Dr Johanna Penell
Lecturer in Veterinary Infectious Disease Epidemiology and One Health
About
Biography
Johanna earned her veterinary degree (MSc Vet Med) at the Swedish University of Agricultural Sciences and after some months of mainly large animal practice she enrolled a PhD education in Veterinary Epidemiology at the same university. The main focus of her PhD project was evaluation of the quality of information in two large equine data bases including health data and then to use these sources to describe disease incidence and proportional morbidity in horses in Sweden. During the PhD training Johanna took time off in summers to do clinical work as a first opinion vet in the field. Johanna's postdoctoral training took place at the Institute of Environmental Medicine, Karolinska Institute in Stockholm with main focus on health effects of air pollution exposure using four local cohorts but also collaboration with ~20 other centres in Europe to address this issue. She moved on to the unit of Occupational and Environmental Medicine at Uppsala University investigating health effects related to exposure to persistent environmental pollutants such as dioxin, flame retardants and PCBs before accepting the position here at University of Surrey. Johanna is co-supervising one PhD student studying air pollution effects and one investigating sub-clinical viral infections in racing trotters including gamma herpes virus. In September 2014 Johanna joined the University of Surrey as Lecturer in Veterinary Infectious Disease Epidemiology and One Health. Her longstanding research interest is within epidemiology as a tool to investigate various disease and health aspects in animals and humans. With this position, Johanna is looking forward to developing her experience within epidemiologic research and to being involved in the education of the next generation of veterinarians and veterinary scientists.
Research interests
Johanna's overall research interests are within veterinary and human epidemiology including investigating health effects of environmental exposures such as air pollution and environmental pollutants, infectious disease epidemiology, disease prevalence and distribution, and validation of data. In addition, with this position at the University of Surrey, Johanna is keen on focusing on the One Health strategy including e.g. animal disease surveillance, food safety, infectious disease within micro ecosystems, psychological aspects of animal/human interactions, and antibiotic resistance.
Teaching
MSc Veterinary Microbiology: Molecular Epidemiology of Infectious Diseases (MMVM003)BVMSci - Veterinary Medicine and Science:
Departmental duties
To act as the committee representative in The Association for Veterinary Teaching and Research Work (AVTRW) for University of Surrey School of Veterinary Medicine
Affiliations
Karolinska Institutet, Stockholm, Sweden
Publications
Dimakopoulou K, Samoli E, Beelen R, Stafoggia M, Andersen ZJ, Hoffmann B, Fischer P, Nieuwenhuijsen M, Vineis P, Xun W, Hoek G, Raaschou-Nielsen O, Oudin A, Forsberg B, Modig L, Jousilahti P, Lanki T, Turunen A, Oftedal B, Nafstad P, Schwarze PE, Penell J, Fratiglioni L, Andersson N, Pedersen N, Korek M, De Faire U, Eriksen KT, Tjønneland A, Becker T, Wang M, Bueno-de-Mesquita B, Tsai MY, Eeftens M, Peeters PH, Meliefste K, Marcon A, Krämer U, Kuhlbusch TA, Vossoughi M, Key T, de Hoogh K, Hampel R, Peters A, Heinrich J, Weinmayr G, Concin H, Nagel G, Ineichen A, Jacquemin B, Stempfelet M, Vilier A, Ricceri F, Sacerdote C, Pedeli X, Katsoulis M, Trichopoulou A, Brunekreef B, Katsouyanni K (2014) Air pollution and nonmalignant respiratory mortality in 16 cohorts within the ESCAPE project., Am J Respir Crit Care Med189(6)pp. 684-696
RATIONALE: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. OBJECTIVES: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). METHODS: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. MEASUREMENTS AND MAIN RESULTS: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. CONCLUSIONS: In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality.
Beelen R, Stafoggia M, Raaschou-Nielsen O, Andersen ZJ, Xun WW, Katsouyanni K, Dimakopoulou K, Brunekreef B, Weinmayr G, Hoffmann B, Wolf K, Samoli E, Houthuijs D, Nieuwenhuijsen M, Oudin A, Forsberg B, Olsson D, Salomaa V, Lanki T, Yli-Tuomi T, Oftedal B, Aamodt G, Nafstad P, De Faire U, Pedersen NL, Östenson CG, Fratiglioni L, Penell J, Korek M, Pyko A, Eriksen KT, Tjønneland A, Becker T, Eeftens M, Bots M, Meliefste K, Wang M, Bueno-de-Mesquita B, Sugiri D, Krämer U, Heinrich J, de Hoogh K, Key T, Peters A, Cyrys J, Concin H, Nagel G, Ineichen A, Schaffner E, Probst-Hensch N, Dratva J, Ducret-Stich R, Vilier A, Clavel-Chapelon F, Stempfelet M, Grioni S, Krogh V, Tsai MY, Marcon A, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Tamayo I, Amiano P, Dorronsoro M, Katsoulis M, Trichopoulou A, Vineis P, Hoek G (2014) Long-term exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts., Epidemiology25(3)pp. 368-378
BACKGROUND: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. METHODS: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 ¼m (PM2.5), less than 10 ¼m (PM10), and 10 ¼m to 2.5 ¼m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. RESULTS: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 ¼g/m and for PM10, 1.22 (0.91-1.63) per 10 ¼g/m. CONCLUSION: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
Beelen R, Hoek G, Raaschou-Nielsen O, Stafoggia M, Andersen ZJ, Weinmayr G, Hoffmann B, Wolf K, Samoli E, Fischer PH, Nieuwenhuijsen MJ, Xun WW, Katsouyanni K, Dimakopoulou K, Marcon A, Vartiainen E, Lanki T, Yli-Tuomi T, Oftedal B, Schwarze PE, Nafstad P, de Faire U, Pedersen NL, Östenson CG, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Overvad K, Sørensen M, Eeftens M, Peeters PH, Meliefste K, Wang M, Bas Bueno-De-Mesquita H, Sugiri D, Krämer U, Heinrich J, De Hoogh K, Key T, Peters A, Hampel R, Concin H, Nagel G, Jaensch A, Ineichen A, Tsai MY, Schaffner E, Probst-Hensch NM, Schindler C, Ragettli MS, Vilier A, Clavel-Chapelon F, Declercq C, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Katsoulis M, Trichopoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Sokhi RS, Vineis P, Brunekreef B (2015) Natural-cause mortality and long-term exposure to particle components: An Analysis of 19 European cohorts within the multi-center ESCAPE project, Environmental Health Perspectives123(6)pp. 525-533
© 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. oBjectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori?selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions d 2.5 ¼m (PM2.5 ) and d 10 ¼m (PM10 ) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5 .
