Leveraging Real-World Data in Safety Signal Assessment.

PURPOSE: TransCelerate BioPharma surveyed its member biopharmaceutical companies to understand current practices and identify opportunities to complement safety signal assessment with rapid real-world data (RWD) analysis. METHODS: A voluntary 30-question questionnaire regarding the use of RWD in safety signal assessment was disseminated to subject matter experts at all TransCelerate member companies in July 2022. Responses were blinded, aggregated, summarized, and presented. RESULTS: Eighteen of 20 member companies provided responses to the questionnaire. Sixteen (89%) companies reported actively leveraging RWD in their signal assessment processes. Of 18 respondent companies, 8 (44%) routinely use rapid approaches to RWD analysis, 7 (39%) utilize rapid RWD analysis non-routinely or in a pilot setting, 2 (11%) are considering using rapid RWD analysis, and 1 (6%) has no plans to use rapid RWD analysis for their signal assessment. Most companies reported that RWD adds context to and improves quality of signal assessments. To conduct RWD analysis for signal assessment, 16 of 17 (94%) respondent companies utilize or plan to utilize internally available data, 8 (47%) utilize both internal and external data, and 3 (18%) utilize data networks. Respondents identified key challenges to rapidly performing RWD analyses, including data access/availability, time for analysis execution, and uncertainties regarding acceptance of minimal or non-protocolized approaches by health authorities. CONCLUSION: Biopharmaceutical companies reported that they see value in the use of rapid RWD analyses for complementing signal assessments. Future work is recommended to offer a framework and process for use of rapid use of RWD analyses in signal assessment.

Temperature, myocardial infarction, and mortality: effect modification by individual- and area-level characteristics.

BACKGROUND: Although several studies have examined associations between temperature and cardiovascular-disease-related mortality, fewer have investigated the association between temperature and the development of acute myocardial infarction (MI). Moreover, little is known about who is most susceptible to the effects of temperature. METHODS: We analyzed data from the Worcester Heart Attack Study, a community-wide investigation of acute MI in residents of the Worcester (MA) metropolitan area. We used a case-crossover approach to examine the association of apparent temperature with acute MI occurrence and with all-cause in-hospital and postdischarge mortality. We examined effect modification by sociodemographic characteristics, medical history, clinical complications, and physical environment. RESULTS: A decrease in an interquartile range in apparent temperature was associated with an increased risk of acute MI on the same day (hazard ratio = 1.15 [95% confidence interval = 1.01-1.31]). Extreme cold during the 2 days prior was associated with an increased risk of acute MI (1.36 [1.07-1.74]). Extreme heat during the 2 days prior was also associated with an increased risk of mortality (1.44 [1.06-1.96]). Persons living in areas with greater poverty were more susceptible to heat. CONCLUSIONS: Exposure to cold increased the risk of acute MI, and exposure to heat increased the risk of dying after an acute MI. Local area vulnerability should be accounted for as cities prepare to adapt to weather fluctuations as a result of climate change.

Influenza epidemics, seasonality, and the effects of cold weather on cardiac mortality.

BACKGROUND: More people die in the winter from cardiac disease, and there are competing hypotheses to explain this. The authors conducted a study in 48 US cities to determine how much of the seasonal pattern in cardiac deaths could be explained by influenza epidemics, whether that allowed a more parsimonious control for season than traditional spline models, and whether such control changed the short term association with temperature. METHODS: The authors obtained counts of daily cardiac deaths and of emergency hospital admissions of the elderly for influenza during 1992-2000. Quasi-Poisson regression models were conducted estimating the association between daily cardiac mortality, and temperature. RESULTS: Controlling for influenza admissions provided a more parsimonious model with better Generalized Cross-Validation, lower residual serial correlation, and better captured Winter peaks. The temperature-response function was not greatly affected by adjusting for influenza. The pooled estimated increase in risk for a temperature decrease from 0 to -5°C was 1.6% (95% confidence interval (CI) 1.1-2.1%). Influenza accounted for 2.3% of cardiac deaths over this period. CONCLUSIONS: The results suggest that including epidemic data explained most of the irregular seasonal pattern (about 18% of the total seasonal variation), allowing more parsimonious models than when adjusting for seasonality only with smooth functions of time. The effect of cold temperature is not confounded by epidemics.

