Raymond M Agius

Publications of Raymond M Agius

• Is there a place for a computer based asthma hazard prediction model in clinical practice?

  Authors: Jacques André Pralong, Martin J Seed, André Cartier, Raymond M Agius, Manon Labrecque

  Occupational and environmental medicine. 05/2012;

• Does socio-economic status modify the effect of particulate air pollution on cardiorespiratory mortality?

  Authors: Melanie Carder, Roseanne McNamee, Iain Beverland, Robert A Elton, Geoff Cohen, James Boyd, Martie van van Tongeren, Raymond M Agius

  Occupational and environmental medicine. 09/2009;

  OBJECTIVES: To investigate whether deprivation index modifies the acute effect of black smoke on cardiorespiratory mortality. METHODS: Generalised linear Poisson regression models were used toOBJECTIVES: To investigate whether deprivation index modifies the acute effect of black smoke on cardiorespiratory mortality. METHODS: Generalised linear Poisson regression models were used to investigate whether deprivation index (as measured by the Carstairs deprivation index) modified the acute effect of black smoke on mortality in the two largest Scottish cities (Glasgow and Edinburgh) between January 1981 and December 2001. Lag periods of up to one month were assumed for the effects of black smoke. RESULTS: Deprivation index significantly modified the effect of black smoke on mortality with black smoke effects generally increasing as level of deprivation increased. The interaction coefficient from a parametric model assuming a linear interaction between black smoke (microgm-3) and deprivation in their effect on mortality - equivalent to a test of 'linear trend' across Carstairs Categories - was significant for all mortality outcomes. In a model where black smoke effects were estimated independently for each deprivation category, the estimated increase in respiratory mortality over the ensuing one-month period associated with a 10microgm-3 increase in the mean black smoke concentration was 8.0 percent (95% CI: 5.1, 10.9) for subjects residing in the 'most' deprived category (Carstairs category 7) compared to 3.7 percent (95% CI: -0.7, 8.4) for subjects residing in the 'least' deprived category (Carstairs category 1). CONCLUSIONS: The results suggest a stronger effect of black smoke on mortality among people living in more deprived areas. The effect was greatest for respiratory mortality although significant trends were also seen for other groups. If corroborated, these findings could have important public health implications.

• GSTM1 copy number and lung cancer risk.

  Authors: Philip A J Crosbie, Philip V Barber, Kathryn L Harrison, Alan R Gibbs, Raymond M Agius, Geoffrey P Margison, Andrew C Povey

  Mutation research. 06/2009; 664(1-2):1-5.

  The GSTM1 null genotype is associated with a small increased lung cancer risk when compared to controls with at least one copy of the GSTM1 gene. As two copies of the GSTM1 gene might provide moreThe GSTM1 null genotype is associated with a small increased lung cancer risk when compared to controls with at least one copy of the GSTM1 gene. As two copies of the GSTM1 gene might provide more protection than a single copy, we have determined GSTM1 copy number in a lung cancer case-control study. Cases with incident lung cancer were identified through a Bronchoscopy Unit and two separate hospital based control groups with non-malignant disease were selected with one from the same Bronchoscopy Unit and the other from a chest clinic at the same hospital. Subjects with at least one GSTM1 copy had a decreased lung cancer risk whatever the control group: the odds ratio (95% CI), after adjustment for age, gender and smoking duration, was 0.64 (0.41-0.98) and 0.54 (0.32-0.91) with bronchoscopy and chest clinic controls, respectively. Lung cancer risk varied with GSTM1 copy number with chest clinic controls only: the OR was 0.56 (0.32-0.97) for one copy of the GSTM1 gene and with two copies 0.43 (0.15-1.22), a trend that was significant (p=0.02): with bronchoscopy controls the trend was not significant (p=0.07). Results then confirm that the presence of GSTM1 provides protection against the risk of lung cancer. In addition there is equivocal evidence that this protection varies with the number of gene copies.

• A time-series study of the health effects of water-soluble and total-extractable metal content of airborne particulate matter.