Cesaroni G, Forastiere F, Stafoggia M, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, de Faire U, Erbel R, Eriksen KT, Fratiglioni L, Galassi C, Hampel R, Heier M, Hennig F, Hilding A, Hoffmann B, Houthuijs D, Jöckel KH, Korek M, Lanki T, Leander K, Magnusson PK, Migliore E, Ostenson CG, Overvad K, Pedersen NL, J JP, Penell J, Pershagen G, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Salomaa V, Swart W, Turunen AW, Vineis P, Weinmayr G, Wolf K, de Hoogh K, Hoek G, Brunekreef B, Peters A (2014) Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project., BMJ348
OBJECTIVES: To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). DESIGN: Prospective cohort studies and meta-analysis of the results. SETTING: Cohorts in Finland, Sweden, Denmark, Germany, and Italy. PARTICIPANTS: 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. MAIN OUTCOME MEASURES: Modelled concentrations of particulate matter <2.5 ¼m (PM2.5), 2.5-10 ¼m (PMcoarse), and <10 ¼m (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. RESULTS: 5157 participants experienced incident events. A 5 ¼g/m(3) increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 ¼g/m(3) increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 ¼g/m(3) for PM2.5 (1.18, 1.01 to 1.39, for 5 ¼g/m(3) increase in PM2.5) and below 40 ¼g/m(3) for PM10 (1.12, 1.00 to 1.27, for 10 ¼g/m(3) increase in PM10). Positive but non-significant associations were found with other pollutants. CONCLUSIONS: Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.
Penell JC, Bonnett BN, Pringle J, Egenvall A (2009) Validation of computerized diagnostic information in a clinical database from a national equine clinic network., Acta veterinaria Scandinavica51
BACKGROUND: Computerized diagnostic information offers potential for epidemiological research; however data accuracy must be addressed. The principal aim of this study was to evaluate the completeness and correctness of diagnostic information in a computerized equine clinical database compared to corresponding hand written veterinary clinical records, used as gold standard, and to assess factors related to correctness. Further, the aim was to investigate completeness (epidemiologic sensitivity), correctness (positive predictive value), specificity and prevalence for diagnoses for four body systems and correctness for affected limb information for four joint diseases. METHODS: A random sample of 450 visits over the year 2002 (nvisits=49,591) was taken from 18 nation wide clinics headed under one company. Computerized information for the visits selected and copies of the corresponding veterinary clinical records were retrieved. Completeness and correctness were determined using semi-subjective criteria. Logistic regression was used to examine factors associated with correctness for diagnosis. RESULTS: Three hundred and ninety six visits had veterinary clinical notes that were retrievable. The overall completeness and correctness were 91% and 92%, respectively; both values considered high. Descriptive analyses showed significantly higher degree of correctness for first visits compared to follow up visits and for cases with a diagnostic code recorded in the veterinary records compared to those with no code noted. The correctness was similar regardless of usage category (leisure/sport horse, racing trotter and racing thoroughbred) or gender.For the four body systems selected (joints, skin and hooves, respiratory, skeletal) the completeness varied between 71% (respiration) and 91% (joints) and the correctness ranged from 87% (skin and hooves) to 96% (respiration), whereas the specificity was >95% for all systems. Logistic regression showed that correctness was associated with type of visit, whether an explicit diagnostic code was present in the veterinary clinical record, and body system. Correctness for information on affected limb was 95% and varied with joint. CONCLUSION: Based on the overall high level of correctness and completeness the database was considered useful for research purposes. For the body systems investigated the highest level of completeness and correctness was seen for joints and respiration, respectively.
Lind L, Penell J, Luttropp K, Nordfors L, Syvänen AC, Axelsson T, Salihovic S, van Bavel B, Fall T, Ingelsson E, Lind PM (2013) Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population., Environ Int59pp. 456-461
Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p=0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p=0.009) only in subjects with one G-allele (n=103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p=0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis.
Hampel R, Peters A, Beelen R, Brunekreef B, Cyrys J, de Faire U, de Hoogh K, Fuks K, Hoffmann B, Hüls A, Imboden M, Jedynska A, Kooter I, Koenig W, Künzli N, Leander K, Magnusson P, Männistö S, Penell J, Pershagen G, Phuleria H, Probst-Hensch N, Pundt N, Schaffner E, Schikowski T, Sugiri D, Tiittanen P, Tsai MY, Wang M, Wolf K, Lanki T, ESCAPE TRANSPHORM study groups (2015) Long-term effects of elemental composition of particulate matter on inflammatory blood markers in European cohorts., Environ Int82pp. 76-84
BACKGROUND: Epidemiological studies have associated long-term exposure to ambient particulate matter with increased mortality from cardiovascular and respiratory disorders. Systemic inflammation is a plausible biological mechanism behind this association. However, it is unclear how the chemical composition of PM affects inflammatory responses. OBJECTIVES: To investigate the association between long-term exposure to elemental components of PM and the inflammatory blood markers high-sensitivity C-reactive protein (hsCRP) and fibrinogen as part of the European ESCAPE and TRANSPHORM multi-center projects. METHODS: In total, 21,558 hsCRP measurements and 17,428 fibrinogen measurements from cross-sections of five and four cohort studies were available, respectively. Residential long-term concentrations of particulate matter <10¼m (PM10) and <2.5¼m (PM2.5) in diameter and selected elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium, zinc) were estimated based on land-use regression models. Associations between components and inflammatory markers were estimated using linear regression models for each cohort separately. Cohort-specific results were combined using random effects meta-analysis. As a sensitivity analysis the models were additionally adjusted for PM mass. RESULTS: A 5ng/m(3) increase in PM2.5 copper and a 500ng/m(3) increase in PM10 iron were associated with a 6.3% [0.7; 12.3%] and 3.6% [0.3; 7.1%] increase in hsCRP, respectively. These associations between components and fibrinogen were slightly weaker. A 10ng/m(3) increase in PM2.5 zinc was associated with a 1.2% [0.1; 2.4%] increase in fibrinogen; confidence intervals widened when additionally adjusting for PM2.5. CONCLUSIONS: Long-term exposure to transition metals within ambient particulate matter, originating from traffic and industry, may be related to chronic systemic inflammation providing a link to long-term health effects of particulate matter.
