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Living close to livestock farms has been associated with increased symptoms in patients with chronic obstructive pulmonary disease (COPD). The causes of these effects are still poorly understood. This panel study attempts to assess the acute effects of livestock-related air pollution in patients with COPD living in an area with intensive livestock farming in the Netherlands. Between February 2015 and July 2016, 82 participants took spirometry measurements twice daily (morning and evening) during a 3-month period, resulting in 12,672 FEV 1 and PEF records. Participants also kept a diary on respiratory symptoms as well as livestock-related odor annoyance. Daily average ammonia (NH 3 ) (a proxy for livestock-related air pollution) and fine particulate matter (PM 10 ) levels were collected from monitoring stations in the area. Lung function was analyzed as decrements of >10% and >20% from their median as well as absolute values. Self-reported odor annoyance was analyzed as a dichotomous variable. All analyses were done using generalized estimated equations. We adjusted for humidity, temperature, linear trend, and took multiple testing into account. We found an odds ratio of 1.14 95%CI [1.05; 1.25] for decrements >20% in morning FEV 1 per interquartile range (12 µg/m 3 ) increase in NH 3 concentration (lag 2). Odor annoyance was negatively associated with evening PEF (-4.46 l/min 95%CI [-7.59; -1.33]). Sensitivity analyses showed a stronger effect in participants with worse baseline lung function. No associations with symptoms were found. Our results show acute effects of livestock-related air pollution on lung function in COPD patients living in close proximity to livestock farms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We previously observed an increased incidence of pneumonia in persons living near goat and poultry farms, using animal presence around the home to define exposure. However, it is unclear to what extent individual mobility and time spent outdoors close to home contributes to this increased risk. Therefore, the aim of the current study was to investigate the role of mobility patterns and time spent outdoors in the vicinity of goat or poultry farms in relation to pneumonia risk. In a rural Dutch cohort, 941 members logged their mobility using GPS trackers for 7 days. Pneumonia was diagnosed in 83 subjects (participants reported that pneumonia had been diagnosed by a medical doctor, or recorded in EMR from general practitioners, 2011-2014). We used logistic regression to evaluate pneumonia-risk by presence of goat farms within 500 and 1000 m around the home and around GPS-tracks (only non-motorised mobility), also we evaluated whether more time spent outdoors increased pneumonia-risks. We observed a clearly increased risk of pneumonia among people living in close proximity to goat farms, ORs increased with closer distances of homes to farms (500 m: 6.2 (95% CI 2.2-16.5) 1000 m: 2.5 (1.4-4.3)) The risk increased for individuals who spent more time outdoors close to home, but only if homes were close to goat farms (within 500 m and often outdoors: 12.7 (3.6-45.4) less often: 2.0 (0.3-9.2), no goat farms and often outdoors: 1.0 (0.6-1.6)). For poultry we found no increased risks. Pneumonia-risks increased when people lived near goat farms, especially when they spent more time outdoors, mobility does not seem to add to these risks., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Exposure to farm environments during childhood and adult life seems to reduce the risk of atopic sensitisation. Most studies have been conducted among farmers, but people living in rural areas may have similar protective effects for atopy. This study aims to investigate the association between residential proximity to livestock farms and atopy among non-farming adults living in a rural area in the Netherlands., Methods: We conducted a cross-sectional study among 2443 adults (20-72 years). Atopy was defined as specific IgE to common allergens and/or total IgE ≥100 IU/mL. Residential proximity to livestock farms was assessed as 1) distance to the nearest pig, poultry, cattle or any farm, 2) number of farms within 500 m and 1000 m, and 3) modelled annual average fine dust emissions from farms within 500 m and 1000 m. Data were analysed with multiple logistic regression and generalised additive models., Results: The prevalence of atopy was 29.8%. Subjects living at short distances from farms (<327 m, first tertile) had a lower odds for atopy compared with subjects living further away (>527 m, third tertile) (OR 0.79, 95% CI 0.63 