was expressed as the number of Defined Daily Dosages Animal per month (DDDA/animal-month) per farm by animal sector, antimicrobial line (first, second, and third), antimicrobial class, and farm type. Seasonality of AMU was analyzed using Generalized Additive Models (GAMs) with DDDA/animal-month as outcome variable, and year and month as independent variables. Year and month were modelled as smooth terms represented with penalized regression splines.Significant seasonality of AMU was found in the cattle and pig sectors, but not in broilers. Significant seasonality of AMU was found mainly for first-line antimicrobials. In the cattle sector, a significant increase during winter was found for the use of amphenicols (an increase of 23.8%) and long-acting macrolides (an increase of 3.4%). In the pig sector, seasonality of AMU was found for pleuromutilins (p < 0.001) with an increase of 20% in October-November. The seasonality of pleuromutilins was stronger in sows/piglets (an increase of 47%) than in fattening pigs (16% increase). Only in fattening pigs, the use of amphenicols showed a significant seasonality with an increase of 11% during winter (P < 0.001). AMU in cattle and pig sectors shows seasonal variations likely caused by seasonality of diseases. In broilers, no AMU seasonality was observed, possibly due to the controlled environment in Dutch farms. In the context of the one health concept, future studies are necessary to explore whether this seasonality is present in other populations and whether it has implications for antimicrobial resistance in humans through the food chain.

Increased risk of pneumonia amongst residents living near goat farms in different livestock-dense regions in the Netherlands.

BACKGROUND: Previous studies, performed between 2009-2019, in the Netherlands observed an until now still unexplained increased risk for pneumonia among residents living close to goat farms. Since data were collected in the provinces Noord-Brabant and Limburg (NB-L), an area with relatively high air pollution levels and proximity to large industrial areas in Europe, the question remains whether the results are generalizable to other regions. In this study, a different region, covering the provinces Utrecht, Gelderland, and Overijssel (UGO) with a similar density of goat farms, was included to assess whether the association between goat farm proximity and pneumonia is consistently observed across the Netherlands. METHODS: Data for this study were derived from the Electronic Health Records (EHR) of 21 rural general practices (GPs) in UGO, for 2014-2017. Multi-level analyses were used to compare annual pneumonia prevalence between UGO and data derived from rural reference practices ('control area'). Random-effects meta-analysis (per GP practice) and kernel analyses were performed to study associations of pneumonia with the distance between goat farms and patients' home addresses. RESULTS: GP diagnoses of pneumonia occurred 40% more often in UGO compared to the control area. Meta-analysis showed an association at a distance of less than 500m (~70% more pneumonia compared to >500m) and 1000m (~20% more pneumonia compared to >1000m). The kernel-analysis for three of the four individual years showed an increased risk up to a distance of one or two kilometers (2-36% more pneumonia; 10-50 avoidable cases per 100,000 inhabitants per year). CONCLUSIONS: The positive association between living in the proximity of goat farms and pneumonia in UGO is similar to the previously found association in NB-L. Therefore, we concluded that the observed associations are relevant for regions with goat farms in the entire country.

Exposure to soluble platinum salts in precious metal refinery workers over a 17-year period.

BACKGROUND: Occupational exposure to soluble chlorinated platinum (Pt) salts, commonly called chloroplatinates, is a known cause of Pt salt sensitisation (PSS) and occupational asthma. We aimed to model inhalable soluble Pt salts exposure levels based on measurements in precious metal refineries for use in a retrospective cohort study on PSS. METHODS: Five platinum refineries located in the United Kingdom (3 sites), United States, and South Africa provided time weighted average inhalable soluble Pt salts exposure data, measured in 2,982 personal air samples over a 17-year period (2000-2016). We used a Bayesian hierarchical model to estimate geometric mean (GM) exposure levels for each refinery and job title over time. RESULTS: The GM of measured exposure levels over all facilities was 92 ng/m3 with a geometric standard deviation (GSD) of 9.07. Facility-specific GMs ranged from 48 ng/m3 (GSD 15.3) to 242 ng/m3 (GSD 5.99). Exposure modelling showed that soluble Pt salts exposure levels declined approximately 10% per year in two of the five facilities, but there were no clear time trends in the other facilities. A priori specified exposure groups captured most of the between-jobs differences, which helps to accurately predict exposures for jobs with no measurement data available. CONCLUSIONS: We applied exposure modelling to estimate time, refinery, and job-specific soluble Pt salts exposures. A significant annual decline in exposure levels was observed in two of the five participating facilities. Modelled exposure levels can be linked to individual workers' job history for exposure-response analysis of PSS in an epidemiological study.