Associations between air temperature and cardio-respiratory mortality in the urban area of Beijing, China: a time-series analysis.

BACKGROUND: Associations between air temperature and mortality have been consistently observed in Europe and the United States; however, there is a lack of studies for Asian countries. Our study investigated the association between air temperature and cardio-respiratory mortality in the urban area of Beijing, China. METHODS: Death counts for cardiovascular and respiratory diseases for adult residents (≥15 years), meteorological parameters and concentrations of particulate air pollution were obtained from January 2003 to August 2005. The effects of two-day and 15-day average temperatures were estimated by Poisson regression models, controlling for time trend, relative humidity and other confounders if necessary. Effects were explored for warm (April to September) and cold periods (October to March) separately. The lagged effects of daily temperature were investigated by polynomial distributed lag (PDL) models. RESULTS: We observed a J-shaped exposure-response function only for 15-day average temperature and respiratory mortality in the warm period, with 21.3°C as the threshold temperature. All other exposure-response functions could be considered as linear. In the warm period, a 5°C increase of two-day average temperature was associated with a RR of 1.098 (95% confidence interval (95%CI): 1.057-1.140) for cardiovascular and 1.134 (95%CI: 1.050-1.224) for respiratory mortality; a 5°C decrease of 15-day average temperature was associated with a RR of 1.040 (95%CI: 0.990-1.093) for cardiovascular mortality. In the cold period, a 5°C increase of two-day average temperature was associated with a RR of 1.149 (95%CI: 1.078-1.224) for respiratory mortality; a 5°C decrease of 15-day average temperature was associated with a RR of 1.057 (95%CI: 1.022-1.094) for cardiovascular mortality. The effects remained robust after considering particles as additional confounders. CONCLUSIONS: Both increases and decreases in air temperature are associated with an increased risk of cardiovascular mortality. The effects of heat were immediate while the ones of cold became predominant with longer time lags. Increases in air temperature are also associated with an immediate increased risk of respiratory mortality.

Road traffic noise: self-reported noise annoyance versus GIS modelled road traffic noise exposure.

BACKGROUND AND OBJECTIVES: self-reported road traffic noise annoyance is commonly used in epidemiological studies for assessment of potential health effects. Alternatively, some studies have used geographic information system (GIS) modelled exposure to road traffic noise as an objective parameter. The aim of this study was to analyse the association between noise exposure due to neighbouring road traffic and the noise annoyance of adults, taking other determinants into consideration. METHODS: parents of 951 Munich children from the two German birth cohorts GINIplus and LISAplus reported their annoyance due to road traffic noise at home. GIS modelled road traffic noise exposure (L(den), maximum within a 50 m buffer) from the noise map of the city of Munich was available for all families. GIS-based calculated distance to the closest major road (≥10,000 vehicles per day) and questionnaire based-information about family income, parental education and the type of the street of residence were explored for their potential influence. An ordered logit regression model was applied. The noise levels (L(den)) and the reported noise annoyance were compared with an established exposure-response function. RESULTS: the correlation between noise annoyance and noise exposure (L(den)) was fair (Spearman correlation r(s) = 0.37). The distance to a major road and the type of street were strong predictors for the noise annoyance. The annoyance modelled by the established exposure-response function and that estimated by the ordered logit model were moderately associated (Pearson's correlation r(p) = 0.50). CONCLUSIONS: road traffic noise annoyance was associated with GIS modelled neighbouring road traffic noise exposure (L(den)). The distance to a major road and the type of street were additional explanatory factors of the noise annoyance appraisal.

Air temperature and the occurrence of myocardial infarction in Augsburg, Germany.