Egenvall A, Penell J, Bonnett BN, Blix J, Pringle J (2008) Demographics and costs of colic in Swedish horses., J Vet Intern Med22(4)pp. 1029-1037
BACKGROUND: Colic is an important cause of morbidity and mortality in horses. In Sweden, an insurance database with diagnostic medical information is maintained on >30% of the nation's horse population. HYPOTHESIS: The objective was to describe the occurrence of colic, defined by costly veterinary care and life claims, in horses at 1 insurance company during 1997-2002. HORSES: All horses (<21 years of age) with complete insurance for veterinary care and life during the period 1997-2002 were included. METHODS: Colic was defined as conditions where the main clinical sign was abdominal pain and the problem was related to the gastrointestinal system. The analyses included measures of incidence by sex, breed group, age categories, geographical location (urban/other), survival to and survival after colic, medical cost for colic, and multivariable modeling of risk factors related to the event of colic. RESULTS: In all, 116,288 horses contributed to 341,564 horse years at risk (HYAR). There were 3,100 horses with a colic diagnosis, of which 27% were settled for life insurance. The median gross cost for veterinary care was 4,729 Swedish Kronor (SEK). The overall occurrence and mortality rate of colic was 91 and 24 events per 10,000 HYAR. Survival after colic at 1 month was 76% (95% confidence interval: 75-78%). CONCLUSIONS AND CLINICAL IMPORTANCE: The occurrence of colic varied with breed group, age, and season. The mortality rates probably reflected the true mortality of colic. The veterinary care rates most likely underestimated of the risk colic because they represent relatively costly events.
Perez L, Wolf K, Hennig F, Penell J, Basagaña X, Foraster M, Aguilera I, Agis D, Beelen R, Brunekreef B, Cyrys J, Fuks KB, Adam M, Baldassarre D, Cirach M, Elosua R, Dratva J, Hampel R, Koenig W, Marrugat J, de Faire U, Pershagen G, Probst-Hensch NM, de Nazelle A, Nieuwenhuijsen MJ, Rathmann W, Rivera M, Seissler J, Schindler C, Thiery J, Hoffmann B, Peters A, Künzli N (2015) Air pollution and atherosclerosis: A cross-sectional analysis of four European cohort studies in the ESCAPE study, Environmental Health Perspectives123(6)pp. 597-605
© 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.Background: In four European cohorts, we investigated the cross-sectional association between long-term exposure to air pollution and intima-media thickness of the common carotid artery (CIMT), a preclinical marker of atherosclerosis. Methods: Individually assigned levels of nitrogen dioxide, nitrogen oxides, particulate matter d 2.5 ¼m (PM2.5 ), absorbance of PM2.5 (PM2.5abs ), PM10 , PMcoarse , and two indicators of resi-dential proximity to highly trafficked roads were obtained under a standard exposure protocol (European Study of Cohorts for Air Pollution Effects?ESCAPE study) in the Stockholm area (Sweden), the Ausburg and Ruhr area (Germany), and the Girona area (Spain). We used linear regression and meta-analyses to examine the association between long-term exposure to air pollution and CIMT. results: The meta-analysis with 9,183 individuals resulted in an estimated increase in CIMT (geometric mean) of 0.72% (95% CI: ?0.65%, 2.10%) per 5-¼g/m3 increase in PM2.5 and 0.42% (95% CI: ?0.46%, 1.30%) per 10?5/m increase in PM2.5abs . Living in proximity to high traffic was also positively but not significantly associated with CIMT. Meta-analytic estimates for other pollut-ants were inconsistent. Results were similar across different adjustment sets and sensitivity analyses. In an extended meta-analysis for PM2.5 with three other previously published studies, a 0.78% (95% CI: ?0.18%, 1.75%) increase in CIMT was estimated for a 5-¼g/m3 contrast in PM2.5 . conclusions: Using a standardized exposure and analytical protocol in four European cohorts, we found that cross-sectional associations between CIMT and the eight ESCAPE markers of long-term residential air pollution exposure did not reach statistical significance. The additional meta-analysis of CIMT and PM2.5 across all published studies also was positive but not significant.