to 0.98). Significant associations in the same direction were found with distance to the nearest pig or cattle farm. The associations between atopy and livestock farm exposure were somewhat stronger in subjects who grew up on a farm., Conclusions: Living in close proximity to livestock farms seems to protect against atopy. This study provides evidence that protective effects of early-life and adult farm exposures may extend beyond farming populations., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Prior to the 2007-2010 Q fever epidemic in the Netherlands, the seroprevalence of antibodies against Coxiella burnetii in the general population was 1.5%, which is low compared to other countries. We aimed to determine the seroprevalence after the Q fever epidemic among people living in the affected area, compare the seroprevalence with the incidence of Q fever notifications during the 2007-2010 Q fever epidemic, and to identify farm exposures associated with having antibodies against C. burnetii., Methods: During the period March 2014-February 2015, residents aged 18-70 years from two provinces were invited by general practitioners to complete a questionnaire on their symptoms and personal characteristics and to submit a blood sample. We used the mandatory provincial database of livestock licences to calculate distance to farms/farm animals for each participant. To compare ELISA-positive participants for C. burnetii antibodies with those who were negative, we calculated prevalence ratios (PR) using binominal regression. We compared the C. burnetii seroprevalence in the period March 2014-February 2015 with the incidence of Q fever notifications during the 2007-2010 Q fever epidemic at municipal level by calculating the Spearman correlation coefficient., Results: Of the 2296 participants (response rate: 34%), 6.1% (n = 139, 95% CI 5.1-7.1%) had C. burnetii antibodies (range in municipalities: 1.7-14.1%). C. burnetii seroprevalence was higher in individuals living within 1000 m of goat farms (PR 3.0; 95% CI 1.4-6.4) or within 1000 m of > 50 goats (PR 1.9; 95% CI 1.2-3.0). Seroprevalence increased with decreasing distance to the closest goat farm that was infected during the epidemic years (< 500 m, PR 9.5, 95% CI 2.8-32; 500-1000 m, PR 4.5, 95% CI 2.6-7.7; 1000-1500 m, PR 2.2, 95% CI 1.1-4.3, 1500-2000 m, PR 1.2, 95% CI 0.6-2.5; > 2000 reference group). There was no significant correlation between C. burnetii seroprevalence and Q fever incidence during the 2007-2010 epidemic (r s  = 0.42, p = 0.156)., Conclusions: Results showed a remarkable spatial variation in C. burnetii seroprevalence in a relatively small livestock dense area. It confirms previous evidence that the Q fever epidemic was primarily the result of airborne C. burnetii transmission from Q fever affected goat farms.

Rationale: Livestock farm emissions may not only affect respiratory health of farmers but also of neighboring residents., Objectives: To explore associations between spatial and temporal variation in pollutant emissions from livestock farms and lung function in a general, nonfarming, rural population in the Netherlands., Methods: We conducted a cross-sectional study in 2,308 adults (age, 20-72 yr). A pulmonary function test was performed measuring prebronchodilator and post-bronchodilator FEV 1 , FVC, FEV 1 /FVC, and maximum mid-expiratory flow (MMEF). Spatial exposure was assessed as (1) number of farms within 500 m and 1,000 m of the home, (2) distance to the nearest farm, and (3) modeled annual average fine dust emissions from farms within 500 m and 1,000 m of the home address. Temporal exposure was assessed as week-average ambient particulate matter <10 μm in diameter and ammonia (NH 3 ) concentrations before lung function measurements. Data were analyzed with generalized additive models (smoothing)., Measurements and Main Results: A negative association was found between the number of livestock farms within a 1,000-m buffer from the home address and MMEF, which was more pronounced in participants without atopy. No associations were found with other spatial exposure variables. Week-average particulate matter <10 μm in diameter and NH 3 levels were negatively associated with FEV 1 , FEV 1 /FVC, and MMEF. In a two-pollutant model, only NH 3 remained associated. A 25-μg/m 3 increase in NH 3 was associated with a 2.22% lower FEV 1 (95% confidence interval, -3.69 to -0.74), FEV 1 /FVC of -1.12% (-1.96 to -0.28), and MMEF of -5.67% (-8.80 to -2.55)., Conclusions: Spatial and temporal variation in livestock air pollution emissions are associated with lung function deficits in nonfarming residents.