Microbial exposures in moisture-damaged schools and associations with respiratory symptoms in students: A multi-country environmental exposure study.

Moisture-damaged buildings are associated with respiratory symptoms and underlying diseases among building occupants, but the causative agent(s) remain a mystery. We first identified specific fungal and bacterial taxa in classrooms with moisture damage in Finnish and Dutch primary schools. We then investigated associations of the identified moisture damage indicators with respiratory symptoms in more than 2700 students. Finally, we explored whether exposure to specific taxa within the indoor microbiota may explain the association between moisture damage and respiratory health. Schools were assessed for moisture damage through detailed inspections, and the microbial composition of settled dust in electrostatic dustfall collectors was determined using marker-gene analysis. In Finland, there were several positive associations between particular microbial indicators (diversity, richness, individual taxa) and a respiratory symptom score, while in the Netherlands, the associations tended to be mostly inverse and statistically non-significant. In Finland, abundance of the Sphingomonas bacterial genus and endotoxin levels partially explained the associations between moisture damage and symptom score. A few microbial taxa explained part of the associations with health, but overall, the observed associations between damage-associated individual taxa and respiratory health were limited.

Oxidative capacity and hemolytic activity of settled dust from moisture-damaged schools.

Exposure to moisture-damaged indoor environments is associated with adverse respiratory health effects, but responsible factors remain unidentified. In order to explore possible mechanisms behind these effects, the oxidative capacity and hemolytic activity of settled dust samples (n = 25) collected from moisture-damaged and non-damaged schools in Spain, the Netherlands, and Finland were evaluated and matched against the microbial content of the sample. Oxidative capacity was determined with plasmid scission assay and hemolytic activity by assessing the damage to isolated human red blood cells. The microbial content of the samples was measured with quantitative PCR assays for selected microbial groups and by analyzing the cell wall markers ergosterol, muramic acid, endotoxins, and glucans. The moisture observations in the schools were associated with some of the microbial components in the dust, and microbial determinants grouped together increased the oxidative capacity. Oxidative capacity was also affected by particle concentration and country of origin. Two out of 14 studied dust samples from moisture-damaged schools demonstrated some hemolytic activity. The results indicate that the microbial component connected with moisture damage is associated with increased oxidative stress and that hemolysis should be studied further as one possible mechanism contributing to the adverse health effects of moisture-damaged buildings.

Quantitative assessment of antimicrobial resistance in livestock during the course of a nationwide antimicrobial use reduction in the Netherlands.

OBJECTIVES: To quantify associations between antimicrobial use and acquired resistance in indicator Escherichia coli over a period of time which involved sector-wide antimicrobial use reductions in broilers and pigs (years 2004-14), veal calves (2007-14) and dairy cattle (2005-14). Prevalence estimates of resistance were predicted for a hypothetical further decrease in antimicrobial use. METHODS: Data reported annually for the resistance surveillance programme in the Netherlands were retrieved. Two multivariate random-effects logistic models per animal sector were used to relate total and class-specific antimicrobial use (as defined daily dosages per animal per year, DDDA/Y) with the probability of E. coli resistance to a panel of 10 antimicrobial agents. RESULTS: Positive dose-response relationships (ORs) were obtained from all models. Specific resistance phenotypes were more often associated with total antimicrobial use than with class-specific use. The most robust associations were found in pigs and veal calves. Resistance to historically widely used antimicrobials (e.g. penicillins, tetracyclines) was, in relative terms, less influenced by drug use changes over time than resistance to newer or less prescribed antimicrobials (e.g. third-/fourth-generation cephalosporins, fluoroquinolones). In pigs and veal calves, prevalence estimates for the most common resistance phenotypes were projected to decline ∼5%-25% during 2014-16 if total antimicrobial use reduction reached 80%; projections for poultry and dairy cows were more modest. CONCLUSIONS: Epidemiological evidence indicated that drug use history and co-selection of resistance are key elements for perpetuation of resistance. Data suggest that recent Dutch policies aimed at reducing total use of antimicrobials have decreased E. coli resistance in the pig and veal calf production sectors while the impact on the dairy cattle and poultry sectors is less clear.