Wolf K, Stafoggia M, Cesaroni G, Andersen ZJ, Beelen R, Galassi C, Hennig F, Migliore E, Penell J, Ricceri F, Sørensen M, Turunen AW, Hampel R, Hoffmann B, Kälsch H, Laatikainen T, Pershagen G, Raaschou-Nielsen O, Sacerdote C, Vineis P, Badaloni C, Cyrys J, de Hoogh K, Eriksen KT, Jedynska A, Keuken M, Kooter I, Lanki T, Ranzi A, Sugiri D, Tsai MY, Wang M, Hoek G, Brunekreef B, Peters A, Forastiere F (2015) Long-term Exposure to Particulate Matter Constituents and the Incidence of Coronary Events in 11 European Cohorts., Epidemiology26(4)pp. 565-574
BACKGROUND: Long-term exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity and mortality but little is known about the role of the chemical composition of PM. This study examined the association of residential long-term exposure to PM components with incident coronary events. METHODS: Eleven cohorts from Finland, Sweden, Denmark, Germany, and Italy participated in this analysis. 5,157 incident coronary events were identified within 100,166 persons followed on average for 11.5 years. Long-term residential concentrations of PM < 10 ¼m (PM10), PM < 2.5 ¼m (PM2.5), and a priori selected constituents (copper, iron, nickel, potassium, silicon, sulfur, vanadium, and zinc) were estimated with land-use regression models. We used Cox proportional hazard models adjusted for a common set of confounders to estimate cohort-specific component effects with and without including PM mass, and random effects meta-analyses to pool cohort-specific results. RESULTS: A 100 ng/m³ increase in PM10 K and a 50 ng/m³ increase in PM2.5 K were associated with a 6% (hazard ratio and 95% confidence interval: 1.06 [1.01, 1.12]) and 18% (1.18 [1.06, 1.32]) increase in coronary events. Estimates for PM10 Si and PM2.5 Fe were also elevated. All other PM constituents indicated a positive association with coronary events. When additionally adjusting for PM mass, the estimates decreased except for K. CONCLUSIONS: This multicenter study of 11 European cohorts pointed to an association between long-term exposure to PM constituents and coronary events, especially for indicators of road dust.
Penell JC, Egenvall A, Bonnett BN, Pringle J (2007) Validation of computerized Swedish horse insurance data against veterinary clinical records, Preventive Veterinary Medicine82(3-4)pp. 236-251
The aim was to evaluate the agreement between computerized insurance data in a large Swedish horse insurance database and the information in the corresponding clinical records (CR). A random sample of 400 veterinary care and 140 life claims was included. Information on name of the horse, breed and gender, year of birth, specific diagnosis and system diagnosis (e.g. joints, digestive and skeletal) was compared between sources. The concordance for demographic variables was categorized as agreement, disagreement or data missing. For diagnostic information, the categories were agreement, minor disagreement and major disagreement and for system information agreement or disagreement. There were missing values for demographic information in the CR, varying from 2% for name to 16% for breed. The overall agreement for demographic information was >94% (disregarding missing data), 92% for system and 84% for specific diagnosis. For veterinary care and life claims, the observed agreement for diagnosis was 85 and 83%, minor disagreement 6 and 5%, and major disagreement 9 and 12%, respectively. Using the CR data as gold standard, for the systems evaluated (joints, digestive, skeletal, skin and hooves), sensitivity varied between 62% (skin) and 89% (digestive) whereas the specificity was >96% for all systems. The positive predictive values ranged from 86% (skin) to 97% (digestive). Logistic regression analysis was used to examine factors associated with agreement for diagnosis. Analyses were performed separately for veterinary care and life claims. Factors examined were type of visit (clinic/field), treating veterinarian/clinic (categorized as district veterinarians, private practitioners, small clinics, medium clinics and, for the clinics with e20 claims, the specific clinics), computerized or manual CR, processing clerk, whether the CR was included in the paper file, if the claim was rejected or reimbursed, system diagnosis and if a immediate settlement (in analysis for veterinary care claims) or death certificate (in analysis for life claims) was included in the paper file. For veterinary care claims, in the logistic regression model type of visit was significantly associated with agreement, with clinic visits generating better agreement than field visits. © 2007 Elsevier B.V. All rights reserved.
Egenvall A, Nødtvedt A, Penell J, Gunnarsson L, Bonnett BN (2009) Insurance data for research in companion animals: benefits and limitations., Acta Vet Scand51
The primary aim of this article is to review the use of animal health insurance data in the scientific literature, especially in regard to morbidity or mortality in companion animals and horses. Methods and results were compared among studies on similar health conditions from different nations and years. A further objective was to critically evaluate benefits and limitations of such databases, to suggest ways to maximize their utility and to discuss the future use of animal insurance data for research purposes. Examples of studies on morbidity, mortality and survival estimates in dogs and horses, as well as neoplasia in dogs, are discussed.We conclude that insurance data can and should be used for research purposes in companion animals and horses. Insurance data have been successfully used, e.g. to quantify certain features that may have been hitherto assumed, but unmeasured. Validation of insurance databases is necessary if they are to be used in research. This must include the description of the insured population and an evaluation of the extent to which it represents the source population. Data content and accuracy must be determined over time, including the accuracy/consistency of diagnostic information. Readers must be cautioned as to limitations of the databases and, as always, critically appraise findings and synthesize information with other research. Similar findings from different study designs provide stronger evidence than a sole report. Insurance data can highlight common, expensive and severe conditions that may not be evident from teaching hospital case loads but may be significant burdens on the health of a population.