BACKGROUND: Air temperature changes have been associated with cardiovascular mortality and morbidity. The objective of this study was to examine in detail the registry-based myocardial infarction (MI) rates and coronary deaths in relation to air temperature in the area of Augsburg, Germany. METHODS AND RESULTS: Between 1995 and 2004, the Monitoring Trends and Determinants on Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA) registry recorded 9801 cases of MI and coronary deaths. Over the same period, meteorological parameters and air pollutant concentrations were measured in the study region. Poisson regression analyses adjusting for time trend, relative humidity, season, and calendar effects were used to estimate immediate, delayed, and cumulative temperature effects on the occurrence of MIs. The daily rates of total MI, nonfatal and fatal events, and incident and recurrent events were analyzed. For the total MI cases, a 10 degrees C decrease in 5-day average temperature was associated with a relative risk of 1.10 (95% confidence interval, 1.04 to 1.15). The effect of temperature on the occurrence of nonfatal events showed a delayed pattern, whereas the association with fatal MI was more immediate. No association could be observed for recurrent events. The effects of temperature decreases on total MI cases were more pronounced in years with higher average temperatures and were visible in summer. CONCLUSIONS: We observed an inverse relationship between temperature and MI occurrence not only during winter but also during summer. Thus, our results suggest not a pure "cold effect" but an influence of unusual temperature decreases.

Ambient air pollution and daily mortality among survivors of myocardial infarction.

BACKGROUND: Certain subgroups in the general population, such as persons with existing cardiovascular or respiratory disease, may be more likely to experience adverse health effects from air pollution. METHODS: In this European multicenter study, 25,006 myocardial infarction (MI) survivors in 5 cities were recruited from 1992 to 2002 via registers, and daily mortality was followed for 6 to 12 years in relation to ambient particulate and gaseous air pollution exposure. Daily air pollution levels were obtained from central monitor sites, and particle number concentrations were measured in 2001 and estimated retrospectively based on measured pollutants and meteorology. City-specific effect estimates from time-series analyses with Poisson regression were pooled over all 5 cities. RESULTS: Particle number concentrations and PM10 averaged over 2 days (lag 0-1) were associated with increased total nontrauma mortality for patients of age 35 to 74 (5.6% [95% confidence interval, 2.8%-8.5%] per 10,000/cm and 5.1% [1.6%-9.3%] per 10 microg/m, respectively). For longer averaging times (5 and 15 days), carbon monoxide and nitrogen dioxide were also associated with mortality. There were no clear associations with ozone or sulfur dioxide. CONCLUSION: Exposure to traffic-related air pollution was associated with daily mortality in MI survivors. Point estimates suggest a stronger effect of air pollution in MI survivors than among the general population.

Elemental carbon exposure at residence and survival after acute myocardial infarction.

BACKGROUND: Particulate air pollution has been consistently related to cardiovascular mortality. Some evidence suggests that particulate matter may accelerate the atherosclerotic process. Effects of within-city variations of particulate air pollution on survival after an acute cardiovascular event have been little explored. METHODS: We conducted a cohort study of hospital survivors of acute myocardial infarction (MI) from the Worcester, MA, metropolitan area to investigate the long-term effects of within-city variation in traffic-related air pollution on mortality. The study builds on an ongoing community-wide investigation examining changes over time in MI incidence and case-fatality rates. We included confirmed cases of MI in 1995, 1997, 1999, 2001, and 2003. Long-term survival status was ascertained through 2005. A validated spatiotemporal land use regression model for traffic-related air pollution was developed and annual averages of elemental carbon at residence estimated. The effect of estimated elemental carbon on the long-term mortality of patients discharged after MI was analyzed using a Cox proportional hazards model, controlling for a variety of demographic, medical history, and clinical variables. RESULTS: Of the 3895 patients with validated MI, 44% died during follow-up. Exposure to estimated elemental carbon in the year of entry into the study was 0.44 microg/m on average. All-cause mortality increased by 15% (95% confidence interval = 0.03%-29%) per interquartile range increase in estimated yearly elemental carbon (0.24 microg/m) after the second year of survival. No association between traffic-related pollution and all-cause mortality was observed during the first 2 years of follow-up. CONCLUSIONS: Chronic traffic-related particulate air pollution is associated with increased mortality in hospital survivors of acute MI after the second year of survival.

