Pooled biological specimens for human biomonitoring of environmental chemicals : opportunities and limitations

Biomonitoring has become the ‘gold standard’ in assessing chemical exposures, and plays an important role in risk assessment. The pooling of biological specimens – combining multiple individual specimens into a single sample – can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends, or to identify susceptible populations in a cost-effective manner. Pooled samples provide an estimate of central tendency, and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of samples collected, the number of pools required, and the number of specimens to combine per pool in order to maximize the type and robustness of the data. Creative pooling strategies can be used to explore exposure-outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific individuals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment, and in certain circumstances, allows quantification of samples approaching the limit of detection. In addition, use of pooled samples can provide population estimates while avoiding ethical difficulties that may be associated with reporting individual results.

Benefits of publicly available data

The National Morbidity, Mortality, and Air Pollution Study (NMMAPS) was designed to examine the health effects of air pollution in the United States. The primary question was whether particulate matter was responsible for the associations between air pollution and daily mortality. Secondary questions concerned measurement error in air pollution and mortality displacement.1 Since then, NMMAPS has been used to answer many important questions in environmental epidemiology...

Estimating vulnerable windows of exposure to air pollution during pregnancy

Exposure to air pollution during pregnancy is a potential cause of adverse birth outcomes such as preterm birth and stillbirth. The risk of exposure may be greater during vulnerable windows of the pregnancy which might only be weeks long. We demonstrate a method to find these windows based on smoothing the risk of weekly exposure using conditional autoregression. We use incidence density sampling to match cases with adverse birth outcomes to controls whose gestation lasted at least as long as the case. This matching means that cases and controls are have equal length exposure periods, rather than comparing, for example, cases with short gestations to controls with longer gestations. We demonstrate the ability of the method to find vulnerable windows using two simulation studies. We illustrate the method by examining the association between particulate matter air pollution and stillbirth in Brisbane, Australia.

Challenges to environmental toxicology and epidemiology : where do we stand and which way do we go?

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today’s settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene–environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.

Exploratory spatial analysis of social and environmental factors associated with the incidence of Ross River Virus in Brisbane, Australia

We used geographic information systems and a spatial analysis approach to explore the pattern of Ross River virus (RRV) incidence in Brisbane, Australia. Climate, vegetation and socioeconomic data in 2001 were obtained from the Australian Bureau of Meteorology, the Brisbane City Council and the Australian Bureau of Statistics, respectively. Information on the RRV cases was obtained from the Queensland Department of Health. Spatial and multiple negative binomial regression models were used to identify the socioeconomic and environmental determinants of RRV transmission. The results show that RRV activity was primarily concentrated in the northeastern, northwestern, and southeastern regions in Brisbane. Multiple negative binomial regression models showed that the spatial pattern of RRV disease in Brisbane seemed to be determined by a combination of local ecologic, socioeconomic, and environmental factors.

The Queensland study of melanoma : Environmental and genetic associations (Q-MEGA); Study design, baseline characteristics, and repeatability of phenotype and sun exposure measures

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the world’s highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002-2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

Preliminary spatiotemporal analysis of the association between socio-environmental factors and suicide

Background: The seasonality of suicide has long been recognised. However, little is known about the relative importance of socio-environmental factors in the occurrence of suicide in different geographical areas. This study examined the association of climate, socioeconomic and demographic factors with suicide in Queensland, Australia, using a spatiotemporal approach. Methods: Seasonal data on suicide, demographic variables and socioeconomic indexes for areas in each Local Government Area (LGA) between 1999 and 2003 were acquired from the Australian Bureau of Statistics. Climate data were supplied by the Australian Bureau of Meteorology. A multivariable generalized estimating equation model was used to examine the impact of socio-environmental factors on suicide. Results: The preliminary data analyses show that far north Queensland had the highest suicide incidence (e.g., Cook and Mornington Shires), while the south-western areas had the lowest incidence (e.g., Barcoo and Bauhinia Shires) in all the seasons. Maximum temperature, unemployment rate, the proportion of Indigenous population and the proportion of population with low individual income were statistically significantly and positively associated with suicide. There were weaker but not significant associations for other variables. Conclusions: Maximum temperature, the proportion of Indigenous population and unemployment rate appeared to be major determinants of suicide at a LGA level in Queensland.