Background: The home address is a common spatial proxy for exposure assessment in epidemiological studies but mobility may introduce exposure misclassification. Mobility can be assessed using self-reports or objectively measured using GPS logging but self-reports may not assess the same information as measured mobility. We aimed to assess mobility patterns of a rural population in the Netherlands using GPS measurements and self-reports and to compare GPS measured to self-reported data, and to evaluate correlates of differences in mobility patterns., Method: In total 870 participants filled in a questionnaire regarding their transport modes and carried a GPS-logger for 7 consecutive days. Transport modes were assigned to GPS-tracks based on speed patterns. Correlates of measured mobility data were evaluated using multiple linear regression. We calculated walking, biking and motorised transport durations based on GPS and self-reported data and compared outcomes. We used Cohen's kappa analyses to compare categorised self-reported and GPS measured data for time spent outdoors., Results: Self-reported time spent walking and biking was strongly overestimated when compared to GPS measurements. Participants estimated their time spent in motorised transport accurately. Several variables were associated with differences in mobility patterns, we found for instance that obese people (BMI > 30 kg/m 2 ) spent less time in non-motorised transport (GMR 0.69-0.74) and people with COPD tended to travel longer distances from home in motorised transport (GMR 1.42-1.51)., Conclusions: If time spent walking outdoors and biking is relevant for the exposure to environmental factors, then relying on the home address as a proxy for exposure location may introduce misclassification. In addition, this misclassification is potentially differential, and specific groups of people will show stronger misclassification of exposure than others. Performing GPS measurements and identifying explanatory factors of mobility patterns may assist in regression calibration of self-reports in other studies.

Objectives: Patients with chronic obstructive pulmonary disease (COPD) constitute a potentially susceptible group towards environmental exposures such as livestock farm emissions, given their compromised respiratory health status. The primary aim of this study was to examine the association between livestock exposure and comorbidities and coexisting symptoms and infections in COPD patients., Methods: Data were collected from 1828 COPD patients (without co-occurring asthma) registered in 23 general practices and living in a rural area with a high livestock density. Prevalence of comorbid diseases/disorders and coexisting symptoms/infections were based on electronic health records from the year 2012. Various indicators of individual exposure to livestock were estimated based on residential addresses, using a geographic information system., Results: At least one comorbid disorder was present in 69% of the COPD patients (especially cardiac disorders and depression, while 49% had at least one coexisting symptom and/or infection (especially upper respiratory tract infections, respiratory symptoms and pneumonia). Half of the COPD-patients resided less than 500m of the nearest farm. Some positive as well as inverse associations were found between the examined outcomes and exposure estimates, although not consistent., Conclusions: Despite the high prevalence of coexisting chronic and acute conditions presented in primary care by in COPD patients, this investigation found no convincing evidence for an association with livestock exposure estimates. There is a need for a replication of the present findings in studies with a longitudinal design, on different groups of potentially susceptible patients. Future research should also elucidate the biological plausibility of possible protective effects of exposure., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Previous research conducted in 2009 found a significant positive association between pneumonia in humans and living close to goat and poultry farms. However, as this result might have been affected by a large goat-related Q fever epidemic, the aim of the current study was to re-evaluate this association, now that the Q-fever epidemic had ended. In 2014/15, 2,494 adults (aged 20-72 years) living in a livestock-dense area in the Netherlands participated in a medical examination and completed a questionnaire on respiratory health, lifestyle and other items. We retrieved additional information for 2,426/2,494 (97%) participants from electronic medical records (EMR) from general practitioners. The outcome was self-reported, physician-diagnosed pneumonia or pneumonia recorded in the EMR in the previous three years. Livestock license data was used to determine exposure to livestock. We quantified associations between livestock exposures and pneumonia using odds ratios adjusted for participant characteristics and comorbidities (aOR). The three-year cumulative frequency of pneumonia was 186/2,426 (7.7%). Residents within 2,000m of a farm with at least 50 goats had an increased risk of pneumonia, which increased the closer they lived to the farm (2,000m aOR 1.9, 95% CI 1.4-2.6; 500m aOR 4.4, 95% CI 2.0-9.8). We found no significant associations between exposure to other farm animals and pneumonia. However, when conducting sensitivity analyses using pneumonia outcome based on EMR only, we found a weak but statistically significant association with presence of a poultry farm within 1,000m (aOR: 1.7, 95% CI 1.1-2.7). Living close to goat and poultry farms still constitute risk factors for pneumonia. Individuals with pneumonia were not more often seropositive for Coxiella burnetii, indicating that results are not explained by Q fever. We strongly recommend identification of pneumonia causes by the use of molecular diagnostics and investigating the role of non-infectious agents such as particulate matter or endotoxins.