Back H, Ullman K, Leijon M, Soderlund R, Penell J, Stahl K, Pringle J, Valarcher J-F (2015) Genetic variation and dynamics of infections of equid herpesvirus 5 in individual horses, JOURNAL OF GENERAL VIROLOGY97pp. 169-178 SOC GENERAL MICROBIOLOGY
Wang M, Beelen R, Stafoggia M, Raaschou-Nielsen O, Andersen ZJ, Hoffmann B, Fischer P, Houthuijs D, Nieuwenhuijsen M, Weinmayr G, Vineis P, Xun WW, Dimakopoulou K, Samoli E, Laatikainen T, Lanki T, Turunen AW, Oftedal B, Schwarze P, Aamodt G, Penell J, De Faire U, Korek M, Leander K, Pershagen G, Pedersen NL, Östenson CG, Fratiglioni L, Eriksen KT, Sørensen M, Tjønneland A, Bueno-de-Mesquita B, Eeftens M, Bots ML, Meliefste K, Krämer U, Heinrich J, Sugiri D, Key T, de Hoogh K, Wolf K, Peters A, Cyrys J, Jaensch A, Concin H, Nagel G, Tsai MY, Phuleria H, Ineichen A, Künzli N, Probst-Hensch N, Schaffner E, Vilier A, Clavel-Chapelon F, Declerq C, Ricceri F, Sacerdote C, Marcon A, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Katsoulis M, Trichopoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Sokhi RS, Brunekreef B, Katsouyanni K, Hoek G (2014) Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts: results from the ESCAPE and TRANSPHORM projects., Environ Int66pp. 97-106
BACKGROUND: Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only. AIMS: The aim of this study was to examine the association of PM composition with cardiovascular mortality. METHODS: We used data from 19 European ongoing cohorts within the framework of the ESCAPE (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport related Air Pollution and Health impacts--Integrated Methodologies for Assessing Particulate Matter) projects. Residential annual average exposure to elemental constituents within particle matter smaller than 2.5 and 10 ¼m (PM2.5 and PM10) was estimated using Land Use Regression models. Eight elements representing major sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc). Cohort-specific analyses were conducted using Cox proportional hazards models with a standardized protocol. Random-effects meta-analysis was used to calculate combined effect estimates. RESULTS: The total population consisted of 322,291 participants, with 9545 CVD deaths. We found no statistically significant associations between any of the elemental constituents in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84-1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% CI: 0.93-1.47), and S in PM2.5 (1.08, 95% CI: 0.95-1.22) and PM10 (1.09, 95% CI: 0.90-1.32). CONCLUSION: In a joint analysis of 19 European cohorts, we found no statistically significant association between long-term exposure to 8 elemental constituents of particles and total cardiovascular mortality.
Korek MJ, Bellander TD, Lind T, Bottai M, Eneroth KM, Caracciolo B, De Faire UH, Fratiglioni L, Hilding A, Leander K, Magnusson PKE, Pedersen NL, Östenson CG, Pershagen G, Penell JC (2015) Traffic-related air pollution exposure and incidence of stroke in four cohorts from Stockholm, Journal of Exposure Science and Environmental Epidemiology25(5)pp. 517-523
© 2015 Nature America, Inc. All rights reserved.We investigated the risk of stroke related to long-term ambient air pollution exposure, in particular the role of various exposure time windows, using four cohorts from Stockholm County, Sweden. In total, 22,587 individuals were recruited from 1992 to 2004 and followed until 2011. Yearly air pollution levels resulting from local road traffic emissions were assessed at participant residences using dispersion models for particulate matter (PM10 ) and nitrogen oxides (NOX ). Cohort-specific hazard ratios were estimated for time-weighted air pollution exposure during different time windows and the incidence of stroke, adjusted for common risk factors, and then meta-analysed. Overall, 868 subjects suffered a non-fatal or fatal stroke during 238,731 person-years of follow-up. An increment of 20 ¼g/m3 in estimated annual mean of road-traffic related NOX exposure at recruitment was associated with a hazard ratio of 1.16 (95% CI 0.83-1.61), with evidence of heterogeneity between the cohorts. For PM10 , an increment of 10 ¼g/m3 corresponded to a hazard ratio of 1.14 (95% CI 0.68-1.90). Time-window analyses did not reveal any clear induction-latency pattern. In conclusion, we found suggestive evidence of an association between long-term exposure to NOX and PM10 from local traffic and stroke at comparatively low levels of air pollution.
Egenvall A, Penell JC, Bonnett BN, Olson P, Pringle J (2006) Mortality of Swedish horses with complete life insurance between 1997 and 2000: Variations with sex, age, breed and diagnosis, Veterinary Record158(12)pp. 397-406
The aim of this study was to evaluate the potential usefulness of the database maintained by the Swedish insurance company Agria for providing mortality statistics on Swedish horses. Mortality statistics (incidence rates and survival) were calculated, both crudely and stratified by sex, age, breed, breed group and diagnosis, for the horses with complete life insurance, which covers most health problems. The total mortality was 415 (95 per cent confidence interval [CI] 399 to 432) deaths per 10,000 horse-years at risk, and the diagnostic mortality, including only deaths with an assigned diagnosis, was 370 (95 per cent CI 355 to 386) deaths per 10,000 horse-years at risk. The diagnostic mortality of geldings was 459 (95 per cent CI 431 to 487), of mares 345 (95 per cent CI 322 to 365) and of stallions 214 (95 per cent CI 182 to 247) deaths per 10,000 horse-years at risk. The mortality rates increased with age and differed widely between breeds. Survival analysis showed that the median age at death of the horses enrolled before they were one year of age was 18-8 years. The most common cause of death or euthanasia was joint problems, which were responsible for 140 (95 per cent CI 130 to 149) deaths per 10,000 horse-years at risk. The results of multivariable models developed by using Poisson regression generally agreed well with the crude results.
Stafoggia M, Cesaroni G, Peters A, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, Cyrys J, de Faire U, de Hoogh K, Eriksen KT, Fratiglioni L, Galassi C, Gigante B, Havulinna AS, Hennig F, Hilding A, Hoek G, Hoffmann B, Houthuijs D, Korek M, Lanki T, Leander K, Magnusson PK, Meisinger C, Migliore E, Overvad K, Ostenson CG, Pedersen NL, Pekkanen J, Penell J, Pershagen G, Pundt N, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Swart WJ, Turunen AW, Vineis P, Weimar C, Weinmayr G, Wolf K, Brunekreef B, Forastiere F (2014) Long-term exposure to ambient air pollution and incidence of cerebrovascular events: results from 11 European cohorts within the ESCAPE project., Environ Health Perspect122(9)pp. 919-925
BACKGROUND: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. OBJECTIVES: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. METHODS: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) d 2.5 ¼m in diameter], coarse PM (PM between 2.5 and 10 ¼m), PM10 (PM d 10 ¼m), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation. RESULTS: A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-¼g/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those e 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 ¼g/m3 (HR = 1.33, 95% CI: 1.01, 1.77). CONCLUSIONS: We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value.