Exposure-response analyses for platinum salt-exposed workers and sensitization: A retrospective cohort study among newly exposed workers using routinely collected surveillance data.

BACKGROUND: Chloroplatinate salts are well-known respiratory sensitizing agents leading to work-related sensitization and allergies in the work environment. No quantitative exposure-response relation has been described for chloroplatinate salts. OBJECTIVE: We sought to evaluate the quantitative exposure-response relation between occupational chloroplatinate exposure and sensitization. METHODS: A retrospective cohort study was conducted using routinely collected health surveillance data and chloroplatinate exposure data. Workers who newly entered work between January 1, 2000, and December 31, 2010, were included, and the relation between measured chloroplatinate exposure and sensitization (as determined by skin prick test responses) was analyzed in more than 1000 refinery workers from 5 refineries for whom a total of more than 1700 personal exposure measurements were available. RESULTS: A clear exposure-response relation was observed, most strongly for more recent platinum salt exposure. Average or cumulative exposure over the follow-up period was less strongly associated with sensitization risk. The exposure-response relation was modified by smoking and atopy. CONCLUSIONS: Indications exist that recent exposure explains the risk of platinum salt sensitization most strongly. The precision of the estimate of the exposure-response relation derived from this data set appears superior to previous epidemiologic studies conducted on platinum salt sensitization and as a result, might have possible utility for the development of preventive strategies.

Domestic use of bleach and infections in children: a multicentre cross-sectional study.

OBJECTIVE: To report the effects of bleach use at home on the frequency of infections in 9102 school-age children participating in the HITEA project. METHODS: Parents of pupils aged 6-12 years from schools in Barcelona province (Spain), Utrecht province (the Netherlands) and Eastern and Central Finland were administered a questionnaire including questions on the frequency of infections (influenza, tonsillitis, sinusitis, otitis, bronchitis and pneumonia) in the past 12 months and bleach use at home. We developed multivariable mixed-effects multilogistic regression models to obtain relative risk ratios (RRR) and their 95% CI per country, and combined the RRR using random-effects meta-analyses. RESULTS: Bleach use was common in Spain (72%, n=1945) and uncommon in Finland (7%, n=279). Overall, the prevalence of infections (recurrent or once) was higher among children of bleach users. Significant combined associations were shown for influenza only once (RRR=1.20, 95% CI 1.04 to 1.38), recurrent tonsillitis (RRR=1.35, 95% CI 1.07 to 1.71) and any infection (RRR=1.18, 95% CI 1.01 to 1.38). CONCLUSIONS: Passive exposure to cleaning bleach in the home may have adverse effects on school-age children's health by increasing the risk of respiratory and other infections. The high frequency of use of disinfecting irritant cleaning products may be of public health concern, also when exposure occurs during childhood.

Dampness, bacterial and fungal components in dust in primary schools and respiratory health in schoolchildren across Europe.