Background: COPD-diagnosis is confirmed by post-bronchodilator (BD) spirometry. However, epidemiological studies often rely on pre-BD spirometry, self-reports, or medical records. This population-based study aims to determine COPD-prevalence based on four different operational definitions and their level of agreement, and to compare associations between COPD-definitions and risk factors., Methods: COPD-prevalence in 1,793 adults from the general Dutch population (aged 18-70 years) was assessed based on self-reported data, Electronic Medical Records (EMR), and post-BD spirometry: using the FEV1/FVC below the lower limit of normal (LLN) and GOLD fixed cut-off (FEV1/FVC <0.70). Using spirometry as a reference, sensitivity was calculated for self-reported and EMR-based COPD. Associations between COPD and known risk factors were assessed with logistic regression. Data were collected as part of the cross-sectional VGO study (Livestock Farming and Neighboring Residents' Health Study)., Results: The highest prevalence was found based on spirometry (GOLD: 10.9%, LLN: 5.9%), followed by self-report (4.6%) and EMR (2.9%). Self-reported or EMR-based COPD identified less than 30% of all COPD-cases based on spirometry. The direction of association between known risk factors and COPD was similar across the four definitions, however, magnitude and significance varied. Especially indicators of allergy were more strongly associated with self-reported COPD compared to the other definitions., Conclusions: COPD-prevalence varied depending on the used definition. A substantial number of subjects with spirometry-based COPD cannot be identified with questionnaires or medical records which can cause underestimation of COPD-prevalence. The influence of the different COPD-definitions on associations with known risk factors was limited.

Previous studies investigating health conditions of individuals living near livestock farms generally assessed short time windows. We aimed to take time-specific differences into account and to compare the prevalence of various health conditions over seven consecutive years. The sample consisted of 156,690 individuals registered in 33 general practices in a (rural) area with a high livestock density and 101,015 patients from 23 practices in other (control) areas in the Netherlands. Prevalence of health conditions were assessed using 2007-2013 electronic health record (EHR) data. Two methods were employed to assess exposure: 1) Comparisons between the study and control areas in relation to health problems, 2) Use of individual estimates of livestock exposure (in the study area) based on Geographic Information System (GIS) data. A higher prevalence of chronic bronchitis/bronchiectasis, lower respiratory tract infections and vertiginous syndrome and lower prevalence of respiratory symptoms and emphysema/COPD was found in the study area compared with the control area. A shorter distance to the nearest farm was associated with a lower prevalence of upper respiratory tract infections, respiratory symptoms, asthma, COPD/emphysema, allergic rhinitis, depression, eczema, vertiginous syndrome, dizziness and gastrointestinal infections. Especially exposure to cattle was associated with less health conditions. Living within 500m of mink farms was associated with increased chronic enteritis/ulcerative colitis. Livestock-related exposures did not seem to be an environmental risk factor for the occurrence of health conditions. Nevertheless, lower respiratory tract infections, chronic bronchitis and vertiginous syndrome were more common in the area with a high livestock density. The association between exposure to minks and chronic enteritis/ulcerative colitis remains to be elucidated., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Several studies have reported associations between farming and respiratory health in neighboring residents. Health effects are possibly linked to fine dust and endotoxin emissions from livestock farms. Little is known about levels of these air pollutants in