  Authors: Mathew R Heal, Robert A Elton, Leon R Hibbs, Raymond M Agius, Iain J Beverland

  Occupational and environmental medicine. 06/2009;

  OBJECTIVES: To assess whether adverse acute cardiopulmonary health outcomes are associated with concentration of trace metals in airborne particulate matter. METHODS: Daily PM10 and PM2.5 wasOBJECTIVES: To assess whether adverse acute cardiopulmonary health outcomes are associated with concentration of trace metals in airborne particulate matter. METHODS: Daily PM10 and PM2.5 was collected for one year in Edinburgh, UK, and the water-soluble and total-extractable content of 11 trace metals determined in each sample. Time series were analysed using generalised additive Poisson regression models, including adjustment for minimum temperature and loess smoothing of trends. Methods were explored of extending the time series of metal concentration in daily PM10 for the previous 7 years using multiple regression of the variation in metal content for the 1 year of measurements and the associated variation in air mass source region and other concurrently-measured potential predictor variables. RESULTS: The 1 year of direct measurements showed no evidence of significant associations of particle-bound metal concentration with health outcomes beyond that expected by chance. Analysis of the extended time series showed significant positive associations with cardiovascular admissions both for total PM10 and for a number of the metals (e.g. Cu, Fe, Ni, V, Zn) but the metal effects were no longer significant after adjusting for PM10. CONCLUSIONS: Within the limitations of its power, the epidemiological results have not provided evidence for associations between particle-bound metal concentrations and adverse health outcomes that are substantially greater than for total PM. The generally strong correlations between metal and total PM suggest that quantifying independent effects of PM metal exposure on health will be difficult, even using more powerful time series of direct measurements.

• Methods for the prediction of low-molecular-weight occupational respiratory sensitizers.

  Authors: Martin J Seed, Paul Cullinan, Raymond M Agius

  Current opinion in allergy and clinical immunology. 05/2008; 8(2):103-9.

  PURPOSE OF REVIEW: There is recognition that respiratory sensitization is an occupational hazard of high concern. Despite international regulatory requirements there is no established protocol forPURPOSE OF REVIEW: There is recognition that respiratory sensitization is an occupational hazard of high concern. Despite international regulatory requirements there is no established protocol for the efficient prospective identification of chemical respiratory sensitizers. We review the predictive behaviour of available methods and suggest a possible high-throughput protocol. RECENT FINDINGS: Animal or in-vitro tests specific to respiratory exposure and resulting in direct asthma-related outcomes have not been developed, although the use of a local lymph node assay originally designed for skin sensitization has been advocated in a respiratory context. Various methods have been used to develop quantitative structure-activity relationship models for prediction of low-molecular-weight organic chemical respiratory sensitizers. The estimated negative predictive value for all of the published models is 1, but their differences in positive predictive value can be exploited. SUMMARY: The most pragmatic as well as valid approach for screening large numbers of industrial chemicals for respiratory sensitization hazard is likely to consist of an algorithm starting with quantitative structure-activity relationship models. Further corroboration from animal or human data, however, may be required for chemicals with a positive result by quantitative structure-activity relationship.

• Association between lung cancer risk and single nucleotide polymorphisms in the first intron and codon 178 of the DNA repair gene, O6-alkylguanine-DNA alkyltransferase.

  Authors: Philip A J Crosbie, Gail McGown, Mary R Thorncroft, Paul N S O'Donnell, Philip V Barber, Sarah J Lewis, Kathryn L Harrison, Raymond M Agius, Mauro F Santibáñez-Koref, Geoffrey P Margison, Andrew C Povey

  International journal of cancer. Journal international du cancer. 02/2008; 122(4):791-5.

  The association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase, which are associated withThe association between lung cancer risk and 2 polymorphisms, rs12268840 and rs2308327 (codon K178R), in the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase, which are associated with interindividual differences in activity, have been investigated in 3 hospital-based case-control studies. Genotyping was carried out on 617 subjects of whom 255 had lung cancer. In 2 of the 3 series, there was a significant inverse association between the 178R allele and case status (p < 0.05). In a meta-analysis, the odds ratio (95% CI) associated with the 178R allele relative to the 178K allele was 0.64 (0.45-0.92, p = 0.01) and 0.51 (0.24-1.11, p = 0.09) in fixed effects and random effects models, respectively. In a pooled analysis, after adjustment for sex, age, pack years and series, the OR (95% CI) for a heterozygote was 0.67 (0.45-1.01) and for a 178R homozygote was 0.10 (0.01-0.94); the trend for a decreased risk with the number of R alleles was significant (p = 0.008). This trend was particularly pronounced in heavy smokers (trend test p = 0.003), but not significant in light smokers (p = 0.73). There was no evidence of an association between rs12268840 and lung cancer risk. These results suggest that the R allele may protect against lung cancer, specifically in heavy smokers, an effect that may result from this polymorphism affecting the function of the MGMT protein and/or levels in MGMT activity.