P2-486 Environmental temperature variation and morbidity: a meta-analysis

Extreme temperatures have been shown to have a detrimental effect on health. Hot temperatures can increase the risk of mortality, particularly in people suffering from cardiorespiratory diseases. Given the onset of climate change, it is critical that the impact of temperature on health is understood, so that effective public health strategies can correctly identify vulnerable groups within the population. However, while effects on mortality have been extensively studied, temperature–related morbidity has received less attention. This study applied a systematic review and meta–analysis to examine the current literature relating to hot temperatures and morbidity.

Estimating the effects of environmental exposures using a weighted mean of monitoring stations

The health effects of environmental hazards are often examined using time series of the association between a daily response variable (e.g., death) and a daily level of exposure (e.g., temperature). Exposures are usually the average from a network of stations. This gives each station equal importance, and negates the opportunity for some stations to be better measures of exposure. We used a Bayesian hierarchical model that weighted stations using random variables between zero and one. We compared the weighted estimates to the standard model using data on health outcomes (deaths and hospital admissions) and exposures (air pollution and temperature) in Brisbane, Australia. The improvements in model fit were relatively small, and the estimated health effects of pollution were similar using either the standard or weighted estimates. Spatial weighted exposures would be probably more worthwhile when there is either greater spatial detail in the health outcome, or a greater spatial variation in exposure.

Traffic-related fine and ultrafine particle exposures of professional drivers and illness : An opportunity to better link exposure science and epidemiology to address an occupational hazard?

Exposures to traffic-related air pollution (TRAP) can be particularly high in transport microenvironments (i.e. in and around vehicles) despite the short durations typically spent there. There is a mounting body of evidence that suggests that this is especially true for fine (b2.5 μm) and ultrafine (b100 nm, UF) particles. Professional drivers, who spend extended periods of time in transport microenvironments due to their job, may incur exposures markedly higher than already elevated non-occupational exposures. Numerous epidemiological studies have shown a raised incidence of adverse health outcomes among professional drivers, and exposure to TRAP has been suggested as one of the possible causal factors. Despite this, data describing the range and determinants of occupational exposures to fine and UF particles are largely conspicuous in their absence. Such information could strengthen attempts to define the aetiology of professional drivers' illnesses as it relates to traffic combustion-derived particles. In this article, we suggest that the drivers' occupational fine and UF particle exposures are an exemplar case where opportunities exist to better link exposure science and epidemiology in addressing questions of causality. The nature of the hazard is first introduced, followed by an overview of the health effects attributable to exposures typical of transport microenvironments. Basic determinants of exposure and reduction strategies are also described, and finally the state of knowledge is briefly summarised along with an outline of the main unanswered questions in the topic area.