ambient air in livestock dense areas. We aimed to explore temporal and spatial variation of PM10 and endotoxin concentrations, and the association with livestock-related spatial and meteorological temporal determinants. From March till September 2011, one week average PM10 samples were collected using Harvard Impactors at eight sites (residential gardens) representing a variety of nearby livestock-related characteristics. A background site was included in the study area, situated at least 500m away from the nearest farm. PM10 mass was determined by gravimetric analysis and endotoxin level by means of Limulus-Amebocyte-Lysate assay. Data were analyzed using mixed models. The range between sites of geometric mean concentrations was for PM10 19.8-22.3µg/m 3 and for endotoxin 0.46-0.66EU/m 3 . PM10 concentrations and spatial variation were very similar for all sites, while endotoxin concentrations displayed a more variable pattern over time with larger differences between sites. Nonetheless, the temporal pattern at the background location was highly comparable to the sites mean temporal pattern both for PM10 and endotoxin (Pearson correlation: 0.92, 0.62). Spatial variation was larger for endotoxin than for PM10 (within/between site variance ratio: 0.63, 2.03). Spatial livestock-related characteristics of the surroundings were more strongly related to endotoxin concentrations, while temporal determinants were more strongly related to PM10 concentrations. The effect of local livestock-related sources on PM10 concentration was limited in this study carried out in a livestock dense area. The effect on endotoxin concentrations was more profound. To gain more insight in the effect of livestock-related sources on ambient levels of PM10 and endotoxin, measurements should be based on a broader set of locations., (Copyright © 2016. Published by Elsevier Inc.)

Background: Recent serological studies indicate that hepatitis E virus (HEV) is endemic in industrialised countries. The increasing trend in the number of autochthonous cases of HEV genotype 3 in Western European countries, stresses the importance to get insight in the exact routes of exposure. Pigs are the main animal reservoir, and zoonotic food-borne transmission of HEV is proven. However, infected pigs can excrete large amounts of virus via their faeces enabling environmental transmission of HEV to humans. This might pose a risk for of neighbouring residents of livestock farming., Methods: Within a large study on the health of people living in the vicinity of livestock farming we performed a cross-sectional population-based serological survey among 2,494 non-farming adults from the general population in a livestock-dense area in the south of the Netherlands. Participants completed risk factor questionnaires and blood samples of 2,422 subjects (median age 58 years, range 20-72) were tested for anti-HEV IgG using an enzyme immune assay (Wantai). The aim of this study was to determine the HEV seroprevalence and to assess whether seropositivity in adults was associated with living in the vicinity of pig farms., Results: The average seroprevalence of HEV was 28.7% (95% CI: 26.9-30.5). Determinants associated with an increased risk for HEV seropositivity were male gender and low level of education. There was a clear trend of increasing prevalence with increasing age (Chi-square test for linear trend, X 2  = 83.1; p < 0.001). A high number of pigs within 1,000 m of the residential address was not a risk factor for seropositivity., Conclusions: This study confirmed the high HEV seroprevalence (29%) in the general population of the Netherlands, but presence of antibodies was not associated with residential proximity to pig farms. The prevalence increased with age from 10% in adolescents to 33% among those aged 50 and above, supporting the assumption of a cumulative lifetime exposure to HEV in the Netherlands as well as a higher infection pressure in the past. Our findings cannot refute the assumption that transmission is primarily food-borne.