BACKGROUND: Respiratory health effects of damp housing are well recognised, but less is known about the effect of dampness and water damage in schools. The HITEA study previously reported a higher prevalence of respiratory symptoms in pupils from moisture damaged schools, but the role of specific microbial exposures remained unclear. OBJECTIVES: To study associations between school dampness, levels of fungal and bacterial markers, respiratory symptoms and lung function in children. METHODS: Primary schools in Spain, the Netherlands and Finland were selected on the basis of the observed presence (n=15) or absence (n=10) of moisture, dampness and/or mould. Settled dust was repeatedly sampled in 232 classrooms and levels of 14 different microbial markers and groups of microbes were determined. Parental reports of respiratory symptoms were available from 3843 children aged 6-12 years, of whom 2736 provided acceptable forced spirometry testing. Country-specific associations between exposure and respiratory health were evaluated by multilevel mixed-effects logistic and linear regression models and combined using random-effects meta-analysis. RESULTS: The prevalence of respiratory symptoms was higher in moisture damaged schools, being more pronounced in Finnish pupils. Effects on lung function were not apparent. Levels of microbial markers were generally higher in moisture damaged schools, varied by season and were lower in Finnish schools. Wheeze tended to be inversely associated with microbial levels. All other respiratory symptoms were not consistently associated with microbial marker levels. CONCLUSIONS: Health effects of moisture and microbial exposures may vary between countries, but this requires further study.

Allergens and ß-glucans in dutch homes and schools: characterizing airborne levels.

BACKGROUND: Indoor air quality has an effect on respiratory health. Children are more vulnerable to a decreased indoor air quality as their lungs are still developing. We measured levels of allergens and ß-(1,3)-glucans in 19 school buildings and determined whether measured levels could be reproduced. School levels were compared to those in 169 homes and the effect of building characteristics on both home and school exposure was explored. METHODS: Electrostatic Dust fall Collectors were placed in school buildings for 8 weeks and in homes for 2 weeks to collect settled airborne dust. Cat, dog, and mouse allergen levels, domestic mite antigen levels and ß-(1,3)-glucans were measured in the extracts from the collectors. Results were corrected for sampling duration. Using questionnaire data, relations between measured levels and building and classroom characteristics were explored. RESULTS: In schools, exposure levels were highest in classrooms and were influenced by the socioeconomic status of the children, the season measurements were performed, moisture status of the building and pet ownership. Repeated measurements in different seasons and over the years showed significantly different levels. Home exposure was influenced by socioeconomic status, occupancy and pet ownership. Domestic mite antigen was found in higher levels in extracts from homes compared to schools while pet allergen levels were 13 times higher in schools compared to homes without pets. For mouse allergen overall levels of exposure were low but still two times higher in schools compared to homes. Levels of ß-(1,3)-glucans were also approximately two times higher in schools than in homes. CONCLUSION: Exposure levels of several allergens and ß-(1,3)-glucans in schools differ over time and are higher than in homes. For children, exposure levels measured at school could contribute to their total exposure as especially animal allergen levels can be much higher in schools compared to homes.

Dampness and mould in schools and respiratory symptoms in children: the HITEA study.

BACKGROUND: The adverse respiratory health effects of dampness and mould in the home have been extensively reported, but few studies have evaluated the health effects of such exposures in schools. OBJECTIVES: To assess the associations between dampness and mould in school buildings and respiratory symptoms among 6-12-year-old pupils in three European countries with different climates. METHODS: Based on information from self-reports and observations, we selected 29 primary schools with and 27 without moisture damage in Spain, the Netherlands and Finland. Information on respiratory symptoms and potential determinants was obtained using a parent-administered questionnaire among 6-12-year-old pupils. Country-specific associations between moisture damage and respiratory symptoms were evaluated using multivariable multilevel mixed effects logistic regression analysis. RESULTS: Data from 9271 children were obtained. Nocturnal dry cough was consistently associated with moisture damage at school in each of the three countries: OR 1.15; 95% CI 1.00 to 1.30 with p for heterogeneity 0.54. Finnish children attending a moisture damaged school more often had wheeze (OR 1.36; CI 1.04 to 1.78), nasal symptoms (OR 1.34; CI 1.05 to 1.71) and respiratory-related school absence (OR 1.50; CI 1.10 to 2.03). No associations with these symptoms were found in the Netherlands or Spain (p for heterogeneity <0.05). CONCLUSIONS: Moisture damage in schools may have adverse respiratory health effects in pupils. Finnish school children seem to be at higher risk, possibly due to quantitative and/or qualitative differences in exposure.