The epidemiology of basal cell carcinoma

Basal cell carcinoma (BCC) is a skin cancer of particular importance to the Australian community. Its rate of occurrence is highest in Queensland, where 1% to 2% of people are newly affected annually. This is an order of magnitude higher than corresponding incidence estimates in European and North American populations. Individuals with a sun-sensitive complexion are particularly susceptible because sun exposure is the single most important causative agent, as shown by the anatomic distribution of BCC which is in general consistent with the levels of sun exposure across body sites. A distinguishing feature of BCC is the occurrence of multiple primary tumours within individuals, synchronously or over time, and their diagnosis and treatment costs contribute substantially to the major public health burden caused by BCC. A primary knowledge gap about BCC pathogenesis however was an understanding of the true frequency of multiple BCC occurrences and their body distribution, and why a proportion of people do develop more than one BCC in their life. This research project sought to address this gap under an overarching research aim to better understand the detailed epidemiology of BCC with the ultimate goal of reducing the burden of this skin cancer through prevention. The particular aim was to document prospectively the rate of BCC occurrence and its associations with constitutional and environmental (solar) factors, all the while paying special attention to persons affected by more than one BCC. The study built on previous findings and recent developments in the field but set out to confirm and extend these and propose more adequate theories about the complex epidemiology of this cancer. Addressing these goals required a new approach to researching basal cell carcinoma, due to the need to account for the phenomenon of multiple incident BCCs per person. This was enabled by a 20 year community-based study of skin cancer in Australians that provided the methodological foundation for this thesis. Study participants were originally randomly selected in 1986 from the electoral register of all adult residents of the subtropical township of Nambour in Queensland, Australia. On various occasions during the study, participants were fully examined by dermatologists who documented cumulative photodamage as well as skin cancers. Participants completed standard questionnaires about skin cancer-related factors, and consented to have any diagnosed skin cancers notified to the investigators by regional pathology laboratories in Queensland. These methods allowed 100% ascertainment of histologically confirmed BCCs in this study population. 1339 participants had complete follow-up to the end of 2007. Statistical analyses in this thesis were carried out using SAS and SUDAAN statistical software packages. Modelling methods, including multivariate logistic regressions, allowed for repeated measures in terms of multiple BCCs per person. This innovative approach gave new findings on two levels, presented in five chapters as scientific papers: 1. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population The incidence of people affected multiple times by BCC was 705 per 100,000 person years compared to an incidence rate of people singly affected of 935 per 100,000 person years. Among multiply and singly affected persons alike, site-specific BCC incidence rates were far highest on facial subsites, followed by upper limbs, trunk, and then lower limbs 2. Melanocytic nevi and basal cell carcinoma: is there an association? BCC risk was significantly increased in those with forearm nevi (Odds Ratios (OR) 1.43, 95% Confidence Intervals (CI) 1.09-1.89) compared to people without forearm nevi, especially among those who spent their time mainly outdoors (OR 1.6, 95%CI 1.1-2.3) compared to those who spent their time mainly indoors. Nevi on the back were not associated with BCC. 3. Clinical signs of photodamage are associated with basal cell carcinoma multiplicity and site: a 16-year longitudinal study Over a 16-year follow-up period, 58% of people affected by BCC developed more than one BCC. Among these people 60% developed BCCs across different anatomic sites. Participants with high numbers of solar keratoses, compared to people without solar keratoses, were most likely to experience the highest BCC counts overall (OR 3.3, 95%CI 1.4-13.5). Occurrences of BCC on the trunk (OR 3.3, 95%CI 1.4-7.6) and on the limbs (OR 3.7, 95%CI 2.0-7.0) were strongly associated with high numbers of solar keratoses on these sites. 4. Occurrence and determinants of basal cell carcinoma by histological subtype in an Australian community Among 1202 BCCs, 77% had a single growth pattern and 23% were of mixed histological composition. Among all BCCs the nodular followed by the superficial growth patterns were commonest. Risk of nodular and superficial BCCs on the head was raised if 5 or more solar keratoses were present on the face (OR 1.8, 95%CI 1.2-2.7 and OR 4.5, 95%CI 2.1-9.7 respectively) and similarly on the trunk in the presence of multiple solar keratoses on the trunk (OR 4.2, 95%CI 1.5-11.9 and OR 2.2, 95%CI 1.1-4.4 respectively). 5. Basal cell carcinoma and measures of cumulative sun exposure: an Australian longitudinal community-based study Dermal elastosis was more likely to be seen adjacent to head and neck BCCs than trunk BCCs (p=0.01). Severity of dermal elastosis increased on each site with increasing clinical signs of cutaneous sun damage on that site. BCCs that occurred without perilesional elastosis per se, were always found in an anatomic region with signs of photodamage. This thesis thus has identified the magnitude of the burden of multiple BCCs. It does not support the view that people affected by more than one BCC represent a distinct group of people who are prone to BCCs on certain body sites. The results also demonstrate that BCCs regardless of site, histology or order of occurrence are strongly associated with cumulative sun exposure causing photodamage to the skin, and hence challenge the view that BCCs occurring on body sites with typically low opportunities for sun exposure or of the superficial growth pattern are different in their association with the sun from those on typically sun-exposed sites, or nodular BCCs, respectively. Through dissemination in the scientific and medical literature, and to the community at large, these findings can ultimately assist in the primary and secondary prevention of BCC, perhaps especially in high-risk populations.