Objective: Living in an area with a high density of livestock farms has been associated with adverse respiratory health effects in some studies. As patients with COPD and asthma already have a compromised respiratory function and chronic airway inflammation, they are expected to be at increased risk for adverse respiratory health effects. The objective of this study was to assess the association between livestock exposure and exacerbations in COPD and asthma., Methods: 899 COPD and 2546 asthma patients from 15 general practices in a rural area with a high livestock density and 933 COPD and 2310 asthma patients from 15 practices in a control area in the Netherlands were included. Occurrence of exacerbations was based on the pharmaceutical treatment of exacerbations in COPD and asthma patients using 2006-2012 prescription data of electronic medical records. Farm exposure was assessed by comparing the study area with the control area, and with individual exposure estimates in the study area using Geographic Information System data., Results: The exacerbation rate was higher in the study area compared with the control area in COPD (IRR: 1.28; 95%CI: 1.06-1.55), but not in asthma patients (IRR: 0.87; 95%CI: 0.72-1.05). In general, individual exposure estimates in the study area were not associated with exacerbations. COPD patients living within a 500m radius of up to12,499 chickens had a 36% higher exacerbation rate (IRR: 1.36; 95%CI: 1.03-1.79)., Conclusions: Living in an area with a high livestock density is a risk factor for exacerbations in COPD patients. The environmental exposure responsible for this increased risk remains to be elucidated., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

One of the largest Q fever outbreaks ever occurred in the Netherlands from 2007-2010, with 25 fatalities among 4,026 notified cases. Airborne dispersion of Coxiella burnetii was suspected but not studied extensively at the time. We investigated temporal and spatial variation of Coxiella burnetii in ambient air at residential locations in the most affected area in the Netherlands (the South-East), in the year immediately following the outbreak. One-week average ambient particulate matter < 10 μm samples were collected at eight locations from March till September 2011. Presence of Coxiella burnetii DNA was determined by quantitative polymerase chain reaction. Associations with various spatial and temporal characteristics were analyzed by mixed logistic regression. Coxiella burnetii DNA was detected in 56 out of 202 samples (28%). Airborne Coxiella burnetii presence showed a clear seasonal pattern coinciding with goat kidding. The spatial variation was significantly associated with number of goats on the nearest goat farm weighted by the distance to the farm (OR per IQR: 1.89, CI: 1.31-2.76). We conclude that in the year after a large Q fever outbreak, temporal variation of airborne Coxiella burnetii is suggestive to be associated with goat kidding, and spatial variation with distance to and size of goat farms. Aerosol measurements show to have potential for source identification and attribution of an airborne pathogen, which may also be applicable in early stages of an outbreak.

Several studies have investigated the effect of livestock farm emissions on the respiratory health of local residents, but results are inconsistent. This study aims to explore associations between the presence of livestock farms and respiratory health in an area of high-density livestock farming in the Netherlands. We focused especially on associations between farm exposures and respiratory symptoms within subgroups of potentially susceptible patients with a pre-existing lung disease.In total, 14 875 adults (response rate 53.4%) completed a questionnaire concerning respiratory health, smoking habits and personal characteristics. Different indicators of livestock farm exposures relative to the home address were computed using a geographic information system.Prevalence of chronic obstructive pulmonary disease (COPD) and asthma was lower among residents living within 100 m of a farm (OR 0.47, 95% CI 0.24-0.91 and OR 0.65, 95% CI 0.45-0.93, respectively). However, >11 farms in 1000 m compared to fewer than four farms in 1000 m (fourth quartile versus first quartile) was associated with wheezing among COPD patients (OR 1.71, 95% CI 1.01-2.89). Using general practitioners' electronic medical records, we demonstrated that selection bias did not affect the observed associations.Our data suggest a protective effect of livestock farm emissions on the respiratory health of residents. Nonetheless, COPD patients living near livestock farms reported more respiratory symptoms, suggesting an increased risk of exacerbations., (Copyright ©ERS 2015.)

Coxiella burnetii is thought to infect humans primarily via airborne transmission. However, air measurements of C. burnetii are sparse. We detected C. burnetii DNA in inhalable and PM10 (particulate matter with an aerodynamic size of 10 μm or less) dust samples collected at three affected goat farms, demonstrating that low levels of C. burnetii DNA are present in inhalable size fractions.