• No association between N7-methyldeoxyguanosine and 8-oxodeoxyguanosine levels in human lymphocyte DNA.

  Authors: Kathryn L Harrison, Philip A J Crosbie, Raymond M Agius, Philip V Barber, Mark Carus, Geoffrey P Margison, Andrew C Povey

  Mutation research. 09/2006; 600(1-2):125-30.

  To examine associations between two different classes of DNA damage that can occur through endogenous processes or exogenous exposures such as smoking, N7-methyldeoxyguanosine (N7-MedG) andTo examine associations between two different classes of DNA damage that can occur through endogenous processes or exogenous exposures such as smoking, N7-methyldeoxyguanosine (N7-MedG) and 8-oxodeoxyguanosine (8-oxodG) levels were measured in lymphocyte DNA from 22 bronchoscopy patients. 8-OxodG and N7-MedG was detected in 100% and 91% of samples, respectively with 8-oxodG levels being approx 20 times higher (mean 8.39+/-3.578-oxodG/10(6)dG versus 0.41+/-0.33 N7-MedG/10(6) dG) which provides an indication of the relative importance of the agents that induce oxidative DNA damage or alkylation damage. The sources of these genotoxic lesions remain to be established but N7-MedG and 8-oxodG levels were not correlated (r(2)<0.01) suggesting that there is no association between alkylating agent and reactive oxygen species exposure, their metabolism and/or the DNA repair processes that can remove this DNA damage.

• No association between N7-methyldeoxyguanosine and 8-oxodeoxyguanosine levels in human lymphocyte DNA

  Authors: Kathryn L. Harrison, Philip A.J. Crosbie, Raymond M. Agius, Philip V. Barber, Mark Carus, Geoffrey P. Margison, Andrew C. Povey

  Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.

  To examine associations between two different classes of DNA damage that can occur through endogenous processes or exogenous exposures such as smoking, N7-methyldeoxyguanosine (N7-MedG) andTo examine associations between two different classes of DNA damage that can occur through endogenous processes or exogenous exposures such as smoking, N7-methyldeoxyguanosine (N7-MedG) and 8-oxodeoxyguanosine (8-oxodG) levels were measured in lymphocyte DNA from 22 bronchoscopy patients. 8-OxodG and N7-MedG was detected in 100% and 91% of samples, respectively with 8-oxodG levels being approx 20 times higher (mean 8.39 ± 3.57 8-oxodG/106dG versus 0.41 ± 0.33 N7-MedG/106 dG) which provides an indication of the relative importance of the agents that induce oxidative DNA damage or alkylation damage. The sources of these genotoxic lesions remain to be established but N7-MedG and 8-oxodG levels were not correlated (r2 < 0.01) suggesting that there is no association between alkylating agent and reactive oxygen species exposure, their metabolism and/or the DNA repair processes that can remove this DNA damage.

• Interpretation of variations in fine, coarse and black smoke particulate matter concentrations in a northern European city

  Authors: Mathew R. Heal, Leon R. Hibbs, Raymond M. Agius, Iain J. Beverland

  Atmospheric Environment.

  The PM2.5, PMcoarse and black smoke (BS) particle metrics broadly reflect different source contributions to PM10. The aim of this study was to generate data for PM2.5 at an urban background site inThe PM2.5, PMcoarse and black smoke (BS) particle metrics broadly reflect different source contributions to PM10. The aim of this study was to generate data for PM2.5 at an urban background site in the UK, and to use the daily collocated measurement of PM2.5, PM10 (and hence PMcoarse) and BS to yield insight into source influences on particulate matter for input to developing PM air quality policy. Mean daily PM10, PM2.5 and BS for a year of measurement in Edinburgh were 15.5, 8.5 and 6.6 μg m−3. The PM2.5 data were well-within possible future limit values proposed by the European Commission Clean Air For Europe programme. Daily PM2.5 and PM10 were significantly correlated (r2=0.75) with PM2.5 contributing 54%, on average, to PM10. The daily BS:PM10 and BS:PM2.5 ratios were more variable, and significantly lower in summer than in winter, reflecting the greater contribution of non-black photochemical secondary particles to PM10 in summer. Analysis with respect to wind showed a dominant influence of dispersion on BS and PM2.5 but both dispersion and a wind-driven suspension influence on PMcoarse. The latter was higher than in central England (averaging about one-third of the PMcoarse), and greater for on-shore wind direction, suggesting a sea-salt source for this component in addition to other particle resuspension contributions. Overall, the data showed that excursions in PM10 were driven more by variations in PM2.5 than by PMcoarse or BS. Both PM2.5 and its proportion to PM10 were significantly elevated for air-masses passing over continental Europe and the British Isles, whereas BS varied less with air-mass origin, supporting the conclusion that concentrations of particulate matter, particularly of finer PM, are strongly influenced by regional scale synoptic meteorology (presumed to be predominantly secondary PM), whereas BS is dominated more by local sources. Comparison of BS with a nearby rural site suggested that approximately three-quarters, on average, of the urban BS was local in origin.