Intensity of physical exertion and triggering of myocardial infarction: a case-crossover study.

AIMS: Acute myocardial infarction (AMI) can be precipitated or triggered by discrete transient exposures including physical exertion. We evaluated whether the risk of having an AMI triggered by physical exertion exhibits an exposure-response relationship, and whether it varies by ambient temperature or by taking place indoors or outdoors. METHODS AND RESULTS: We conducted a case-crossover study within the Myocardial Infarction Registry in Augsburg, Germany in 1999-2003. One thousand three hundred and one patients reported levels of activity and time spent outdoors on the day of AMI and three preceding days in an interview. The case-crossover analyses showed an association of physical exertion with AMI symptom onset within 2 h, which was strong for strenuous exertion (METs >or= 6) [relative risk (RR) 5.7, 95% confidence interval (CI) 3.6-9.0), and still significant for moderate exertion (METs = 5) (RR 1.6, 95% CI 1.2-2.1) compared to very light or no exertion. Strenuous exertion outside was associated with a four-fold larger RR of AMI symptom onset than exertion performed indoors, which was not explained by temperature. CONCLUSION: This study confirms previous results and shows a graded exposure-response relationship between physical exertion intensity and triggering of AMI onset. These findings may have implications for behavioural guidance of people at risk of AMI.

Exposure to traffic and the onset of myocardial infarction.

BACKGROUND: An association between exposure to vehicular traffic in urban areas and the exacerbation of cardiovascular disease has been suggested in previous studies. This study was designed to assess whether exposure to traffic can trigger myocardial infarction. METHODS: We conducted a case-crossover study in which cases of myocardial infarction were identified with the use of data from the Cooperative Health Research in the Region of Augsburg Myocardial Infarction Registry in Augsburg, in southern Germany, for the period from February 1999 to July 2001. There were 691 subjects for whom the date and time of the myocardial infarction were known who had survived for at least 24 hours after the event, completed the registry's standardized interview, and provided information on factors that may have triggered the myocardial infarction. Data on subjects' activities during the four days preceding the onset of symptoms were collected with the use of patient diaries. RESULTS: An association was found between exposure to traffic and the onset of a myocardial infarction within one hour afterward (odds ratio, 2.92; 95 percent confidence interval, 2.22 to 3.83; P<0.001). The time the subjects spent in cars, on public transportation, or on motorcycles or bicycles was consistently linked with an increase in the risk of myocardial infarction. Adjusting for the level of exercise on a bicycle or for getting up in the morning changed the estimated effect of exposure to traffic only slightly (odds ratio for myocardial infarction, 2.73; 95 percent confidence interval, 2.06 to 3.61; P<0.001). The subject's use of a car was the most common source of exposure to traffic; nevertheless, there was also an association between time spent on public transportation and the onset of a myocardial infarction one hour later. CONCLUSIONS: Transient exposure to traffic may increase the risk of myocardial infarction in susceptible persons.

Air pollution and inflammation (interleukin-6, C-reactive protein, fibrinogen) in myocardial infarction survivors.

BACKGROUND: Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation. OBJECTIVES: Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles. METHODS: A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004. We compared repeated measurements of interleukin 6 (IL-6), fibrinogen, and C-reactive protein (CRP) with concurrent levels of air pollution. We collected hourly data on particle number concentrations (PNC), mass concentrations of particulate matter (PM) < 10 microm (PM(10)) and < 2.5 microm (PM(2.5)), gaseous pollutants, and meteorologic data at central monitoring sites in each city. City-specific confounder models were built for each blood marker separately, adjusting for meteorology and time-varying and time-invariant covariates. Data were analyzed with mixed-effects models. RESULTS: Pooled results show an increase in IL-6 when concentrations of PNC were elevated 12-17 hr before blood withdrawal [percent change of geometric mean, 2.7; 95% confidence interval (CI), 1.0-4.6]. Five day cumulative exposure to PM(10) was associated with increased fibrinogen concentrations (percent change of arithmetic mean, 0.6; 95% CI, 0.1-1.1). Results remained stable for smokers, diabetics, and patients with heart failure. No consistent associations were found for CRP. CONCLUSIONS: Results indicate an immediate response to PNC on the IL-6 level, possibly leading to the production of acute-phase proteins, as seen in increased fibrinogen levels. This might provide a link between air pollution and adverse cardiac events.

Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities.

BACKGROUND: Ambient air pollution has been associated with increases in acute morbidity and mortality. The objective of this study was to evaluate the short-term effects of urban air pollution on cardiac hospital readmissions in survivors of myocardial infarction, a potentially susceptible subpopulation. METHODS AND RESULTS: In this European multicenter cohort study, 22,006 survivors of a first myocardial infarction were recruited in Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; and Stockholm, Sweden, from 1992 to 2000. Hospital readmissions were recorded in 1992 to 2001. Ambient nitrogen dioxide, carbon monoxide, ozone, and mass of particles <10 microm (PM10) were measured. Particle number concentrations were estimated as a proxy for ultrafine particles. Short-term effects of air pollution on hospital readmissions for myocardial infarction, angina pectoris, and cardiac causes (myocardial infarction, angina pectoris, dysrhythmia, or heart failure) were studied in city-specific Poisson regression analyses with subsequent pooling. During follow-up, 6655 cardiac readmissions were observed. Cardiac readmissions increased in association with same-day concentrations of PM10 (rate ratio [RR] 1.021, 95% CI 1.004 to 1.039) per 10 microg/m3) and estimated particle number concentrations (RR 1.026 [95% CI 1.005 to 1.048] per 10,000 particles/cm3). Effects of similar strength were observed for carbon monoxide (RR 1.014 [95% CI 1.001 to 1.026] per 200 microg/m3 [0.172 ppm]), nitrogen dioxide (RR 1.032 [95% CI 1.013 to 1.051] per 8 microg/m3 [4.16 ppb]), and ozone (RR 1.026 [95% CI 1.001 to 1.051] per 15 microg/m3 [7.5 ppb]). Pooled effect estimates for angina pectoris and myocardial infarction readmissions were comparable. CONCLUSIONS: The results suggest that ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in 5 European cities.

Pre-natal and post-natal exposure to respiratory infection and atopic diseases development: a historical cohort study.

BACKGROUND: According to the hygiene hypothesis, infections in early life protect from allergic diseases. However, in earlier studies surrogate measures of infection rather than clinical infections were associated with decreased frequencies of atopic diseases. Exposure to infection indicating sub-clinical infection rather than clinical infection might protect from atopic diseases. OBJECTIVE: to investigate whether exposure to acute respiratory infections within pregnancy and the first year of life is associated with atopic conditions at age 5-14 years and to explore when within pregnancy and the first year of life this exposure is most likely to be protective. METHODS: Historical cohort study: Population level data on acute respiratory infections from the routine reporting system of the former German Democratic Republic were linked with individual data from consecutive surveys on atopic diseases in the same region (n = 4672). Statistical analyses included multivariate logistic regression analysis and polynomial distributed lag models. RESULTS: High exposure to acute respiratory infection between pregnancy and age one year was associated with overall reduced odds of asthma, eczema, hay fever, atopic sensitization and total IgE. Exposure in the first 9 months of life showed the most pronounced effect. Adjusted odds ratio's for asthma, hay fever, inhalant sensitization and total IgE were statistical significantly reduced up to around half. CONCLUSION: Exposure to respiratory infection (most likely indicating sub-clinical infection) within pregnancy and the first year of life may be protective in atopic diseases development. The post-natal period thereby seems to be particularly important.

Comparison of different methods in analyzing short-term air pollution effects in a cohort study of susceptible individuals.