Lanki T, Hampel R, Tiittanen P, Andrich S, Beelen R, Brunekreef B, Dratva J, Faire UD, Fuks KB, Hoffmann B, Imboden M, Jousilahti P, Koenig W, Mahabadi AA, Künzli N, Pedersen NL, Penell J, Pershagen G, Probst Hensch NM, Schaffner E, Schindler C, Sugiri D, Swart WJR, Tsai MY, Turunen AW, Weinmayr G, Wolf K, Yli-Tuomi T, Peters A (2015) Air pollution from road traffic and systemic inflammation in adults: A cross-sectional analysis in the European ESCAPE project, Environmental Health Perspectives123(8)pp. 785-791
© 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved.Background: Exposure to particulate matter air pollution (PM) has been associated with cardiovascular diseases. Objectives: In this study we evaluated whether annual exposure to ambient air pollution is associated with systemic inflammation, which is hypothesized to be an intermediate step to cardiovascular disease. Methods: Six cohorts of adults from Central and Northern Europe were used in this crosssectional study as part of the larger ESCAPE project (European Study of Cohorts for Air Pollution Effects). Data on levels of blood markers for systemic inflammation?high-sensitivity C-reactive protein (CRP) and fibrinogen?were available for 22,561 and 17,428 persons, respectively. Land use regression models were used to estimate cohort participants? long-term exposure to various size fractions of PM, soot, and nitrogen oxides (NOx ). In addition, traffic intensity on the closest street and traffic load within 100 m from home were used as indicators of traffic air pollution exposure. Results: Particulate air pollution was not associated with systemic inflammation. However, cohort participants living on a busy (> 10,000 vehicles/day) road had elevated CRP values (10.2%; 95% CI: 2.4, 18.8%, compared with persons living on a quiet residential street with < 1,000 vehicles/day). Annual NOx concentration was also positively associated with levels of CRP (3.2%; 95% CI: 0.3, 6.1 per 20 ¼g/m3), but the effect estimate was more sensitive to model adjustments. For fibrinogen, no consistent associations were observed. Conclusions: Living close to busy traffic was associated with increased CRP concentrations, a known risk factor for cardiovascular diseases. However, it remains unclear which specific air pollutants are responsible for the association.
Raaschou-Nielsen O, Andersen ZJ, Beelen R, Samoli E, Stafoggia M, Weinmayr G, Hoffmann B, Fischer P, Nieuwenhuijsen MJ, Brunekreef B, Xun WW, Katsouyanni K, Dimakopoulou K, Sommar J, Forsberg B, Modig L, Oudin A, Oftedal B, Schwarze PE, Nafstad P, De Faire U, Pedersen NL, Ostenson CG, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Sørensen M, Tjønneland A, Ellermann T, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita B, Key TJ, de Hoogh K, Concin H, Nagel G, Vilier A, Grioni S, Krogh V, Tsai MY, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Tamayo I, Amiano P, Dorronsoro M, Trichopoulou A, Bamia C, Vineis P, Hoek G (2013) Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)., Lancet Oncol14(9)pp. 813-822
BACKGROUND: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 ¼m (PM10), less than 2·5 ¼m (PM2·5), and between 2·5 and 10 ¼m (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS: The 312?944 cohort members contributed 4?013?131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 ¼g/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 ¼g/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 ¼g/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION: Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING: European Community's Seventh Framework Programme.
Egenvall A, Bonnett BN, Olson P, Penell J, Emanuelson U (2006) Association between costly veterinary-care events and 5-year survival of Swedish insured warmblooded riding horses., Prev Vet Med77(1-2)pp. 122-136
Our objective was to estimate the 5-year survival to death in insured warmblooded riding horses (as reflected by a life-insurance claim) in horses with or without at least one costly veterinary-care event (VCE) in 1997. We also determined the impacts of gender, age, previous diagnosis of veterinary claim, geographic variables, cost for veterinary claims and life-insurance value upon the survival. The design was a retrospective cohort study using a population of warmblooded riding horses insured in a Swedish animal-insurance company (Agria Insurance, P.O. 70306, SE-107 23 Stockholm, Sweden) in 1997. All horses in this population had insurance both for veterinary-care and life ("complete" insurance reimbursing the insurance holder for most medical problems). We followed two cohorts (2,495 horses with > or = 1 VCE and 15,576 horses with no VCE in year 1997). The median VCE cost in horses with > or =1 VCE was 3,800 SEK, with 10th and 90th percentiles of 1,400 and 11,400 SEK respectively. In total 944 of the 2,495 horses (38%) in the VCE-positive cohort and 2,962 of the 15,576 horses (19%) in the VCE-negative cohort had died (had a settled life-insurance claim) after the follow-up time. An exponential-regression model showed that geldings had a higher risk of claimed death compared to mares and mares had a higher risk compared to stallions. The risk of death increased linearly with age. The risk of death increased with increasing life-insurance value. Horses with previous lameness had the lowest survival, and for high-cost claims this increased risk was not associated with age.
Back H, Ullman K, Treiberg Berndtsson L, Riihimäki M, Penell J, Ståhl K, Valarcher JF, Pringle J (2015) Viral load of equine herpesviruses 2 and 5 in nasal swabs of actively racing Standardbred trotters: Temporal relationship of shedding to clinical findings and poor performance, Veterinary Microbiology179(3-4)pp. 142-148
© 2015 Elsevier B.V.The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492 (74%) positive for EHV-5. Furthermore, 176 (27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters.