• Total and water-soluble trace metal content of urban background PM10, PM2.5 and black smoke in Edinburgh, UK

  Authors: Mathew R. Heal, Leon R. Hibbs, Raymond M. Agius, Iain J. Beverland

  Atmospheric Environment.

  Toxicological studies have implicated trace metals in airborne particles as possible contributors to respiratory and/or cardiovascular inflammation. As part of an epidemiological study, co-located 24Toxicological studies have implicated trace metals in airborne particles as possible contributors to respiratory and/or cardiovascular inflammation. As part of an epidemiological study, co-located 24 h samples of PM10, PM2.5 and black smoke (BS) were collected for 1 year at an urban background site in Edinburgh, and each sample sequentially extracted with ultra-pure water, then concentrated HNO3/HCl, and analysed for Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd and Pb. This yields a comprehensive data set for UK urban airborne trace metal. The median (n>349) daily water-soluble metal concentration in PM2.5 ranged from 0.05 ng m−3 for Ti to 5.1 ng m−3 for Pb; and in PM10 from 0.18 ng m−3 for Ti to 11.7 ng m−3 for Fe. Median daily total (i.e. water+acid-extractable) metal concentration in PM2.5 ranged from 0.3 ng m−3 for As to 27.6 ng m−3 for Fe; and in PM10 from 0.37 ng m−3 for As to 183 ng m−3 for Fe. The PM2.5:PM10 ratio varied considerably with metal, from <17%, on average, for Ti and Fe, to >70% for V, As, Cd and Pb. The 11 trace metals constituted proportionally more of the PM10–2.5 fraction than of the PM2.5 fraction (0.9%). The proportion of water-soluble metal in each size-fraction varied considerably, from <10% water-soluble Fe and Ti in PM10−2.5, to >50% water-soluble V, Zn, As and Cd in PM2.5. Although Fe generally dominated the trace metal, water-soluble metal also contained significant Zn, Pb and Cu, and for all size and solubility fractions >90% of trace metal was comprised of Fe, Zn, Pb and Cu. Statistical analyses suggested three main sources: traffic; static combustion; and crustal. The association of metals with traffic (Cu, Fe, Mn, Pb, Zn) was consistent with traffic-induced non-exhaust “resuspension” rather than direct exhaust emission. Meteorology contributed to the wide variation in daily trace metal concentration. The proportion of trace metal in particles varied significantly with the air mass source and was highest on days for trajectories traversing over land. For Mn, Fe, Cu, Zn, As and Pb there was greater correlation of metal concentration with BS mass than with either PM10 or PM2.5 mass, suggesting that BS reflectance monitoring could be a cost-effective surrogate measure of particle metal concentration in urban background air.

• The Metal Content of Airborne Particles in Edinburgh: Application to Epidemiological Research

  Authors: Leon R Hibbs, Iain J Beverland, Mat R. Heal, Raymond M Agius, Rob Elton, D Fowler, J N Cape

  Metals are putative causative agents in the association between ill health and exposure to airborne particles. We present preliminary results from an epidemiological study using exposure metrics ofMetals are putative causative agents in the association between ill health and exposure to airborne particles. We present preliminary results from an epidemiological study using exposure metrics of metal contained in PM 10 , PM 2.5 and black smoke. A 1 yr monitoring and analysis campaign has been completed for 11 metals at 24 h sampling resolution. Empirical models of environmental determinants of metal concentration have been used to retrospectively extrapolate the pollutant time series. We are currently evaluating whether the use of metal concentration explains more of the variance in the population exposure-response relationship compared with the use of particle mass concentration alone.