BACKGROUND: Short-term fluctuations of ambient air pollution have been associated with exacerbation of cardiovascular disease. A multi-city study was designed to assess the probability of recurrent hospitalization in a cohort of incident myocardial infarction survivors in five European cities. The objective of this paper is to discuss the methods for analyzing short-term health effects in a cohort study based on a case-series. METHODS: Three methods were considered for the analyses of the cohort data: Poisson regression approach, case-crossover analyses and extended Cox regression analyses. The major challenge of these analyses is to appropriately consider changes within the cohort over time due to changes in the underlying risk following a myocardial infarction, slow time trends in risk factors within the population, dynamic cohort size and seasonal variation. RESULTS: Poisson regression analyses, case-crossover analyses and Extended Cox regression analyses gave similar results. Application of smoothing methods showed the capability to adequately model the complex time trends. CONCLUSION: From a practical point of view, Poisson regression analyses are less time-consuming, and therefore might be used for confounder selection and most of the analyses. However, replication of the results with Cox models is desirable to assure that the results are independent of the analytical approach used. In addition, extended Cox regression analyses would allow a joint estimation of long-term and short-term health effects of time-varying exposures.

Particulate air pollution and nonfatal cardiac events. Part I. Air pollution, personal activities, and onset of myocardial infarction in a case-crossover study.

We conducted a prospective case-crossover study to assess the association of particulate air pollution with onset of nonfatal myocardial infarction (MI). Patients who had survived MIs between February 1999 and July 2001 were identified based on the Coronary Event Registry in Augsburg, Southern Germany. The study included 851 MI subjects with known date and time of MI who had survived the first 24 hours and had completed the Registry's standard interview. Of these subjects, 691 provided case and control information for subject-specific MI triggers collected by a diary assessing the 4 days before symptom onset. The exposures of interest were the total number concentration (TNC) of particles as an indicator for ultrafine particles and the mass of particles with an aerodynamic diameter no larger than 2.5 microm (PM2.5). We conducted conditional logistic regression analyses using different control-selection strategies in a case-crossover approach, and Poisson regression analyses of the time-series data.

Aerosol particle number concentration measurements in five European cities using TSI-3022 condensation particle counter over a three-year period during health effects of air pollution on susceptible subpopulations.

In this study, long-term aerosol particle total number concentration measurements in five metropolitan areas across Europe are presented. The measurements have been carried out in Augsburg, Barcelona, Helsinki, Rome, and Stockholm using the same instrument, a condensation particle counter (TSI model 3022). The results show that in all of the studied cities, the winter concentrations are higher than the summer concentrations. In Helsinki and in Stockholm, winter concentrations are higher by a factor of two and in Augsburg almost by a factor of three compared with summer months. The winter maximum of the monthly average concentrations in these cities is between 10,000 cm(-3) and 20,000 cm(-3), whereas the summer min is approximately 5000-6000 cm(-3). In Rome and in Barcelona, the winters are more polluted compared with summers by as much as a factor of 4-10. The winter maximum in both Rome and Barcelona is close to 100,000 cm(-3), whereas the summer minimum is > 10,000 cm(-3). During the weekdays the maximum of the hourly average concentrations in all of the cities is detected during the morning hours between 7 and 10 a.m. The evening maxima were present in Barcelona, Rome, and Augsburg, but these were not as pronounced as the morning ones. The daily maxima in Helsinki and Stockholm are close or even lower than the daily minima in the more polluted cities. The concentrations between these two groups of cities are different with a factor of about five during the whole day. The study pointed out the influence of the selection of the measurement site and the configuration of the sampling line on the observed concentrations.

Triggering of acute myocardial infarction by different means of transportation.