Korek MJ, Bellander TD, Lind T, Bottai M, Eneroth KM, Caracciolo B, de Faire UH, Fratiglioni L, Hilding A, Leander K, Magnusson PK, Pedersen NL, Östenson CG, Pershagen G, Penell JC (2015) Traffic-related air pollution exposure and incidence of stroke in four cohorts from Stockholm., J Expo Sci Environ Epidemiol25(5)pp. 517-523
We investigated the risk of stroke related to long-term ambient air pollution exposure, in particular the role of various exposure time windows, using four cohorts from Stockholm County, Sweden. In total, 22,587 individuals were recruited from 1992 to 2004 and followed until 2011. Yearly air pollution levels resulting from local road traffic emissions were assessed at participant residences using dispersion models for particulate matter (PM10) and nitrogen oxides (NOX). Cohort-specific hazard ratios were estimated for time-weighted air pollution exposure during different time windows and the incidence of stroke, adjusted for common risk factors, and then meta-analysed. Overall, 868 subjects suffered a non-fatal or fatal stroke during 238,731 person-years of follow-up. An increment of 20 ¼g/m(3) in estimated annual mean of road-traffic related NOX exposure at recruitment was associated with a hazard ratio of 1.16 (95% CI 0.83-1.61), with evidence of heterogeneity between the cohorts. For PM10, an increment of 10 ¼g/m(3) corresponded to a hazard ratio of 1.14 (95% CI 0.68-1.90). Time-window analyses did not reveal any clear induction-latency pattern. In conclusion, we found suggestive evidence of an association between long-term exposure to NOX and PM10 from local traffic and stroke at comparatively low levels of air pollution.
Back H, Penell J, Pringle J, Isaksson M, Ronéus N, Treiberg Berndtsson L, Ståhl K (2015) A longitudinal study of poor performance and subclinical respiratory viral activity in Standardbred trotters., Veterinary Record Open2(1)
INTRODUCTION: While clinical respiratory disease is considered a main cause of poor performance in horses, the role of subclinical respiratory virus infections is less clear and needs further investigation. AIMS AND OBJECTIVES: In this descriptive longitudinal study the relationship of markers of subclinical respiratory viral activity to occurrence of poor performance in racing Standardbred trotters was investigated. MATERIAL AND METHODS: 66 elite Standardbred trotters were followed for 13?months by nasal swabs analysed with qPCR for equine influenza virus, equine arteritis virus, equine rhinitis B virus (ERBV), equine herpesvirus type 1(EHV-1) and equine herpesvirus type 4 (EHV-4) and serology to equine rhinitis A virus (ERAV), ERBV, EHV-1 and EHV-4, as well as the acute phase protein serum amyloid A (SAA). Findings on lab analyses were subsequently assessed for possible correlations to workload performance and trainer opinion measures of poor performance. RESULTS: Despite occurrence of poor performance and subclinical viral activity the authors were unable to detect association neither between subclinical viral activity and poor performance, nor between SAA elevations and either viral activity or poor performance. CONCLUSIONS: Consistent with earlier study results, antibody titres to ERBV remained high for at least a year and few horses two years or older were seronegative to either ERAV or ERBV. In absence of clinical signs, serology to common respiratory viruses appears to have little diagnostic benefit in evaluation of poor performance in young athletic horses.
Lind PM, Penell J, Salihovic S, van Bavel B, Lind L (2014) Circulating levels of p,p'-DDE are related to prevalent hypertension in the elderly., Environ Res129pp. 27-31
BACKGROUND: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women. METHODS: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure e140mmHg or a diastolic blood pressure e90mmHg, and/or use of antihypertensive medication. RESULTS: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 1.35 for a 1 SD change, 95% CI 1.17-1.56, p<0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06-1.43, p=0.006). CONCLUSION: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure.
Penell J, Lind L, Salihovic S, van Bavel B, Lind PM (2014) Persistent organic pollutants are related to the change in circulating lipid levels during a 5 year follow-up., Environ Res134pp. 190-197
When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data indicate that exposure to POPs may change lipid values. The aim of the present study is to investigate if POP levels can predict future changes in levels of circulating lipids. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-three different POPs, including 16 polychlorinated biphenyls (PCBs), five organochlorine pesticides, one dioxin (OCDD) and one flame retardant brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) at age 70. Strong relationships were seen among the baseline levels of the non-dioxin-like PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipid-normalized levels were used compared to wet-weight based levels. On the contrary, for two of the pesticides, hexachlorobenzene and trans-nonachlordane, levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol, in particular for wet-weight based levels. However, these relationships were only significant for wet-weight PCB 194 following adjustment for multiple testing. None of the POPs was related to the change in serum triglycerides. When investigating the association between the change in total serum cholesterol and LDL-cholesterol across different categories of change in BMI, we noted robust results especially in the group with stable BMI, suggesting that the observed relationships were not due to fluctuations in BMI over time. In conclusion, POPs are related to the change in lipids over time, especially LDL-cholesterol. This may explain why POP exposure previously has been linked to atherosclerosis and cardiovascular disease.