Endotoxin levels in homes and classrooms of Dutch school children and respiratory health.

Several studies describe indoor pollutant exposure in homes and to a lesser extent in schools. Population studies that include both environments are sparse. This study aims to assess endotoxin levels in primary schools and homes of children. Endotoxin was also studied in relation to asthma and sensitisation. 10 schools with (index) and without (reference) dampness were selected, based on reports and inspections. Cases and controls were selected from 169 homes based on the presence or absence of asthma-like symptoms of children. Classroom and bedroom airborne settled dust was sampled using electrostatic dust fall collectors. Average endotoxin levels in schools ranged from 2178 to 6914 endotoxin units (EU)·m(-2) per week compared with 462-1285 EU·m(-2) per week in homes. After mutual adjustment for home and school endotoxin, school endotoxin was positively associated with nonatopic asthma (OR 1.11, 95% CI 0.97-1.27), while no associations with endotoxin were found at home. The high endotoxin levels in schools compared with homes indicate that exposure at school can contribute considerably to environmental endotoxin exposure of children and teachers. Our results also suggest that endotoxin in schools may be associated with nonatopic asthmatic symptoms in pupils, although the results require reproduction because of the modest sample size.

Palliative medicine update: a multidisciplinary approach.

Palliative medicine is a young specialty that is officially recognized in relatively few countries. The World Health Organization published an adapted definition in 2002, describing palliative care as an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness. When the accent is shifting from curative to palliative, the goal of management is the maintenance or improvement of the patient's quality of life. The different dimensions of palliative care and the multitude of types of care to be provided require a multidisciplinary, well-functioning team, effective communication and a clear task division between primary and hospital care. Considering the complexity of care for incurable patients, a multidisciplinary approach is a prerequisite to balance curative and palliative intervention options. Optimal functioning of a team requires excellent training, communication and a description of the tasks and responsibilities of each team member. More and more advanced care planning is introduced in palliative care, focusing on an early identification of patients in a palliative trajectory and on the prevention of annoying symptoms, hoping that this approach results in an improved quality of life for the individual patient, less useless technical investigations and a better end-of-life care on the place the patient and his family desires.

Swimming pool attendance and respiratory symptoms and allergies among Dutch children.

OBJECTIVES: To describe associations among swimming, respiratory health, allergen sensitisation and Clara cell protein 16 (CC16) levels in Dutch schoolchildren. Trichloramine levels in swimming pool air were determined to assess potential exposure levels. METHODS: Respiratory health and pool attendance information was collected from 2359 children, aged 6-13 years. Serum from 419 children was tested for allergen sensitisation and CC16 levels. Trichloramine levels were assessed in nine swimming facilities. RESULTS: Trichloramine levels ranged from 0.03 to 0.78 mg/m3 (average 0.21 mg/m3). Reported swimming pool attendance and trichloramine exposure were both not associated with asthma, wheezing, rhinitis or CC16 levels. Birch and house dust mite sensitisation were associated with recent indoor swimming (OR>1.86), but not after considering recent swimming frequency multiplied by trichloramine levels. Sensitisation to house dust mites was associated with frequent baby swimming (ORs=1.75; 95% CI 1.09 to 2.79). Furthermore, sensitisation was associated with lower serum CC16 levels. CC16 levels were associated with average trichloramine concentrations in pools; however, not after considering swimming frequency multiplied by trichloramine levels. CONCLUSIONS: Measured trichloramine levels were comparable with other studies but lower than in an earlier Dutch study. Swimming pool attendance was not associated with respiratory symptoms. The association between sensitisation and swimming during the first 2 years of life suggests that early-life exposures might be important, although this needs further study. The interpretation of transient and chronic changes of CC16 and other inflammatory markers in relation to the pool environment and health impacts warrants further investigation. Detailed comparisons with other studies are limited as few studies have measured trichloramine levels.