BACKGROUND: Prior studies have reported an association between traffic-related air pollution in urban areas and exacerbation of cardiovascular disease. We assess here whether time spent in different modes of transportation can trigger the onset of acute myocardial infarction (AMI). DESIGN: We performed a case-crossover study. We interviewed consecutive cases of AMI in the KORA Myocardial Infarction Registry in Augsburg, Southern Germany between February 1999 and December 2003 eliciting data on potential triggers in the four days preceding myocardial infarction onset. RESULTS: A total of 1459 cases with known date and time of AMI symptom onset, who had survived 24 hours after the onset, completed the registry's standard interview on potential triggers of AMI. An association between exposure to traffic and AMI onset 1 hour later was observed (odds ratio: 3.2; 95% confidence interval [CI]: 2.7-3.9, p < 0.001). Using a car was the most common source of traffic exposure; nevertheless, times spent in public transport or on a bicycle were similarly associated with AMI onset 1 hour later. While the highest risk for AMI onset was within 1 hour of exposure to traffic, the elevated risk persisted for up to 6 hours. Women, patients aged 65 years or older, patients not part of the workforce, and those with a history of angina or diabetes exhibited the largest associations between times spent in traffic and AMI onset 1 hour later. CONCLUSION: The data suggest that transient exposure to traffic regardless of the means of transportation may increase the risk of AMI transiently.

Selection of key ambient particulate variables for epidemiological studies - applying cluster and heatmap analyses as tools for data reduction.

The success of epidemiological studies depends on the use of appropriate exposure variables. The purpose of this study is to extract a relatively small selection of variables characterizing ambient particulate matter from a large measurement data set. The original data set comprised a total of 96 particulate matter variables that have been continuously measured since 2004 at an urban background aerosol monitoring site in the city of Augsburg, Germany. Many of the original variables were derived from measured particle size distribution (PSD) across the particle diameter range 3 nm to 10 µm, including size-segregated particle number concentration, particle length concentration, particle surface concentration and particle mass concentration. The data set was complemented by integral aerosol variables. These variables were measured by independent instruments, including black carbon, sulfate, particle active surface concentration and particle length concentration. It is obvious that such a large number of measured variables cannot be used in health effect analyses simultaneously. The aim of this study is a pre-screening and a selection of the key variables that will be used as input in forthcoming epidemiological studies. In this study, we present two methods of parameter selection and apply them to data from a two-year period from 2007 to 2008. We used the agglomerative hierarchical cluster method to find groups of similar variables. In total, we selected 15 key variables from 9 clusters which are recommended for epidemiological analyses. We also applied a two-dimensional visualization technique called "heatmap" analysis to the Spearman correlation matrix. 12 key variables were selected using this method. Moreover, the positive matrix factorization (PMF) method was applied to the PSD data to characterize the possible particle sources. Correlations between the variables and PMF factors were used to interpret the meaning of the cluster and the heatmap analyses.

Estimated personal soot exposure is associated with acute myocardial infarction onset in a case-crossover study.

The current study investigates the association of estimated personal exposure to traffic-related air pollution and acute myocardial infarction (AMI). Cases of AMI were interviewed in the Augsburg KORA Myocardial Infarction Registry from February 1999 through December 2003, and 960 AMI survivors were included in the analyses. The time-varying component of daily personal soot exposure (the temporally variable contribution due to the daily area level of exposure and daily personal activities) was estimated using a linear combination of estimated mean ambient soot concentration, time spent outdoors, and time spent in traffic. The association of soot exposure with AMI onset was estimated in a case-crossover analysis controlling for temperature and day of the week using conditional logistic regression analyses. Estimated personal soot exposure was associated with AMI (relative risk, 1.30 per 1.1 m(-1) × 10(-5) [95% confidence interval, 1.09-1.55]). Estimated ambient soot and measured ambient PM(2.5) particulate matter 2.5 µm and smaller in aerodynamic diameter were not significantly associated with AMI onset. Our results suggest that an increase in risk of AMI in association with personal soot exposure may be in great part due to the contribution of personal soot from individual times spent in traffic and individual times spent outdoors. As a consequence, estimates calculated based on measurements at urban background stations may be underestimations. Health effects of traffic-related air pollution may need to be updated, taking into account individual time spent in traffic and outdoors, to adequately protect the public.