Fuks KB, Weinmayr G, Foraster M, Dratva J, Hampel R, Houthuijs D, Oftedal B, Oudin A, Panasevich S, Penell J, Sommar JN, Sørensen M, Tiittanen P, Wolf K, Xun WW, Aguilera I, Basagaña X, Beelen R, Bots ML, Brunekreef B, Bueno-de-Mesquita HB, Caracciolo B, Cirach M, de Faire U, de Nazelle A, Eeftens M, Elosua R, Erbel R, Forsberg B, Fratiglioni L, Gaspoz JM, Hilding A, Jula A, Korek M, Krämer U, Künzli N, Lanki T, Leander K, Magnusson PK, Marrugat J, Nieuwenhuijsen MJ, Ostenson CG, Pedersen NL, Pershagen G, Phuleria HC, Probst-Hensch NM, Raaschou-Nielsen O, Schaffner E, Schikowski T, Schindler C, Schwarze PE, Søgaard AJ, Sugiri D, Swart WJ, Tsai MY, Turunen AW, Vineis P, Peters A, Hoffmann B (2014) Arterial blood pressure and long-term exposure to traffic-related air pollution: an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)., Environ Health Perspect122(9)pp. 896-905
BACKGROUND: Long-term exposure to air pollution has been hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: We analyzed 15 population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). We modeled residential exposure to particulate matter and nitrogen oxides with land use regression using a uniform protocol. We assessed traffic exposure with traffic indicator variables. We analyzed systolic and diastolic BP in participants medicated and nonmedicated with BP-lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as e 140 mmHg systolic BP, or e 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in nonmedicated participants [0.35 mmHg (95% CI: 0.02, 0.68) and 0.22 mmHg (95% CI: 0.04, 0.40) per 4,000,000 vehicles × m/day, respectively]. The estimated odds ratio (OR) for prevalent hypertension was 1.05 (95% CI: 0.99, 1.11) per 4,000,000 vehicles × m/day. Modeled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts, we observed a weak positive association of high residential traffic exposure with BP in nonmedicated participants, and an elevated OR for prevalent hypertension. The relationship of modeled air pollutants with BP was inconsistent.
Back H, Ullman K, Treiberg Berndtsson L, Riihimäki M, Penell J, Ståhl K, Valarcher JF, Pringle J (2015) Viral load of equine herpesviruses 2 and 5 in nasal swabs of actively racing Standardbred trotters: Temporal relationship of shedding to clinical findings and poor performance., Vet Microbiol179(3-4)pp. 142-148
The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492 (74%) positive for EHV-5. Furthermore, 176 (27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters.
Raaschou-Nielsen O, Beelen R, Wang M, Hoek G, Andersen ZJ, Hoffmann B, Stafoggia M, Samoli E, Weinmayr G, Dimakopoulou K, Nieuwenhuijsen M, Xun WW, Fischer P, Eriksen KT, Sørensen M, Tjønneland A, Ricceri F, de Hoogh K, Key T, Eeftens M, Peeters PH, Bueno-de-Mesquita HB, Meliefste K, Oftedal B, Schwarze PE, Nafstad P, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Penell J, De Faire U, Korek M, Pedersen N, Östenson CG, Pershagen G, Fratiglioni L, Concin H, Nagel G, Jaensch A, Ineichen A, Naccarati A, Katsoulis M, Trichpoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Brunekreef B, Sokhi RS, Katsouyanni K, Vineis P (2015) Particulate matter air pollution components and risk for lung cancer., Environment international87pp. 66-73
Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence.We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis.The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S.This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.
Beelen R, Raaschou-Nielsen O, Stafoggia M, Andersen ZJ, Weinmayr G, Hoffmann B, Wolf K, Samoli E, Fischer P, Nieuwenhuijsen M, Vineis P, Xun WW, Katsouyanni K, Dimakopoulou K, Oudin A, Forsberg B, Modig L, Havulinna AS, Lanki T, Turunen A, Oftedal B, Nystad W, Nafstad P, De Faire U, Pedersen NL, Östenson CG, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Overvad K, Ellermann T, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita B, Sugiri D, Krämer U, Heinrich J, de Hoogh K, Key T, Peters A, Hampel R, Concin H, Nagel G, Ineichen A, Schaffner E, Probst-Hensch N, Künzli N, Schindler C, Schikowski T, Adam M, Phuleria H, Vilier A, Clavel-Chapelon F, Declercq C, Grioni S, Krogh V, Tsai MY, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Tamayo I, Amiano P, Dorronsoro M, Katsoulis M, Trichopoulou A, Brunekreef B, Hoek G (2014) Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project., Lancet383(9919)pp. 785-795
BACKGROUND: Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS: We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 ¼m (PM2.5), less than 10 ¼m (PM10), and between 10 ¼m and 2.5 ¼m (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS: The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 ¼g/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 ¼g/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 ¼g/m(3) (1.07, 1.01-1.13). INTERPRETATION: Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING: European Community's Seventh Framework Program (FP7/2007-2011).
Lind L, Penell J, Syvänen AC, Axelsson T, Ingelsson E, Morris AP, Lindgren C, Salihovic S, van Bavel B, Lind PM (2014) Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample., Environ Res133pp. 135-140
Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures >80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p<0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.
Penell J, Lind L, Fall T, Syvänen AC, Axelsson T, Lundmark P, Morris AP, Lindgren C, Mahajan A, Salihovic S, van Bavel B, Ingelsson E, Lind PM (2014) Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study., Environ Health13(1)
BACKGROUND: Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample. METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). RESULTS: Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals. CONCLUSION: Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.
Künzli N, Perez L, von Klot S, Baldassarre D, Bauer M, Basagana X, Breton C, Dratva J, Elosua R, de Faire U, Fuks K, de Groot E, Marrugat J, Penell J, Seissler J, Peters A, Hoffmann B (2011) Investigating air pollution and atherosclerosis in humans: concepts and outlook., Prog Cardiovasc Dis53(5)pp. 334-343
Although ambient particulate matter contributes to atherosclerosis in animal models, its role in atherogenesis in humans needs to be established. This article discusses concepts, study design, and choice of health outcomes to efficiently investigate the atherogenic role of ambient air pollution, with an emphasis on early preclinical biomarkers of atherosclerosis that are unaffected by short-term exposure to air pollution (eg, carotid intima-media thickness [CIMT] and functional performance of the vessel). Air pollution studies using these end points are summarized. The CIMT is currently the most frequently used outcome in this field (6 studies). The continuous nature of CIMT, the lack of short-term variation, its relationship to atherosclerotic changes in the artery wall, its predictive value for coronary heart disease, and the noninvasiveness of the assessment make it a useful candidate for cross-sectional and longitudinal studies investigating the role of air pollution in atherogenesis.